Gastric Cancer Treatment Protocols 

Updated: Apr 04, 2018
  • 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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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 plus carboplatin 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 plus 5-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 plus capecitabine 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 plus leucovorin 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]

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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]
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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]

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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]

 

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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]

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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 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]

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 [75]  or

  • Irinotecan 150 mg/m2 IV on days 1 and 15 plus  mitomycin 8 mg/m2 IV on day 1; every 28 d [76]  or

  • Irinotecan 125 mg/m2 IV on day 1 plus  mitomycin 5 mg/m2 IV on day 1; every 14 d [77]  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 [78]  or

  • Regorafenib 160 mg PO daily on days 1 to 21; every 28 d [79]   or
  • Nivolumab 3 mg/kg IV on day 1; every 14 d [80]

 

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