Ovarian Cancer Treatment Regimens
|
|
|
|
Ovarian Cancer Treatment Regimens |
|
|
Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. |
|
|
Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The National Comprehensive Cancer Network Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. |
|
|
Note: All recommendations are category 2A unless otherwise indicated. |
|
|
▶Primary Systemic Therapy for Epithelial Ovarian/Fallopian Tube/Primary Peritoneal Cancer1,a |
|
|
REGIMEN |
DOSING |
|
Stage I Disease |
|
|
Carboplatin + Liposomal Doxorubicin2,3 |
Day 1: Carboplatin AUC 5 IV Day 1: Liposomal Doxorubicin 30mg/m2 IV. Repeat every 4 weeks for 3-6 cycles for stage I disease or 6 cycles for stage II-IV disease or high-grade stage I disease. |
|
Docetaxel + Carboplatin4-6 |
Day 1: Docetaxel 60-75mg/m2 IV over 60 minutes, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 3-6 cycles (stage I) or 6 cycles if stage II-IV or high grade serous. |
|
Paclitaxel + Carboplatin (preferred)3,7 |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 3-6 cycles.b OR Days 1,8,15: Paclitaxel 80mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. OR Day 1: Paclitaxel 60mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 2 IV over 30 minutes. Repeat cycle weekly for 18 weeks.c |
|
Stage II-IV Disease |
|
|
IP/IV Regimens |
|
|
Paclitaxel + Cisplatin10 |
Day 1: Paclitaxel 135mg/m2 IV over 3 hours or IV continuous infusion over 24 hours Day 2: Cisplatin 75-100mg/m2 intraperitoneal (IP) infused as rapidly as possible via IP portd Day 8: Paclitaxel 60mg/m2 IP infused as rapidly as possible via IP port.e Repeat cycle every 3 weeks for 6 cycles. |
|
IV Regimens |
|
|
Carboplatin + Liposomal Doxorubicin2,3 |
Day 1: Carboplatin AUC 5 IV Day 1: Liposomal Doxorubicin 30mg/m2 IV. Repeat every 4 weeks for 6 cycles. |
|
Docetaxel + Carboplatin4-6 |
Day 1: Docetaxel 60-75mg/m2 IV over 60 minutes, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. |
|
Paclitaxel + Carboplatin3,7-9 |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. OR Days 1,8,15: Paclitaxel 80mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. OR Day 1: Paclitaxel 60mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 2 IV over 30 minutes. Repeat cycle weekly for 18 weeks.c |
|
Paclitaxel + Carboplatin +Bevacizumab11-14,f |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes Day 1: Bevacizumab 7.5mg/kg IV. Repeat cycle every 3 weeks for 5-6 cycles and continue maintenance bevacizumab for up to 12 additional cycles. OR Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 6 IV over 1 hour. Repeat cycle every 3 weeks for 6 cycles. Starting Day 1 of cycle 2: Bevacizumab 15mg/kg IV over 30-90 minutes every 3 weeks for up to 22 cycles. |
|
Stage III Disease |
|
|
Cisplatin (for Hyperthermic Intraperitoneal Chemotherapy [HIPEC])15 |
Cisplatin 100mg/m2 IP over 90 minutes at time of debulking surgery.d |
|
Elderly Patients (>70 Years) and/or Those With Comorbidities |
|
|
Carboplatin20,21 |
Day 1: Carboplatin AUC 5 IV over 30 minutes. Repeat cycle every 3 weeks. |
|
Paclitaxel + Carboplatin20,22 |
Day 1: Paclitaxel 135mg/m2 IV Day 1: Carboplatin AUC 5 IV. Repeat cycle every 3 weeks for 4 cycles. OR Day 1: Paclitaxel 60mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 2 over 30 minutes. Administer weekly for 18 weeks. |
|
▶Maintenance Therapy for Epithelial Ovarian Cancer/Fallopian Tube/Primary Peritoneal Cancer1 |
|
|
Post-Primary Treatment When Bevacizumab Used as Primary Treatment |
|
|
Stage II, III, IV |
|
|
Bevacizumab (for patients with stable disease)11,13,14,16,f |
Day 1: Bevacizumab 15mg/kg IV. Repeat cycle every 3 weeks. OR Day 1: Bevacizumab 7.5mg/kg IV. Repeat cycle every 3 weeks. |
|
Olaparib (for patients with CR or PR and BRCA1/2 mutations; Category 1 for germline mutations; Category 2A for somatic mutations)17-19 |
Days 1-28: Olaparib 300mg (tablet formulation) twice daily. Repeat cycle every 4 weeks. |
|
Post-Primary Treatment When Bevacizumab Not Used in Primary Therapy |
|
|
Stage II, III, IV |
|
|
Olaparib (for patients with CR or PR and BRCA1/2 mutations; Category 1 for germline mutations; Category 2A for somatic mutations)17-19 |
Days 1-28: Olaparib 300mg (tablet formulation) twice daily. Repeat cycle every 4 weeks. |
|
▶Primary Systemic Therapy for Less Common Epithelial Ovarian Histopathologies1 |
|
|
Carcinosarcoma (Malignant Mixed Mullerian Tumor)g |
|
|
Stage I Disease |
|
|
Carboplatin + Liposomal Doxorubicin (preferred)2,3 |
Day 1: Carboplatin AUC 5 IV Day 1: Liposomal Doxorubicin 30mg/m2 IV. Repeat every 4 weeks for 3-6 cycles. |
|
Docetaxel + Carboplatin (preferred)4-6 |
Day 1: Docetaxel 60-75mg/m2 IV over 60 minutes, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 3-6 cycles (stage I) or 6 cycles if stage II-IV or high grade serous. |
|
Paclitaxel + Carboplatin (preferred)3,7-9 |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 3-6 cycles.b OR Days 1,8,15: Paclitaxel 80mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. OR Day 1: Paclitaxel 60mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 2 IV over 30 minutes. Repeat cycle weekly for 18 weeks. |
|
Stage II-IV Disease |
|
|
IP/IV Regimens |
|
|
Paclitaxel + Cisplatin (preferred)10 |
Day 1: Paclitaxel 135mg/m2 IV over 3 hours or IV continuous infusion over 24 hours Day 2: Cisplatin 75-100mg/m2 intraperitoneal (IP) infused as rapidly as possible via IP portd Day 8: Paclitaxel 60mg/m2 IP infused as rapidly as possible via IP port.e Repeat cycle every 3 weeks for 6 cycles. |
|
IV Regimens |
|
|
Carboplatin + Liposomal Doxorubicin (preferred)2,3 |
Day 1: Carboplatin AUC 5 IV Day 1: Liposomal Doxorubicin 30mg/m2 IV. Repeat every 4 weeks for 3-6 cycles. |
|
Docetaxel + Carboplatin (preferred)4-6 |
Day 1: Docetaxel 60-75mg/m2 IV over 60 minutes, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. |
|
Paclitaxel + Carboplatin (preferred)3,7,8,22 |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. OR Days 1,8,15: Paclitaxel 60mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 2 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. OR Day 1: Paclitaxel 60mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 2 IV over 30 minutes. Repeat cycle weekly for 18 weeks.c |
|
Paclitaxel + Carboplatin +Bevacizumab (preferred)12,13,f,g |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes Day 1: Bevacizumab 7.5mg/kg IV. Repeat cycle every 3 weeks for 5-6 cycles and continue maintenance bevacizumab for up to 12 additional cycles. OR Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 6 IV over 1 hour. Repeat cycle every 3 weeks for 6 cycles. Starting Day 1 of cycle 2: Bevacizumab 15mg/kg IV over 30-90 minutes every 3 weeks for up to 22 cycles. |
|
Stage III Disease |
|
|
Cisplatin (for HIPEC)15 |
Cisplatin 100mg/m2 IP over 90 minutes at the time of interval debulking surgery.d |
|
Stage I-IV Disease – Other Regimens |
|
|
Carboplatin + Ifosfamide23 |
Day 1: Carboplatin AUC 5 IV Day 1: Ifosfamide 3,000mg/m2 IVh Day 1: Mesna 1,000mg/m2 IV. Repeat cycle every 3 weeks for 4-6 cycles. |
|
Cisplatin + Ifosfamide24 |
Days 1-5: Cisplatin 20mg/m2 IV over 60 minutesd Days 1-5: Ifosfamide 1,500mg/m2 IV over 30 minutesh Days 1-5: Mesna 300mg/m2 IV over 15 minutes three times daily, one dose given once immediately prior to Ifosfamide and also 4 and 8 hours after each Ifosfamide dose. Repeat cycle every 3 weeks for 8 cycles (if no prior radiation therapy). OR Days 1-5: Cisplatin 20mg/m2 IV over 60 minutesd Days 1-5: Ifosfamide 1,200mg/m2 IV over 3 hoursh Days 1-5: Mesna 240mg/m2 IV over 15 minutes three times daily, one dose given immediately prior to Ifosfamide and also 4 and 8 hours after each Ifosfamide dose. Repeat cycle every 3 weeks for 8 cycles. |
