Bone Cancer Treatment Regimens

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BONE CANCER TREATMENT REGIMENS

Clinical Trials: The National Comprehensive Cancer Network 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 NCCN 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.

General Treatment Notes1

• Chemotherapy for Ewing's Sarcoma, Mesenchymal Chondrosarcoma, Osteosarcoma, and Undifferentiated Pleomorphic Sarcoma (UPS) should include growth factor support (see NCCN Guidelines for Myeloid Growth Factors).

• Conventional chondrosarcoma (Grades 1–3) has no known standard chemotherapy options.

• Mesenchymal chondrosarcoma: follow Ewing's sarcoma regimens (category 2B).

• Dedifferentiated chondrosarcoma: follow osteosarcoma regimens (category 2B).

• High-Grade Undifferentiated Pleomorphic Sarcoma (UPS): follow osteosarcoma regimens (category 2B)

Chordoma1

Note: All recommendations are category 2A unless otherwise indicated.

REGIMEN

DOSING

Imatinib2,3,4

Days 1-28: Imatinib 800mg orally once daily

OR

Days 1-28: Imatinib 400mg orally twice daily

Repeat cycle every 28 days until disease progression or unacceptable toxicity.

Imatinib + cisplatin5

Days 1-7: Imatinib 400mg orally once daily

Day 1: Cisplatin 25mg/m2 IV over 60 minutes

Repeat cycle weekly until disease progression or unacceptable toxicity.

Imatinib + sirolimus6

Days 1-28: Imatinib 400mg orally once daily

Days 1-28: Sirolimus 2mg orally once daily

Repeat cycle every 28 days until disease progression or unacceptable toxicity

Erlotinib7

Days 1-28: Erlotinib 150mg orally once daily

Repeat cycle every 28 days until disease progression or unacceptable toxicity

Sunitinib8

Days 1-28: Sunitinib 37.5mg orally once daily

Repeat cycle every 28 days until disease progression or unacceptable toxicity

Lapatinib for epidermal growth factor receptor (EGFR)-positive chordomas (Category 2B)9

Days 1-28: Lapatinib 1500mg orally once daily

Repeat cycle every 28 days until disease progression or unacceptable toxicity.

Sorafenib10,11

Days 1-28: Sorafenib 400mg orally twice daily

Repeat cycle until disease progression or unacceptable toxicity

Ewing's Sarcoma and Mesenchymal Chondrosarcoma1

First-line Therapy (Primary/Neoadjuvant/Adjuvant)

VAC/IE (vincristine + doxorubicin + cyclophosphamide alternating with ifosfamide + etoposide)12,13,††

Alternating VAC and IE cycles

VAC cycles

Day 1: Vincristine 2mg/m2 (max 2mg) IV over 5-10 minutes

Day 1: Doxorubicin 75mg/m2 IVP or

Dactinomycin 1250mcg/m2 IVP (Substitute for doxorubicin when cumulative lifetime doxorubicin dose of 375mg/m2 has been met)

Day 1: Cyclophosphamide 1200mg/m2 IV over 60 minutes + Mesna

IE cycles

Days 1-5: Ifosfamide 1800 mg/m2 IV over 3 days + Mesna

Days 1-5: Etoposide 100mg/m2 IV over 60 minutes

Repeat each cycle every 3 weeks for 17 cycles

VAIA (vincristine + dactinomycin [actinomycin D] + ifosfamide + doxorubicin)14,15

Day 1: Vincristine 1.5mg/m2 IV

Days 1-3: Ifosfamide 2,000mg/m2 IV + mesna

Days 1, 3, and 5: Dactinomycin 0.5mg/m2 IV

Days 2 and 4: Doxorubicin 30mg/m2 IV.

Repeat cycle every 21 days for 4 cycles, then proceed to local therapy. After local therapy, high-risk patients should receive 10 additional cycles of VAIA; standard-risk patients should receive 10 additional cycles of VAIA or 10 cycles of VACA:

Day 1: Vincristine 1.5mg/m2 IV + cyclophosphamide 1,200mg/m2 IV + mesna

Days 1, 3, and 5: Dactinomycin 0.5mg/m2 IV

Days 2 and 4: Doxorubicin 30mg/m2 IV.

Repeat cycle every 21 days for 10 cycles.

OR

Days 1, 8, 15, and 22: Vincristine 1.5mg/m2 IV

Days 1, 2, 22, 23, 43, and 44 : Ifosfamide 3,000mg/m2 IV + mesna

Days 1, 2, 43, and 44 : Doxorubicin 30mg/m2 IV

Days 22, 23, and 24: Dactinomycin 0.5mg/m2 IV

After completion of one 9-week cycle, proceed to local therapy. High-risk patients should then receive 3 additional cycles.

