Pancreatic Adenocarcinoma Treatment Regimens
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Pancreatic Adenocarcinoma Treatment Regimens |
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Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. |
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Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced health care 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 provided only to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data become 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. |
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Note: All recommendations are category 2A unless otherwise indicated. |
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▶Neoadjuvant Therapy (Resectable/Borderline Resectable Disease)1,a,b |
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REGIMEN |
DOSING |
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Preferred Regimens |
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FOLFIRINOX (Fluorouracil Continuous Infusion/Leucovorin/ |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Day 1: Irinotecan 180mg/m2 IV over 90 minutes (begin 30 minutes after start of leucovorin infusion) Day 1: Fluorouracil 400mg/m2 IV push, followed by: Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks for 4-12 cycles. |
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Gemcitabine + Albumin-Bound Paclitaxel4,c |
Days 1,8,15: Albumin-bound paclitaxel 125mg/m2 IV over 30 minutes, followed by: Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks for 6 cycles. |
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Modified FOLFIRINOX5-7,c-f |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Day 1: Irinotecan 150mg/m2 IV over 90 minutes (begin 30 minutes after start of leucovorin infusion) Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks for 4-12 cycles. |
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Preferred Regimens Only For Known BRCA1/2 or PALB2 Mutations |
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FOLFIRINOX2,3,c-f |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Day 1: Irinotecan 180mg/m2 IV over 90 minutes (begin 30 minutes after start of leucovorin infusion) Day 1: Fluorouracil 400mg/m2 IV push, followed by: Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks for 4-12 cycles. |
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Gemcitabine + Cisplatin |
Day 1: Cisplatin 25-30mg/m2 IV over 1 hour Day 1: Gemcitabine 750mg/m2 IV over 30 minutes OR Day 1: Gemcitabine IV at a rate of 10mg/m2/minute. Repeat cycle every 2 weeks for 2-6 cycles. |
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Modified FOLFIRINOX5-7,c-f |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Day 1: Irinotecan 150mg/m2 IV over 90 minutes (begin 30 minutes after start of leucovorin infusion) Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks for 4-12 cycles. |
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▶Adjuvant Chemotherapy1 |
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Preferred Regimens |
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Gemcitabine + Capecitabine (Category 1)12,13,f |
Days 1-21: Capecitabine 830mg/m2 orally twice daily Days 1,8,15: Gemcitabine 1000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks for 6 cycles. |
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Modified FOLFIRINOX (Category 1)5-7,d-f |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Day 1: Irinotecan 150mg/m2 IV over 90 minutes (begin 30 minutes after start of leucovorin infusion) Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks. |
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Other Recommended Regimens |
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Capecitabine (Category 2B)14,15,f |
Days 1-14: Capecitabine 1,000mg/m2 orally twice daily. Repeat cycle every 3 weeks for 8 cycles. |
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Fluorouracil Continuous Infusion16,17,f |
Days 1-28: Fluorouracil 250mg/m2 IV continuous infusion over 24 hours daily. Repeat every 6 weeks for 1-4 cycles. |
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Fluorouracil Continuous Infusion Followed by Chemoradiation16,17,f,h |
Days 1-21: Fluorouracil 250mg/m2 IV continuous infusion over 24 hours daily. Administer for one 3-week cycle, followed by: Concurrent chemotherapy and radiation therapy (See Chemoradiation). |
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Fluorouracil Continuous Infusion Followed by Chemoradiation Followed by Fluorouracil Continuous Infusion16,17,f,h |
Days 1-21: Fluorouracil 250mg/m2 IV continuous infusion over 24 hours daily. Administer for one 3-week cycle, followed by: Concurrent chemotherapy and radiation therapy (See Chemoradiation), followed by: Days 1-28: Fluorouracil 250mg/m2 IV continuous infusion over 24 hours daily. Repeat cycle every 6 weeks for 2 cycles. |
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Fluorouracil + Leucovorin (Category 1)18,f |
Days 1-5: Leucovorin 20mg/m2 IV push daily, followed by: Days 1-5: Fluorouracil 425mg/m2 IV push daily. Repeat cycle every 4 weeks for 2-6 cycles. |
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Fluorouracil + Leucovorin Followed by Chemoradiation18,f,h |
Days 1-5: Leucovorin 20mg/m2 IV push daily, followed by: Days 1-5: Fluorouracil 425mg/m2 IV push daily. Repeat cycle every 4 weeks for 2-6 cycles, followed by: concurrent chemotherapy and radiation therapy (See Chemoradiation). |
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Fluorouracil + Leucovorin Followed by Chemoradiation Followed by Fluorouracil + Leucovorin1,f,h |
See NCCN Pancreatic Adenocarcinoma Guidelines1 |
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Gemcitabine (Category 1)9,17,19-21 |
Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks for 2-6 cycles. |
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Gemcitabine Followed by Chemoradiation9,17,19-21,h |
Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks for 2-6 cycles, followed by: Concurrent chemotherapy and radiation therapy (See Chemoradiation). |
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Gemcitabine Followed by Chemoradiation Followed by Gemcitabine1,h |
See NCCN Pancreatic Adenocarcinoma Guidelines1 |
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▶First-Line Chemotherapy for Locally Advanced Disease and Good Performance Status1 |
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Preferred Regimens |
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FOLFIRINOX2,3,d-f,i |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Day 1: Irinotecan 180mg/m2 IV over 90 minutes (begin 30 minutes after start of leucovorin infusion) Day 1: Fluorouracil 400mg/m2 IV push, followed by: Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks for 4-6 cycles (as induction) or every 2 weeks. |
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Gemcitabine + Albumin-Bound Paclitaxel4,j |
Days 1,8,15: Albumin-bound Paclitaxel 125mg/m2 IV over 30 minutes, followed by: Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks for 4-6 cycles (as induction) or every 4 weeks. |
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Modified FOLFIRINOX5-7,d-f,i |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Day 1: Irinotecan 150mg/m2 IV over 90 minutes (begin 30 minutes after start of leucovorin infusion) Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks for 4-6 cycles (as induction) or every 2 weeks. |
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Preferred Regimens Only For Known BRCA1/2 or PALB2 Mutations |
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FOLFIRINOX2,3,d-f,i |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Day 1: Irinotecan 180mg/m2 IV over 90 minutes (begin 30 minutes after start of leucovorin infusion) Day 1: Fluorouracil 400mg/m2 IV push, followed by: Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks for 4-6 cycles (as induction) or every 2 weeks. |
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Gemcitabine + Cisplatin8-11,g |
Days 1,15: Gemcitabine 1,000mg/m2 IV over 30 minutes Days 1,15: Cisplatin 50mg/m2 IV over 1 hour. Repeat cycle every 4 weeks for 4-6 cycles (as induction). |
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Modified FOLFIRINOX5-7,d-f,i |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Day 1: Irinotecan 150mg/m2 IV over 90 minutes (begin 30 minutes after start of leucovorin infusion) Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks for 4-6 cycles (as induction) or every 2 weeks. |
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Other Recommended Regimens |
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Capecitabine (Category 2B)14,15,f |
Days 1-14: Capecitabine 1,000mg/m2 orally twice daily. Repeat cycle every 3 weeks for 4-6 cycles (as induction) or every 3 weeks. |
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CapeOX (Capecitabinef + Oxaliplatin) (Category 2B)22,f |
Days 1-14: Capecitabine 750-1,000mg/m2 orally twice daily Day 1: Oxaliplatin 110-130mg/m2 IV over 2 hours. Repeat cycle every 3 weeks for 4-6 cycles (as induction) or every 3 weeks. |
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Fluorouracil, Continuous Infusion (Category 2B)16,17,f |
Days 1-4: Fluorouracil 1000mg/m2 IV continuous infusion over 24 hours daily. Repeat cycle every 3 weeks for 4-6 cycles (as induction) or every 3 weeks. |
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OFF (Fluorouracil + Leucovorin + Oxaliplatin) (Category 2B)23,24,f |
Days 1,8,15,22: Leucovorin 200mg/m2 IV over 2 hours (leucovorin infusion time should match the infusion time of oxaliplatin when these agents are given concurrently) Days 8,22: Oxaliplatin 85mg/m2 IV over 2 hours, followed by: Days 1,8,15,22: Fluorouracil 2,000mg/m2 IV continuous infusion over 24 hours. Repeat cycle every 6 weeks for 4-6 cycles (induction) or every 6 weeks. |
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Gemcitabine9,17,19-21 |
Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks for 4-6 cycles (as induction) or every 4 weeks. |
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Gemcitabine + Albumin-Bound Paclitaxel + Cisplatin (Category 2B)25,26,g |
Days 1,8: Albumin-bound Paclitaxel 100mg/m2 IV over 30 minutes, followed by: Days 1,8: Cisplatin 25mg/m2 IV over 1 hour, followed by: Days 1,8: Gemcitabine 800mg/m2 IV over 30 minutes. Repeat cycle every 3 weeks for 4-6 cycles (induction) or every 3 weeks, OR Days 1,8: Albumin-bound Paclitaxel 125mg/m2 IV over 30 minutes, followed by: Days 1,8: Cisplatin 25mg/m2 IV over 1 hour, followed by: Days 1,8: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 3 weeks for 4-6 cycles (induction) or every 3 weeks. |
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Gemcitabine + Capecitabine12,13,f |
Days 1-21: Capecitabine 830mg/m2 orally twice daily Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks for 4-6 cycles (as induction) or every 4 weeks. |
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Gemcitabine + Erlotinib27-29 |
Days 1-28: Erlotinib 100mg orally daily Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks for 4-6 cycles (as induction). |
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GTX (Gemcitabine [fixed-dose rate] + Docetaxel + Capecitabinef) (Category 2B)30,k |
Days 4,11: Gemcitabine 750mg/m2 IV at a rate of 10mg/m2/minute, followed by: Days 4,11: Docetaxel 30mg/m2 IV over 1 hour Days 1-14: Capecitabine 750mg/m2 orally twice daily. Repeat cycle every 3 weeks for 4-6 cycles (as induction) or every 3 weeks. |
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Useful in Certain Circumstances |
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Induction chemotherapy with any of the preferred/other regimens (≥4-6 cycles) followed by chemoradiation or SBRT (in selected patients, locally advanced disease without systemic metastases)a |
See NCCN Pancreatic Adenocarcinoma Guidelines1 |
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Chemoradiation or SBRT (in select patients who are not candidates for combination therapy)a,l |
