Gastric cancer
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Section editor | |
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Neeta K. Venepalli, MD, MBA Chicago, IL |
There is significant overlap between regimens for gastric cancer and esophageal cancer, if you can't find the regimen you're looking for here, please try the esophageal cancer page.
71 regimens on this page
108 variants on this page
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Guidelines
CAP/ASCP/ASCO
ESMO
- 2016: Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
ESMO/ESSO/ESTRO
- 2013: Gastric cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
NCCN
Neoadjuvant chemotherapy
ECF
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ECF: Epirubicin, Cisplatin, Fluorouracil
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Cunningham et al. 2006 (MAGIC) | Phase III | Surgery alone | Superior OS |
This is the neoadjuvant portion of pre-planned "perioperative" therapy.
Study included patients with lower esophageal malignancy as well (74% gastric, 14.8% lower esophagus, and 11.2% GE junction).
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion on days 1 to 21
Supportive medications
- Warfarin (Coumadin) 1 mg PO once per day suggested as thrombosis prophylaxis
21-day cycle for 3 cycles
Surgical resection is performed 3 to 6 weeks after the completion of cycle 3, followed in 6 to 12 weeks by adjuvant ECF.
References
- Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. link to original article contains protocol PubMed
FLOT
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FLOT: Fluorouracil, Leucovorin, Oxaliplatin, Taxotere (Docetaxel)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Al-Batran et al. 2017 (FLOT4-AIO) | Phase III | ECF/ECX See link | Superior OS See link |
This is the neoadjuvant portion of pre-planned perioperative chemotherapy.
Chemotherapy
- Fluorouracil (5-FU) 2600 mg/m2 IV continuous 24-hour infusion on day 1
- Folinic acid (Leucovorin) 200 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
- Docetaxel (Taxotere) 50 mg/m2 IV once on day 1
14-day cycle for 4 cycles
Treatment followed by surgery and adjuvant FLOT.
References
- Abstract: Salah-Eddin Al-Batran, Nils Homann, Harald Schmalenberg, Hans-Georg Kopp, Georg Martin Haag, Kim Barbara Luley, Wolff H. Schmiegel, Gunnar Folprecht, Stephan Probst, Nicole Prasnikar, Peter C. Thuss-Patience, Wolfgang Fischbach, Jorg Trojan, Michael Koenigsmann, Claudia Pauligk, Thorsten Oliver Goetze, Elke Jaeger, Johannes Meiler, Martin H. Schuler, and Ralf Hofheinz. Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): A multicenter, randomized phase 3 trial. Journal of Clinical Oncology 2017 35:15_suppl, 4004-4004 link to abstract
Cisplatin & Fluorouracil
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ychou et al. 2011 | Phase III | Surgery alone | Superior OS |
This is the neoadjuvant portion of pre-planned "perioperative" therapy.
Study included patients with lower esophageal malignancy as well (25% gastric, 11% lower esophagus, and 64% GE junction).
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV over 60 minutes once on day 1
- Fluorouracil (5-FU) 800 mg/m2/day IV continuous infusion on days 1 to 5
28-day cycle for 2 to 3 cycles
Treatment followed by surgical resection, then adjuvant cisplatin & 5-FU.
References
- Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. link to original article contains protocol PubMed
Adjuvant therapy
5-FU & Leucovorin, then 5-FU, Leucovorin, RT, then 5-FU & Leucovorin
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RT: Radiation Therapy
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Macdonald et al. 2001 (INT-0116) | Phase III | Surgery alone | Superior OS |
Treatment is to start 20 to 40 days after surgery.
Study included patients with GE junction malignancy as well (20% GE junction) and included patients with a performance status of 2.