VIDE (vincristine + ifosfamide + doxorubicin + etoposide)16

Day 1: Vincristine 1.5 mg/m2 (max 2mg) IV push over 5-10 minutes

Days 1-3: Ifosfamide 3g/mg2 IV continuous infusion over 1-3 hours + Mesna (give concurrently with ifosfamide)

Days 1-3: Doxorubicin 20mg/m2 IV continuous infusion over 4 hours or Dactinomycin 500mcg/m2 IV (Substitute for doxorubicin when cumulative lifetime doxorubicin dose of 375mg/m2 has been met)

Days 1-3: Etoposide 150mg/m2 IV over 1 hour

Repeat cycle every 3 weeks for up to 6 cycles

Primary Therapy for Metastatic Disease at Initial Presentation

VAC/IE (vincristine + doxorubicin + cyclophosphamide alternating with ifosfamide + etoposide)12

Alternating VAC and IE cycles

VAC cycles

Day 1: Vincristine 2mg/m2 (max 2mg) IV over 5-10 minutes

Day 1: Doxorubicin 75mg/m2 IVP or

Dactinomycin 1250mcg/m2 IVP (Substitute for doxorubicin when cumulative lifetime doxorubicin dose of 375mg/m2 has been met)

Day 1: Cyclophosphamide 1200mg/m2 IV over 60 minutes + Mesna

IE cycles

Days 1-5: Ifosfamide 1800 mg/m2 IV over 3 days + Mesna

Days 1-5: Etoposide 100mg/m2 IV over 60 minutes

Repeat each cycle every 3 weeks for 17 cycles

VAIA (vincristine + dactinomycin [actinomycin D] + ifosfamide + doxorubicin)14,15

Day 1: Vincristine 1.5mg/m2 IV

Days 1-3: Ifosfamide 2,000mg/m2 IV + mesna

Days 1, 3, and 5: Dactinomycin 0.5mg/m2 IV

Days 2 and 4: Doxorubicin 30mg/m2 IV.

Repeat cycle every 21 days for 4 cycles, then proceed to local therapy. After local therapy, high-risk patients should receive 10 additional cycles of VAIA; standard-risk patients should receive 10 additional cycles of VAIA of 10 cycles of VACA:

Day 1: Vincristine 1.5mg/m2 IV + cyclophosphamide 1,200mg/m2 IV + mesna

Days 1, 3, and 5: Dactinomycin 0.5mg/m2 IV

Days 2 and 4: Doxorubicin 30mg/m2 IV.

Repeat cycle every 21 days for 10 cycles.

OR

Days 1, 8, 15, and 22: Vincristine 1.5mg/m2 IV

Days 1, 2, 22, 23, 43, and 44 : Ifosfamide 3,000mg/m2 IV + mesna

Days 1, 2, 43, and 44 : Doxorubicin 30mg/m2 IV

Days 22, 23, and 24: Dactinomycin 0.5mg/m2 IV.

After completion of one 9-week cycle, proceed to local therapy. High-risk patients should then receive 3 additional cycles.

VIDE (vincristine + ifosfamide + doxorubicin + etoposide)16

Day 1: Vincristine 1.5 mg/m2 (max 2mg) IV push over 5-10 minutes

Days 1-3: Ifosfamide 3g/mg2 IV continuous infusion over 1-3 hours + Mesna (give concurrently with ifosfamide)

Days 1-3: Doxorubicin 20mg/m2 IV continuous infusion over 4 hours or

Dactinomycin 500mcg/m2 IV (Substitute for doxorubicin when cumulative lifetime doxorubicin dose of 375mg/m2 has been met)

Days 1-3: Etoposide 150mg/m2 IV over 1 hour

Repeat cycle every 3 weeks for up to 6 cycles

VAdriaC (vincristine + doxorubicin + cyclophosphamide + dactinomycin)17

Day 1: Cyclophosphamide 1200mg/m2 IV

Day 1: Vincristine 2mg/m2 (max 2mg) IV

Day 1: Doxorubicin 75mg/m2 IV (for the first 5 cycles) or Dactinomycin 1250mcg/m2 IV (for subsequent cycles)

Repeat cycle every 3 weeks for 17 cycles

Second-line Therapy (Relapsed/Refractory Disease or Metastatic Disease)†††

Cyclophosphamide + topotecan18–21

Days 1–5: Cyclophosphamide 250mg/m2 IV over 30 minutes

Days 1–5: Topotecan 0.75mg/m2 IV over 30 minutes

Repeat cycle every 3 weeks for 12-14 cycles

Irinotecan ± temozolomide22–28

Days 1–5: Temozolomide 100mg/m2/day orally, plus

Days 1–5 and 8–12: Irinotecan 10–20mg/m2/day IV at least 1 hour after temozolomide.

