Report of Two Protocol Planned Interim Analyses in a Randomised Multicentre Phase III Study Comparing Capecitabine with Fluorouracil and Oxaliplatin with Cisplatin in Patients with Advanced Oesophagogastric Cancer Receiving ECF

Overview

Journal Br J Cancer

Specialty Oncology

Date 2005 Jun 2

PMID 15928658

Citations 52

Authors

K Sumpter

C Harper-Wynne

D Cunningham

S Rao

N Tebbutt

A R Norman

C Ward

T Iveson

M Nicolson

T Hickish

M Hill

J Oates

Affiliations

Soon will be listed here.

Abstract

The purpose of the study was to establish the optimal dose of capecitabine (X) to be used within a multicentre, randomised study evaluating the potential roles of oxaliplatin (O) and X in chemonaive patients (pts) with advanced oesophagogastric cancer. Two by two design was used, and pts were randomised to one of four regimens and stratified for extent of disease, performance status (PS) and centre. The treatment regimens are epirubicin, cisplatin, 5-fluorouracil (ECF), EOF, ECX or EOX. Doses: E 50 mg m(-2), C 60 mg m(-2) and O 130 mg m(-2) i.v. 3 weekly; F 200 mg m(-2) day(-1) i.v. and X 500 mg m(-2) b.i.d.(-1) (escalated to 625 mg m(-2) b.i.d.(-1) after results of first interim analysis) p.o., continuously. First interim analysis was performed when 80 pts had been randomised. Dose-limiting fluoropyrimidine toxicities were stomatitis, palmar plantar erythema (PPE) and diarrhoea; 5.1% of X-treated pts experienced grade 3/4 toxicity. Protocol planned dose escalation of X to 625 mg m(-2) b.i.d.(-1) was instituted and a second interim analysis has been performed; results are presented in this paper. A total of 204 pts were randomised at the time of the protocol planned 2nd interim analysis. Grade 3/4 fluoropyrimidine-related toxicity was seen in 13.7% pts receiving F, 8.4% pts receiving X 500 mg m(-2) b.i.d.(-1) and 14.7% pts receiving X 625 mg m(-2) b.i.d.(-1). Combined complete and partial response rates were ECF 31% (95% CI 18.7-46.3), EOF 39% (95% CI 25.9-53.1), ECX 35% (95% CI 21.4-50.3), EOX 48% (95% CI 33.3-62.8). Grade 3/4 fluoropyrimidine toxicity affected 14.7% of pts treated with X 625 mg m(-2) b.i.d.(-1), which is similar to that observed with F, confirming this to be the optimal dose. The replacement of C by O and F by X does not appear to impair efficacy. The trial continues to total accrual of 1000 pts.

Citing Articles

Pathological Complete Response Achieved with XELOX Chemotherapy, HIPEC, and Anti-PD-1 Immunotherapy in Stage IV Gastric Adenocarcinoma with Peritoneal Metastasis: A Case Report and Review of the Literature.

Zhou J, Wang J, Wang W, Sun L, Zhao S, Sun Q J Gastrointest Cancer. 2024; 55(3):1441-1447.

PMID: 38676903 DOI: 10.1007/s12029-024-01056-0.

The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023.

Wang F, Zhang X, Tang L, Wu Q, Cai M, Li Y Cancer Commun (Lond). 2023; 44(1):127-172.

PMID: 38160327 PMC: 10794017. DOI: 10.1002/cac2.12516.

Meta-Analysis of Capecitabine versus 5-Fluorouracil in Advanced Gastric Cancer.

Wu Z, Zhang X, Zhang C, Lin Y Evid Based Complement Alternat Med. 2023; 2023:4946642.

PMID: 37408581 PMC: 10319465. DOI: 10.1155/2023/4946642.

Economic evaluation of FLOT and ECF/ECX perioperative chemotherapy in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma.

Zeng H, Wang C, Song L, Jia S, Zeng X, Liu Q BMJ Open. 2022; 12(11):e060983.

PMID: 36375981 PMC: 9664295. DOI: 10.1136/bmjopen-2022-060983.

Signaling pathways and therapeutic interventions in gastric cancer.

Lei Z, Teng Q, Tian Q, Chen W, Xie Y, Wu K Signal Transduct Target Ther. 2022; 7(1):358.

PMID: 36209270 PMC: 9547882. DOI: 10.1038/s41392-022-01190-w.