See NCCN Pancreatic Adenocarcinoma Guidelines1 |
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▶First-Line Chemotherapy for Locally Advanced Disease and Poor Performance Status1 |
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Preferred Regimens |
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Capecitabine (Category 2B)14,15,f |
Days 1-14: Capecitabine 1,000mg/m2 orally twice daily. Repeat every 3 weeks for 4-6 cycles (as induction). |
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Fluorouracil, Continuous Infusion (Category 2B)16,17,f |
Days 1-4: Fluorouracil 1,000mg/m2 IV continuous infusion over 24 hours daily. Repeat cycle every 3 weeks for 4-6 cycles (induction) or every 3 weeks. |
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Gemcitabine (Category 1)9,17,19-21 |
Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks for 4-6 cycles (as induction) or every 4 weeks. |
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Gemcitabine (fixed-dose rate) (Category 2B)9,17,19-21 |
Days 1,8,15: Gemcitabine 1,000mg/m2 IV at a rate of 10mg/m2/minute. Repeat cycle every 4 weeks. |
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▶First-Line Chemotherapy for Metastatic Disease and Good Performance Status1 |
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Preferred Regimens |
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FOLFIRINOX (Category 1)2,3,d-f,i |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Day 1: Irinotecan 180mg/m2 IV over 90 minutes (begin 30 minutes after start of leucovorin infusion) Day 1: Fluorouracil 400mg/m2 IV push, followed by: Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks. |
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Gemcitabine + Albumin-Bound Paclitaxel (Category 1)4,j |
Days 1,8,15: Albumin-bound Paclitaxel 125mg/m2 IV over 30 minutes, followed by: Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks. |
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Modified FOLFIRINOX5-7,d-f,i |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Day 1: Irinotecan 150mg/m2 IV over 90 minutes (begin 30 minutes after start of leucovorin infusion) Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks. |
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Preferred Regimens Only For Known BRCA1/2 or PALB2 Mutations |
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FOLFIRINOX (Category 1)2,3,d-f,i |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Day 1: Irinotecan 180mg/m2 IV over 90 minutes (begin 30 minutes after start of leucovorin infusion) Day 1: Fluorouracil 400mg/m2 IV push, followed by: Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks. |
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Gemcitabine + Cisplatin8-11,g |
Days 1,15: Gemcitabine 1,000mg/m2 IV over 30 minutes Days 1,15: Cisplatin 50mg/m2 IV over 1 hour. Repeat cycle every 4 weeks. |
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Modified FOLFIRINOX5-7,d-f,i |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Day 1: Irinotecan 150mg/m2 IV over 90 minutes (begin 30 minutes after start of leucovorin infusion) Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks. |
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Other Recommended Regimens |
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CapeOx (Capecitabinef + Oxaliplatin) (Category 2B)22,f |
Days 1-14: Capecitabine 750-1,000mg/m2 orally twice daily Day 1: Oxaliplatin 110-130mg/m2 IV over 2 hours. Repeat cycle every 3 weeks. |
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OFF (Fluorouracil + Leucovorin + Oxaliplatin) (Category 2B)23,24,f |
Days 1,8,15,22: Leucovorin 200mg/m2 IV over 2 hours (leucovorin infusion time should match the infusion time of oxaliplatin when these agents are given concurrently) Days 8,22: Oxaliplatin 85mg/m2 IV over 2 hours, followed by: Days 1,8,15,22: Fluorouracil 2,000mg/m2 IV continuous infusion over 24 hours. Repeat cycle every 6 weeks. |
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Gemcitabine (Category 1)9,17,19-21 |
Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks. |
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Gemcitabine + Albumin-Bound Paclitaxel + Cisplatin25,26,g |
Days 1,8: Albumin-bound Paclitaxel 100mg/m2 IV over 30 minutes, followed by: Days 1,8: Cisplatin 25mg/m2 IV over 1 hour, followed by: Days 1,8: Gemcitabine 800mg/m2 IV over 30 minutes. Repeat cycle every 3 weeks. OR Days 1,8: Albumin-bound Paclitaxel 125mg/m2 IV over 30 minutes, followed by: Days 1,8: Cisplatin 25mg/m2 IV over 1 hour, followed by: Days 1,8: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 3 weeks. |
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Gemcitabine + Capecitabine12,13,f |
Days 1-21: Capecitabine 830mg/m2 orally twice daily Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes Repeat cycle every 4 weeks. |
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Gemcitabine + Erlotinib (Category 1)27-29 |
Days 1-28: Erlotinib 100mg orally daily Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks. |
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GTX (Gemcitabine [Fixed-Dose Rate] + Docetaxel + Capecitabinef) (Category 2B)30,k |
Days 4,11: Gemcitabine 750mg/m2 IV at a rate of 10mg/m2/minute, followed by: Days 4,11: Docetaxel 30mg/m2 IV over 1 hour Days 1-14: Capecitabine 750mg/m2 orally twice daily. Repeat cycle every 3 weeks. |
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Useful in Certain Circumstances |
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Pembrolizumab (for patients with MSI-H, dMMR, or TMB-H [≥10mut/Mb])31-35,a,m |
Day 1: Pembrolizumab 200mg IV over 30 minutes. Repeat cycle every 3 weeks for a maximum of 24 months of therapy. OR Day 1: Pembrolizumab 400mg IV over 30 minutes. Repeat cycle every 6 weeks for a maximum of 24 months of therapy. |
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▶First-Line Chemotherapy for Metastatic Disease and Poor Performance Status1 |
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Preferred Regimens |
