Gastric Cancer Treatment Regimens

Gastric 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 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.


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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.

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

▶Perioperative Chemotherapy1

REGIMEN

DOSING

Preferred Regimens

Capecitabine + Oxaliplatin2-4,a,b

Days 1-14: Capecitabine 1000mg/m2 orally twice daily

Day 1: Oxaliplatin 130mg/m2 IV over 2 hours.

Repeat every 3 weeks for 3 cycles preoperatively and postoperatively for 6 cycles total.

Fluorouracil + Oxaliplatin5,6,b

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with:

Day 1: Leucovorin 200mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 2600mg/m2 IV continuous infusion over 24 hours.

Repeat cycle every 2 weeks for 3 cycles preoperatively and 3 cycles postoperatively for 6 total cycles.

OR

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, 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 1200mg/m2 IV continuous infusion over 24 hours (2400mg/m2 IV over 46-48 hours).

Repeat cycle every 2 weeks for 3 cycles preoperatively and 3 cycles postoperative for a total of 6 cycles.

Fluorouracil + Leucovorin + Oxaliplatin + Docetaxel (FLOT; Category 1)7,b,d,e

Day 1: Docetaxel 50mg/m2 IV over 1 hour

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with:

Day 1: Leucovorin 200mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 2600mg/m2 IV continuous infusion over 24 hours.

Repeat cycle every 2 weeks for 4 cycles preoperatively and 4 cycles postoperatively for a total of 8 cycles.

Other Recommended Regimens

Fluorouracil + Cisplatin (Category 1)8,b,f

Days 1-2: Fluorouracil 1000mg/m IV continuous infusion daily over 24 hours (2000mg/m2 IV over 48 hours)

Day 1: Cisplatin 50mg/m2 IV over 1 hour.

Repeat cycle every 2 weeks for 4 cycles preoperatively and 4 cycles postoperatively for a total of 8 cycles.

▶Preoperative Chemoradiation1

Other Recommended Regimens (no Preferred Regimens)

Capecitabine (Category 2B)9,a,b

Days 1-5: Capecitabine 625-825mg/m2 orally twice daily.

Repeat cycle weekly for 5 weeks with radiation.

Capecitabine + Cisplatin
(Category 2B)10,a,b,f

Days 1-5: Capecitabine 800mg/m2 orally twice daily

Day 1: Cisplatin 30mg/m2 IV over 1 hour.

Repeat cycle every week for 5 weeks with radiation.

Capecitabine + Oxaliplatin
(Category 2B)11,a,b

Days 1,15,29: Oxaliplatin 85mg/m2 IV over 2 hours

Days 1-5, 8-12, 15-19, 22-26, 29-33: Capecitabine 625mg/m2 orally twice daily.

Administer for one 5-week cycle with radiation.

Fluorouracil (Category 2B)12,b

Days 1-5: Fluorouracil 200-250mg/m2 IV continuous infusion over 24 hours daily (1000-1500mg/m2 IV over 120 hours).

Repeat weekly for 5 weeks with concurrent radiation.

Fluorouracil + Cisplatin
(Category 2B)13,14,b,f

Days 1-5: Cisplatin 15mg/m2 IV over 1 hour daily

Days 1-5: Fluorouracil 800mg/m2 IV continuous infusion over 24 hours daily (4000mmg/m2 IV over 120 hours).

Repeat cycle every 3 weeks for 2 cycles with radiation.

OR

Days 1,29: Cisplatin 75-100mg/m2 IV over 1 hour

Days 1-4,29-32: Fluorouracil 750-1000mg/m2 IV continuous infusion over 24 hours daily.

Administer for one 5-week cycle with radiation.

Fluorouracil + Oxaliplatin
(Category 2B)15,16,b

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours

Days 1-4,8-11: Fluorouracil 300mg/m2 IV continuous infusion over 24 hours daily. (1200mg/m2 IV over 96 hours).

Repeat cycle every 2 weeks for 3 cycles with radiation.

OR

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with:

Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Day 1-2: Fluorouracil 800mg/m2 IV continuous infusion over 24 hours. (1600mg/m2 IV over 46-48 hours).