References

Borner M, Schoffski P, de Wit R, Caponigro F, Comella G, Sulkes A . Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer. Eur J Cancer. 2002; 38(3):349-58. DOI: 10.1016/s0959-8049(01)00371-9. View

Zaniboni A, Barni S, Labianca R, Marini G, Pancera G, Giaccon G . Epirubicin, cisplatin, and continuous infusion 5-fluorouracil is an active and safe regimen for patients with advanced gastric cancer. An Italian Group for the Study of Digestive Tract Cancer (GISCAD) report. Cancer. 1995; 76(10):1694-9. DOI: 10.1002/1097-0142(19951115)76:10<1694::aid-cncr2820761004>3.0.co;2-k. View

Kim D, Kim J, Lee S, Kim T, Heo D, Bang Y . Phase II study of oxaliplatin, 5-fluorouracil and leucovorin in previously platinum-treated patients with advanced gastric cancer. Ann Oncol. 2003; 14(3):383-7. DOI: 10.1093/annonc/mdg106. View

Bamias A, Hill M, Cunningham D, Norman A, Ahmed F, Webb A . Epirubicin, cisplatin, and protracted venous infusion of 5-fluorouracil for esophagogastric adenocarcinoma: response, toxicity, quality of life, and survival. Cancer. 1996; 77(10):1978-85. DOI: 10.1002/(SICI)1097-0142(19960515)77:10<1978::AID-CNCR3>3.0.CO;2-D. View

Findlay M, Cunningham D, Norman A, Mansi J, Nicolson M, Hickish T . A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol. 1994; 5(7):609-16. DOI: 10.1093/oxfordjournals.annonc.a058932. View

Koizumi W, Saigenji K, Ujiie S, Terashima M, Sakata Y, Taguchi T . A pilot phase II study of capecitabine in advanced or recurrent gastric cancer. Oncology. 2003; 64(3):232-6. DOI: 10.1159/000069313. View

Cho H, Imada T, Oshima T, Shiozawa M, Rino Y, Takanashi Y . In-vitro effect of a combination of 5-fluorouracil (5-FU) and cisplatin (CDDP) on human gastric cancer cell lines: timing of cisplatin treatment. Gastric Cancer. 2002; 5(1):43-6. DOI: 10.1007/s101200200006. View

Budman D, Meropol N, Reigner B, Creaven P, Lichtman S, Berghorn E . Preliminary studies of a novel oral fluoropyrimidine carbamate: capecitabine. J Clin Oncol. 1998; 16(5):1795-802. DOI: 10.1200/JCO.1998.16.5.1795. View

Therasse P, Arbuck S, Eisenhauer E, Wanders J, Kaplan R, Rubinstein L . New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000; 92(3):205-16. DOI: 10.1093/jnci/92.3.205. View

10.

Raymond E, Faivre S, Coudray A, Louvet C, Gespach C . [Preclinical studies of oxaliplatin in combination chemotherapy]. Bull Cancer. 2001; 88 Spec No:S26-34. View

11.

Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M . Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol. 2001; 19(21):4097-106. DOI: 10.1200/JCO.2001.19.21.4097. View

12.

Evans T, Pentheroudakis G, Paul J, McInnes A, Blackie R, Raby N . A phase I and pharmacokinetic study of capecitabine in combination with epirubicin and cisplatin in patients with inoperable oesophago-gastric adenocarcinoma. Ann Oncol. 2002; 13(9):1469-78. DOI: 10.1093/annonc/mdf243. View

13.

Diaz-Rubio E, Evans T, Tabemero J, Cassidy J, Sastre J, Eatock M . Capecitabine (Xeloda) in combination with oxaliplatin: a phase I, dose-escalation study in patients with advanced or metastatic solid tumors. Ann Oncol. 2002; 13(4):558-65. DOI: 10.1093/annonc/mdf065. View

14.

de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J . Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000; 18(16):2938-47. DOI: 10.1200/JCO.2000.18.16.2938. View

15.

Levi F, Misset J, Brienza S, Adam R, Metzger G, Itzakhi M . A chronopharmacologic phase II clinical trial with 5-fluorouracil, folinic acid, and oxaliplatin using an ambulatory multichannel programmable pump. High antitumor effectiveness against metastatic colorectal cancer. Cancer. 1992; 69(4):893-900. DOI: 10.1002/1097-0142(19920215)69:4<893::aid-cncr2820690410>3.0.co;2-x. View

16.

Glimelius B, Ekstrom K, Hoffman K, Graf W, Sjoden P, Haglund U . Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol. 1997; 8(2):163-8. DOI: 10.1023/a:1008243606668. View

17.

Goldberg R, Sargent D, Morton R, Fuchs C, Ramanathan R, Williamson S . A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2003; 22(1):23-30. DOI: 10.1200/JCO.2004.09.046. View

18.

Ross P, Nicolson M, Cunningham D, Valle J, Seymour M, Harper P . Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol. 2002; 20(8):1996-2004. DOI: 10.1200/JCO.2002.08.105. View

19.

Kim T, Kang Y, Ahn J, Chang H, Yook J, Oh S . Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced gastric cancer. Ann Oncol. 2002; 13(12):1893-8. DOI: 10.1093/annonc/mdf323. View

20.

Murad A, Santiago F, Petroianu A, Rocha P, Rodrigues M, Rausch M . Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer. 1993; 72(1):37-41. DOI: 10.1002/1097-0142(19930701)72:1<37::aid-cncr2820720109>3.0.co;2-p. View