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Capecitabine (Category 2B)14,15,f |
Days 1-14: Capecitabine 1,000mg/m2 orally twice daily. Repeat every 3 weeks. |
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Fluorouracil, Continuous Infusion (Category 2B)16,17,f |
Days 1-4: Fluorouracil 1,000mg/m2 IV continuous infusion over 24 hours daily. Repeat cycle every 3 weeks. |
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Gemcitabine (Category 1)9,17,19-21 |
Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks. |
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Gemcitabine (Fixed-Dose Rate) (Category 2B)9,17,19-21 |
Days 1,8,15: Gemcitabine 1,000mg/m2 IV at a rate of 10mg/m2/minute. Repeat cycle every 4 weeks. |
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Useful in Certain Circumstances |
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Entrectinib (if NTRK gene fusion positive) (Category 2B)36-38 |
Days 1-28: Entrectinib 600mg orally once daily. Repeat cycle every 4 weeks. |
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Larotrectinib (if NTRK gene fusion positive)38-40 |
Days 1-28: Larotrectinib 100mg orally twice daily. Repeat cycle every 4 weeks. |
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Pembrolizumab (for patients with MSI-H, dMMR, or TMB-H [≥10mut/Mb])31-35,a,m |
Day 1: Pembrolizumab 200mg IV over 30 minutes. Repeat cycle every 3 weeks for a maximum of 24 months of therapy. OR Day 1: Pembrolizumab 400mg IV over 30 minutes. Repeat cycle every 6 weeks for a maximum of 24 months of therapy. |
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▶Maintenance Therapy for Patients with Metastatic Disease and Good Performance Status1,n |
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Preferred Regimens |
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Olaparib (for patients with germline BRCA1/2 mutations if previous platinum-based chemotherapy)42-44 |
Days 1-28: Olaparib 300mg orally twice daily. Repeat cycle every 4 weeks. |
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Other Recommended Regimens |
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Capecitabine (if previous first-line FOLFIRINOX)14,15,f |
Days 1-14: Capecitabine 1,000mg/m2 orally twice daily. Repeat cycle every 3 weeks. |
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Gemcitabine (if previous first-line Gemcitabine + Albumin-Bound Paclitaxel) (Category 2B)9,17,19-21 |
Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks. |
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Gemcitabine + Albumin-Bound Paclitaxel, Modified Schedule (if previous first-line Gemcitabine + Albumin-Bound Paclitaxel) (Category 2B)45 |
Days 1,15: Gemcitabine 1,000mg/m2 IV over 30 minutes Days 1,15: Albumin-Bound Paclitaxel 125mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks. |
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Useful in Certain Circumstances |
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Fluorouracil + Leucovorin (Simplified) (if previous first-line FOLFIRINOX)46,47,f,o |
Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by: Day 1: Fluorouracil 400mg/m2 IV push, followed by: Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks. |
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Fluorouracil + Leucovirin + Irinotecan (if previous first-line FOLFIRINOX)46,47,e,f,o |
Day 1: Irinotecan 90mg/m2 IV over 1 hour, concurrent with: Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by: Days 1-2: Fluorouracil 1,000mg/m2 IV continuous infusion (2,000mg/m2 IV over 46 hours), followed by: Day 3: Irinotecan 90mg/m2 IV over 1 hour. Repeat cycle every 2 weeks. |
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FOLFOX (if previous first-line FOLFIRINOX) (Category 2B)48-50,f,p |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, concurrent with: Day 1: Leucovorin 400mg/m2 IV over 2 hours (leucovorin infusion time should match the infusion time of oxaliplatin when these agents are given concurrently), followed by: Days 1-2: Fluorouracil 1,000mg/m2 IV continuous infusion over 24 hours daily (2,000mg/m2 IV over 46 hours). Repeat cycle every 2 weeks. OR Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, concurrent with: Day 1: Leucovorin 400mg/m2 IV over 2 hours (leucovorin infusion time should match the infusion time of oxaliplatin when these agents are given concurrently), followed by: Day 1: Fluorouracil 400mg/m2 IV push, followed by: Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks. |
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Rucaparib (for patients with germline or somatic BRCA1/2 or PALB2 mutations, if previous platinum-based chemotherapy)51,52,q |
Days 1-28: Rucaparib 600mg orally twice daily. Repeat cycle every 4 weeks. |
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▶Subsequent Therapy for Locally Advanced/Metastatic Disease and Therapy for Recurrent Disease: Good Performance Status1 |
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REGIMEN |
DOSING |
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Preferred Regimens |
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Entrectinib (if NTRK gene fusion positive)36-38 |
Days 1-28: Entrectinib 600mg orally once daily. Repeat cycle every 4 weeks. |
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Larotrectinib (if NTRK gene fusion positive)38-40 |
Days 1-28: Larotrectinib 100mg orally twice daily. Repeat cycle every 4 weeks. |
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Pembrolizumab (for patients with MSI-H, dMMR, or TMB-H [≥10mut/Mb])31-35,a,m |
Day 1: Pembrolizumab 200mg IV over 30 minutes. Repeat cycle every 3 weeks for a maximum of 24 months of therapy. OR Day 1: Pembrolizumab 400mg IV over 30 minutes. Repeat cycle every 6 weeks for a maximum of 24 months of therapy. |
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Other Recommended Regimens (if prior gemcitabine-based therapy) |
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Capecitabine14,15,f |
