Gastric Cancer Treatment Protocols 

Updated: Aug 16, 2017
  • Author: Terence D Rhodes, MD, PhD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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General Treatment Recommendations

Treatment decisions should be made with a multidisciplinary team [1] and based on the following:

  • Stage of disease
  • Surgical fitness of the patient
  • The patient’s preference
  • Patient comorbidities

Stage 0 to IA

Endoscopic mucosal resection or surgery is primary treatment for early-stage gastric cancer. Complete surgical resection offers potential for long-term survival.

Stage IB to IIIC, potentially resectable

For medically fit patients, perioperative, neoadjuvant chemotherapy or chemoradiotherapy followed by surgery is appropriate. Perioperative therapy is common practice, with chemoradiotherapy after surgery showing a clear survival benefit. [2]

Medically unfit patients can be treated with chemoradiotherapy or chemotherapy.

Stage IV

Chemotherapy is given for metastatic disease. Local therapy is not indicated.

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Neoadjuvant Chemoradiotherapy Regimens

Preferred regimens

A higher level of evidence supports use of the following regimens; clinical trials have shown strong benefit and there is consensus among experts [1] :

  • Paclitaxel 50 mg/m 2 IV on day 1 plus  carboplatin AUC 2 IV on day 1; weekly for 5 wk [3, 4] (see the Carboplatin AUC Dose Calculation [Calvert formula] calculator) or
  • Cisplatin 75-100 mg/m 2 IV on day 1 plus  5-fluorouracil (5-FU) 750-1000 mg/m 2/day IV continuous infusion on days 1-4 and 29-32; single 35-day cycle [5] or
  • Cisplatin 30 mg/m 2 IV on day 1 plus  capecitabine 800 mg/m 2 PO BID on days 1-5; weekly for 5wk [6] or
  • Cisplatin 15 mg/m 2 IV daily on days 1-5 and days 22-26 plus  5-FU 800 mg/m 2/day IV continuous infusion on days 1-5 and days 22-26; single 35-day cycle [7] or
  • Oxaliplatin 85 mg/m 2 IV on days 1, 15, and 29 plus  capecitabine 625 mg/m 2 PO BID on days 1-5, 8-12, 15-19, 22-26, and 29-33; single 35-day cycle [8] or
  • Oxaliplatin 85 mg/m 2 on days 1, 15, and 29 plus  5-FU 180 mg/m 2 continuous IV infusion daily on days 1-33 [9] or
  • Oxaliplatin 85 mg/m 2 IV on day 1 plus  leucovorin 400 mg/m 2 IV on day 1 plus  5-FU 400 mg/m 2 IVP on day 1 and 5-FU 800 mg/m 2 continuous IV infusion daily on days 1 and 2; every 14 d for three cycles with radiation and three cycles after radiation [10]

Other regimens

A lower level of evidence supports use of the following regimens; smaller studies show benefit of the therapy, and therapy may need to be used on the basis of the clinical situation (eg, limiting toxicities, patient comorbidity) [1] :

  • Oxaliplatin 45-50 mg/m 2 IV on day 1 weekly for 5 wk plus  5-FU 225 mg/m 2 IV daily on days 1-33; single 35-day cycle [11] or
  • Carboplatin AUC 6 IV on days 1 and 22 plus  5-FU 200 mg/m 2 IV daily on days 1-42 [12] or
  • Irinotecan 65 mg/m 2 IV on days 1, 8, 22, and 29 plus  cisplatin 30 mg/m 2 IV on days 1, 8, 22, and 29 [13] or
  • Paclitaxel 45-50 mg/m 2 IV on day 1 plus  5-FU 300 mg/m 2 continuous IV infusion daily on days 1-5; weekly for 5 wk [14] or
  • Paclitaxel 45-50 mg/m 2 IV on day 1 plus  capecitabine 625-825 mg/m 2 PO BID daily on days 1-5; weekly for 5 wk [14, 15]
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Perioperative Chemotherapy Regimens

Treatment consists of three cycles before surgery and three cycles after surgery; the following regimens are used only for adenocarcinoma of the distal esophagus or gastroesophageal junction [1] :

