Gastric Cancer Treatment Protocols 

Updated: Jan 30, 2021
  • Author: Mohammad Muhsin Chisti, MD, FACP; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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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]

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Preoperative 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 (note: infusional fluorouracil can be replaced by capecitabine) [1] :

  • Oxaliplatin 85 mg/m2 IV on day 1 plus  leucovorin 400 mg/m2 IV on day 1 plus  5-fluorouracil (5-FU) 400 mg/m2 IV push (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 [7]  or

  • Oxaliplatin 85 mg/m2 IV on days 1, 15, and 29  for 3 doses plus  capecitabine 625 mg/m2 PO BID on days 1-5 weekly for 5 wk [8] or

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

  • Cisplatin 15 mg/m2 IV daily on days 1-5 plus  5-FU 800 mg/m2/day IV continuous infusion on days 1-5; 21-day cycle for two cycles [10] or

  • Cisplatin 30 mg/m2 IV on day 1 plus capecitabine 800 mg/m2 PO BID on days 1-5; weekly for 5wk [11]  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 [12]  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 [12, 13]

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] :

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Perioperative Chemotherapy Regimens

Note that in regimens that contain a fluoropyrimidine (5-FU or capecitabine), infusional fluorouracil can be replaced by capecitabine.

Preferred regimens

​The FLOT (fluorouracil, oxaliplatin, docetaxel [Taxotere]) regimen is given for four preoperative cycles and then four postoperative cycles, as follows:

  • 5-FU 2600 mg/m 2 IV continuous infusion on day 1 plus  leucovorin 200 mg/m 2  IV on day 1 plus  oxaliplatin 85 mg/m 2 on day 1 plus  docetaxel 50 mg/m 2 on day 1, every 14 days  [16]

The following fluoropyrimidine (5-FU or capecitabine) and oxaliplatin regimens are given in three preoperative cycles and then three postoperative cycles

  • 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 continuous IV infusion daily on days 1 and 2; 14-day cycle [17]
  • Oxaliplatin 85 mg/m plus  5-FU 2600 mg/m 2 IV continuous infusion on day 1 plus  leucovorin 200 mg/m 2 IV on day 1; 14-day cycle [18]
  • Capecitabine 1000 mg/m 2 PO BID on Days 1-14 plus  oxaliplatin 130 mg/m 2 IV on day 1; 21-day cycle [19]

Other regimens

The following regimen is given in four preoperative cycles and then four postoperative cycles:

  • Cisplatin 50 mg/m 2 IV on day 1 plus  5-FU 2000 mg/m 2/day IV continuous infusion daily on days 1-2; 14-day cycle

 

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Postoperative Chemoradiotherapy Regimens

Compared with surgery alone, adjuvant chemotherapy leads to improved overall survival. [20] Postoperative chemotherapy regimens for patients who underwent D2 lymph node dissection 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 [21]   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 1200 mg/m 2 continuous IV infusion daily on days 1 and 2; 14-day cycle [18]
  • Oxaliplatin 85 mg/m 2 plus  5-FU 2600 mg/m 2 IV continuous infusion on day 1 plus  leucovorin 200 mg/m 2 IV on day 1; 14-day cycle [18]

In one trial of patients with D2-resected gastric cancer, the addition of radiotherapy to adjuvant chemotherapy (with capecitabine and cisplatin) improved disease-free survival in patients with node-positive disease and with intestinal-type gastric cancer. However, this finding requires further study. [22]

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

Stage IV

Trastuzumab should be added to first-line chemotherapy for HER2-NEU overexpressing adenocarcinomas. 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 [23]  or

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

  • An FDA-approved biosimilar may be substituted for trastuzumab

Preferred regimens 

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. Oxaliplatin is generally preferred over cisplatin due to lower toxicity. [1]

For HER2 overexpression–positive adenocarcinoma, in combination with trastuzumab:

  • 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 [24] 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 [18]  or

  • Oxaliplatin 130 mg/m2 IV on day 1 plus  capecitabine 1000 mg/m2 PO BID on days 1-14; every 21 d  [19]  or

  • Oxaliplatin 85 mg/m2 IV on day 1 plus  capecitabine 625 mg/m2 PO BID on days 1-14; every 21 d [25]  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  [26]  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 [18, 27]  or

  • Cisplatin 80 mg/m2 IV on day 1 plus  capecitabine 1000 mg/m2 PO BID daily on days 1-14; every 21 d [23, 28]