Days 1-14: Capecitabine 1,000mg/m2 orally twice daily. Repeat cycle every 3 weeks. |
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CapeOx (Capecitabinef + Oxaliplatin)22 |
Days 1-14: Capecitabine 750-1,000mg/m2 orally twice daily Day 1: Oxaliplatin 110-130mg/m2 IV over 2 hours. Repeat cycle every 3 weeks. |
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Fluorouracil, Continuous Infusion16,17,f |
Days 1-4: Fluorouracil 1,000mg/m2 IV continuous infusion over 24 hours daily. Repeat cycle every 3 weeks. |
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Fluorouracil + Leucovorin + Liposomal Irinotecan (Category 1 for metastatic disease)53,e,f,r |
Day 1: Liposomal Irinotecan 70mg/m2 IV over 90 minutes, followed by: Day 1: Leucovorin 400mg/m2 IV over 30 minutes, followed by: Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 over 46 hours). Repeat cycle every 2 weeks. |
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FOLFIRI50,54-56,e,f |
Day 1: Irinotecan 180mg/m2 IV over 90 minutes, concurrent with: Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by: Day 1: Fluorouracil 400mg/m2 IV push, followed by: Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks. OR Day 1: Irinotecan 70mg/m2 IV over 1 hour, concurrent with: Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by: Days 1-2: Fluorouracil 1,000mg/m2 IV continuous infusion over 24 hours daily (2,000mg/m2 IV over 46 hours), followed by: Day 3: Irinotecan 70mg/m2 IV over 1 hour. Repeat cycle every 2 weeks. OR Day 1: Irinotecan 180mg/m2 IV over 90 minutes Days 1-2: Leucovorin 200mg/m2 IV over 2 hours daily, followed by: Days 1-2: Fluorouracil 400mg/m2 IV push daily, followed by: Days 1-2: Fluorouracil 600mg/m2 IV continuous infusion over 24 hours daily (1,200mg/m2 IV over 46 hours). Repeat cycle every 2 weeks. |
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FOLFIRINOX2,3,d-f,i |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Day 1: Irinotecan 180mg/m2 IV over 90 minutes (begin 30 minutes after start of leucovorin infusion) Day 1: Fluorouracil 400mg/m2 IV push, followed by: Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks. |
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FOLFOX48-50,f |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with: Day 1: Leucovorin 400mg/m2 IV over 2 hours (leucovorin infusion time should match the infusion time of oxaliplatin when these agents are given concurrently), followed by: Days 1-2: Fluorouracil 1,000mg/m2 IV continuous infusion over 24 hours daily (2,000mg/m2 IV over 46 hours). Repeat cycle every 2 weeks. OR Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with: Day 1: Leucovorin 400mg/m2 IV over 2 hours (leucovorin infusion time should match the infusion time of oxaliplatin when these agents are given concurrently), followed by: Day 1: Fluorouracil 400mg/m2 IV push, followed by: Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks. |
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FOLFOX (if previous first-line FOLFIRINOX) (Category 2B)48-50,f,p |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, concurrent with: Day 1: Leucovorin 400mg/m2 IV over 2 hours (leucovorin infusion time should match the infusion time of oxaliplatin when these agents are given concurrently), followed by: Days 1-2: Fluorouracil 1,000mg/m2 IV continuous infusion over 24 hours daily (2,000mg/m2 IV over 46 hours). Repeat cycle every 2 weeks. OR Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, concurrent with: Day 1: Leucovorin 400mg/m2 IV over 2 hours (leucovorin infusion time should match the infusion time of oxaliplatin when these agents are given concurrently), followed by: Day 1: Fluorouracil 400mg/m2 IV push, followed by: Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks. |
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Rucaparib (for patients with germline or somatic BRCA1/2 or PALB2 mutations, if previous platinum-based chemotherapy)51,52,q |
Days 1-28: Rucaparib 600mg orally twice daily. Repeat cycle every 4 weeks. |
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Modified FOLFIRINOX5-7,d-f,i |
Day 1: Oxaliplatin 85mg/m2 IV over 2 hours Day 1: Leucovorin 400mg/m2 IV over 2 hours Day 1: Irinotecan 150mg/m2 IV over 90 minutes (begin 30 minutes after start of leucovorin infusion) Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 IV over 46 hours). Repeat cycle every 2 weeks. |
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OFF (Fluorouracil + Leucovorin + Oxaliplatin)23,24,f |
Days 1,8,15,22: Leucovorin 200mg/m2 IV over 2 hours Days 8,22: Oxaliplatin 85mg/m2 IV over 2 hours, followed by: Days 1,8,15,22: Fluorouracil 2,000mg/m2 IV continuous infusion over 24 hours. Repeat cycle every 6 weeks. |
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Other Recommended Regimens (if prior fluoropyrimidine-based therapy) |
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Fluorouracil + Leucovorin + Liposomal Irinotecan (If no prior Irinotecan)53,e,f,r |
Day 1: Liposomal Irinotecan 70mg/m2 IV over 90 minutes, followed by: Day 1: Leucovorin 400mg/m2 IV over 30 minutes, followed by: Days 1-2: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (2,400mg/m2 over 46 hours). Repeat cycle every 2 weeks. |
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Gemcitabine9,17,19-21 |
Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks. |
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Gemcitabine + Albumin-Bound Paclitaxel4,j |
Days 1,8,15: Albumin-bound Paclitaxel 125mg/m2 IV over 30 minutes, followed by: Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks. |
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Gemcitabine + Albumin-Bound Paclitaxel + Cisplatin (Category 2B)25,26,g |
Days 1,8: Albumin-bound Paclitaxel 100mg/m2 IV over 30 minutes, followed by: Days 1,8: Cisplatin 25mg/m2 IV over 1 hour, followed by: Days 1,8: Gemcitabine 800mg/m2 IV over 30 minutes. Repeat cycle every 3 weeks. OR Days 1,8: Albumin-bound Paclitaxel 125mg/m2 IV over 30 minutes, followed by: Days 1,8: Cisplatin 25mg/m2 IV over 1 hour, followed by: Days 1,8: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 3 weeks. |