Preceding treatment
- Surgery with R0 resection (10% underwent D2 dissection, 36% underwent D1 dissection and 54% underwent D0 dissection)
Chemotherapy, part 1
- Fluorouracil (5-FU) 425 mg/m2 IV bolus once per day on days 1 to 5
- Folinic acid (Leucovorin) 20 mg/m2 IV bolus once per day on days 1 to 5
28-day cycle for 1 cycle, followed by:
Chemoradiotherapy
- Fluorouracil (5-FU) 400mg/m2 IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
- Folinic acid (Leucovorin) 20 mg/m2 IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
- Concurrent radiation therapy starting on day 1 with 180 cGy, 5 days per week; 25 fractions given over 5 weeks for a total of 4500 cGy
35-day course, followed by:
Chemotherapy, part 2 (given 1 month after the completion of radiotherapy)
- Fluorouracil (5-FU) 425 mg/m2 IV bolus once per day on days 1 to 5
- Folinic acid (Leucovorin) 20 mg/m2 IV bolus once per day on days 1 to 5
28-day cycle for 2 cycles
References
- Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. link to original article contains protocol PubMed
- Update: Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM, Stemmermann GN, Blanke CD, Macdonald JS. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012 Jul 1;30(19):2327-33. Epub 2012 May 14. link to original article link to PMC article PubMed
Cisplatin & Fluorouracil
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ychou et al. 2011 | Phase III | Surgery alone | Seems to have superior OS |
This is the adjuvant portion of pre-planned "perioperative" therapy.
Study included patients with lower esophageal malignancy as well (25% gastric, 11% lower esophagus, and 64% GE junction).
Preceding treatment
- Neoadjuvant cisplatin & 5-FU and surgery
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV over 60 minutes once on day 28
- Fluorouracil (5-FU) 800 mg/m2/day IV continuous infusion on days 1 to 5
28-day cycle for 3 to 4 cycles, for a total of 6 cycles
References
- Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. link to original article contains protocol PubMed
CX
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CX: Cisplatin, Xeloda (Capecitabine)
XP: Xeloda (Capecitabine), Platinol (Cisplatin)
Regimen
Study | Evidence | Comparator | Efficacy |
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Lee et al. 2011 (ARTIST) | Phase III | XP, then RT, then XP | Might have inferior DFS |
Preceding treatment
- R0 gastrectomy and at least D2 dissection
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
21-day cycle for 6 cycles
References
- Lee J, Lim DH, Kim S, Park SH, Park JO, Park YS, Lim HY, Choi MG, Sohn TS, Noh JH, Bae JM, Ahn YC, Sohn I, Jung SH, Park CK, Kim KM, Kang WK. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012 Jan 20;30(3):268-73. Epub 2011 Dec 19. link to original article contains verified protocol PubMed
- Update: Park SH, Sohn TS, Lee J, Lim DH, Hong ME, Kim KM, Sohn I, Jung SH, Choi MG, Lee JH, Bae JM, Kim S, Kim ST, Park JO, Park YS, Lim HY, Kang WK. Phase III trial to compare adjuvant chemotherapy with capecitabine and cisplatin versus concurrent chemoradiotherapy in gastric cancer: Final report of the adjuvant chemoradiotherapy in stomach tumors trial, including survival and subset analyses. J Clin Oncol. 2015 Oct 1;33(28):3130-6. Epub 2015 Jan 5. link to original article PubMed
ECF
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ECF: Epirubicin, Cisplatin, Fluorouracil
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Cunningham et al. 2006 (MAGIC) | Phase III | Surgery alone | Superior OS |
This is the adjuvant portion of pre-planned "perioperative" therapy.
Study included patients with lower esophageal malignancy as well (74% gastric, 14.8% lower esophagus, and 11.2% GE junction).
Preceding treatment
- Neoadjuvant ECF x 3 and surgery
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion on days 1 to 21
Supportive medications
- Warfarin (Coumadin) 1 mg PO once per day suggested as thrombosis prophylaxis
21-day cycle for 3 cycles
References
- Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. link to original article contains protocol PubMed
FLOT
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FLOT: Fluorouracil, Leucovorin, Oxaliplatin, Taxotere (Docetaxel)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Al-Batran et al. 2017 (FLOT4-AIO) | Phase III | ECF/ECX See link | Superior OS See link |
This is the adjuvant portion of pre-planned perioperative chemotherapy.