Repeat cycle every 2 weeks for 3 cycles with radiation followed by 3 cycles without radiation.

Paclitaxel + Carboplatin (Category 2B)17.18,h

Day 1: Paclitaxel 50mg/m2 IV over 1 hour, followed by:

Day 1: Carboplatin AUC 2 IV over 30 minutes.

Repeat cycle every week for 5 weeks with radiation.

▶Postoperative Chemoradiation1

Fluorouracil (before and after Fluoropyrimidine-based chemoradiation)12,19,20,b,g

Day 1: Leucovorin 400mg/m2 IV, followed by:

Day 1: Fluorouracil 400mg/m2 IV Push, followed by:

Days 1-2: Fluorouracil 1200mg/m2 IV continuous infusion over 24 hours daily (2400mg/m2 IV over 46-48 hours).

Repeat cycle every 2 weeks for 2 cycles before and 4 cycles after chemoradiation.

With radiation:

Days 1-5: Fluorouracil 200-250mg/m2 IV continuous infusion over 24 hours daily (1000-1250mg/m2 IV over 120 hours).

Repeat cycle weekly for 5 weeks with radiation.

Capecitabine (before and after Fluoropyrimidine-based chemoradiation)9,21,a,b,g

Days 1-14: Capecitabine 750-1000mg/m2 orally twice daily.

Administer for one 3-week cycle preceding and two 3-week cycles following chemotherapy/radiation.

With radiation:

Days 1-5: Capecitabine 625-825mg/m2 orally twice daily.

Repeat cycle weekly for 5 weeks with radiation.

▶Postoperative Chemotherapy (for patients who have undergone primary D2 lymph node dissection)1

Preferred Regimens

Capecitabine + Oxaliplatin
(Category 1)2-4,a,b

Days 1-14: Capecitabine 1000mg/m2 orally twice daily

Day 1: Oxaliplatin 130mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks for 8 cycles.

Fluorouracil + Oxaliplatin5,6,b

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with:

Day 1: Leucovorin 200mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 2600mg/m2 IV continuous infusion over 24 hours.

Repeat cycle every 2 weeks for a maximum of 12 cycles.

OR

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, 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 1200mg/m2 IV continuous infusion over 24 hours daily.

Repeat cycle every 2 weeks for a maximum of 12 cycles.

▶Chemoradiation for Unresectable Disease1

Preferred Regimens

Capecitabine + Cisplatin10,a,b,f

Days 1-5: Capecitabine 800mg/m2 orally twice daily

Day 1: Cisplatin 30mg/m2 IV over 1 hour.

Repeat cycle weekly for 5 weeks with radiation.

Capecitabine + Oxaliplatin11,a,b

Days 1,15,29: Oxaliplatin 85mg/m2 over 2 hours

Days 1-5, 8-12, 15-19, 22-26, 29-33: Capecitabine 625mg/m2 orally twice daily.

Administer for one 5-week cycle with radiation.

Fluorouracil + Cisplatin13,b,f

Days 1-5: Fluorouracil 800mg/m2 IV continuous infusion over 24 hours daily (4000mg/m2 IV over 120 hours)

Days 1-5: Cisplatin 15mg/m2 IV over 1 hour daily.

Repeat cycle every 3 weeks for 2 cycles with radiation.

Fluorouracil + Oxaliplatin16,b

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with:

Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 400mg/m2 IV Push, followed by:

Day 1-2: Fluorouracil 800mg/m2 IV continuous infusion over 24 hours. (1600mg/m2 IV over 46-48 hours)

Repeat cycle every 3 weeks for 3 cycles with radiation followed by 3 cycles without radiation.

Other Recommended Regimens

Capecitabine + Paclitaxel
(Category 2B)22,23,a,b,h

Days 1-5: Capecitabine 625-825mg/m2 orally twice daily

Day 1: Paclitaxel 45-50mg/m2 IV over 1 hour.

Repeat cycle weekly for 5 weeks with radiation.

Fluorouracil + Paclitaxel (Category 2B)24,b,h

Day 1: Paclitaxel 45-50mg/m2 IV over 1 hour.