|
Paclitaxel + Ifosfamide (Category 2B)25 |
Day 1: Paclitaxel 135mg/m2 IV over 3 hours Days 1-3: Ifosfamide 1,600mg/m2 IV over 3 hoursh Days 1-3: Mesna 320mg/m2 IV over 15 minutes three times daily (one dose before Ifosfamide, then at 4 and 8 hours from the start of each Ifosfamide dose). Repeat cycle every 3 weeks for 8 cycles. |
|
Clear Cell Carcinoma |
|
|
Stage I Disease |
|
|
Carboplatin + Liposomal Doxorubicin2,3 |
Day 1: Carboplatin AUC 5 IV Day 1: Liposomal Doxorubicin 30mg/m2 IV. Repeat every 4 weeks for 3-6 cycles. |
|
Docetaxel + Carboplatin4-6 |
Day 1: Docetaxel 60-75mg/m2 IV over 60 minutes, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 3-6 cycles (stage I) or 6 cycles if stage II-IV or high grade serous. |
|
Paclitaxel + Carboplatin (preferred)3,7-9 |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 3-6 cycles.b OR Days 1,8,15: Paclitaxel 80mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. OR Day 1: Paclitaxel 60mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 2 IV over 30 minutes. Repeat cycle weekly for 18 weeks.c |
|
Stage II-IV Disease |
|
|
IP/IV Regimens |
|
|
Paclitaxel + Cisplatin10 |
Day 1: Paclitaxel 135mg/m2 IV over 3 hours or IV continuous infusion over 24 hours Day 2: Cisplatin 75-100mg/m2 IP infused as rapidly as possible via IP portd Day 8: Paclitaxel 60mg/m2 IP infused as rapidly as possible via IP port.c Repeat cycle every 3 weeks for 6 cycles. |
|
IV Regimens |
|
|
Carboplatin + Liposomal Doxorubicin2,3 |
Day 1: Carboplatin AUC 5 IV Day 1: Liposomal Doxorubicin 30mg/m2 IV. Repeat every 4 weeks for 6 cycles. |
|
Docetaxel + Carboplatin4-6 |
Day 1: Docetaxel 60-75mg/m2 IV over 60 minutes, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 3-6 cycles (stage I) or 6 cycles if stage II-IV or high grade serous. |
|
Paclitaxel + Carboplatin3,7-9 |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. OR Days 1,8,15: Paclitaxel 80mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. OR Day 1: Paclitaxel 60mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 2 IV over 30 minutes. Repeat cycle weekly for 18 weeks.c |
|
Paclitaxel + Carboplatin + Bevacizumab12-14,f |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes Day 1: Bevacizumab 7.5mg/kg IV. Repeat cycle every 3 weeks for 5-6 cycles and continue maintenance bevacizumab for up to 12 additional cycles. OR Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 6 IV over 1 hour. Repeat cycle every 3 weeks for 6 cycles. Starting Day 1 of cycle 2: Bevacizumab 15mg/kg IV over 30-90 minutes every 3 weeks for up to 22 cycles. |
|
Mucinous Tumors |
|
|
Stage IC Disease |
|
|
Capecitabine + Oxaliplatin26 |
Day 1: Oxaliplatin 130mg/m2 IV over 2 hours Days 1-14: Capecitabine 850mg/m2 orally twice daily. Repeat cycle every 3 weeks for 6 cycles. |
|
Carboplatin + Liposomal Doxorubicin2,3 |
Day 1: Carboplatin AUC 5 IV Day 1: Liposomal Doxorubicin 30mg/m2 IV. Repeat every 4 weeks for 3-6 cycles for stage I disease or 6 cycles for stage II-IV disease or high-grade stage I disease. |
|
Docetaxel + Carboplatin4-6 |
Day 1: Docetaxel 60-75mg/m2 IV over 60 minutes, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 3-6 cycles (stage I) or 6 cycles if stage II-IV or high grade serous. |
|
Fluorouracil + Leucovorin + Oxaliplatin27,28 |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with: Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by: Days 1: Fluorouracil 400mg/m2 IV push Days 1-2: Fluorouracil 1,200mg/m2 IV as a continuous infusion over 24 hours. Repeat cycle every 2 weeks. |
|
Paclitaxel + Carboplatin (preferred)3,7-9 |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 3-6 cycles.b OR Days 1,8,15: Paclitaxel 80mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. OR Day 1: Paclitaxel 60mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 2 IV over 30 minutes. Repeat cycle weekly for 18 weeks.c |
|
Stage II-IV Disease |
|
|
IP/IV Regimens |
|
|
Paclitaxel + Cisplatin10 |
Day 1: Paclitaxel 135mg/m2 IV over 3 hours or IV continuous infusion over 24 hours Day 2: Cisplatin 75-100mg/m2 IP infused as rapidly as possible via IP portd Day 8: Paclitaxel 60mg/m2 IP infused as rapidly as possible via IP port.e Repeat cycle every 3 weeks for 6 cycles. |
|
IV Regimens |
|
|
Capecitabine + Oxaliplatin26 |
Day 1: Oxaliplatin 130mg/m2 IV over 2 hours Days 1-14: Capecitabine 850mg/m2 orally twice daily. Repeat cycle every 3 weeks for 6 cycles. |
|
Capecitabine + Oxaliplatin + Bevacizumab (Category 2B)26,f |
Day 1: Oxaliplatin 130mg/m2 IV over 2 hours Days 1-14: Capecitabine 850mg/m2 orally twice daily Day 1: Bevacizumab 15mg/kg IV. Repeat cycle every 3 weeks for 6 cycles, followed by: Day 1: Bevacizumab 15mg/m2 IV. Repeat cycle every 3 weeks for 12 cycles. |
|
Carboplatin + Liposomal Doxorubicin2,3 |
Day 1: Carboplatin AUC 5 IV Day 1: Liposomal Doxorubicin 30mg/m2 IV. Repeat every 4 weeks for 3-6 cycles for stage I disease or 6 cycles for stage II-IV disease or high-grade stage I disease. |
|
Docetaxel + Carboplatin4-6 |
Day 1: Docetaxel 60-75mg/m2 IV over 60 minutes, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 3-6 cycles (stage I) or 6 cycles if stage II-IV or high grade serous. |
|
Paclitaxel + Carboplatin3,7-9 |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. OR Days 1,8,15: Paclitaxel 80mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. OR Day 1: Paclitaxel 60mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 2 IV over 30 minutes. Repeat cycle weekly for 18 weeks.c |
|
Paclitaxel + Carboplatin + Bevacizumab12-14,f |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes Day 1: Bevacizumab 7.5mg/kg IV. Repeat cycle every 3 weeks for 5-6 cycles and continue maintenance bevacizumab for up to 12 additional cycles. OR Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 6 IV over 1 hour. Repeat cycle every 3 weeks for 6 cycles. Starting Day 1 of cycle 2: Bevacizumab 15mg/kg IV over 30-90 minutes every 3 weeks for up to 22 cycles. |
|
5-Fluorouracil + Leucovorin + Oxalplatin27,28 |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with: Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by: Days 1: Fluorouracil 400mg/m2 IV push Days 1-2: Fluorouracil 1,200mg/m2 IV as a continuous infusion over 24 hours. Repeat cycle every 2 weeks. |
|
5-Fluorouracil + Leucovorin + Oxaliplatin + Bevacizumab (Category 2B)29,30,f |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with: Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by: Days 1: Fluorouracil 400mg/m2 IV push, followed by: Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion daily. Day 1: Bevacizumab 5mg/kg IV. Repeat cycle every 2 weeks for 6 cycles. |
|
Low-Grade Serous or Grade 1 Endometrioid Epithelial Carcinoma |
|
|
Cytotoxic Therapy |
|
|
Stage IC Disease |
|
|
Carboplatin + Liposomal Doxorubicin2,3 |
Day 1: Carboplatin AUC 5 IV Day 1: Liposomal Doxorubicin 30mg/m2 IV. Repeat every 4 weeks for 3-6 cycles for stage I disease or 6 cycles for stage II-IV disease or high-grade stage I disease. |
|
Docetaxel + Carboplatin4-6 |
Day 1: Docetaxel 60-75mg/m2 IV over 60 minutes, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 3-6 cycles. |
|