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Gemcitabine + Cisplatin (for patients with known BRCA1/2 or PALB2 mutations)8-11,g |
Days 1,15: Gemcitabine 1,000mg/m2 IV over 30 minutes Days 1,15: Cisplatin 50mg/m2 IV over 1 hour. Repeat cycle every 4 weeks. |
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Gemcitabine + Erlotinib27-29 |
Days 1-28: Erlotinib 100mg orally daily Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks. |
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Useful in Certain Circumstances |
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Chemoradiation, if not previously given (only for locally advanced disease if primary site is the sole site of progression or select patients with recurrent disease in combination with systemic therapy) |
See NCCN Pancreatic Adenocarcinoma Guidelines1 |
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▶Subsequent Therapy for Locally Advanced/Metastatic Disease and Therapy for Recurrent Disease: Poor Performance Status1 |
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Preferred Regimens |
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Entrectinib (if NTRK gene fusion positive)36-38 |
Days 1-28: Entrectinib 600mg orally once daily. Repeat cycle every 4 weeks. |
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Larotrectinib (if NTRK gene fusion positive)38-40 |
Days 1-28: Larotrectinib 100mg orally twice daily. Repeat cycle every 4 weeks. |
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Pembrolizumab (for patients with MSI-H, dMMR, or TMB-H [≥10mut/Mb])31-35,a,m |
Day 1: Pembrolizumab 200mg IV over 30 minutes. Repeat cycle every 3 weeks for a maximum of 24 months of therapy. OR Day 1: Pembrolizumab 400mg IV over 30 minutes. Repeat cycle every 6 weeks for a maximum of 24 months of therapy. |
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Other Recommended Regimens |
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Capecitabine (Category 2B)14,15,f |
Days 1-14: Capecitabine 1,000mg/m2 orally twice daily. Repeat cycle every 3 weeks. |
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Fluorouracil, Continuous Infusion (Category 2B)16,17,f |
Days 1-4: Fluorouracil 1,000mg/m2 IV continuous infusion over 24 hours daily. Repeat cycle every 3 weeks. |
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Gemcitabine (Category 1)9,17,19-21 |
Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat cycle every 4 weeks. |
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Gemcitabine (fixed-dose rate) (Category 2B)9,17,19-21 |
Days 1,8,15: Gemcitabine 1,000mg/m2 IV at a rate of 10mg/m2/minute. Repeat cycle every 4 weeks. |
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▶Chemoradiation1 |
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Preferred Regimens |
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Capecitabine + Concurrent RT9,57,58,a,f |
Days 1-5 or Days 1-7: Capecitabine 800-900mg/m2 orally twice daily. Repeat cycle weekly for 5-6 cycles with concurrent radiation. |
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Fluorouracil, Continuous Infusion + Concurrent RT17,a,f |
Days 1-5 or Days 1-7: Fluorouracil 250mg/m2 IV continuous infusion over 24 hours daily. Repeat cycle weekly for 6 cycles with concurrent radiation. |
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Other Recommended Regimens |
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Gemcitabine + Concurrent RT59-63,a |
Day 1: Gemcitabine 300-600mg/m2 IV over 30 minutes. Repeat weekly for 6-7 cycles with concurrent radiation. |
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a MSI-H, microsatellite instability-high; dMMR, mismatch repair deficient; TMB-H, tumor mutational burden-high; RT, radiation therapy; SBRT, stereotactic body radiation therapy. b There is limited evidence to recommend specific neoadjuvant regimens off-study, and practices vary with regard to the use of chemotherapy and radiation. Subsequent chemoradiation is sometimes included. When considering neoadjuvant therapy, consultation at a high-volume center is preferred. If neoadjuvant therapy is considered or recommended, treatment at or coordinated through a high-volume center is preferred, when feasible. Participation in a clinical trial is encouraged. c Can be administered with or without subsequent chemoradiation. d FOLFIRINOX or modified FOLFIRINOX should be limited to those with ECOG 0-1. e Patients who are homozygous for the UGT1A1*28 allele or who have a clinical diagnosis of Gilbert’s Syndrome have an increased risk of neutropenia when started on irinotecan. This agent may cause severe diarrhea. — Early diarrhea may be prevented and treated with atropine: atropine 0.25mg IV or subcutaneously at the onset of diarrhea. May repeat 0.25mg IV or subcutaneously in 15 minutes if no response. — Late diarrhea should be treated with loperamide: loperamide 4 mg orally at the onset of diarrhea, then 2mg every 2 hours until the patient is diarrhea-free for 12 hours (maximum 16mg/day). f Patients with dihydropyridine dehydrogenase (DPD) deficiency are unable to metabolize fluorouracil normally and may have severe unexpected toxicity. g Hydration is required with supplemental electrolytes pre- and post-administration of Cisplatin. h If considering chemoradiation due to positive margins, chemotherapy should be given prior to the administration of chemotherapy. i Due to the high toxicity of this regimen, bolus Fluorouracil is often omitted. j Gemcitabine + Albumin-Bound Paclitaxel is reasonable for patients with ECOG 0-2. k For Docetaxel: Premedication with Dexamethasone for fluid retention is required. One recommended dosing strategy is: Dexamethasone 8mg orally the night before, the morning of, and the night of Docetaxel administration. l If patients present with poorly controlled pain or local obstructive symptoms, it may be preferable to start with upfront chemoradiation or SBRT. m Early- and late-onset immune-related adverse events