  • Epirubicin 50 mg/m 2 IV on day 1 plus cisplatin 60 mg/m 2 IV on day 1 plus 5-FU 200 mg/m 2/day IV continuous infusion daily for days 1-21; every 21 d for cycles 1-3 preoperatively and cycles 4-6 postoperatively [2] or
  • Epirubicin 50 mg/m 2 IV on day 1 plus  oxaliplatin 130 mg/m 2 IV on day 1 plus  5-FU 200 mg/m 2/day IV continuous infusion daily for days 1-21; every 21 d for cycles 1-3 preoperatively and cycles 4-6 postoperatively [18] or
  • Epirubicin 50 mg/m 2 IV on day 1 plus  cisplatin 60 mg/m 2 IV on day 1 plus  capecitabine 625 mg/m 2 PO BID daily for days 1-21; every 21 d for cycles 1-3 preoperatively and cycles 4-6 postoperatively [18] or
  • Epirubicin 50 mg/m 2 IV on day 1 plus  oxaliplatin 130 mg/m 2 IV on day 1 plus  capecitabine 625 mg/m 2 PO BID daily for days 1-21; every 21 d for three cycles preoperatively and three cycles postoperatively [18] or
  • Cisplatin 75-80 mg/m 2 IV on day 1 plus 5-FU 800 mg/m 2 continuous IV infusion on days 1-5; every 28 d for 2-3 cycles preoperatively and 3-4 cycles postoperatively for a total of six cycles [19]
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Postoperative Chemoradiotherapy Regimens

Uses of the following postoperative chemoradiotherapy regimens include cancers of the gastroesophageal junction:

  • Leucovorin 20 mg/m 2 IVP on days 1-5 plus  5-FU 425 mg/m 2 IVP daily on days 1-5, every 28 d (cycles 1, 3, and 4 given before and after radiation); for cycle 2, give leucovorin 20 mg/m 2 IVP on days 1-4 and 31-33 plus  5-FU 400 mg/m 2 IVP daily on days 1-4, every 35 d (cycle 2 given with radiation) [20]

NOTE: The National Comprehensive Cancer Network (NCCN) panel does not recommend the above specified doses or schedule, because of concerns regarding toxicity; instead, the panel recommends using one of the following modified regimens.

One cycle before and two cycles after chemoradiation:

  • Capecitabine 750-1000 mg/m 2 PO BID on days 1-14; every 28 d (one cycle before and two cycles after chemoradiation)
  • Leucovorin 400 mg/m 2 IV on days 1 and 15 or days 1, 2, 15, and 16 plus  5-FU 400 mg/m 2 IVP on days 1 and 15 or days 1, 2, 15, and 16 and  5-FU 1200 mg/m 2 continuous IV infusion over 24 h daily on days 1, 2, 15 and 16, every 14 d (one cycle before radiation and two cycles after radiation) [21]

With radiation:

  • 5-FU 200-250 mg/m 2/day continuous IV infusion on days 1-5 or 1-7; weekly for 5 wk [22] or
  • Capecitabine 625-825 mg/m 2 PO BID daily for days 1-5 or 1-7; weekly for 5 wk [23]
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Postoperative Chemotherapy Regimens

Postoperative chemotherapy regimens include the following:

  • Oxaliplatin 130 mg/m 2 IV on day 1 plus capecitabine 1000 mg/m 2 PO BID on days 1-14; every 21 d for eight cycles [24] or
  • Cisplatin 60 mg/m 2 IV on day 1 plus capecitabine 1000 mg/m 2 PO BID on days 1-14; every 21 d for six cycles [25]

First-Line Chemotherapy for Metastatic or Locally Advanced Cancer (where local therapy not indicated)

Stage IV

For HER2-NEU overexpressing adenocarcinomas, trastuzumab can be added to cisplatin plus fluoropyrimidine (eg, 5-FU, capecitabine) regimens (except regimens containing an anthracycline) [1] :

  • Trastuzumab 8 mg/kg IV loading dose on day 1 of cycle 1, then 6 mg/kg IV; every 21 d with chemotherapy [26] or
  • Trastuzumab 6 mg/kg IV loading dose on day 1 of cycle 1, then 4 mg/kg IV every 14 d with chemotherapy

Preferred regimens [1]

Two-drug regimens are preferred because of lower toxicity; reserve three-drug regimens for patients who are medically fit and have access to frequent follow-up