Preceding treatment
- Neoadjuvant FLOT x 4, then surgery
Chemotherapy
- Fluorouracil (5-FU) 2600 mg/m2 IV continuous 24-hour infusion on day 1
- Folinic acid (Leucovorin) 200 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
- Docetaxel (Taxotere) 50 mg/m2 IV once on day 1
14-day cycle for 4 cycles
References
- Abstract: Salah-Eddin Al-Batran, Nils Homann, Harald Schmalenberg, Hans-Georg Kopp, Georg Martin Haag, Kim Barbara Luley, Wolff H. Schmiegel, Gunnar Folprecht, Stephan Probst, Nicole Prasnikar, Peter C. Thuss-Patience, Wolfgang Fischbach, Jorg Trojan, Michael Koenigsmann, Claudia Pauligk, Thorsten Oliver Goetze, Elke Jaeger, Johannes Meiler, Martin H. Schuler, and Ralf Hofheinz. Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): A multicenter, randomized phase 3 trial. Journal of Clinical Oncology 2017 35:15_suppl, 4004-4004 link to abstract
Observation
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Regimen
Study | Evidence | Comparator | Efficacy |
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Sakuramoto et al. 2007 (ACTS-GC) | Phase III | S-1 | Inferior OS |
No further treatment after surgery.
Preceding treatment
- R0 gastrectomy with at least D2 dissection
References
- Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K; ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007 Nov 1;357(18):1810-20. Erratum in: N Engl J Med. 2008 May 1;358(18):1977. link to original article contains verified protocol PubMed
- Update: Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011 Nov 20;29(33):4387-93. Epub 2011 Oct 17. link to original article PubMed
S-1 monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sakuramoto et al. 2007 (ACTS-GC) | Phase III | Observation | Superior OS |
Preceding treatment
- R0 gastrectomy with at least D2 dissection, within 6 weeks
Chemotherapy
- Tegafur, gimeracil, oteracil (S-1) as follows:
- BSA less than 1.25 m2: 40 mg PO BID on days 1 to 28
- BSA between 1.25 and 1.5 m2: 50 mg PO BID on days 1 to 28
- BSA 1.5 m2 or more: 60 mg PO BID on days 1 to 28
42-day cycles for one year
References
- Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K; ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007 Nov 1;357(18):1810-20. Erratum in: N Engl J Med. 2008 May 1;358(18):1977. link to original article contains verified protocol PubMed
- Update: Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011 Nov 20;29(33):4387-93. Epub 2011 Oct 17. link to original article PubMed
- Tsuburaya A, Yoshida K, Kobayashi M, Yoshino S, Takahashi M, Takiguchi N, Tanabe K, Takahashi N, Imamura H, Tatsumoto N, Hara A, Nishikawa K, Fukushima R, Nozaki I, Kojima H, Miyashita Y, Oba K, Buyse M, Morita S, Sakamoto J. Sequential paclitaxel followed by tegafur and uracil (UFT) or S-1 versus UFT or S-1 monotherapy as adjuvant chemotherapy for T4a/b gastric cancer (SAMIT): a phase 3 factorial randomised controlled trial. Lancet Oncol. 2014 Jul;15(8):886-93. Epub 2014 Jun 18. link to original article PubMed
Metastatic or locally advanced disease, first-line
Cisplatin & S-1
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Koizumi et al. 2008 (SPIRITS) | Phase III (E) | S-1 | Seems to have superior OS |
Fujitani et al. 2016 (REGATTA) | Non-randomized portion of RCT |
Note: in REGATTA, there was no difference in outcome amongst patients who did or did not undergo surgery.