Paclitaxel + Carboplatin (preferred)3,7-9 |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 3-6 cycles.b OR Days 1,8,15: Paclitaxel 80mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. OR Day 1: Paclitaxel 60mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 2 IV over 30 minutes. Repeat cycle weekly for 18 weeks.c |
|
Stage II-IV Disease |
|
|
IP/IV Regimens |
|
|
Paclitaxel + Cisplatin10 |
Day 1: Paclitaxel 135mg/m2 IV over 3 hours or IV continuous infusion over 24 hours Day 2: Cisplatin 75-100mg/m2 IP infused as rapidly as possible via IP portd Day 8: Paclitaxel 60mg/m2 IP infused as rapidly as possible via IP port.e Repeat cycle every 3 weeks for 6 cycles. |
|
IV Regimens |
|
|
Docetaxel + Carboplatin4-6 |
Day 1: Docetaxel 60-75mg/m2 IV over 60 minutes, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 3-6 cycles (stage I) or 6 cycles if stage II-IV or high grade serous. |
|
Paclitaxel + Carboplatin3,7-9 |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. OR Days 1,8,15: Paclitaxel 80mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. OR Day 1: Paclitaxel 60mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 2 IV over 30 minutes. Repeat cycle weekly for 18 weeks.c |
|
Paclitaxel + Carboplatin + Bevacizumab12-14,f |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes Day 1: Bevacizumab 7.5mg/kg IV. Repeat cycle every 3 weeks for 5-6 cycles and continue maintenance bevacizumab for up to 12 additional cycles. OR Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 6 IV over 1 hour. Repeat cycle every 3 weeks for 6 cycles. Starting Day 1 of cycle 2: Bevacizumab 15mg/kg IV over 30-90 minutes every 3 weeks for up to 22 cycles. |
|
Hormonal Therapy Stage IC-IV (Category 2B) |
|
|
Anastrozole (Category 2B)31-34 |
Days 1-28: Anastrozole 1mg orally daily. Repeat cycle every 4 weeks for 5 years or until disease progression or unacceptable toxicity. |
|
Exemestane (Category 2B)35-37 |
Days 1-28: Exemestane 25mg orally daily after a meal. Repeat cycle every 4 weeks. |
|
Letrozole (Category 2B)36,38,39 |
Days 1-28: Letrozole 2.5mg orally daily. Repeat cycle every 4 weeks. |
|
Leuprolide Acetate (Category 2B)40,41 |
Day 1: Leuprolide 3.75mg IM. Repeat cycle every 4 weeks. OR Day 1: Leuprolide 11.25mg IM. Repeat cycle every 3 months. |
|
Tamoxifen (Category 2B)42-43 |
Days 1-28: Tamoxifen 20mg orally twice daily. Repeat cycle every 4 weeks. |
|
Malignant Germ Cell Tumors |
|
|
BEP (Bleomycin + Etoposide + Cisplatin)44,i |
Days 1-5: Cisplatin 20mg/m2 IV over 60 minutesd Days 1-5: Etoposide 100mg/m2 IV over 60 minutes Days 1,8,15: Bleomycin 30 units IV over 10 minutes. Repeat cycle every 3 weeks for 3-4 cycles. |
|
Etoposide + Carboplatin (for patients with stage IB-III resected dysgerminoma for whom minimizing toxicity is critical)45 |
Day 1: Carboplatin 400mg/m2 IV over 30 minutes Days 1-3: Etoposide 120mg/m2 IV over 60 minutes. Repeat cycle every 4 weeks for 3 cycles. |
|
Malignant Sex Cord-Stromal Tumors |
|
|
BEP (Bleomycin + Etoposide + Cisplatin)46 |
Days 1-5: Cisplatin 20mg/m2 IV over 60 minutesd Days 1-5: Etoposide 100mg/m2 IV over 60 minutes Days 1,8,15: Bleomycin 30 units IV over 10 minutes. Repeat cycle every 3 weeks for 3-4 cycles. |
|
Paclitaxel + Carboplatin (Category 2B)47,48 |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. |
|
▶Systemic Therapy for Recurrent Platinum-Sensitive Epithelial Ovarian (Including Less Common Ovarian Histopathologies)/Fallopian Tube/Primary Peritoneal Cancer1 |
|
|
Preferred Regimens |
|
|
Cytotoxic Therapy |
|
|
Carboplatin + Gemcitabine21 |
Days 1,8: Gemcitabine 800-1,000mg/m2 IV over 30 minutes, followed by: Day 1: Carboplatin AUC 4 IV over 30 minutes. Repeat cycle every 3 weeks. |
|
Carboplatin + Gemicitabine + Bevacizumab11,49,f,j |
Days 1,8: Gemcitabine 1,000mg/m2 IV over 30 minutes Day 1: Carboplatin AUC 4 IV over 30 minutes Day 1: Bevacizumab 15mg/kg IV. Repeat cycle every 3 weeks for 6-10 cycles, followed by: Day 1: Bevacizumab 15mg/kg IV. Repeat cycle every 3 weeks. |
|
Carboplatin + Liposomal Doxorubicin2,3 |
Day 1: Carboplatin AUC 5 IV over 30 minutes Day 1: Liposomal Doxorubicin 30mg/m2 IV. Repeat cycle every 4 weeks. |
|
Carboplatin + Liposomal Doxorubicin + Bevacizumab2,11,50,f |
Day 1: Liposomal Doxorubicin 30mg/m2 IV Day 1: Carboplatin AUC 5 IV over 30 minutes Days 1,15: Bevacizumab 10mg/kg IV. Repeat cycle every 4 weeks. |
|
Carboplatin + Paclitaxel3,7-9 |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles.b OR Days 1,8,15: Paclitaxel 60mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 2 IV over 30 minutes. Repeat cycle every 3 weeks for 6 cycles. OR Day 1: Paclitaxel 60mg/m2 IV over 1 hour, followed by: Day 1: Carboplatin AUC 2 IV over 30 minutes. Repeat cycle weekly for 18 weeks.c |
|
Carboplatin + Paclitaxel + Bevacizumab11-14,f,j |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes Day 1: Bevacizumab 7.5mg/kg IV. Repeat cycle every 3 weeks for 5-6 cycles and continue maintenance bevacizumab for up to 12 additional cycles. OR Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 6 IV over 1 hour. Repeat cycle every 3 weeks for 6 cycles. Starting Day 1 of cycle 2: Bevacizumab 15mg/kg IV over 30-90 minutes every 3 weeks for up to 22 cycles. |
|
Cisplatin + Gemicitabine51,52 |
Days 1,8: Gemcitabine 600-750mg/m2 IV over 30 minutes Days 1,8: Cisplatin 30mg/m2 IV over 60 minutes. Repeat cycle every 3 weeks. |
|
Targeted Therapy (Single Agents) |
|
|
Bevacizumab53-54,f |
Day 1: Bevacizumab 15mg/kg IV. Repeat cycle every 3 weeks. |
|
Niraparib55,56,k |
Days 1-28: Niraparib 300mg orally daily. Repeat cycle every 4 weeks. |
|
Olaparib17,57,l |
Days 1-28: Olaparib 300mg (tablet formulation) twice daily. Repeat cycle every 4 weeks. |
|
Rucaparib58-60,n |
Days 1-28: Rucaparib 600mg orally twice daily. Repeat cycle every 4 weeks. |
|
Other Recommended Regimens |
|
|
Cytotoxic Therapy |
|
|
Albumin-Bound Paclitaxel61 |
Day 1: Albumin-Bound Paclitaxel 260mg/m2 IV over 30 minutes. Repeat cycle every 3 weeks. |
|
Carboplatin + Docetaxel4-6,62 |
Day 1: Docetaxel 60-75mg/m2 IV over 60 minutes, followed by: Day 1: Carboplatin AUC 5-6 IV over 30 minutes. Repeat cycle every 3 weeks. |
|
Carboplatin + Paclitaxel (weekly)8 |
Days 1,8,15: Paclitaxel 80mg/m2 IV over 60 minutes, followed by: Day 1: Carboplatin AUC 5 IV over 30 minutes. Repeat every 3 weeks for 6 cycles. |
|
Capecitabine63 |
Days 1-14: Capcitabine 1,000mg/m2 orally twice daily. Repeat cycle every 3 weeks. |
|
Carboplatin20,21 |
Day 1: Carboplatin AUC 5 IV over 30 minutes. Repeat cycle every 3 weeks. |
|
Cisplatin64 |
Day 1: Cisplatin 75mg/m2 IV over 60 minutes.d Repeat cycle every 3 weeks. |
|
Cyclophosphamide65 |
Day 1: Cyclophoshamide 750mg/m2 IV over 60 minutes. Repeat cycle every 3 weeks. |
|
Doxorubicin66,67 |
Day 1: Doxorubicin 60mg/m2 IV push. Repeat cycle every 3 weeks. |
|
Ifosfamide68 |
Days 1-5: Mesna 200-240mg/m2 IV over 15 minutes three times daily, one dose before Ifosfamide, then at 4 and 8 hours from the start of each Ifosfamide dose Days 1-5: Ifosfamide 1,000-1,200mg/m2 IV over 3 hours.h Repeat cycle every 4 weeks. |
|
Irinotecan69 |
Days 1,8,15: Irinotecan 100mg/m2 IV over 30-90 minutes. Repeat cycle every 4 weeks. |
|
Melphalan70 |
Days 1-5: Melphalan 3.5mg/m2 orally twice daily. Repeat cycle every 4 weeks. |
|
Oxaliplatin71 |
Day 1: Oxaliplatin 130mg/m2 IV over 2 hours. Repeat cycle every 3 weeks. |
|