  • Docetaxel 75 mg/m 2 IV on day 1 plus  cisplatin 75 mg/m 2 IV on day 1 plus  5-FU 1000 mg/m 2/day continuous IV infusion on days 1-5; every 28 d [27]
  • NOTE: NCCN panel does not recommend the above specified doses or schedule because of concerns regarding toxicity; instead, use one of the following modified regimens:
  • Docetaxel 40 mg/m 2 IV on day 1 plus  leucovorin 400 mg/m 2 IV on day 1 plus  5-FU 400 mg/m 2 IV on day 1 plus  5-FU 1000 mg/m 2/day continuous IV infusion on days 1 and 2 plus  cisplatin 40 mg/m 2 IV on day 3; every 14 d [28] or
  • Docetaxel 50 mg/m 2 IV on day 1 plus  oxaliplatin 85 mg/m 2 IV on day 1 plus  5-FU 1200 mg/m 2/day continuous IV infusion on days 1 and 2; every 14 d [32] or
  • Docetaxel 75 mg/m 2 IV on day 1 plus  carboplatin AUC 6 IV on day 2 plus  5-FU 1200 mg/m 2/day continuous IV infusion on days 1-3; every 21 d [33] or
  • Epirubicin 50 mg/m 2 IV on day 1 plus  cisplatin 60 mg/m 2 IV on day 1 plus  5-FU 200 mg/m 2/day continuous IV infusion on days 1-21; every 21 d [34, 35] or
  • Epirubicin 50 mg/m 2 IV on day 1 plus  oxaliplatin 130 mg/m 2 on day 1 plus  5-FU 200 mg/m 2/day continuous IV infusion on days 1-21; every 21 d [35] or
  • Epirubicin 50 mg/m 2 IV on day 1 plus  cisplatin 60 mg/m 2 IV on day 1 plus  capecitabine 625 mg/m 2 PO BID daily on days 1-21; every 21 d [35] or
  • Epirubicin 50 mg/m 2 IV on day 1 plus  oxaliplatin 130 mg/m 2 IV on day 1 plus  capecitabine 625 mg/m 2 PO BID daily on days 1-21; every 21 d [35] or
  • Cisplatin 75-100 mg/m 2 IV on day 1 plus  5-FU 750-1000 mg/m 2/day continuous IV infusion over 24 h on days 1-4; every 28 d [36] or
  • Cisplatin 50 mg/m 2 IV on day 1 plus  leucovorin 200 mg/m 2 IV on day 1 plus  5-FU 2000 mg/m 2/day continuous IV infusion on day 1; every 14 d [37, 38] or
  • Cisplatin 80 mg/m 2 IV on day 1 plus  capecitabine 1000 mg/m 2 PO BID daily on days 1-14; every 21 d [26, 39]
  • Oxaliplatin 85 mg/m 2 IV on day 1 plus  leucovorin 400 mg/m 2 IV on day 1 plus  5-FU 400 mg/m 2 IVP on day 1 plus  5-FU 1200 mg/m 2/day continuous IV infusion on days 1 and 2; every 14 d [40] or
  • Oxaliplatin 85 mg/m 2 IV on day 1 plus  leucovorin 200 mg/m 2 IV on day 1 plus  5-FU 2600 mg/m 2/day continuous IV infusion on day 1; every 14 d [37] or
  • Oxaliplatin 130 mg/m 2 IV on day 1 plus  capecitabine 1000 mg/m 2 PO BID on days 1-14; every 21 d [41]
  • Irinotecan 80 mg/m 2 IV on day 1 plus  leucovorin 500 mg/m 2 IV on day 1 plus  5-FU 2000 mg/m 2/day continuous IV infusion on day 1; weekly for 6 wk followed by 1 wk off treatment [42] or 2 wk off treatment [43, 92] or
  • Irinotecan 150 mg/m 2 IV on day 1 plus  leucovorin 20 mg/m 2 IV on day 1 plus  5-FU 1000 mg/m 2 /day continuous IV infusion on days 1 and 2; every 14 d [91]

Other regimens [1] :

