Gastric Cancer Treatment Protocols 

Updated: Feb 27, 2019
Author: Mohammad Muhsin Chisti, MD, FACP; Chief Editor: N Joseph Espat, MD, MS, FACS 

General Treatment Recommendations

Tumors involving the esophagogastric junction (EGJ) with the tumor epicenter no more than 2 cm into the proximal stomach are staged as esophageal cancers, while EGJ tumors with their epicenter located more than 2 cm into the proximal stomach are staged as stomach cancers, as are all cardia cancers not involving the EGJ.

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

Surgery is the primary treatment for early-stage gastric cancer. Complete surgical resection offers the potential for long-term survival.

Laparoscopic resection is an emerging modality that may improve operative mortality, but requires additional investigation.[2] Endoscopic mucosal resection and endoscopic submucosal dissection should be performed only in experienced medical centers.[1]

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 in patients who did not receive preoperative chemotherapy[3] . For patients who received preoperative chemotherapy, the addition of postoperative radiotherapy has not demonstrated additional benefit.[4]

Medically unfit patients can be treated with chemoradiotherapy or chemotherapy.

Stage IV

Chemotherapy based around a doublet or triplet platinum/fluoropyrimidine combination is given for metastatic disease. Local therapy is not indicated. HER2 and PD-L1 testing are recommended upon confirmation of metastatic disease.[1, 5]

Trastuzumab should be added to first-line chemotherapy in HER2-NEU overexpressing metastatic adenocarcinomas.[6, 5]

 

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/m2 IV on day 1 pluscarboplatin AUC 2 IV on day 1; weekly for 5 wk[7, 8] (see the Carboplatin AUC Dose Calculation [Calvert formula] calculator)or

  • Cisplatin 75-100 mg/m2 IV on day 1 plus5-fluorouracil (5-FU) 750-1000 mg/m2/day IV continuous infusion on days 1-4 and 29-32; single 35-day cycle[9]  or

  • Cisplatin 30 mg/m2 IV on day 1 pluscapecitabine 800 mg/m2 PO BID on days 1-5; weekly for 5wk[10]  or

  • Cisplatin 15 mg/m2 IV daily on days 1-5 and days 22-26 plus 5-FU 800 mg/m2/day IV continuous infusion on days 1-5 and days 22-26; single 35-day cycle[11]  or

  • Oxaliplatin 85 mg/m2 IV on days 1, 15, and 29 plus capecitabine 625 mg/m2 PO BID on days 1-5, 8-12, 15-19, 22-26, and 29-33; single 35-day cycle[12] or

  • Oxaliplatin 85 mg/m2 on days 1, 15, and 29 plus 5-FU 180 mg/m2 continuous IV infusion daily on days 1-33[13]  or

  • Oxaliplatin 85 mg/m2 IV on day 1 plusleucovorin 400 mg/m2 IV on day 1 plus 5-FU 400 mg/m2 IVP on day 1 and 5-FU 800 mg/m2 continuous IV infusion daily on days 1 and 2; every 14 d for three cycles with radiation and three cycles after radiation[14]

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/m2 IV on day 1 weekly for 5 wk plus 5-FU 225 mg/m2 IV daily on days 1-33; single 35-day cycle[15]  or

  • Carboplatin AUC 6 IV on days 1 and 22 plus 5-FU 200 mg/m2 IV daily on days 1-42[16]  or

  • Irinotecan 65 mg/m2 IV on days 1, 8, 22, and 29 plus cisplatin 30 mg/m2 IV on days 1, 8, 22, and 29[17] or

  • Paclitaxel 45-50 mg/m2 IV on day 1 plus 5-FU 300 mg/m2 continuous IV infusion daily on days 1-5; weekly for 5 wk[18]  or

  • Paclitaxel 45-50 mg/m2 IV on day 1 plus capecitabine 625-825 mg/m2 PO BID daily on days 1-5; weekly for 5 wk[18, 19]

 

Perioperative Chemotherapy Regimens

The following regimens consist 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]  ("ECF" regimen and variants):

  • Epirubicin 50 mg/m2 IV on day 1 plus cisplatin 60 mg/m2 IV on day 1 plus 5-FU 200 mg/m2/day IV continuous infusion daily for days 1-21; every 21 d for six cycles—three preoperatively and three postoperatively[3]  or

  • Epirubicin 50 mg/m2 IV on day 1 plus oxaliplatin 130 mg/m2 IV on day 1 plus 5-FU 200 mg/m2/day IV continuous infusion daily for days 1-21; every 21 d for six cycles—three preoperatively and three postoperatively[20]  or