Paclitaxel64,72 |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours. Repeat cycle every 3 weeks. OR Days 1,8,15,22: Paclitaxel 80mg/m2 (Max BSA = 2m2) IV over 60 minutes. Repeat cycle every 4 weeks for 3 cycles, followed by: Days 1,8,15: Paclitaxel 80mg/m2 (Max BSA = 2m2) over 60 minutes beginning with cycle 4. Repeat cycle every 4 weeks. |
|
Pemetrexed73,74 |
Day 1: Pemetrexed 500-900mg/m2 IV over 10 minutes. Repeat cycle every 3 weeks. |
|
Vinorelbine75 |
Days 1,8: Vinorelbine 30mg/m2 IV over 5-10 minutes. Repeat cycle every 3 weeks. |
|
Targeted Therapy |
|
|
Pazopanib (Category 2B)76,77 |
Days 1-28: Pazopanib 800mg orally once daily. Repeat cycle every 4 weeks. |
|
Niraparib + Bevacizumab56,78,f |
Days 1-28: Niraparib 300mg orally once daily. Repeat cycle every 4 weeks, with: Day 1: Bevacizumab 15mg/kg IV. Repeat cycle every 3 weeks. |
|
Hormonal Therapy |
|
|
Anastrozole31-34 |
Days 1-28: Anastrozole 1mg orally daily. Repeat cycle every 4 weeks for 5 years or until disease progression or unacceptable toxicity. |
|
Exemestane35-37 |
Days 1-28: Exemestane 25mg orally daily after a meal. Repeat cycle every 4 weeks. |
|
Letrozole36,38,39 |
Days 1-28: Letrozole 2.5mg orally daily. Repeat cycle every 4 weeks. |
|
Leuprolide Acetate40,41 |
Day 1: Leuprolide 3.75mg IM. Repeat cycle every 4 weeks. OR Day 1: Leuprolide 11.25mg IM. Repeat cycle every 3 months. |
|
Megestrol Acetate79,80 |
See NCCN Ovarian Cancer Guidelines.1 |
|
Tamoxifen42,43 |
Days 1-28: Tamoxifen 20mg orally twice daily. Repeat cycle every 4 weeks. |
|
Useful in Certain Circumstances |
|
|
Cytotoxic Therapy for Mucinous Carcinoma |
|
|
Capecitabine + Oxaliplatin26 |
Day 1: Oxaliplatin 130mg/m2 IV over 2 hours Days 1-14: Capecitabine 850mg/m2 orally twice daily. Repeat cycle every 3 weeks. |
|
Capecitabine + Oxaliplatin + Bevacizumab (Category 2B)26,f |
Day 1: Oxaliplatin 130mg/m2 IV over 2 hours Days 1-14: Capecitabine 850mg/m2 orally twice daily. Day 1: Bevacizumab 15mg/kg IV. Repeat cycle every 3 weeks for 6 cycles, followed by: Day 1: Bevacizumab 15mg/kg IV for 12 cycles |
|
Fluorouracil + Leucovorin + Oxaliplatin27,28 |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with: Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by: Days 1: Fluorouracil 400mg/m2 IV push Days 1-2: Fluorouracil 1,200mg/m2 IV as a continuous infusion over 24 hours. Repeat cycle every 2 weeks. |
|
Fluorouracil + Leucovorin + Oxaliplatin + Bevacizumab (Category 2B)29,30,f |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with: Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by: Days 1: Fluorouracil 400mg/m2 IV push, followed by: Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion daily. Day 1: Bevacizumab 5mg/kg IV. Repeat cycle every 2 weeks. |
|
Carboplatin + Albumin-Bound Paclitaxel (for confirmed hypersensitivity)61,81 |
Days 1,8,15: Albumin-Bound Paclitaxel 100mg/m2 IV over 30 minutes Day 1: Carboplatin AUC 5 IV over 30 minutes. Repeat cycle every 4 weeks. |
|
Cytotoxic Therapy for Patients Aged >70 Years |
|
|
Carboplatin + Paclitaxel20,22 |
Day 1: Paclitaxel 135mg/m2 IV Day 1: Carboplatin AUC 5 IV. Repeat cycle every 3 weeks. |
|
Cytotoxic Therapy for Clear Cell Carcinoma |
|
|
Irinotecan + Cisplatin82 |
Days 1,8,15: Irinotecan 60mg/m2 IV over 90 minutes Day 1: Cisplatin 60mg/m2 IV over 1 hour.d Repeat cycle every 4 weeks. |
|
Hormone Therapy for Low-Grade Serous Carcinoma” |
|
|
Fulvestrant83,84 |
Day 1 (Cycle 1): Fulvestant 500mg IM Day 15 (Cycle 1): Fulvestant 250mg IM. Administer for one 4-week cycle, followed by: Day 1 (Cycle 2 and beyond): Fulvestrant 250mg IM. Repeat cycle every 4 weeks. |
|
Immunotherapy |
|
|
Pembrolizumab (for MSI-H or dMMR solid tumors)85-87 |
Day 1: Pembrolizumab 200mg IV over 30 minutes. Repeat cycle every 3 weeks. |
|
Targeted Therapy (single agents) |
|
|
Entrectinib (for NTRK gene-fusion positive tumors)88-91 |
Days 1-28: Entrectinib 600mg orally once daily. Repeat cycle every 4 weeks. |
|
Larotrectinib (for NTRK gene-fusion positive tumors)92,93 |
Days 1-28: Larotrectinib 100mg orally twice daily. Repeat cycle every 4 weeks. |
|
Trametinib (for low-grade serous carcinoma)94,95 |
Days 1-28: Trametinib 2mg orally once daily. Repeat cycle every 4 weeks |
|
▶Systemic Therapy for Recurrent Platinum-Resistant Epithelial Ovarian (Including Less Common Ovarian Histopathologies)/Fallopian Tube/Primary Peritoneal Cancer1 |
|
|
Preferred Regimens |
|
|
Cytotoxic Therapy |
|
|
Cyclophosphamide (oral) + Bevacizumab11,96,f |
Days 1: Bevacizumab 10mg/kg IV. Repeat cycle every 2 weeks, with: Days 1-28: Cyclophosphamide 50mg orally daily. Repeat cycle every 4 weeks. |
|
Docetaxel97 |
Day 1: Docetaxel 100mg/m2 IV over 60 minutes. Repeat cycle every 3 weeks. |
|
Etoposide (oral)98 |
Days 1-21: Etoposide 50mg/m2 orally daily (titrated as patient tolerates to a maximum of 60mg/m2 orally daily). Repeat cycle every 4 weeks. OR Days 1-21: Etoposide 30mg/m2 orally (titrated as patient tolerates to a maximum of 60mg/m2 orally daily). Repeat cycle every 4 weeks. |
|
Gemcitabine99,100 |
Days 1,8,15: Gemcitabine 1000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks. OR Days 1,8: Gemcitabine 1,000mg/m2 over 30 minutes. Repeat cycle every 3 weeks. |
|
Liposomal Doxorubicin99,100 |
Day 1: Liposomal Doxorubicin 40-50mg/m2 IV. Repeat cycle every 4 weeks. |
|
Liposomal Doxorubicin + Bevacizumab101,f |
Day 1: Liposomal Doxorubicin 40mg/m2 IV. Days 1,15: Bevacizumab 10mg/kg IV. Repeat cycle every 4 weeks. |
|
Paclitaxel (weekly)72 |
Days 1,8,15,22: Paclitaxel 80mg/m2 (Max BSA=2m2) IV over 60 minutes. Repeat every 4 weeks for cycles 1-3, followed by: Days 1,8,15: Paclitaxel 80mg/m2 (Max BSA=2m2) IV over 60 minutes. Repeat every 4 weeks beginning with cycle 4. |
|
Paclitaxel (weekly) + Bevacizumab11,101,f |
Days 1,8,15,22: Paclitaxel 80mg/m2 IV over 60 minutes. Days 1,15: Bevacizumab 10mg/kg IV. Repeat cycle every 4 weeks. |
|
Topotecan102,103 |
Days 1-5: Topotecan 1.5mg/m2 IV over 30 minutes. Repeat cycle every 3 weeks. OR Days 1,8,15: Topotecan 3-4mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks. |
|
Topotecan + Bevacizumab11,101,f |
Days 1,8,15: Topotecan 4mg/m2 IV over 30 minutes Days 1,15: Bevacizumab 10mg/kg IV. Repeat cycle every 4 weeks. |
|
Targeted Therapy (Single Agents) |
|
|
Bevacizumab53-54,f |
Day 1: Bevacizumab 15mg/kg IV. Repeat cycle every 3 weeks. |
|
Niraparib55,56,k |
Days 1-28: Niraparib 300mg orally daily. Repeat cycle every 4 weeks. |
|
Olaparib17,57,l |
Days 1-28: Olaparib 300mg (tablet formulation) twice daily. Repeat cycle every 4 weeks. |
|
Rucaparib58-60,m |
Days 1-28: Rucaparib 600mg orally twice daily. Repeat cycle every 4 weeks. |
|
Other Recommended Regimens |
|
|
Cytotoxic Therapy |
|
|
Albumin-Bound Paclitaxel61 |
Day 1: Albumin-Bound Paclitaxel 260mg/m2 IV over 30 minutes. Repeat cycle every 3 weeks. |
|
Capecitabine63 |
Days 1-14: Capecitabine 1000mg/m2 orally twice daily. Repeat cycle every 3 weeks. |
|
Cyclophosphamide65 |
Day 1: Cyclophoshamide 750mg/m2 IV over 60 minutes. Repeat cycle every 3 weeks. |
|
Doxorubicin66,67 |
Day 1: Doxorubicin 60mg/m2 IV push. Repeat cycle every 3 weeks. |
|
Ifosfamide68 |
Days 1-5: Mesna 200-240mg/m2 IV over 15 minutes three times daily, one dose before Ifosfamide, then at 4 and 8 hours from the start of each Ifosfamide dose Days 1-5: Ifosfamide 1,000-1,200mg/m2 IV over 3 hours.h Repeat cycle every 4 weeks. |
|
Irinotecan69 |
Days 1,8,15: Irinotecan 100mg/m2 IV over 30-90 minutes. Repeat cycle every 4 weeks. |
|
Melphalan70 |
Days 1-5: Melphalan 3.5mg/m2 orally twice daily. Repeat cycle every 4 weeks. |
|
Oxaliplatin71 |