  • Paclitaxel 135-200 mg/m 2 IV on day 1 plus  cisplatin 75 mg/m 2 IV on day 2; every 21 d [45] or
  • Paclitaxel 90 mg/m 2 IV on day 1 plus  cisplatin 50 mg/m 2 IV on day 1; every 14 d [46] or
  • Paclitaxel 200 mg/m 2 IV on day 1 plus  carboplatin AUC 5 IV on day 1; every 21 d [47] or
  • Docetaxel 70-85 mg/m 2 IV on day 1 plus  cisplatin 70-75 mg/m 2 IV on day 1; every 21 d [30, 48, 49] or
  • Docetaxel 35 mg/m 2 IV on days 1 and 8 plus  irinotecan 50 mg/m 2 IV on days 1 and 8; every 21 d [50] or
  • Leucovorin 400 mg/m 2 IV on day 1 plus  5-FU 400 mg/m 2 IVP on day 1 plus  5-FU 1200 mg/m 2/day continuous IV infusion on days 1 and 2; every 14 d [38] or
  • 5-FU 800 mg/m 2/day continuous IV infusion on days 1-5; every 28 d [51] or
  • Capecitabine 1000-1250 mg/m 2 PO BID daily on days 1-14; every 21 d [52] or
  • Docetaxel 75-100 mg/m 2 IV on day 1; every 21 d [53] or
  • Paclitaxel 135-250 mg/m 2 IV on day 1; every 21 d [54] or
  • Paclitaxel 80 mg/m 2 IV on day 1 weekly; every 28 d [55]
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Second-Line Chemotherapy for Metastatic or Locally Advanced Cancer (Where Local Therapy Not Indicated)

Stage IV

For HER2-NEU overexpressing adenocarcinomas, trastuzumab can be added to other chemotherapy regimens (except regimens containing an anthracycline) [1] ;

  • Trastuzumab 8 mg/m 2 IV loading dose on day 1 of cycle 1, then 6 mg/m 2 IV; every 21 d with chemotherapy [26] or
  • Trastuzumab 6 mg/kg IV loading dose on day 1 of cycle 1, then 4 mg/kg IV every 14 d with chemotherapy

Preferred regimens [1] :

  • Ramucirumab 8 mg/kg IV on day 1; every 14 d [64] or
  • Ramucirumab 8 mg/kg IV on days 1 and 15 plus paclitaxel IV 80 mg/m 2 on days 1, 8, and 15; every 28 d [93]
  • Docetaxel 75-100 mg/m 2 IV on day 1; every 21 d [53] or
  • Paclitaxel 135-250 mg/m 2 IV on day 1; every 21 d [54] or
  • Paclitaxel 80 mg/m 2 IV on day 1 weekly; every 28 d [55] or
  • Paclitaxel 80 mg/m 2 IV on days 1, 8, and 15; every 28 d [56] or
  • Irinotecan 250-350 mg/m 2 IV on day 1; every 21 d [57] or
  • Irinotecan 150-180 mg/m 2 IV on day 1; every 14 d [58, 59, 56] or
  • Irinotecan 125 mg/m 2 IV on days 1 and 8; every 21 d [58, 59]

Other regimens [1] :

  • Irinotecan 65 mg/m 2 IV on days 1 and 8 plus cisplatin 25-30 mg/m 2 IV on days 1 and 8; every 21 d [40, 60] or
  • Irinotecan 250 mg/m 2 IV on day 1 plus capecitabine 1000 mg/m 2 PO BID daily on days 1-14; every 21 d [61] or
  • Irinotecan 180 mg/m 2 IV on day 1 plus leucovorin 400 mg/m 2 IV on day 1 plus 5-FU 400 mg/m 2 IVP on day 1 plus 5-FU 600-1200 mg/m 2/day continuous IV infusion on days 1 and 2; every 14 d [62, 63] or
  • Docetaxel 35 mg/m 2 IV on days 1 and 8 plus irinotecan 50 mg/m 2 IV on days 1 and 8; every 21 d [50]

Alternative regimens to consider:

  • Mitomycin 6 mg/m 2 IV on day 1 plus  irinotecan 125 mg/m 2 on days 2 and 9; every 28 d [65] or
  • Irinotecan 150 mg/m 2 IV on days 1 and 15 plus  mitomycin 8 mg/m 2 IV on day 1; every 28 d [66] or
  • Irinotecan 125 mg/m 2 IV on day 1 plus  mitomycin 5 mg/m 2 IV on day 1; every 14 d [67] or
  • Mitomycin 10 mg/m 2 IV on days 1 and 22 plus  leucovorin 500 mg/m 2 IV on day 1 plus  5-FU 2600 mg/m 2/day continuous IV infusion on day 1; weekly for 6 wk, followed by 2 wk off treatment [68]
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