Inclusion criteria for REGATTA included the presence of a single non-curable factor (ex: hepatic, peritoneal, and para-aortic mets), see link for further details
SPIRITS trial included patients with ECOG of 2 (3% of patients)
Preceding treatment
- REGATTA: Non-laparoscopic gastrectomy with D1 lymphadenectomy versus no surgery
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 8
- Tegafur, gimeracil, oteracil (S-1) as follows:
- BSA less than 1.25 m2: 40 mg PO BID on days 1 to 21
- BSA at least 1.25 m2 and less than 1.5 m2: 50 mg PO BID on days 1 to 21
- BSA 1.5 m2 or more: 60 mg PO BID on days 1 to 21
35-day cycles
References
- Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. Epub 2008 Feb 20. link to SD article contains verified protocol PubMed
- Fujitani K, Yang HK, Mizusawa J, Kim YW, Terashima M, Han SU, Iwasaki Y, Hyung WJ, Takagane A, Park DJ, Yoshikawa T, Hahn S, Nakamura K, Park CH, Kurokawa Y, Bang YJ, Park BJ, Sasako M, Tsujinaka T; REGATTA study investigators. Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Lancet Oncol. 2016 Mar;17(3):309-18. Epub 2016 Jan 26. link to SD article contains verified protocol PubMed
CX
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CX: Cisplatin, Xeloda (Capecitabine)
XP: Xeloda (Capecitabine), Platinol (Cisplatin)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kang et al. 2009 | Phase III | Cisplatin & Fluorouracil | Non-inferior PFS |
Ohtsu et al. 2011 (AVAGAST) | Phase III (C) | Capecitabine, Bevacizumab | Seems not superior |
Lordick et al. 2013 (EXPAND) | Phase III (C) | Capecitabine, Cisplatin, Cetuximab | Seems not superior |
Kim et al. 2014 | Phase III (C) | Capecitabine, Cisplatin, Simvastatin | Seems not superior |
The following studies included patients with GE junction malignancy as well:
- Ohtsu et al: (86% gastric and 14% GE junction) and included patients with ECOG of 2
- Lordic et al: (83% gastric, 16% GE junction and 1% unknown)
- Kim et al: (79% gastric, 16% GE junction and 5% unknown)
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 2 hours once on day 1
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
- Lordick et al. 2013 gave Capecitabine (Xeloda) 1000 mg/m2 PO BID from the evening of day 1 to the morning of day 15 (28 doses per cycle)
- Ohtsu et al. gave FU 800 mg/m2 IV as a continuous infusion on D1-5 instead of capecitabine for patients unable to take oral medications
Supportive medications
- Some protocols: "Hyperhydration" for Cisplatin (Platinol)
21-day cycles, varied duration (see below)
Subsequent treatment
- AVAGAST: after 6 cycles, capecitabine maintenance
- Kim et al. 2014: after 8 cycles, capecitabine maintenance
References
- Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. link to original article contains verified protocol PubMed content property of HemOnc.org
- Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. link to original article contains verified protocol PubMed
- Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Götte H, Melezínková H, Moehler M; Arbeitsgemeinschaft Internistische Onkologie (AIO) and EXPAND Investigators. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):490-9. Epub 2013 Apr 15. link to original article contains verified protocol PubMed
- Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, Lee HR, Kang WK. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014 Nov;50(16):2822-30. Epub 2014 Sep 15. link to original article contains verified protocol PubMed
CX & Trastuzumab
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CX: Cisplatin, Xeloda (Capecitabine)
Regimen #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Shah et al. 2017 (HELOISE) | Phase IIIb | CX & HD-Trastuzumab | Seems not superior |
Patients had overexpression of HER2 protein by immunohistochemistry AND gene amplification by in-situ hybridisation.
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Capecitabine (Xeloda) 800 mg/m2 PO BID on days 1 to 14
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Subsequent cycles: 6 mg/kg IV once on day 1
21-day cycle for up to 6 cycles; trastuzumab alone continued until progression of disease or unacceptable toxicity
Regimen #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bang et al. 2010 (ToGA) | Phase III | CX | Superior OS |
Patients had overexpression of HER2 protein by immunohistochemistry OR gene amplification by fluorescence in-situ hybridisation.