Days 1-5: Fluorouracil 300mg/m2 IV continuous infusion over 24 hours daily (1500mg/m2 IV over 120 hours).

Repeat cycle weekly for 5 weeks with radiation.

▶First-Line Systemic Therapy for Unresectable Locally Advanced, Recurrent or Metastatic Disease (Oxaliplatin is generally preferred over cisplatin due to lower toxicity)1

Preferred Regimens (for HER2 Overexpression Positive Adenocarcinoma)

Capecitabine + Cisplatin + Trastuzumab (Category 1)25-27,a,b,f,i

Days 1-14: Capecitabine 1000mg/m2 orally twice daily

Day 1: Cisplatin 80mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks.

Day 1 of Cycle 1: Trastuzumab 8mg/kg IV over 90 minutes, followed by:

Day 1 beginning with Cycle 2: Trastuzumab 6mg/kg IV over 30 minutes.

Repeat cycle every 3 weeks.

OR

Day 1 of Cycle 1: Trastuzumab 6mg/kg IV over 90 minutes, followed by:

Day 1 beginning with Cycle 2: Trastuzumab 4mg/kg IV over 30 minutes.

Repeat cycle every 2 weeks.

Capecitabine + Oxaliplatin +

Trastuzumab2-4,25,28,29,a,b,i

Days 1-14: Capecitabine 1000mg/m2 orally twice daily

Day 1: Oxaliplatin 130mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks.

OR

Days 1-14: Capecitabine 625mg/m2 orally twice daily

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks.

Day 1 of Cycle 1: Trastuzumab 8mg/kg IV over 90 minutes, followed by:

Day 1 beginning with Cycle 2: Trastuzumab 6mg/kg IV over 30 minutes.

Repeat cycle every 3 weeks.

OR

Day 1 of Cycle 1: Trastuzumab 6mg/kg IV over 90 minutes, followed by:

Day 1 beginning with Cycle 2: Trastuzumab 4mg/kg IV over 30 minutes.

Repeat cycle every 2 weeks.

Fluorouracil + Cisplatin + Trastuzumab (Category 1)25,30-32,b,f,i

Day 1: Cisplatin 50mg/m2 IV over 1 hour

Day 1: Leucovorin 200mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 2000mg/m2 IV continuous infusion over 24 hours.

Repeat cycle every 2 weeks.

OR

Day 1: Cisplatin 75-100mg/m2 IV over 1 hour

Days 1-4: Fluorouracil 750-1000mg/m2 IV continuous infusion over 24 hours (3000-4000mg/m2 IV over 96 hours).

Repeat cycle for 4 weeks.

Day 1 of Cycle 1: Trastuzumab 8mg/kg IV over 90 minutes, followed by:

Day 1 beginning with Cycle 2: Trastuzumab 6mg/kg IV over 30 minutes.

Repeat cycle every 3 weeks.

OR

Day 1 of Cycle 1: Trastuzumab 6mg/kg IV over 90 minutes, followed by:

Day 1 beginning with Cycle 2: Trastuzumab 4mg/kg IV over 30 minutes.

Repeat cycle every 2 weeks.

Fluorouracil + Oxaliplatin + Trastuzumab6,25,b,i

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, 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 1200mg/m2 IV continuous infusion over 24 hours daily (2400mg/m2 IV over 46-48 hours).

Repeat cycle every 2 weeks.

Day 1 of Cycle 1: Trastuzumab 8mg/kg IV over 90 minutes, followed by:

Day 1 beginning with Cycle 2: Trastuzumab 6mg/kg IV over 30 minutes.

Repeat cycle every 3 weeks.

OR

Day 1 of Cycle 1: Trastuzumab 6mg/kg IV over 90 minutes, followed by:

Day 1 beginning with Cycle 2: Trastuzumab 4mg/kg IV over 30 minutes.

Repeat cycle every 2 weeks.

Preferred Regimens (HER2 Overexpression Negative Adenocarcinoma)

Capecitabine + Cisplatin27,a,b,f

Days 1-14: Capecitabine 1000mg/m2 orally twice daily

Day 1: Cisplatin 80mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks.

