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Sections Gastric Cancer Treatment Protocols
General Treatment Recommendations
Preoperative Chemoradiotherapy Regimens
Perioperative Chemotherapy Regimens
Postoperative Chemoradiotherapy Regimens
First-Line Chemotherapy for Metastatic or Locally Advanced Cancer (Where Local Therapy Not Indicated)
Second-Line Chemotherapy for Metastatic or Locally Advanced Cancer (Where Local Therapy Not Indicated)
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References

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]}

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]:

Paclitaxel 50 mg/m² IV on day 1 plus carboplatin area under the curve (AUC) 2 IV on day 1; weekly for 5 wk^{[14, 15]}(see the Carboplatin AUC Dose Calculation [Calvert formula] calculator) or

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 ²on 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 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]
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

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]

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]

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 ≥1 ^{[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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Sections Gastric Cancer Treatment Protocols
General Treatment Recommendations
Preoperative Chemoradiotherapy Regimens
Perioperative Chemotherapy Regimens
Postoperative Chemoradiotherapy Regimens
First-Line Chemotherapy for Metastatic or Locally Advanced Cancer (Where Local Therapy Not Indicated)
Second-Line Chemotherapy for Metastatic or Locally Advanced Cancer (Where Local Therapy Not Indicated)
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References

Gastric Cancer Treatment Protocols

General Treatment Recommendations

Stage 0 to IA

Stage IB to IIIC, potentially resectable

Stage IV

Preoperative Chemoradiotherapy Regimens

Preferred regimens

Other regimens

Perioperative Chemotherapy Regimens

Preferred regimens

Other regimens

Postoperative Chemoradiotherapy Regimens

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

Stage IV

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

Stage IV

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