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Subsequent cycles: 6 mg/kg IV once on day 1
21-day cycles
References
- Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. link to original article contains verified protocol PubMed
- Shah MA, Xu RH, Bang YJ, Hoff PM, Liu T, Herráez-Baranda LA, Xia F, Garg A, Shing M, Tabernero J. HELOISE: Phase IIIb randomized multicenter study comparing standard-of-care and higher-dose trastuzumab regimens combined with chemotherapy as first-line therapy in patients with human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2017 Aug 1;35(22):2558-2567. Epub 2017 Jun 2.link to original article contains verified protocol PubMed
ECC
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ECC: Epirubicin, Cisplatin, Capecitabine
ECX: Epirubicin, Cisplatin, Xeloda (Capecitabine)
Regimen #1, continuous capecitabine
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Catenacci et al. 2017 (RILOMET-1) | Randomized Phase II | ECX & Rilotumumab | Superior OS |
Patients had unresectable or metastatic MET-positive gastric or gastro-esophageal junction cancer.
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Capecitabine (Xeloda) 625 mg/m2 PO BID
21-day cycle for up to 10 cycles
Regimen #2, intermittent capecitabine
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Konings et al. 2010 | Randomized Phase II | ECC+P | Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV bolus once on day 1, given first
- Cisplatin (Platinol) 60 mg/m2 IV over 3 hours once on day 1, given second
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
21-day cycle for up to 6 cycles
References
- Konings IR, van der Gaast A, van der Wijk LJ, de Jongh FE, Eskens FA, Sleijfer S. The addition of pravastatin to chemotherapy in advanced gastric carcinoma: a randomised phase II trial. Eur J Cancer. 2010 Dec;46(18):3200-4. Epub 2010 Aug 18. link to original article contains verified protocol PubMed
- Catenacci DVT, Tebbutt NC, Davidenko I, Murad AM, Al-Batran SE, Ilson DH, Tjulandin S, Gotovkin E, Karaszewska B, Bondarenko I, Tejani MA, Udrea AA, Tehfe M, De Vita F, Turkington C, Tang R, Ang A, Zhang Y, Hoang T, Sidhu R, Cunningham D. Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1467-1482. Epub 2017 Sep 25. link to original article contains verified protocol PubMed
Irinotecan monotherapy
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Regimen
Study | Evidence |
---|---|
Enzinger et al. 2005 | Phase II |
Note: In contrast to the primary references, some guidelines list a dosing schedule of 125 mg/m2 IV once per day on days 1 & 8, with 21-day cycles. Enzinger et al. 2005 comment that "when irinotecan is used as a single-agent, a tri-weekly schedule may be preferable."
Chemotherapy
- Irinotecan (Camptosar) 125 mg/m2 IV over 90 minutes once per day on days 1, 8, 15, 22
42-day cycles
References
- Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci. 2005 Dec;50(12):2218-23. link to original article PubMed
Maintenance after first-line therapy
Capecitabine monotherapy
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Regimen
Study | Evidence |
---|---|
Ohtsu et al. 2011 (AVAGAST) | Non-randomized portion of RCT |
Kim et al. 2014 | Non-randomized portion of RCT |
Preceding treatment
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
21-day cycles
References
- Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. link to original article contains verified protocol PubMed
- Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, Lee HR, Kang WK. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014 Nov;50(16):2822-30. Epub 2014 Sep 15. link to original article contains verified protocol PubMed
Metastatic or locally advanced disease, subsequent lines of therapy
Best supportive care
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Thuss-Patience et al. 2011 | Phase III | Irinotecan | Seems to have inferior OS |
Kang et al. 2012 | Phase III | Docetaxel Irinotecan |
Inferior OS |
No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.