Capecitabine + Oxaliplatin2-4,a,b

Days 1-14: Capecitabine 1000mg/m2 orally twice daily

Day 1: Oxaliplatin 130mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks.

Capecitabine + Oxaliplatin + Nivolumab (PD-L1 CPS ≥ 5) (Category 1)33,34,a,b,j

Day 1: Nivolumab 360mg IV over 30 minutes

Day 1: Oxaliplatin 130mg/m2 IV over 2 hours

Days 1-14: Capecitabine 1000mg/m2 orally twice daily.

Repeat cycle every 3 weeks.

Fluorouracil + Cisplatin30-32,b,f

Day 1: Cisplatin 50mg/m2 IV over 1 hour

Day 1: Leucovorin 200mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 2000mg/m2 IV continuous infusion over 24 hours.

Repeat cycle every 2 weeks.

OR

Day 1: Cisplatin 75-100mg/m2 IV over 1 hour

Days 1-4: Fluorouracil 750-1000mg/m2 IV continuous infusion over 24 hours (3000-4000mg/m2 IV over 96 hours).

Repeat cycle for 4 weeks.

Fluorouracil + Oxaliplatin5,35,b

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with:

Day 1: Leucovorin 200mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 2600mg/m2 IV continuous infusion over 24 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, followed by:

Day 1: Fluorouracil 400mg/m2 IV Push, followed by:

Days 1,2: Fluorouracil 1200mg/m2 IV continuous infusion over 24 hours daily (2400mg/m2 IV over 46-48 hours).

Repeat cycle every 2 weeks.

Fluorouracil + Oxaliplatin + Nivolumab (PD-L1 CPS ≥ 5) (Category 1)33-35,b,j,p

Day 1: Nivolumab 240mg IV over 30 minutes.

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with:

Day 1: Leucovorin 400mg/m2 IV over 2 hours

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1200mg/m2 IV continuous infusion over 24 hours daily (2400mg/m2 IV over 46-48 hours).

Repeat cycle every 2 weeks.

Other Recommended Regimens (for HER2 Overexpression Positive Adenocarcinoma)

Capecitabine + Cisplatin + Trastuzumab + Pembrolizumab25,26,27,36,37,a,b,f,I,j

Days 1-14: Capecitabine 1000mg/m2 orally twice daily

Day 1: Cisplatin 80mg/m2 IV over 2 hours.

Day 1 of Cycle 1: Trastuzumab 8mg/kg IV over 90 minutes, followed by:

Day 1 beginning with Cycle 2: Trastuzumab 6mg/kg IV over 30 minutes

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks.

Capecitabine + Oxaliplatin + Trastuzumab + Pembrolizumab2,25,26,36,37,a,b,I,j

Days 1-14: Capecitabine 1000mg/m2 orally twice daily

Day 1: Oxaliplatin 130mg/m2 IV over 2 hours.

Day 1 of Cycle 1: Trastuzumab 8mg/kg IV over 90 minutes, followed by:

Day 1 beginning with Cycle 2: Trastuzumab 6mg/kg IV over 30 minutes

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks.

Fluorouracil + Cisplatin + Trastuzumab + Pembrolizumab25-27,36,37,b,f,I,j

Day 1: Cisplatin 80mg/m2 IV over 1 hour

Days 1-5: Fluorouracil 800mg/m2 IV continuous infusion over 24 hours.

Day 1 of Cycle 1: Trastuzumab 8mg/kg IV over 90 minutes, followed by:

Day 1 beginning with Cycle 2: Trastuzumab 6mg/kg IV over 30 minutes

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks.

Fluorouracil + Oxaliplatin + Trastuzumab + Pembrolizumab5,25,26,35,36,37,b,I,j

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with:

Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 400mg/m2 IV Psh, followed by:

Days 1,2: Fluorouracil 1200mg/m2 IV continuous infusion over 24 hours daily.

Repeat cycle every 2 weeks.

OR

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with:

Day 1: Leucovorin 200mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 2600mg/m2 IV continuous infusion over 24 hours.