Repeat cycle every 3 or 4 weeks.

Ifosfamide (high dose) ± etoposide29,30

Days 1–5: Ifosfamide 1,800mg/m2/day IV + mesna

Days 1–5: Etoposide 100mg/m2/day IV.

Repeat every 3 weeks for 12 cycles.

Ifosfamide + carboplatin + etoposide31

Days 1 and 2: Carboplatin 400mg/m2/day IV, plus

Days 1–5: Ifosfamide 1,800mg/m2/day IV + mesna + etoposide 100mg/m2/day IV.

Repeat cycle every 3 weeks for up to 12 cycles (median 1 cycle).

Ifosfamide + carboplatin + etoposide31

Days 1 and 2: Carboplatin 400mg/m2/day IV, plus

Days 1–5: Ifosfamide 1,800mg/m2/day IV + mesna + etoposide 100mg/m2/day IV.

Repeat cycle every 3 weeks for up to 12 cycles (median 1 cycle).

Docetaxel + gemcitabine32

Days 1 and 8: Gemcitabine 675mg/m2 IV, plus

Day 8: Docetaxel 75–100mg/m2 IV.

Repeat cycle every 3 weeks for up to 13 cycles (median 4 cycles).

Vincristine + irinotecan

References and specific dosing guidance from the NCCN's Guideline Panel will be included in the next Guideline update.

Giant Cell Tumor of Bone1

Denosumab33–35

Days 1, 8, and 15: Denosumab 120mg subcutaneously for first cycle only

Followed by

Day 1: Denosumab 120mg subcutaneously

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity

Interferon alfa-2b35–37

Interferon alfa-2b (3,000,000 units/m2) 48 to 72 hours postoperatively OR

increasing dosage from 4 x 106 units 3 times a week to 9 × 106 units 3 times a week.

Osteosarcoma and Dedifferentiated Chrondrosarcoma1

First-line Therapy (Primary/Neoadjuvant/Adjuvant Therapy or Metastatic Disease)

Cisplatin + doxorubicin38–40

Days 1–3: Doxorubicin 25mg/m2/day IV, plus

Day 1: Cisplatin 100mg/m2 IV continuous infusion.

Repeat cycle every 3 weeks for 6 cycles.

MAP (high-dose methotrexate + cisplatin + doxorubicin)40–43

Preoperative Chemotherapy

Days 1 and 28: Methotrexate 8g/m2 IV followed by citrovorum factor rescue

Days 7-9 and 34-36: Cisplatin 120mg/m2 by intra-arterial infusion for 72 hours

Days 9 and 36: Doxorubicin 60mg/m2 IV starting 8 hours after the beginning of cisplatin.

Postoperative Chemotherapy (Necrosis ≥90%)

Days 1, 48, 96, and 144: Doxorubicin 45mg/m2/day for 2 consecutive days in a 4-hour IV infusion

Days 21, 69, and 117: Methotrexate 8g/m2 IV followed by citrovorum factor rescue

Days 27, 75, and 123: Cisplatin 120mg/m2 by intra-arterial infusion for 72 hours.

Postoperative Chemotherapy (Necrosis <90%)

Days 1, 69, 138, and 207: Doxorubicin 45mg/m2/day for 2 consecutive days in a 4-hour IV infusion

Days 21, 90, and 159: Ifosfamide 2g/m2/day IV for 5 consecutive days in 90 minutes + mesna

Days 42, 111, and 180: Methotrexate 8g/m2 IV followed by citrovorum factor rescue

Days 48, 117, and 186: Etoposide 120mg/m2/day in a 1-hour infusion for 3 days.

Doxorubicin + cisplatin + ifosfamide + high-dose methotrexate44

Days 0, 6, 18, 27, and 36: Methotrexate 12g/m2 as a 4-hour infusion, increased by 2g/m2 if the hour-4 level of serum methotrexate in the previous course was <1000 µmol/L

Days 1, 7, 19, 28, and 37: Cisplatin 60mg/m2/day as a 48-hour continuous IV infusion (total dose 120mg/m2)

Days 1 and 7: Doxorubicin (preoperative): 75mg/m2 as a 24-hour continuous IV infusion

Day 12: Surgery

Days 13, 22, and 31: Doxorubicin (postoperative): 90mg/m2 as a 24-hour continuous IV infusion

Days 4, 10, 16, 25, and 34: Ifosfamide: 3 g/m2/day as a 120-hour (5-day) continuous IV infusion (total dose 15g/m2).