affecting multiple organ systems can occur in patients receiving immune checkpoint inhibitors. Patients with neurologic or life-threatening autoimmune disorders as well as receiving high levels of immunosuppression for their underlying disease should be approached with caution when considering immunotherapy. All patients will require extensive resources including ongoing intensive monitoring and supportive care. n Patients who have response or stable disease after 4-6 months of chemotherapy may undergo maintenance therapy. ECOG 0-2 for combination regimens; ECOG 0-3 for single agent options. o Fluorouracil +/- Irinotecan may be considered for maintenance therapy in the case of oxaliplatin-related progressive neuropathy or allergy to oxaliplatin. p While FOLFOX is not commonly used in the maintenance setting, it may be considered as an alternative to irinotecan-based therapy when GI toxicity is a concern. q For patients who did not have disease progression following their most recent platinum-based chemotherapy. r Fluorouracil + Leucovorin + Liposomal Irinotecan is a reasonable second-line option for patients with ECOG 0-2. |
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References |
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1. Referenced with permission from NCCN Clinical Practice Guidelines in Oncology™. Pancreatic Adenocarcinoma. V.1.2022. Available at: https://www.nccn.org/ professionals/physician_gls/pdf/pancreatic.pdf. Accessed August 22, 2022. 2. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-1825. 3. Suker M, Beumer BR, Sadot E, et al. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol. 2016;17(6):801-810. 4. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691-1703. 5. Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med. 2018;379(25):2395-2406. 6. Katz MH, Marsh R, Herman JM, et al. Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design. Ann Surg Oncol. 2013;20(8):2787-2795. 7. Stein SM, James ES, Deng Y, et al. Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. Br J Cancer. 2016;114(7):737-743. 8. Heinemann V, Quietzsch D, Gieseler F, et al. Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol. 2006;24(24):3946-3952. 9. Krishnan S, Rana V, Janjan NA, et al. Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy. Cancer. 2007;110(1):47-55. 10. Varadhachary GR, Wolff RA, Crane CH, et al. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(21):3487-3495. 11. O’Reilly EM, Lee JW, Zalupski M, et al. Randomized,multicenter, phase II trial of gemcitabine and cisplatin with or without veliparib in patients with pancreas adenocarcinoma and a germlineBRCA/PALB2 mutation. J Clin Oncol. 2020;38(13):1378-1388. 12. Cunningham D, Chau I, Stocken DD, et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009;27(33):5513-5518. 13. Neoptolemos JP, Palmer DH, Ghaneh P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389(10073):1011-1024. 14. Boeck S, Vehling-Kaiser U, Waldschmidt D, et al. Erlotinib 150 mg daily plus chemotherapy in advanced pancreatic cancer: an interim safety analysis of a multicentesr, randomized, cross-over phase III trial of the ‘Arbeitsgemeinschaft Internistische Onkologie’. Anticancer Drugs. 2010;21(1):94-100. 15. Cartwright TH, Cohn A, Varkey JA, et al. Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. J Clin Oncol. 2002;20(1):160-164. 16. Ducreux M, Mitry E, Ould-Kaci M, et al. Randomized phase II study evaluating oxaliplatin alone, oxaliplatin combined with infusional 5-FU, and infusional 5-FU alone in advanced pancreatic carcinoma patients. Ann Oncol. 2004;15(3):467-473. 17. Regine WF, Winter KA, Abrams RA, et al. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008;299(9):1019-1026. 18. Neoptolemos JP, Stocken DD, Bassi C, et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010;304(10):1073-1081. 19. Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310(4):1473-1481. 20. Tempero M, Plunkett W, Ruiz Van Haperen V, et al. Randomized phase II comparison of dose-intense gemcitabine: thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Oncol. 2003;21(18):3402-3408. 21. Van Laethem JL, Hammel P, Mornex F, et al. Adjuvant gemcitabine alone versus gemcitabine-based chemoradiotherapy after curative resection for pancreatic cancer: a randomized EORTC-40013-22012/FFCD-9203/GERCOR phase II study. J Clin Oncol. 2010;28(29):4450-4456. 22. Xiong HQ, Varadhachary GR, Blais JC, Hess KR, Abbruzzese JL, Wolff RA. Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as second-line therapy for patients with advanced pancreatic cancer. Cancer. 2008;113(8):2046-2052. 23. Oettle H, Riess H, Stieler JM, et al. Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the CONKO-003 trial. J Clin Oncol. 2014;32(23):2423-2429. 24. Pelzer U, Schwaner I, Stieler J, et al. Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group. Eur J Cancer. 2011;47(11):1676-1681. 25. Jameson GS, Borazanci E, Babiker HM, et al. Response rate following albumin-bound paclitaxel plus gemcitabine plus cisplatin treatment among patients with advanced pancreatic cancer: A Phase 1b/2 pilot clinical trial. JAMA Oncol. 2019;6(1):125-132. 26. Shroff RT, Javle MM, Xiao L, et al. Gemcitabine, cisplatin, and nab-paclitaxel for the treatment of advanced biliary tract cancers: A phase 2 clinical trial. JAMA Oncol. 2019;5(6):824-830. 27. Erlotinib (Tarceva) [package insert]. Melville, NY: OSI Pharmaceuticals, Inc. October 2016. https://www.gene.com/download/pdf/tarceva_prescribing.pdf. Accessed August 22, 2022. 28. Hammel P, Huguet F, van Laethem JL, et al. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: The LAP07 randomized clinical trial. JAMA. 2016;315(17):1844-1853. 29. Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25(15):1960-1966. 30. Fine RL, Fogelman DR, Schreibman SM, et al. The gemcitabine, docetaxel, and capecitabine (GTX) regimen for metastatic pancreatic cancer: a retrospective analysis. Cancer Chemother Pharmacol. 2008;61(1):167-175. doi:10.1007/s00280-007-0473-0 31. Pembrolizumab (Keytruda). [package insert]. Whitehouse Station, NJ: Merck & Co., Inc. August 2022. https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf. Accessed August 22, 2022. 