Day 1: Oxaliplatin 130mg/m2 IV over 2 hours. Repeat cycle every 3 weeks. |
|
Paclitaxel64,72 |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours. Repeat cycle every 3 weeks. OR Days 1,8,15,22: Paclitaxel 80mg/m2 (Max BSA = 2m2) IV over 60 minutes for cycles 1-3, followed by: Days 1,8,15: Paclitaxel 80mg/m2 (Max BSA =2m2) IV over 60 minutes beginning with cycle 4. Repeat cycle every 4 weeks. |
|
Pemetrexed73,74 |
Day 1: Pemetrexed 500-900mg/m2 IV over 10 minutes. Repeat cycle every 3 weeks. |
|
Sorafenib + Topotecan104,105 |
Days 1-5: Topotecan 1.25mg/m2 IV over 30 minutes Days 6-15: Sorafenib 400mg twice daily. Repeat cycle every 3 weeks for 6 cycles, followed by: Days 1-28: Sorafenib 400mg twice daily. Repeat cycle every 4 weeks. |
|
Vinorelbine75 |
Days 1,8: Vinorelbine 30mg/m2 IV over 5-10 minutes. Repeat cycle every 3 weeks. |
|
Hormonal Therapy |
|
|
Anastrozole31-34 |
Days 1-28: Anastrozole 1mg orally daily. Repeat cycle every 4 weeks for 5 years or until disease progression or unacceptable toxicity. |
|
Exemestane35-37 |
Days 1-28: Exemestane 25mg orally daily after a meal. Repeat cycle every 4 weeks. |
|
Letrozole36,38,39 |
Days 1-28: Letrozole 2.5mg orally daily. Repeat cycle every 4 weeks. |
|
Leuprolide Acetate40,41 |
Day 1: Leuprolide 3.75mg IM. Repeat cycle every 4 weeks. OR Day 1: Leuprolide 11.25mg IM. Repeat cycle every 3 months. |
|
Megestrol Acetate79,80 |
See NCCN Ovarian Cancer Guidelines.1 |
|
Tamoxifen42,43 |
Days 1-28: Tamoxifen 20mg orally twice daily. Repeat cycle every 4 weeks. |
|
Targeted Therapy (Single Agents) |
|
|
Pazopanib (Category 2B)76,77 |
Day 1-28: Pazopanib 800mg orally once daily. Repeat cycle every 4 weeks. |
|
Useful in Certain Circumstances |
|
|
Hormonal Therapy |
|
|
Fulvestrant (for low-grade serous carcinoma)83,84 |
Day 1 (Cycle 1): Fulvestant 500mg IM Day 15 (Cycle 1): Fulvestant 250mg IM. Administer for one 4-week cycle, followed by: Day 1 (Cycle 2 and beyond): Fulvestrant 250mg IM. Repeat cycle every 4 weeks. |
|
Immunotherapy |
|
|
Pembrolizumab (for MSI-H or dMMR solid tumors)86,87 |
Day 1: Pembrolizumab 200mg IV over 30 minutes. Repeat cycle every 3 weeks. |
|
Targeted Therapy (single agents) |
|
|
Entrectinib (for NTRK gene-fusion positive tumors)88-91 |
Days 1-28: Entrectinib 600mg orally once daily. Repeat cycle every 4 weeks. |
|
Larotrectinib (for NTRK gene-fusion positive tumors)92,93 |
Days 1-28: Larotrectinib 100mg orally twice daily. Repeat cycle every 4 weeks. |
|
Trametinib (for low-grade serous carcinoma)94,95 |
Days 1-28: Trametinib 2mg orally daily. Repeat cycle every 4 weeks. |
|
▶Systemic Therapy for Recurrent Malignant Germ Cell Tumors1 |
|
|
Potentially Curative Cytotoxic Therapy |
|
|
High-dose chemotherapyn |
See NCCN Ovarian Cancer Guidelines.1 |
|
TIP (Paclitaxel + Ifosfamide + Cisplatin)106 |
Day 1: Paclitaxel 250mg/m2 IV continuous infusion over 24 hours Days 2-5: Ifosfamide 1,500mg/m2 IV over 3 hoursh Days 2-5: Mesna 300mg/m2 IV over 15 minutes three times daily, one dose before Ifosfamide, then at 4 and 8 hours from the start of each Ifosfamide dose Days 2-5: Cisplatin 25mg/m2 IV over 60 minutes.d Repeat cycle every 3 weeks. |
|
Palliative Cytotoxic Therapy |
|
|
Cisplatin + Etoposide107 |
Days 1-5: Cisplatin 20mg/m2 IV over 60 minutes Days 1-5: Etoposide 100mg/m2 IV over 60 minutes. Repeat cycle every 3 weeks. |
|
Docetaxel108 |
Day 1: Docetaxel 75mg/m2 IV over 60 minutes. Repeat cycle every 3 weeks. |
|
Docetaxel + Carboplatin108 |
Day 1: Docetaxel 75mg/m2 over 60 minutes, followed by: Day 1: Carboplatin AUC 5 IV over 30 minutes. Repeat cycle every 3 weeks. |
|
Paclitaxel109 |
Day 1: Paclitaxel 175-225mg/m2 IV over 3 hours. Repeat cycle every 3 weeks. |
|
Paclitaxel + Carboplatin64 |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5 IV over 30 minutes. Repeat cycle every 3 weeks. |
|
Paclitaxel + Gemcitabine110 |
Days 1,8,15: Paclitaxel 110mg/m2 IV over 3 hours, followed by: Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks. |
|
Paclitaxel + Ifosfamide106 |
Day 1: Paclitaxel 250mg/m2 IV continuous infusion over 24 hours Days 2-5: Ifosfamide 1,500mg/m2 IV over 3 hours dailyh Days 2-5: Mesna 300mg/m2 IV over 15 minutes three times daily, one dose before Ifosfamide, then at 4 and 8 hours from the start of each Ifosfamide dose Repeat cycle every 3 weeks. |
|
TIP (Paclitaxel + Ifosfamide + Cisplatin)106 |
Day 1: Paclitaxel 250mg/m2 IV continuous infusion over 24 hours Days 2-5: Ifosfamide 1,500mg/m2 IV over 3 hoursh Days 2-5: Mesna 300mg/m2 IV over 15 minutes three times daily, one dose before ifosfamide, then at 4 and 8 hours from the start of each Ifosfamide dose Days 2-5: Cisplatin 25mg/m2 IV over 60 minutes.d Repeat cycle every 3 weeks. |
|
VAC (Vincristine + Dactinomycin + Cyclophosphanide)111 |
Days 1,8,15,22: Vincristine 1.5mg/m2 (maximum 2mg) IV over 5-10 minutes Days 1-5: Dactinomycin 300mcg/m2 IV push Days 1-5: Cyclophosphamide 150mg/m2 IV over 60 minutes. Repeat cycle every 4 weeks. |
|
VeIP (Vinblastine + Ifosfamide + Cisplatin)112 |
Days 1-2: Vinblastine 0.11mg/kg IV over 5-10 minutes Days 1-5: Ifosfamide 1,200mg/m2 IV over 3 hoursh Days 1-5: Mesna 240mg/m2 IV over 15 minutes three times daily, one dose before Ifosfamide, then at 4 and 8 hours from the start of each Ifosfamide dose Days 1-5: Cisplatin 20mg/m2 IV over 60 minutes.d Repeat cycle every 3 weeks. |
|
VIP (Etoposide + Ifosfamide + Cisplatin)113,114 |
Days 1-5: Etoposide 75mg/m2 IV over 60 minutes Days 1-5: Ifosfamide 1,200mg/m2 IV over 3 hoursh Days 1-5: Mesna 240mg/m2 IV over 15 minutes three time daily, one dose before Ifosfamide, then at 4 and 8 hours from the start of each Ifosfamide dose Days 1-5: Cisplatin 20mg/m2 IV over 60 minutes.d Repeat cycle every 3 weeks. |
|
▶Systemic Therapy for Recurrent Malignant Sex Cord-Stromal Tumors1 |
|
|
Cytotoxic Therapy |
|
|
Docetaxel108 |
Day 1: Docetaxel 75mg/m2 IV over 60 minutes. Repeat cycle every 3 weeks. |
|
Paclitaxel47,115 |
Day 1: Paclitaxel 135-175mg/m2 IV over 3 hours. Repeat cycle every 3 weeks. |
|
Paclitaxel + Carboplatin47,48 |
Day 1: Paclitaxel 175mg/m2 IV over 3 hours, followed by: Day 1: Carboplatin AUC 5 IV over 30 minutes. Repeat cycle every 3 weeks. |
|
Paclitaxel + Ifosfamide116 |
Day 1: Paclitaxel 135mg/m2 IV continuous infusion over 3 hours Days 1-3: Ifosfamide 1,600mg/m2 IV over 3 hoursh Days 2-5: Mesna 320mg/m2 IV over 15 minutes three times daily, one dose before Ifosfamide, then at 4 and 8 hours from the start of each Ifosfamide dose Repeat cycle every 3 weeks. |
|
VAC (Vincristine + Dactinomycin + Cyclophosphanide)111 |
Days 1,8,15,22: Vincristine 1.5mg/m2 (maximum 2mg) over 5-10 minutes Days 1-5: Dactinomycin 300mg/m2 IV push daily Days 1-5: Cyclophosphamide 150mg/m2 IV over 60 minutes. Repeat cycle every 4 weeks. |
|
Hormonal Therapy |
|
|
Anastrozole31-34 |
Days 1-28: Anastrozole 1mg orally daily. Repeat cycle every 4 weeks for 5 years or until disease progression or unacceptable toxicity. |
|
Exemestane35-37 |
Days 1-28: Exemestane 25mg orally daily after a meal. Repeat cycle every 4 weeks. |
|
Letrozole36,38,39 |
Days 1-28: Letrozole 2.5mg orally daily. Repeat cycle every 4 weeks. |
|
Leuprolide Acetate (for granulosa cell tumors)117,118 |
Day 1: Leuprolide 7.5mg IM. Repeat cycle every 4 weeks. OR Day 1: Leuprolide 22.5mg IM. Repeat cycle every 84 days. |
|
Tamoxifen42,43 |
Days 1-28: Tamoxifen 20mg orally twice daily. Repeat cycle every 4 weeks. |
|
Targeted Therapy |
|
|
Bevacizumab (single agent)11,119,120,f |