  • Epirubicin 50 mg/m2 IV on day 1 plus cisplatin 60 mg/m2 IV on day 1 plus capecitabine 625 mg/m2 PO BID daily for days 1-21; every 21 d for six cycles—three preoperatively and three postoperatively[20]  or

  • Epirubicin 50 mg/m2 IV on day 1 plus oxaliplatin 130 mg/m2 IV on day 1 plus capecitabine 625 mg/m2 PO BID daily for days 1-21; every 21 d for six cycles—three preoperatively and three postoperativelyy[20]  or

See the list below:

  • ​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; two or three cycles preoperatively and three or four cycles postoperatively for a total of six cycles [21]

​The following regimen consists of four 14-day cycles preoperatively and then adjuvant therapy with the same regimen ("FLOT" regimen):

  • 5-FU 2600 mg/m 2 IV plus  folinic acid 200 mg/m 2  plus  oxaliplatin 85 mg/m 2  plus  docetaxel 50 mg/m 2 [22]
 

Postoperative Chemoradiotherapy Regimens

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

  • Leucovorin 20 mg/m2 IVP on days 1-5 plus 5-FU 425 mg/m2 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/m2 IVP on days 1-4 and 31-33 plus 5-FU 400 mg/m2 IVP daily on days 1-4, every 35 d (cycle 2 given with radiation)[23]

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.[1]

One cycle before and two cycles after chemoradiation:

  • Capecitabine 750-1000 mg/m2 PO BID on days 1-14; every 28 d (one cycle before and two cycles after chemoradiation)

  • Leucovorin 400 mg/m2 IV on days 1 and 15 or days 1, 2, 15, and 16 plus 5-FU 400 mg/m2 IVP on days 1 and 15 or days 1, 2, 15, and 16 and 5-FU 1200 mg/m2 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)[24]

With radiation:

  • 5-FU 200-250 mg/m2/day continuous IV infusion on days 1-5 or 1-7; weekly for 5 wk[25]  or

  • Capecitabine 625-825 mg/m2 PO BID daily for days 1-5 or 1-7; weekly for 5 wk[26]

 

Postoperative Chemotherapy Regimens

Postoperative chemotherapy regimens for patients who underwent D2 lymph node dissection include the following:

  • Oxaliplatin 130 mg/m2 IV on day 1 plus capecitabine 1000 mg/m2 PO BID on days 1-14; every 21 d for eight cycles[27]  or

  • Cisplatin 60 mg/m2 IV on day 1 plus capecitabine 1000 mg/m2 PO BID on days 1-14; every 21 d for six cycles[28]

In one trial, postoperative adjuvant chemotherapy with capecitabine and cisplatin compared with postoperative chemoradiotherapy showed inferior disease-free survival, which may suggest that in patients who have undergone D2 lymph node dissection, chemoradiotherapy may be superior.  However, this requires further study.[29]

Compared with adjuvant chemotherapy, observation postoperatively leads to decreased overall survival.[30]

 

 

First-Line Chemotherapy for Metastatic or Locally Advanced Cancer (Where Local Therapy Not Indicated)

Stage IV

For HER2-NEU overexpressing adenocarcinomas, trastuzumab should be added to first-line chemotherapy consisting of cisplatin plus a fluoropyrimidine (eg, 5-FU, capecitabine) but is not recommended in regimens containing an anthracycline.[1]  Trastuzumab is used as follows:

  • Trastuzumab 8 mg/kg IV loading dose on day 1 of cycle one, then 6 mg/kg IV; every 21 d with chemotherapy[31]  or

  • Trastuzumab 6 mg/kg IV loading dose on day 1 of cycle one, 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/m2 IV on day 1 plus cisplatin 75 mg/m2 IV on day 1 plus 5-FU 1000 mg/m2/day continuous IV infusion on days 1-5; every 28 d[32]

Note that the NCCN panel does not recommend the above specified doses or schedule because of concerns regarding toxicity, and instead suggests using one of the following modified regimens:

  • Docetaxel 40 mg/m2 IV on day 1 plus leucovorin 400 mg/m2 IV on day 1 plus 5-FU 400 mg/m2 IV on day 1 plus 5-FU 1000 mg/m2/day continuous IV infusion on days 1 and 2 plus cisplatin 40 mg/m2 IV on day 3; every 14 d[33]  or