32. Lala M, Li TR, de Alwis DP, et al. A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation. Eur J Cancer. 2020;131:68-75. 33. Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409-413. 34. Le DT, Uram JN, Wang H, et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015;372(26):2509-2520. 35. Marabelle A, Le DT, Ascierto PA, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: Results from the phase II KEYNOTE-158 study. J Clin Oncol. 2020;38(1):1-10. 36. Entrectinib (Rozlytrek) [package insert]. South San Francisco, CA: Genentech USA, Inc. July 2022. https://www.gene.com/download/pdf/rozlytrek_prescribing.pdf. Accessed August 22,2022. 37. Drilon A, Siena S, Ou SI, et al. Safety and antitumor activity of the multitargeted pan-TRK, ROS1, and ALK Inhibitor entrectinib: Combined results from two phase I trials (ALKA-372-001 and STARTRK-1). Cancer Discov. 2017;7(4):400-409. 38. Doebele RC, Drilon A, Paz-Ares L, et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1/2 trials. Lancet Oncol. 2020;21(2):271-282. 39. Larotrectinib (Vitrakvi). [package insert]. Stamford, CT: Loxo Oncology, Inc. March 2021. https://labeling.bayerhealthcare.com/html/products/pi/vitrakvi_PI.pdf. Accessed August 22, 2022. 40. Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion- positive cancers in Adults and Children. N Engl J Med. 2018;378(8):731-739. 41. Hong DS, DuBois SG, Kummar S, et al. Larotrectinib in patients with TRK fusion- positive solid tumors: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol. 2020;21(4):531-540. 42. Olaparib (Lynparza). [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals. March 2022. https://den8dhaj6zs0e.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/00997c3f-5912-486f-a7db-930b4639cd51/00997c3f-5912-486f-a7db-930b4639cd51_viewable_rendition__v.pdf. Accessed August 22, 2022. 43. Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019;381(4):317-327. 44. Kaufman B, Shapira-Frommer R, Schmutzler RK, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015;33(3):244-250. 45. Ahn DH, Krishna K, Blazer M, et al. A modified regimen of biweekly gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer is both tolerable and effective: a retrospective analysis. Ther Adv Med Oncol. 2017;9(2):75-82. 46. Hammel P, Vitellius C, Boisteau E, et al. Maintenance therapies in metastatic pancreatic cancer: present and future with a focus on PARP inhibitors. Ther Adv Med Oncol. 2020;12. 47. Dahan L, Williet N, LeMalirot K, et al. Randomized phase II trial evaluating two sequential treatments in first-line of metastatic pancreatic cancer: Results of the PANOPTIMOX-PRODIGE 35 trial. J Clin Oncol. 2021;39(29):3242-3249. 48. Chung V, McDonough S, Philip PA, et al. Effect of Selumetinib and MK-2206 vs oxaliplatin and fluorouracil in patients with metastatic pancreatic cancer after prior therapy: SWOG S1115 study randomized clinical trial. JAMA Oncol. 2017;3(4):516-522. 49. Gill S, Ko YJ, Cripps C, et al. PANCREOX: A randomized phase III study of fluorouracil/ leucovorin with or without oxaliplatin for second-line advanced pancreatic cancer in patients who have received gemcitabine-based chemotherapy. J Clin Oncol. 2016;34(32):3914-3920. 50. Yoo C, Hwang JY, Kim JE, et al. A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer. Br J Cancer. 2009;101(10):1658-1663. 51. Rucaparib (Rubraca). [package insert]. Boulder, CO: Clovis Oncology, Inc. June 2022. https://clovisoncology.com/pdfs/RubracaUSPI.pdf. Accessed August 22, 2022. 52. Reiss KA, Mick R, O’Hara MH, et al. Phase II study of maintenance rucaparib in patients with platinum-sensitive advanced pancreatic cancer and a pathogenic germline or somatic variant in BRCA1, BRCA2, or PALB2. J Clin Oncol. 2021;39(22): 2497-2505. 53. Wang-Gillam A, Li CP, Bodoky G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016;387(10018):545-557. 54. Neuzillet C, Hentic O, Rousseau B, et al. FOLFIRI regimen in metastatic pancreatic adenocarcinoma resistant to gemcitabine and platinum-salts. World J Gastroenterol. 2012;18(33):4533-4541. 55. Pointet AL, Tougeron D, Pernot S, et al. Three fluoropyrimidine-based regimens in routine clinical practice after nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer: An AGEO multicenter study. Clin Res Hepatol Gastroenterol. 2020;44(3):295-301. 56. Zaniboni A, Aitini E, Barni S, et al. FOLFIRI as second-line chemotherapy for advanced pancreatic cancer: a GISCAD multicenter phase II study. Cancer Chemother Pharmacol. 2012;69(6):1641-1645. 57. Hurt CN, Mukherjee S, Bridgewater J, et al. Health-related quality of life in SCALOP, a randomized phase 2 trial comparing chemoradiation therapy regimens in locally advanced pancreatic ancer. Int J Radiat Oncol Biol Phys. 2015;93(4):810-818. 58. Kim HS, Yi SY, Jun HJ, et al. Definitive chemoradiation therapy with capecitabine in locally advanced pancreatic cancer. Anticancer Drugs. 2010;21(1):107-112. 59. Evans DB, Varadhachary GR, Crane CH, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(21):3496-3502. 60. Habermehl D, Kessel K, Welzel T, et al. Neoadjuvant chemoradiation with Gemcitabine for locally advanced pancreatic cancer. Radiat Oncol. 2012;7:28. Published 2012 Mar 2. 61. Hurt CN, Falk S, Crosby T, et al. Long-term results and recurrence patterns from SCALOP: a phase II randomised trial of gemcitabine- or capecitabine-based chemoradiation for locally advanced pancreatic cancer. Br J Cancer. 2017;116(10): 1264-1270. 62. Loehrer PJ Sr, Feng Y, Cardenes H, et al. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011;29(31):4105-4112. 63. Mukherjee S, Hurt CN, Bridgewater J, et al. Gemcitabine-based or capecitabine- based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial. Lancet Oncol. 2013;14(4):317-326. |
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(Revised 9/2022; NCCN Pancreatic Adenocarcinoma Guidelines v1.2022) © 2022 by Haymarket Media, Inc. |
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