Day 1: Bevacizumab 15mg/kg IV. Repeat cycle every 3 weeks. |
|
a. Any of the primary IV regimens for stage II-IV disease can be used as neoadjuvant therapy before interval debulking surgery for confirmed poor surgical candidate or low likelihood of optimal cytoreduction. After neoadjuvant therapy and interval debulking any of the primary IV or IV/IP options can be considered as adjuvant therapy. A minimum of 6 cycles of treatment is recommended, including at least 3 cycles of adjuvant therapy after interval debulking surgery. b. 6 cycles for stage I high-grade serous disease; 3-6 cycles for all other histologies. c. Regimen may be considered for those with poor performance status. d. Hydration is required with supplemental electrolytes pre- and post-administration of Cisplatin. e. The published randomized trial regimen used IV continuous infusion paclitaxel over 24 hours. f. An FDA-approved biosimilar is an appropriate substitute for bevacizumab. g. Chemotherapy as per epithelial ovarian cancer is preferred over other regimens. h. Hydration is required pre- and postadministration of Ifosfamide. i. 3 cycles for good risk disease (Category 2B); 4 cycles for poor risk disease. j. If response after chemotherapy, bevacizumab can be continued as maintenance therapy until disease progression or unacceptable toxicity. Discontinue bevacizumab before initiating maintenance therapy with a PARP inhibitor. k. For patients treated with 3 or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficient (HRD)-positive status defined by either: (1) a deleterious or suspected deleterious BRCA mutation; or (2) genomic instability and progression >6months after response to the last platinum-based chemotherapy. l. For patients with deleterious germline BRCA-mutated (as detected by an FDA-approved test or other validated test performed in a CLIA-approved facility) advanced ovarian cancer who have been treated with 3 or more lines of chemotherapy. m. For patients with deleterious germline and/or somatic BRCA mutated (as detected by an FDA-approved test or other validated test performed in a CLIA-approved facility) advanced ovarian cancer who have been treated with two or more lines of chemotherapy. n. High-dose chemotherapy regimens vary among institutions. |
|
|
References |
|
|
1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology™. Ovarian Cancer v3.2019. https://nccn.org/professionals/physician_gls/pdf/ovarian.pdf. Accessed December 23, 2019. 2. Pujade-Lauraine E, Wagner U, et al. Pegylated liposomal doxorubicin and carboplatin compared with paclitaxel and carboplatin for patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer in late relapse. J Clin Oncol. 2010;28:3322-3329. 3. Pignata S, Scambia G, Ferrandina G, et al. Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial. J Clin Oncol. 2011;29:3628-3635. 4. Vasey PA, Jayson GC, Gordon A, et al. Phase III randomized trial of docetaxel- carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst. 2004;96:1682-1691. 5. Markman M, Kennedy A, Webster K, et al. Combination chemotherapy with carboplatin and docetaxel in the treatment of cancers of the ovary and fallopian tube and primary carcinoma of the peritoneum. J Clin Oncol. 2001;19:1901-1905. 6. Strauss HG, Henze A, Teichmann A, et al. Phase II trial of docetaxel and carboplatin in recurrent platinum-sensitive ovarian, peritoneal and tubal cancer. Gynecol Oncol. 2007;104:612-616. 7. Ozols RF, Bundy BN, Greer BE, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2003;21:3194-3200. 8. Katsumata N, Yasuda M, Takahashi F, et al. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009;374:1331-1338. 9. Pignata S, Scambia G, Katsaros D, et al. Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicenter, open-label, phase 3 trial. Lancet Oncol. 2014;15:395-405. 10. Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354:34-43. 11. Bevacizumab (Avastin) [package insert]. South San Francisco, CA: Genentech, Inc: 2019. 12. Perren TJ, Swart AM, Pfisterer J, et al. A phase 2 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365:2484-2496. 13. Oza AM, Cook AD, Pfisterer J, et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015;16:928-936. 14. Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473-2483. 15. Van Driel WJ, Koole SN, Sikorska K, et al. Hyperthermic intraperiotoneal chemotherapy in ovarian cancer. N Engl J Med. 2018;378:230-240. 16. Marchetti C, Muzii L, Romito A, Benedetti Panici P. First-line treatment of women with advanced ovarian cancer: focus on bevacizumab. Onco Targets Ther. 2019;12:1095–1103. 17. Olaparib (Lynparza) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP: 2019. 18. Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;27:2495-2505. 19. Pujade-Lauraine E, Ledermann JA, Selle F, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation ((SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo- controlled, phase 2 trial. Lancet Oncol. 2017;18:1274-1284. 20. Von Gruenigen VE, Huang HQ, Beumer JH, et al. Chemotherapy completion in elderly women with ovarian, primary peritoneal or fallopian tube cancer — An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol. 2017;144:459-467. 21. Pfisterer J, Plante M, Vergote I, et al. Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. J Clin Oncol. 2006;24:4699-4707. 22. Pignata S, Breda E, Scambia G, et al. A phase II study of weekly carboplatin and paclitaxel as first-line treatment of elderly patients with advanced ovarian cancer. A Multicentre Italian Trial in Ovarian cancer (MITO-5) study. Crit Rev Oncol Hematol. 2008;66:229-236. 23. Dandamudi RK, Aslam S, Walji N, et al. Chemotherapy for uterine carcinosarcoma with carboplatin, ifosfamide and mesna. Anticancer Res. 2015;35:4841-4847. 24. 24.Sutton G, Brunetto VL, Kilgore L, et al. A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study. Gynecol Oncol. 2000;79:147-153. 25. Homesley HD, Filiaci V, Markman M,et al. Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2007;10;25:526-531. 26. Gore M, Hackshaw , Brady WE, et al. An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor. Gynecol Oncol. 2019;153:541–548. 27. Cheeseman SL, Joel SP, Chester JD, et al. A ‘modifed de Gramont’ regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. Br J Cancer. 2002;87:393-399. 28. Sato S, Itamochi H, Kigawa J, et al. Combination chemotherapy of oxaliplatin and 5-fluorouracil may be an effective regimen for mucinous adenocarcinoma of the ovary: a potential treatment strategy. Cancer Sci. 2009;100:546-551. 29. Ricci F, Affatato R, Carrassa L, et al. Recent insights into mucinous ovarian carcinoma. Int J Mol Sci.2018;19:E1569. 30. Venook AP, Nidezwiecki D, Lenz HJ, et al. Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer: A randomized clinical trial. JAMA. 2017;317:2392-2401. 31. Anastrozole (Arimidex) [package insert]. Baudette, MN: ANI Pharmaceuticals; Inc.; 2018. 32. Del Carmen MG, Fuller AF, Matulonis U, et al. Phase II trial of anastrozole in women with asymptomatic Mullerian cancer. Gynecol Oncol. 2003;91:596-602. 33. Bonventura A, O’Connell RL, Mapagu C, et al. Paragon (ANZGOG-0903): Phase 2 study of anastrozole in women with estrogen or progesterone receptor-positive platinum- resistant or refractory recurrent ovarian cancer. Int J Gynecol Cancer. 2017;27:900-906. 34. Tang M. O’Connell RL, Amant F, et al. PARAGON: A phase II study of anastrozole in patients with estrogen receptor-positive recurrent/metastatic low-grade ovarian cancers and serous borderline ovarian tumors. Gynecol Oncol. 