​For HER overexpression–negative adenocarcinoma:

  • Fluorouracil or capecitabine plus  oxaliplatin plus  nivolumab (PDL1 CPS ≥ 5)

    See the list below:

    • Nivolumab 360 mg IV day 1 plus  capecitabine 1000 mg/m2 PO BID on days 1-14 plus  oxaliplatin 130 mg/m2 IV day 1; every 21 days
    • Nivolumab 240 mg IV day 1 plus  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
  • Fluorouracil or capecitabine  plus oxaliplatin
  • Fluorouracil or capecitabine  plus cisplatin

Other regimens [1] :

  • ​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 [29]  or 2 wk off treatment [30, 31] 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 1200 mg/m2 /day continuous IV infusion on days 1 and 2; every 14 d [32]

  • Paclitaxel 135-250 mg/m2 IV on day 1; every 21 d [33]  or

  • Paclitaxel 80 mg/m2 IV on day 1 weekly; every 28 d [34]   or

  • Paclitaxel 135-200 mg/m2 IV on day 1 plus  cisplatin 75 mg/m2 IV on day 2; every 21 d [35]  or

  • Paclitaxel 90 mg/m2 IV on day 1 plus  cisplatin 50 mg/m2 IV on day 1; every 14 d [36]  or

  • Paclitaxel 200 mg/m2 IV on day 1 plus  carboplatin AUC 5 IV on day 1; every 21 d [37]  or

  • Docetaxel 75-100 mg/m2 IV on day 1; every 21 d [38] or

  • 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 [39]

See the list below:

  • 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 [40]  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 [41]  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 [42]  or

  • Docetaxel 70-85 mg/m2 IV on day 1 plus  cisplatin 70-75 mg/m2 IV on day 1; every 21 d [43, 44, 45]  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 [27]  or

  • 5-FU 800 mg/m2/day continuous IV infusion on days 1-5; every 28 d [46]  or

  • Capecitabine 1000-1250 mg/m2 PO BID daily on days 1-14; every 21 d [47]

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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 deruxtecan is approved for locally advanced and metastatic HER2-positive gastric and gastroesophageal junction adenocarcinoma in adults who have received a prior trastuzumab-based regimen. [48]  The regimen is as follows:

  • Trastuzumab deruxtecan 6.4 mg/kg IV every 3 weeks (21-day cycle); continue until disease progression or unacceptable toxicity

Preferred regimens [1] :

  • 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 [49]  or

  • Docetaxel 75-100 mg/m2 IV on day 1; every 21 d [38]  or

  • Paclitaxel 135-250 mg/m2 IV on day 1; every 21 d [33]  or

  • Paclitaxel 80 mg/m2 IV on day 1 weekly; every 28 d [34]  or

  • Paclitaxel 80 mg/m2 IV on days 1, 8, and 15; every 28 d [50]  or

  • Irinotecan 250-350 mg/m2 IV on day 1; every 21 d [51]  or

  • Irinotecan 150-180 mg/m2 IV on day 1; every 14 d [52, 53, 50]  or

  • Irinotecan 125 mg/m2 IV on days 1 and 8; every 21 d [52, 53]

For second-line or subsequent therapy for MSI-high or deficient MMR tumors OR  third-line or subsequent therapy for gastric adenocarcinoma with PD-L1 expression by CPS ≥ [54, 55] :

  • Pembrolizumab 200mg IV q3wk or 400 mg IV q6wk [56, 57, 58]

Other regimens [1] :

  • Ramucirumab 8 mg/kg IV on day 1; every 14 d [59]  or

  • 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 [24, 60]  or

  • Irinotecan 250 mg/m2 IV on day 1 plus  capecitabine 1000 mg/m2 PO BID daily on days 1-14; every 21 d [61]  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 [62, 19]  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 [63]

For NTRK gene fusion-positive tumors

  • Entrectinib 600 mg PO daily [64]
  • Larotrectinib 100 mg PO BID [65]

Useful in certain circumstances (advanced gastric and gastroesophageal junction adenocarcinoma, together gastroesophageal adenocarcinoma [GEA])

Ramucirumab 8 mg/kg IV on day 1 plus  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 1200 mg/m2/day continuous IV infusion on days 1 and 2; every 14 d [66]

For third-line or subsequent therapy:

Used for metastatic gastric or 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. Only consider in patients with low-volume gastric cancer who have minimal or no symptoms and are able to swallow pills. [67]

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

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