  • Docetaxel 50 mg/m2 IV on day 1 plus oxaliplatin 85 mg/m2 IV on day 1 plus 5-FU 1200 mg/m2/day continuous IV infusion on days 1 and 2; every 14 d[34]  or

  • Docetaxel 75 mg/m2 IV on day 1 plus carboplatin AUC 6 IV on day 2 plus 5-FU 1200 mg/m2/day continuous IV infusion on days 1-3; every 21 d[35]  or

  • Epirubicin 50 mg/m2 IV on day 1 plus cisplatin 60 mg/m2 IV on day 1 plus 5-FU 200 mg/m2/day continuous IV infusion on days 1-21; every 21 d[36, 37]  or

  • Epirubicin 50 mg/m2 IV on day 1 plus oxaliplatin 130 mg/m2 on day 1 plus 5-FU 200 mg/m2/day continuous IV infusion on days 1-21; every 21 d[37]  or

  • Epirubicin 50 mg/m2 IV on day 1 plus cisplatin 60 mg/m2 IV on day 1 plus capecitabine 625 mg/m2 PO BID daily on days 1-21; every 21 d[37]  or

  • Epirubicin 50 mg/m2 IV on day 1 plus oxaliplatin 130 mg/m2 IV on day 1 plus capecitabine 625 mg/m2 PO BID daily on days 1-21; every 21 d[37]  or

  • Cisplatin 75-100 mg/m2 IV on day 1 plus 5-FU 750-1000 mg/m2/day continuous IV infusion over 24 h on days 1-4; every 28 d[38]  or

  • Cisplatin 50 mg/m2 IV on day 1 plus leucovorin 200 mg/m2 IV on day 1 plus 5-FU 2000 mg/m2/day continuous IV infusion on day 1; every 14 d[39, 40]  or

  • Cisplatin 80 mg/m2 IV on day 1 plus capecitabine 1000 mg/m2 PO BID daily on days 1-14; every 21 d[31, 41]

  • Oxaliplatin 85 mg/m2 IV on day 1 plus leucovorin 400 mg/m2 IV on day 1 plus 5-FU 400 mg/m2 IVP on day 1 plus 5-FU 1200 mg/m2/day continuous IV infusion on days 1 and 2; every 14 d[42]  or

  • Oxaliplatin 85 mg/m2 IV on day 1 plus leucovorin 200 mg/m2 IV on day 1 plus 5-FU 2600 mg/m2/day continuous IV infusion on day 1; every 14 d[39]  or

  • Oxaliplatin 130 mg/m2 IV on day 1 plus capecitabine 1000 mg/m2 PO BID on days 1-14; every 21 d[43]

  • Irinotecan 80 mg/m2 IV on day 1 plus leucovorin 500 mg/m2 IV on day 1 plus 5-FU 2000 mg/m2/day continuous IV infusion on day 1; weekly for 6 wk followed by 1 wk off treatment[44]  or 2 wk off treatment[45, 46] or

  • Irinotecan 150 mg/m2 IV on day 1 plus leucovorin 20 mg/m2 IV on day 1 plus 5-FU 1000 mg/m2 /day continuous IV infusion on days 1 and 2; every 14 d[47]

Other regimens[1]

  • Paclitaxel 135-200 mg/m2 IV on day 1 plus cisplatin 75 mg/m2 IV on day 2; every 21 d[48]  or

  • Paclitaxel 90 mg/m2 IV on day 1 plus cisplatin 50 mg/m2 IV on day 1; every 14 d[49]  or

  • Paclitaxel 200 mg/m2 IV on day 1 plus carboplatin AUC 5 IV on day 1; every 21 d[50]  or

  • Docetaxel 70-85 mg/m2 IV on day 1 plus cisplatin 70-75 mg/m2 IV on day 1; every 21 d[51, 52, 53]  or

  • Docetaxel 35 mg/m2 IV on days 1 and 8 plus irinotecan 50 mg/m2 IV on days 1 and 8; every 21 d[54]  or

  • Leucovorin 400 mg/m2 IV on day 1 plus 5-FU 400 mg/m2 IVP on day 1 plus 5-FU 1200 mg/m2/day continuous IV infusion on days 1 and 2; every 14 d[40]  or

  • 5-FU 800 mg/m2/day continuous IV infusion on days 1-5; every 28 d[55]  or

  • Capecitabine 1000-1250 mg/m2 PO BID daily on days 1-14; every 21 d[56]  or

  • Docetaxel 75-100 mg/m2 IV on day 1; every 21 d[57]  or

  • Paclitaxel 135-250 mg/m2 IV on day 1; every 21 d[58]  or

  • Paclitaxel 80 mg/m2 IV on day 1 weekly; every 28 d[59]