2019;154:531-538. 35. Exemestane (Aromasin) [package insert]. New York, NY: Pfizer, Inc.: 2018. 36. Gershenson DM, Sun CC, Iyer RB, et al. Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum. Gynecol Oncol. 2012;125:661-666. 37. Verma S, Alhayki M, Le T, et al. Phase II study of exemestane (E) in refractory ovarian cancer (ROC). J Clin Oncol. 2006;24(18_suppl): Abstract 5026. 38. Letrozole (Femara) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp.; 2018. 39. Papadimitriou CA, Markaki S, Siapkaras J, et al. Hormonal therapy with letrozole for relapsed epithelial ovarian cancer. Long-term results of a phase II study. Oncology. 2004;66:112-117. 40. Du BA, Meier W, Luck HJ, et al. Chemotherapy versus hormonal treatment in platinum- and paclitaxel-refractory ovarian cancer: a randomised tiral of the German Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group Ovarian Cancer. Ann Oncol. 2002;13:251-257. 41. Marinaccio M, D’Addario V, Serrati A. et al. Leuprolide acetate as a salvage therapy in relapsed epithelial ovarian cancer. Eur J Gynaecol Oncol. 1996;17:286-288. 42. Tamoxifen (Novladex) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2004. 43. Markman M, Iseminger KA, Hatch KD, et al. Tamoxifen in platinum-refractory ovarian cancer: a Gynecologic Oncology Group Ancillary Report. Gynecol Oncol. 1996;62:4-6. 44. Williams S, Blessing JA, Liao SY, et al. Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group. J Clin Oncol. 1994;12:701-706. 45. Williams SD, Kauderer J, Burnett AF, et al. Adjuvant therapy of completely resected dysgerminoma with carboplatin and etoposide: a trial of the Gynecologic Oncology Group. Gynecol Oncol. 2004;95:496-499. 46. Pautier P, Gutierrez-Bonnaire M, Rey A, et al. Combination of bleomycin, etoposide, and cisplatin for the treatment of advanced ovarian granulosa cell tumors. Int J Gynecol Cancer. 2008;18:446-452. 47. Brown J, Shvartsman HS, Deavers MT, et al. The activity of taxanes compared with bleomycin, etoposide, and cisplatin in the treatment of sex cord-stromal ovarian tumors. Gynecol Oncol. 2005;97:489-496. 48. Brown J, Shvartsman HS, Deavers MT, et al. The activity of taxanes in the treatment of sex cord-stromal ovarian tumors. J Clin Oncol. 2004;22:3517-3523. 49. Aghajanian C, Blank SV, Goff BA, et al. OCEANS: a randomized, double-blind, placebo- controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012;30L2039-2045. 50. Pfisterer J, Dean AP, Baumann K, et al. Carboplatin/pegylated liposomal doxorubicin/ bevacizumab in patients with recurrent ovarian cancer. A prospective randomized phase III ENGOT/GCIC-Intergroup study [AGO Study Group, AGO-Austria, ANZGOG, GINECO, SGCTC). Ann Oncol. 2019;28(suppl_8):vii332. 51. Nagourney RA, Brewer CA, Radecki S, et al. Phase II trial of gemcitabine plus cisplatin repeating doublet therapy in previously treated, relapsed ovarian cancer patients. Gynecol Oncol. 2003;88:35-39. 52. Rose PG. Gemcitabine reverses platinum resistance in platinum-resistant ovarian and peritoneal carcinoma. Int J Gynecol Cancer. 2005;(15_Suppl):18-22. 53. Burger RA, Sill MW, Monk BJ, et al. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007;25:5165-5171. 54. Cannistra SA, Matulonis UA, Penson RT, et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol. 2007;25:5180-5186. 55. Moore KN, Secord AA, Geller MA, et al. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicenter, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019;20:636-648. 56. Niraparib (Zejula) [package insert]. Waltham, MA. Tesaro, Inc. 2019. 57. Kaufman B, Shapira-Frommer R, Schmulzler RK, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015;33:244-250. 58. Rucaparib (Rubraca) [package insert]. Boulder, CO: Clovis Oncology, Inc.; 2018. 59. Swisher EM, Lin KK, Oza AM, et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part I): an international, multicenter, open-label, phase 2 trial. Lancet Oncol. 2017;18:75-78. 60. Coleman RL, Oza AM, Lorusso D, et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:1949-1961. 61. Teneriello MG, Tseng PC, Crozier M, et al. Phase II evaluation of nanoparticle albumin- bound paclitaxel in platinum-sensitive patients with recurrent ovarian, peritoneal, or fallopian tube cancer. J Clin Oncol. 2009;27:1426-1431. 62. Kushner DM, Connor JP, Sanchez F, et al. Weekly docetaxel and carboplatin for recurrent ovarian and peritoneal cancer: a phase II trial. Gynecol Oncol. 2007;05:358-364. 63. Wolf JK, Bodurka DC, Verschraegen C, et al. A phase II trial of oral capecitabine in patients with platinum–and taxane–refractory ovarian, fallopian tube, or peritoneal cancer. Gynecol Oncol. 2006;102:468-474. 64. Parmar MK, Ledermann JA, Colombo N, et al. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003;361:2099-2106. 65. McGuire WP, Hoskins WJ, Brady MF, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996;334:1-6. 66. Bolis G, D’Incalci M, Gramellini F, et al. Adriamycin in ovarian cancer patients resistant to cyclophosphamide70.Wadler S, Yeap B, Vogl S, Carbone P. Randomized trial of initial therapy with melphalan versus cisplatin-based combination chemotherapy in patients with advanced ovarian carcinoma: initial and long term results— Eastern Cooperative Oncology Group Study E2878. Cancer. 1996;77:733-742. Eur J Cancer. 1978;14:1401-1402. 67. Hubbard S, Barker P, Young RC. Adriamycin therapy for advanced ovarian cancer recurrent after chemotherapy. Cancer Treat Rep. 1978;62:1375-1377. 68. Markman M, Hakes T, Reichman B, et al. Ifosfamide and mesna in previously treated advanced epithelial ovarian cancer: activity in platinum-resistant disease. J Clin Oncol. 1992;10:243-248. 69. Matsumoto K, Katsumata N, Yamanaka Y, et al. The safety and efficacy of the weekly dosing of irinotecan for platinum- and taxanes-resistant epithelial ovarian cancer. Gynecol Oncol. 2006 Feb;100:412-416. 70. Wadler S, Yeap B, Vogl S, Carbone P. Randomized trial of initial therapy with melphalan versus cisplatin-based combination chemotherapy in patients with advanced ovarian carcinoma: initial and long term results—Eastern Cooperative Oncology Group Study E2878. Cancer. 1996;77:733-742. 71. Dieras V, Bougnoux P, Petit T, et al. Multicentre phase II study of oxaliplatin as a single- agent in cisplatin/carboplatin +/- taxane-pretreated ovarian cancer patients. Ann Oncol. 2002;13:258-266. 72. Markman M, Blessing J, Rubin SC, et al. Phase II trial of weekly paclitaxel (80 mg/m2) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: a Gynecologic Oncology Group study. Gynecol Oncol. 2006;101:436-440. 73. Miller DS, Blessing JA, Krasner CN, et al. Phase II evaluation of pemetrexed in the treatment of recurrent or persistent platinum-resistant ovarian or primary peritoneal carcinoma: a study of the Gynecologic Oncology Group. J Clin Oncol. 2009;27:2686-2691. 74. Vergote I, Calvert H, Kania M, et al. A randomised, double-blind, phase II study of two doses of pemetrexed in the treatment of platinum-resistant, epithelial ovarian or primary peritoneal cancer. Eur J Cancer. 2009;45:1415-1423. 75. Rothenberg ML, Liu PY, Wilczynski S, et al. Phase II trial of vinorelbine for relapsed ovarian cancer: a Southwest Oncology Group study. Gynecol Oncol. 2004;95:506-512. 76. Pazopanib (Votrient) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals, Corp.; 2017. 77. Friedlander M, Hancock KC, Richin D, et al. A phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer. Gynecol Oncol. 