Repeat cycle every 2 weeks.

Day 1 of Cycle 1: Trastuzumab 8mg/kg IV over 90 minutes, followed by:

Day 1 beginning with Cycle 2: Trastuzumab 6mg/kg IV over 30 minutes.

Repeat cycle every 3 weeks.

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks.

Other Recommended Regimens23,24,i

Capecitabine38,a,b

Days 1-14: Capecitabine 1000-1250mg/m2 orally twice daily.

Repeat cycle for 3 weeks.

Docetaxel39,40,e

Day 1: Docetaxel 75-100mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks.

Docetaxel + Cisplatin41-43,e,f

Day 1: Docetaxel 70-85mg/m2 over 1 hour, followed by:

Day 1: Cisplatin 70-75mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks.

Docetaxel + Carboplatin + Fluorouracil (Category 2B)44,b,e

Day 1: Docetaxel 75mg/m2 IV over 1 hour

Day 2: Carboplatin AUC 6 IV over 30 minutes

Days 1-3: Fluorouracil 1,200mg/m2 IV continuous infusion over 24 hours daily (3600mg/m2 IV over 72 hours).

Repeat cycle every 3 weeks.

Docetaxel + Cisplatin + Fluorouracil45,b,e,f

Day 1: Docetaxel 40mg/m2 IV over 1 hour, followed by:

Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1000mg/m2 IV continuous infusion over 24 hours daily (2000mg/m2 IV over 48 hours)

Day 3: Cisplatin 40mg/m2 IV over 1 hour.

Repeat cycle every 2 weeks.

Docetaxel + Oxaliplatin + Fluorouracil46,b,e

Day 1: Docetaxel 50mg/m2 IV over 1 hour

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours

Days 1-2: Fluorouracil 1200mg/m2 IV continuous infusion over 24 hours daily (2400mg/m2 IV over 48 hours).

Repeat cycle for 2 weeks.

Fluorouracil31,47

Days 1-5: Fluorouracil 800mg/m2 IV continuous infusion over 24 hours daily (4000mg/m2 IV over 120 hours).

Repeat cycle every 4 weeks.

OR

Day 1: Leucovorin 400mg/m2 IV over 2 hours, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil: 1200mg/m2 IV continuous infusion over 24 hours daily on Days 1-2 (2400mg/m2 IV over 46-48 hours).

Repeat cycle every 2 weeks.

Fluorouracil + Irinotecan48,49,a-c

Day 1: Irinotecan 180mg/m2 IV over 90 minutes, with:

Day 1: Leucovorin 400mg/m2 IV over 90 minutes, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1200mg/m2 IV continuous infusion over 24 hours daily (2400mg/m2 IV over 46-48 hours).

Repeat cycle every 2 weeks.

Paclitaxel50-53,h

Day 1: Paclitaxel 135-250mg/m2 IV over 3 hours.

Repeat cycle every 3 weeks.

OR

Day 1,8,15,22: Paclitaxel 80mg/m2 IV over 1 hour.

Repeat cycle every 4 weeks.

Paclitaxel + Carboplatin54,h

Day 1: Paclitaxel 200mg/m2 IV over 3 hours, followed by:

Day 1: Carboplatin AUC 5mg IV over 30 minutes.

Repeat cycle every 3 weeks.

Paclitaxel + Cisplatin55,56,f,h

Day 1: Paclitaxel 90mg/m2 IV over 3 hours, followed by:

Day 1: Cisplatin 50mg/m2 IV over 1 hour.

Repeat cycle every 2 weeks.

OR

Day 1: Paclitaxel 135-200mg/m2 IV over 3 hours, followed by:

Day 2: Cisplatin 75mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks.

Useful In Certain Circumstances (HER2 Overexpression Negative)

Capecitabine + Oxaliplatin + Nivolumab (PD-L 1 CPS 1-4) (Category 2B)33,34,a,b,j,p

Day 1: Nivolumab 360mg IV over 30 minutes

Day 1: Oxaliplatin 130mg/m2 IV over 2 hours

Days 1-14: Capecitabine 1000mg/m2 orally twice daily.