 

Second-Line Chemotherapy for Metastatic or Locally Advanced Cancer (Where Local Therapy Not Indicated)

Stage IV

For HER2-NEU overexpressing adenocarcinomas, trastuzumab should be added to first-line chemotherapy consisting of cisplatin plus a fluoropyrimidine (eg, 5-FU, capecitabine) but is not recommended in regimens containing an anthracycline.[1]  Trastuzumab is used as follows:

  • Trastuzumab 8 mg/m2 IV loading dose on day 1 of cycle one, then 6 mg/m2 IV; every 21 d with chemotherapy[31] or

  • Trastuzumab 6 mg/kg IV loading dose on day 1 of cycle one, then 4 mg/kg IV every 14 d with chemotherapy

Preferred regimens[1] :

  • Ramucirumab 8 mg/kg IV on day 1; every 14 d[60]  or

  • Ramucirumab 8 mg/kg IV on days 1 and 15 plus paclitaxel IV 80 mg/m2 on days 1, 8, and 15; every 28 d[61]  or

  • Docetaxel 75-100 mg/m2 IV on day 1; every 21 d[57]  or

  • Paclitaxel 135-250 mg/m2 IV on day 1; every 21 d[58]  or

  • Paclitaxel 80 mg/m2 IV on day 1 weekly; every 28 d[59]  or

  • Paclitaxel 80 mg/m2 IV on days 1, 8, and 15; every 28 d[62]  or

  • Irinotecan 250-350 mg/m2 IV on day 1; every 21 d[63]  or

  • Irinotecan 150-180 mg/m2 IV on day 1; every 14 d[64, 65, 62]  or

  • Irinotecan 125 mg/m2 IV on days 1 and 8; every 21 d[64, 65]

For MSI-high or deficient MMR tumors that have progressed despite fluoropyrimidine- and platinum-containing chemotherapy [66]  :

  • Pembrolizumab 200mg IV on day 1; every 21 d[67, 68]

Metastatic gastric or gastroesophageal junction adenocarcinoma tumors expressing PD-L1 ≥ 1 (or third line or subsequent therapy)[69] :

  • Pembrolizumab 200mg IV on day 1; every 21 d[70]

Other regimens[1] :

  • Irinotecan 65 mg/m2 IV on days 1 and 8 plus cisplatin 25-30 mg/m2 IV on days 1 and 8; every 21 d[42, 71]  or

  • Irinotecan 250 mg/m2 IV on day 1 plus capecitabine 1000 mg/m2 PO BID daily on days 1-14; every 21 d[72]  or

  • Irinotecan 180 mg/m2 IV on day 1 plus leucovorin 400 mg/m2 IV on day 1 plus 5-FU 400 mg/m2 IVP on day 1 plus 5-FU 600-1200 mg/m2/day continuous IV infusion on days 1 and 2; every 14 d[73, 74]  or

  • Docetaxel 35 mg/m2 IV on days 1 and 8 plus irinotecan 50 mg/m2 IV on days 1 and 8; every 21 d[54]

Tipiracil/trifluridine:

The FDA approved tipiracil/trifluridine in February 2019 for metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma previously treated with at least 2 prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy[75]

Dose based on trifluridine component rounded to nearest 5-mg increment

35 mg/m2 PO BID with food on Days 1-5 and Days 8-12 of each 28-day cycle; not to exceed 80 mg/dose until disease progression or unacceptable toxicity

Alternative regimens to consider:

  • Mitomycin 6 mg/m2 IV on day 1 plus irinotecan 125 mg/m2 on days 2 and 9; every 28 d[76]  or

  • Irinotecan 150 mg/m2 IV on days 1 and 15 plus mitomycin 8 mg/m2 IV on day 1; every 28 d[77]  or

  • Irinotecan 125 mg/m2 IV on day 1 plus mitomycin 5 mg/m2 IV on day 1; every 14 d[78]  or

  • Mitomycin 10 mg/m2 IV on days 1 and 22 plus leucovorin 500 mg/m2 IV on day 1 plus 5-FU 2600 mg/m2/day continuous IV infusion on day 1; weekly for 6 wk, followed by 2 wk off treatment[79]  or

  • Regorafenib 160 mg PO daily on days 1 to 21; every 28 d [80]   or
  • Nivolumab 3 mg/kg IV on day 1; every 14 d[81]