2010;119:32-37. 78. Mirza MR, Avall Lundqvist E, Birrer A, et al. Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomized, phase 2, superiority trial. Lancet Oncol. 2019;20:1409-1419. 79. Van Der Vange N, Greggi S, Burger CW et al. Experience with hormonal therapy in advanced epithelial ovarian cancer. Acta Oncol. 1995;34:813-820. 80. Wiernik PH, Greenwald ES, Ball H, et al. High-dose megestrol acetate in the treatment of patients with ovarian cancer who have undergone previous treatment: Eastern Cooperative Oncology Group Study PD884. Am J Clin Oncol. 1998;21:565-567. 81. Benigno BB, Burrell MO, Daugherty P, et al. A phase II nonrandomized study of nab-paclitaxel plus carboplatin in patients with recurrent platinum-sensitive ovarian cancer. J Clin Oncol. 2010;28(15-Suppl):Abstract 5011. 82. Sugiyama T, Okamoto A, Enomoto T, et al. Randomized phase III trial of irinotecan plus cisplatin compared with paclitaxel plus carboplatin as first-line chemotherapy for ovarian clear cell carcinoma: JGOG3017/GCIG Trial. J Clin Oncol. 2016;34:2881-2887. 83. Fulvestrant (Faslodex) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP: 2019. 84. Argenta PA, Thomas SG, Judson PL, et al. A phase II study of fulvestrant in the treatment of multiply-recurrent epithelial ovarian cancer. Gynecol Oncol. 2009;113:205-209. 85. Pembrolizumab (Keytruda) [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; 2019. 86. Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409-413. 87. Matulonis UA, Shapira-Frommer R, Santin A, et al. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: Interim results from the phase 2 KEYNOTE-100 study. J Clin Oncol. 2018;36(15_suppl):Abstract 5511. 88. Entrectinib (Rozlytrek) [package insert]. South San Francisco, CA: Genentech USA, Inc.; 2019. 89. Demetri GD, Paz-Ares K, Farago AF, et al. Efficacy and safety of entrectinib in patients with NTRK fusion-positive tumours: Pooled analysis of STARTRK-2, STARTRK-1, and ALKA-372-001. Ann Oncol. 2018;29(suppl_9): Abstract LBA4. 90. Siena S, Doebele RC, Shaw AT, et al. Efficacy of entrectinib in patients (pts) with solid tumors and central nervous system (CNS) metastases: Integrated analysis from three clinical trials. J Clin Oncol. 2017;(15_suppl):Abstract 3017. 91. Robinson GW, Gajjar AJ, Gauvain KM, et al. Phase 1/1B trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors including central nervous system (CNS) tumors. J Clin Oncol. 2019;37(15_suppl): Abstract 10009. 92. Larotrectinib (Vitrakvi) [package insert]. Whippany, NJ: Bayer Healthcare Pharmaceuticals Inc.; 2019. 93. Drilon A, T.W. Laetsch TW, Kummar SG, et al. Efficacy of larotrectinib in TRK fusion–positive cancers in adults and children. N Engl J Med. 2018;378:731–739. 94. Gershenson DM, Miller A, Brady M, et al. A randomized phase II/III study to assess the efficacy of trametinib in patients with recurrent or progressive low-grade serous ovarian or peritoneal cancer. Ann Oncol. 2009;30(suppl_5): Abstract LBA61. 95. Trametinib (Mekinist) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals, Corp; 2019. 96. Barber EL, Zsiros E, Lurain JR, et al. The combination of intravenous bevacizumab and metronomic oral cyclophosphamide is an effective regimen for platinum- resistant recurrent ovarian cancer. J Gynecol Oncol. 2013;24:258-264. 97. Rose PG, Blessing JA, Ball HG, et al. A phase II study of docetaxel in paclitaxel- resistant ovarian and peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2003;88:130-135. 98. Rose PG, Blessing JA, Mayer AR, Homesley HD. Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1998;16:405-410. 99. Ferrandina G, Ludovisi M, Lorusso D, et al. Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. J Clin Oncol. 2008;26:890-896. 100. Mutch DG, Orlando M, Goss T, et al. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2007;25:2811-2818. 101. Pujade-Lauraine E, Hilpert F, Weber B, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014;32:1302-1308. 102. Gordon AN, Tonda M, Sun S, et al. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol. 2004;95:1-8. 103. Sehouli J, Stengel D, Harter P, et al. Topotecan weekly versus conventional 5-day schedule in patients with platinum-resistant ovarian cancer: a randomized multicenter phase II trial of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J Clin Oncol. 2011;29:242-248. 104. Sorafenib (Nexavar) [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; 2018. 105. Chekerov R, Hilpert F, Mahner S, et al. Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): a multicenter, randomized, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2018;19:1247-1258. 106. Kondagunta GV, Bacik J, Donadio A, et al. Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors. J Clin Oncol. 2005;23:6549-6555. 107. Kondagunta GV, Bacik J, Bajorin D, et al. Etoposide and cisplatin chemotherapy for metastatic good-risk germ cell tumors. J Clin Oncol. 2005;23:9290-9244. 108. Pfisterer J, du Bois A, Wagner U, et al. Docetaxel and carboplatin as first-line chemotherapy in patients with advanced gynecological tumors. A phase I/II trial of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-OVAR) Ovarian Cancer Study Group. Gynecol Oncol. 2004;92:949-956. 109. Bokemeyer C, Beyer J, Metzner B, et al. Phase II study of paclitaxel in patients with relapsed or cisplatin-refractory testicular cancer. Ann Oncol. 1996;7:31-34. 110. Hinton S, Catalano P, Einhorn LH, et al. Phase II study of paclitaxel plus gemcitabine in refractory germ cell tumors (E9897): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2002;20:1859-1863. 111. Slayton RE, Park RC, Silverberg SG, et al. Vincristine, dactinomycin, and cyclophosphamide in the treatment of malignant germ cell tumors of the ovary. A Gynecologic Oncology Group Study (a final report). Cancer. 1985;56:243-248. 112. Loehrer PJ Sr, Gonin R, Nichols CR, et al. Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor. J Clin Oncol. 1998;16:2500-2504. 113. Hinton S, Catalano PJ, Einhorn LH, et al. Cisplatin, etoposide and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors: final analysis of an intergroup trial. Cancer. 2003;97:1869-1875. 114. Nichols CR, Catalano PJ, Crawford ED, et al. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol. 1998;16:1287-1293. 115. Burton ER, Brady M, Homesley HD, et al. A phase II study of paclitaxel for the treatment of ovarian stromal tumors: An NRG Oncology/Gynecology Oncology Group Study. Gynecol Oncol. 2016;140:48-52. 116. Homesley HD, Fillaci V, Markman M, et al. Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2007;25:526-531. 117. Fishman A, Kudelka AP, Tresukosol D, et al. Leuprolide acetate for treating refractory or persistent ovarian granulosa cell tumor. J Reprod Med. 1996;41:393-396. 118. Teoh D, Freedman R, Sollman PT. Nearly 30 years of treatment for recurrent granulosa cell tumor of the ovary: A case report and review of the literature. Case Rep Oncol. 2010;3:14-18. 119. Brown J, Brady WE, Schink J, et al. Efficacy and safety of bevacizumab in recurrent sex cord-stromal ovarian tumors: results of a phase 2 trial of the Gynecologic Oncology Group. Cancer. 2014;120:344-351. 120. Tao X, Siid AK, Deavers MT, et al. Anti-angiogenesis therapy with bevacizumab for patients with ovarian granulosa cell tumors. Gynecol Oncol. 2009;114:431-436. |
|
|
(Revised 2/2020; NCCN Ovarian Cancer Guidelines v3.2019) © 2020 by Haymarket Media, Inc. |
|