References
- Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. link to original article contains verified protocol PubMed
- Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. link to original article PubMed
Docetaxel monotherapy
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Regimen #1, 60 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kang et al. 2012 | Phase III (E) | Best supportive care | Superior OS |
Chemotherapy
- Docetaxel (Taxotere) 60 mg/m2 IV once on day 1
21-day cycles
Regimen #2, 75 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Thuss-Patience et al. 2017 (GATSBY) | Phase III (C) | T-DM1 | Seems not superior |
Patients had HER2-positive disease.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycles
References
- Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. link to original article contains protocol PubMed
- Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. link to original article contains protocol PubMed
Irinotecan monotherapy
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Regimen #1, q3wk dosing
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Thuss-Patience et al. 2011 | Phase III (E) | Best supportive care | Seems to have superior OS |
Chemotherapy
- Irinotecan (Camptosar) as follows:
- Cycle 1: 250 mg/m2 (maximum dose of 500 mg) IV over 30 minutes once on day 1
- Cycles 2 to 10 (depending on toxicity): 350 mg/m2 IV over 30 minutes once on day 1
Supportive medications
- Atropine (Atropen) 0.25 mg SC before irinotecan as prophylaxis against cholinergic symptoms
- 5-HT3 antagonist
- Dexamethasone (Decadron)
21-day cycle for up to 10 cycles
Regimen #2, alternate q3wk dosing
Study | Evidence | Comparator |
---|---|---|
Roy et al. 2013 | Randomized Phase II | Docetaxel Irinotecan liposome |
Chemotherapy
- Irinotecan (Camptosar) 300 mg/m2 IV over 90 minutes once on day 1
21-day cycles
Regimen #3, q2wk dosing
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kang et al. 2012 | Phase III (E) | Best supportive care | Superior OS |
Chemotherapy
- Irinotecan (Camptosar) 150 mg/m2 IV once on day 1
14-day cycles
Regimen #4, 4 weeks out of 6
Study | Evidence |
---|---|
Enzinger et al. 2005 | Phase II |
Note: In contrast to the primary references, some guidelines list a dosing schedule of 125 mg/m2 IV once per day on days 1 & 8, with 21-day cycles. Enzinger et al. 2005 comment that "when irinotecan is used as a single-agent, a tri-weekly schedule may be preferable."
Chemotherapy
- Irinotecan (Camptosar) 125 mg/m2 IV over 60 minutes (Mühr-Wilkenshoff et al. 2003) or 90 minutes (Enzinger et al. 2005) once per day on days 1, 8, 15, 22
42-day cycles
References
- Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. link to original article contains verified protocol PubMed
- Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. link to original article PubMed
- Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. link to original article PubMed
Nivolumab monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kang et al. 2017 (ATTRACTION-2) | Phase III | Placebo | Superior OS |
Immunotherapy
- Nivolumab (Opdivo) 3 mg/kg IV once on day 1
14-day cycles
References
- Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461-2471. Epub 2017 Oct 6. link to original article contains verified protocol PubMed
Paclitaxel monotherapy
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Regimen #1, weekly
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Thuss-Patience et al. 2017 (GATSBY) | Phase III (C) | T-DM1 | Seems not superior |
Patients had HER2-positive disease.
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per week
Continued until progression
Regimen #2, 3 out of 4 weeks
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Wilke et al. 2014 (RAINBOW) | Phase III | Ramucirumab & Paclitaxel | Seems to have inferior OS |
Eligibility criteria for patients in RAINBOW included: "documented objective radiological or clinical disease progression during or within 4 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline."