Ifosfamide + cisplatin + epirubicin45

Day 1: Cisplatin 100mg/m2 IV

Day 1: Epirubicin 90 mg/m2 IV

Days 2-4: Ifosfamide 2000 mg/m2 IV over 3 hours + Equivalent dose of Mesna

Repeat every 3 weeks for 6 cycles (3 cycles preoperatively and 3 cycles postoperatively)

Second-line Therapy (Relapsed/Refractory or Metastatic Disease)

Carboplatin + ifosfamide + etoposide31

Days 1 and 2: Carboplatin 400mg/m2/day IV, plus

Days 1–5: Ifosfamide 1,800mg/m2/day IV + mesna + etoposide 100mg/m2/day IV.

Repeat cycle every 3 weeks for up to 12 cycles (median 1 cycles).

Gemcitabine + docetaxel32

Days 1 and 8: Gemcitabine 675mg/m2 IV, plus

Day 8: Docetaxel 75–100mg/m2 IV.

Repeat cycle every 3 weeks for up to 13 cycles (median 4 cycles).

Cyclophosphamide + topotecan21

Days 1–5: Cyclophosphamide 250mg/m2 IV over 30 minutes

Days 1–5: Topotecan 0.75mg/m2 IV over 30 minutes

Repeat cycle every 3 weeks for 12–14 cycles.

Sorafenib54

Days 1-28: Sorafenib 400mg twice daily

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity

Ifosfamide (high dose) ± etoposide29,48

Days 1–5: Ifosfamide 1,800mg/m2/day IV + mesna, plus

Days 1–5: Etoposide 100mg/m2/day IV.

Repeat every 3 weeks for 12 cycles.

Cyclophosphamide + etoposide46

Day 1: Cyclophosphamide 4,000mg/m2 3-hour IV infusion; all patients received mesna 1,400mg/m2 before and after 4 hours and 8 hours from cyclophosphamide start

Days 2–4: Etoposide 100mg/m2 over 1 hour twice daily for 3 days on Days 2, 3, and 4 (total dose 600mg/m2).

Repeat in 21-28 days for total of two cycles.

Gemcitabine47

Days 1 and 8: Gemcitabine 1,200mg/m2 IV

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity

High-dose methotrexate + etoposide + ifosfamide49

Weeks 1, 2, 3, 7, 8, 12, and 13: High-dose methotrexate IV

Weeks 4 and 9: Etoposide 75mg/m2/day IV + ifosfamide 3g/m2/day + mesna 3.6mg/m2/day continuous IV infusion for 4 days.

Sorafenib + everolimus55

Sorafenib 800mg orally + everolimus 5mg orally once daily until disease progression or unacceptable toxicity.

153Sm-EDTMP (for relapsed or refractory disease beyond second-line therapy)50

Samarium-153 ethylene diamine tetramethylene phosphonate (153Sm-EDTMP) 1.0, 3.0, 4.5, 6.0, 12.0, 19.0, or 30.0mCi/kg can be considered; however, the 30mCi/kg dosage requires peripheral-blood progenitor cell grafts with more than x 106 CD34(+)/kg to overcome the myeloa47 vfects of skeletal irradiation.

223RA51–53

Three 75kBq/kg 223RA infusion given in 4-week intervals (total administered dose of 14.44MBq or 0.390mCi); 223RA doses of 50kBq/kg and 100Bq/kg are being investigated.

For MSI-H/dMMR tumors

Pembrolizumab56

Day 1: Pembrolizumab 10mg/kg IV once daily

Repeat cycle every 14 days until disease progression or unacceptable toxicity.

* Indicated for high-grade chondrosarcoma for systemic recurrence.

Dactinomycin can be substituted for doxorubicin because of concerns regarding cardiotoxicity.

†† In patients younger than 18 years, evidence supports 2-week compressed treatment

††† Vincristine could be added to any of the regimens

†††† Pembrolizumab is a systemic treatment option for adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options. Not for Giant Cell Tumor of Bone or Chordoma.

References

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(Revised 6/2018)

© 2018 by Haymarket Media, Inc.

(Revised 6/2018)

© 2018 by Haymarket Media, Inc.


Bone Cancer Drug Monographs

Bone and Connective Tissue Cancer

COSMEGEN Doxorubicin HCl Doxorubicin HCl Solution
HALAVEN LARTRUVO Methotrexate for injection
Methotrexate injection VINCASAR PFS VOTRIENT
XGEVA YONDELIS

Data provided by the Monthly Prescribing Reference (MPR) Hematology/Oncology Edition.

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