Repeat cycle every 3 weeks.

Fluorouracil + Oxaliplatin + Nivolumab (PD-L 1 CPS 1-4) (Category 2B)33-35,b,j,p

Day 1: Nivolumab 240mg IV over 30 minutes.

Day 1: Oxaliplatin 85mg/m2 IV over 2 hours, with:

Day 1: Leucovorin 400mg/m2 IV over 2 hours

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1200mg/m2 IV continuous infusion over 24 hours daily (2400mg/m2 IV over 46-48 hours).

Repeat cycle every 2 weeks.

▶Second-Line or Subsequent Systemic Therapy for Unresectable Locally Advanced, Recurrent or Metastatic Disease1,k

Preferred Regimens

Docetaxel (Category 1)39,40,e

Day 1: Docetaxel 75-100mg/m2 IV over 1 hour.

Repeat cycle every 3 weeks.

Fam-trastuzumab deruxtecan-nxki57,58,e,l

Day 1: Fam-trastuzumab deruxtecan-nxki 6.4mg/kg IV.

Repeat cycle for 3 weeks.

Fluorouracil + Irinotecan48,49,c

Day 1: Irinotecan 180mg/m2 IV over 90 minutes, concurrent with:

Day 1: Leucovorin 400mg/m2 IV over 90 minutes, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1200mg/m2 IV continuous infusion over 24 hours daily (2400mg/m2 IV over 46-48 hours).

Repeat cycle every 2 weeks.

Irinotecan (Category 1)59-62,a,c

Day 1: Irinotecan 150-180mg/m2 over 90 minutes.

Repeat cycle every 2 weeks.

OR

Day 1: Irinotecan 250-350mg/m2 IV over 90 minutes.

Repeat cycle every 3 weeks.

OR

Day 1,8: Irinotecan 125mg/m2 IV over 90 minutes.

Repeat cycle every 3 weeks.

Paclitaxel (Category 1)50-53,h

Day 1: Paclitaxel 135-250mg/m2 IV over 3 hours.

Repeat cycle every 3 weeks.

OR

Days 1,8,15,22: Paclitaxel 80mg/m2 IV over 1 hour.

Repeat cycle every 4 weeks.

OR

Days 1,8,15: Paclitaxel 80mg/m2 IV over 60 minutes.

Repeat cycle every 4 weeks.

Ramucirumab + Paclitaxel (Category 1)63,64,h,m,n

Days 1,15: 8mg/kg IV over 1 hour

Days 1,8,15: Paclitaxel 80mg/m2 IV over 1 hour.

Repeat cycle every 4 weeks.

Trifluridine + Tipiracil (for third-line or subsequent therapy) (Category 1)65,66

Days 1-5 and Days 8-12: 35mg/m2 (maximum 80mg) based on the Trifluridine component orally twice daily. (Total dose should not exceed 160mg/day).

Repeat cycle every 4 weeks.

Other Recommended Regimens

Docetaxel + Irinotecan (Category 2B)67,a,c,e

Day 1,8: Docetaxel 35mg/m2 IV over 1 hour

Day 1,8: Irinotecan 50mg/m2 IV over 1 hour.

Repeat cycle every 3 weeks.

Fluorouracil + Leucovorin + Irinotecan + Ramucirumab48,63,68-70,a-d,m,n

Day 1: Ramucirumab 8mg/kg IV over 1 hour

Day 1: Irinotecan 180mg/m2 IV over 90 minutes, with:

Day 1: Leucovorin 400mg/m2 IV over 90 minutes, followed by:

Day 1: Fluorouracil 400mg/m2 IV push, followed by:

Days 1-2: Fluorouracil 1200mg/m2 IV continuous infusion over 24 hours (2400mg/m2 IV over 46-48 hours).

Repeat cycle every 2 weeks.

Irinotecan + Cisplatin35,71,a,c,f

Day 1,8: Cisplatin 25-30mg/m2 IV over 1 hour, followed by:

Day 1,8: Irinotecan 65mg/m2 IV over 90 minutes

Repeat cycle every 3 weeks.