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
References
- Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. link to original article contains verified protocol PubMed
- Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. link to original article contains protocol PubMed
- Bang YJ, Xu RH, Chin K, Lee KW, Park SH, Rha SY, Shen L, Qin S, Xu N, Im SA, Locker G, Rowe P, Shi X, Hodgson D, Liu YZ, Boku N. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1637-1651. Epub 2017 Nov 2. link to original article PubMed
Pembrolizumab monotherapy
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Regimen
Study | Evidence | ORR |
---|---|---|
Fuchs et al. 2017 (KEYNOTE-059) | Phase II | 11% (95% CI 8-16) |
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 2 years or disease progression
References
- Abstract: Charles S. Fuchs, Toshihiko Doi, Raymond Woo-Jun Jang, Kei Muro, Taroh Satoh, Manuela Machado, ...Weijing Sun, Shadia Ibrahim Jalal, Manish A. Shah, Jean-Philippe Metges, Marcelo Garrido, Talia Golan, Mario Mandala, Zev A. Wainberg, Daniel V.T. Catenacci, Yung-Jue Bang, Jiangdian Wang, Minori Koshiji, Rita P. Dalal, Harry H. Yoon (2017). KEYNOTE-059 cohort 1: Efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer. Journal of Clinical Oncology 35, no. 15_suppl (May 2017) 4003-4003. link to abstract
Placebo
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Fuchs et al. 2013 (REGARD) | Phase III (C) | Ramucirumab | Seems to have inferior OS |
Pavlakis et al. 2016 (INTEGRATE) | Randomized Phase II (C) | Regorafenib | Inferior PFS |
Kang et al. 2017 (ATTRACTION-2) | Randomized Phase II (C) | Nivolumab | Inferior OS |
Patients in REGARD previously had "disease progression within 4 months of the last dose of first-line platinum-containing or fluoropyrimidine-containing chemotherapy for metastatic disease, or within 6 months of the last dose of platinum-containing or fluoropyrimidine-containing adjuvant treatment."
No active antineoplastic treatment.
References
- Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-9. Epub 2013 Oct 3.link to original article contains verified protocol PubMed
- Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, Bang YJ, Alcindor T, O'Callaghan CJ, Burnell MJ, Tebbutt NC, Rha SY, Lee J, Cho JY, Lipton LR, Wong M, Strickland A, Kim JW, Zalcberg JR, Simes J, Goldstein D. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): A multinational placebo-controlled phase II trial. J Clin Oncol. 2016 Aug 10;34(23):2728-35. Epub 2016 Jun 20. link to original article contains verified protocol link to PMC article PubMed
- Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461-2471. Epub 2017 Oct 6. link to original article contains verified protocol PubMed
Ramucirumab monotherapy
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Regimen
Study | Evidence | ORR | Comparator | Comparator ORR | Efficacy | Pt Population |
---|---|---|---|---|---|---|
Fuchs et al. 2013 (REGARD) | Phase III (E) | 3% | Placebo | 3% | Seems to have superior OS | Chemo exposed |
Patients in REGARD previously had "disease progression within 4 months of the last dose of first-line platinum-containing or fluoropyrimidine-containing chemotherapy for metastatic disease, or within 6 months of the last dose of platinum-containing or fluoropyrimidine-containing adjuvant treatment."
Chemotherapy
- Ramucirumab (Cyramza) 8 mg/kg IV once every 2 weeks
Given until progression of disease, unacceptable toxicity, or death
References
- Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-9. Epub 2013 Oct 3.link to original article contains verified protocol PubMed
Ramucirumab & Paclitaxel
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Regimen
Study | Evidence | ORR | Comparator | Comparator ORR | Efficacy | Pt Population |
---|---|---|---|---|---|---|
Wilke et al. 2014 (RAINBOW) | Phase III (E) | 28% (95% CI 23-33%) | Paclitaxel | 16% (95% CI 13-20%) | Seems to have superior OS | Chemo exposed |
Eligibility criteria for patients in RAINBOW included: "documented objective radiological or clinical disease progression during or within 4 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline."
Chemotherapy
- Ramucirumab (Cyramza) 8 mg/kg IV once per day on days 1 & 15
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
References
- Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. link to original article contains verified protocol PubMed
Regorafenib monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Pavlakis et al. 2016 (INTEGRATE) | Randomized Phase II (E) | Placebo | Superior PFS |
Chemotherapy
- Regorafenib (Stivarga) 160 mg PO once per day on days 1 to 21
28-day cycles
References
- Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, Bang YJ, Alcindor T, O'Callaghan CJ, Burnell MJ, Tebbutt NC, Rha SY, Lee J, Cho JY, Lipton LR, Wong M, Strickland A, Kim JW, Zalcberg JR, Simes J, Goldstein D. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): A multinational placebo-controlled phase II trial. J Clin Oncol. 2016 Aug 10;34(23):2728-35. Epub 2016 Jun 20. link to original article contains verified protocol link to PMC article PubMed