Irinotecan + Ramucirumab63,72,a,c,m,n

Day 1: Irinotecan 150mg/m2 IV over 90 minutes

Day 1: Ramucirumab 8mg/kg IV over 1 hour.

Repeat cycle every 2 weeks.

Ramucirumab (Category 1)63,73,m,n

Day 1: Ramucirumab 8mg/kg IV over 1 hour.

Repeat cycle every 2 weeks.

Useful in Certain Circumstances

Entrectinib74-76,a,o (NTRK gene fusion-positive tumors)

Days 1-28: Entrectinib 600mg orally once daily.

Repeat cycle for 4 weeks.

Larotrectinib (NTRK gene fusion-positive tumors)77,78,a,o

Days 1-28: Larotrectinib 100mg orally twice daily.

Repeat cycle every 4 weeks.

Pembrolizumab (second-line/subsequent therapy for MSI-H/dMMR tumors) (second-line/subsequent therapy for tumor mutational burden-high ≥10 mutations/megabase) (third-line/subsequent therapy for PD-L1 expression levels by CPS ≥1)36,79-84,p,q

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks up, up to 24 months of therapy.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes. Repeat cycle every 6 weeks, up to 24 months of therapy.

  a Capecitabine has multiple potential drug-drug interactions and/or drug-food interactions.

  b Caution: Patients with dihydropyrimidine dehydrogenase (DPD) deficiency are unable to metabolize this agent normally and may have severe unexpected toxicity.

  c 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.

  d For leucovorin: The dose listed above is based on racemic leucovorin product. LEVOleucovorin is not interchangeable and the product doses are not equivalent.

  e Docetaxel: Premedication with dexamethasone for fluid retention is required. One recommended dosing strategy is: Dexamethasone 8mg orally twice daily for three consecutive days starting 1 day prior to Docetaxel administration.

  f Recommended cisplatin hydration: Sodium chloride 0.9% with KCl 10 mEq per liter and magnesium sulfate 4 mEq (1 gram) per liter infused IV at a rate of 250-500 mL/hour pre- and post-Cisplatin administration for a total of 1000 mL to be infused. Supplement electrolytes are not solely for replacement and should be considered for all patients as clinically indicated.

  g Alternatively, radiation can be administered concurrently with fluorouracil or capecitabine.

  h Paclitaxel: Premedication for hypersensitivity is required: H2 antagonist: Famotidine 20 mg IV/orally (or equivalent H2 blocker) 30-60 minutes pre-Paclitaxel, AND H1 antagonist: Diphenhydramine 12.5 – 50 mg IV/PO 30-60 minutes pre-Paclitaxel, AND Dexamethasone: Dexamethasone 10 mg IV 30 minutes pre-Paclitaxel. In the absence of infusion reactions for Doses 1-3, may consider Dexamethasone 4 mg IV 30 minutes pre-Paclitaxel starting with Dose 4.

  i Trastuzumab should be added to first-line chemotherapy for HER2 overexpression positive adenocarcinoma. An FDA-approved biosimilar is an appropriate substitute for Trastuzumab.

  j If no prior tumor progression while on therapy with a checkpoint inhibitor.

  k Dependent on prior therapy and performance status.

  l Do not substitute fam-tratuzumab deruxtecan-nxki for or with ado-trastuzumab emtansine or standard Trastuzumab. The products are structurally and functionally different and are not interchangeable. Product doses are not equivalent.

  m Ramucirumab: Premedication for infusion reactions is required. The recommended dosing is: Diphenhydramine 12.5-50 mg IV/orally 30 minutes pre-Ramucirumab.

  n Ramucirumab Extreme caution should be used in patients with Child-Pugh B or C hepatic impairment.

  o NTRK: Neurotrophic tyrosine receptor kinase.

  p MSI-H/dMMR: Microsatellite instability-high; deficient MisMatch Repair

  q PD-L1 CPS: Programmed death-ligand 1 combined positive score.

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(Revised 7/2021; NCCN Gastric Cancer Guidelines v3.2021) © 2021 by Haymarket Media, Inc.

This article originally appeared on Cancer Therapy Advisor