BACKGROUND: Standard chemotherapy for patients with metastatic colorectal cancer (mCRC) or gastric cancer (GC) consists of two-drug, usually fluoropyrimidine-based, combinations, with or without the addition of biological agents. Studies of triple-drug regimens combining 5-fluorouracil (5-FU)/folinic acid (FA) with both oxaliplatin and irinotecan have shown promising efficacy in studies of patients with mCRC or GC. However, improved efficacy has often been achieved at the expense of high rates of grade 3 or 4 toxicities such as neutropenia and diarrhoea, occasionally even resulting in toxic deaths. OBJECTIVE/ METHODS: We performed a phase II study of previously untreated patients with mCRC or GC to assess the safety and efficacy of our 5-fluorouracil/folinic acid/oxaliplatin/irinotecan (FUFOXIRI) regimen with weekly administration of irinotecan 70 mg/m(2), oxaliplatin 50 mg/m(2), FA 500 mg/m(2) and 5-FU 2000 mg/m(2) on days 1, 8, 15 and 22, repeated from day 36. RESULTS: A total of 22 patients were enrolled, 11 each with mCRC and GC receiving a median of four cycles per patient. The FUFOXIRI regimen was generally well tolerated with no toxic deaths, neutropenic fever or grade 4 toxicities. Most common grade 3 side effects were diarrhoea and neutropenia each affecting 24% of patients. Dose reductions due to toxicity were performed in 48% of all and 60% of patients having received at least two cycles of FUFOXIRI. The overall response rate was 46% (all partial responses), 55% and 36% for patients with mCRC and GC, respectively. Median progression-free survival for all patients, mCRC and GC patients was 9.5, 10.0 and 8.0 months, respectively. The median overall survival for all patients was 16.5, 18.0 and 15.0 months for patients with mCRC and GC, respectively. CONCLUSION: These data show excellent tolerance and efficacy of the FUFOXIRI regimen in both mCRC and GC. Therefore, FUFOXIRI is a promising backbone for future studies incorporating biologic 'targeted' agents for the treatment of gastrointestinal cancers.
BACKGROUND: Standard chemotherapy for patients with metastatic colorectal cancer (mCRC) or gastric cancer (GC) consists of two-drug, usually fluoropyrimidine-based, combinations, with or without the addition of biological agents. Studies of triple-drug regimens combining 5-fluorouracil (5-FU)/folinic acid (FA) with both oxaliplatin and irinotecan have shown promising efficacy in studies of patients with mCRC or GC. However, improved efficacy has often been achieved at the expense of high rates of grade 3 or 4 toxicities such as neutropenia and diarrhoea, occasionally even resulting in toxic deaths. OBJECTIVE/ METHODS: We performed a phase II study of previously untreated patients with mCRC or GC to assess the safety and efficacy of our 5-fluorouracil/folinic acid/oxaliplatin/irinotecan (FUFOXIRI) regimen with weekly administration of irinotecan 70 mg/m(2), oxaliplatin 50 mg/m(2), FA 500 mg/m(2) and 5-FU 2000 mg/m(2) on days 1, 8, 15 and 22, repeated from day 36. RESULTS: A total of 22 patients were enrolled, 11 each with mCRC and GC receiving a median of four cycles per patient. The FUFOXIRI regimen was generally well tolerated with no toxic deaths, neutropenic fever or grade 4 toxicities. Most common grade 3 side effects were diarrhoea and neutropenia each affecting 24% of patients. Dose reductions due to toxicity were performed in 48% of all and 60% of patients having received at least two cycles of FUFOXIRI. The overall response rate was 46% (all partial responses), 55% and 36% for patients with mCRC and GC, respectively. Median progression-free survival for all patients, mCRC and GC patients was 9.5, 10.0 and 8.0 months, respectively. The median overall survival for all patients was 16.5, 18.0 and 15.0 months for patients with mCRC and GC, respectively. CONCLUSION: These data show excellent tolerance and efficacy of the FUFOXIRI regimen in both mCRC and GC. Therefore, FUFOXIRI is a promising backbone for future studies incorporating biologic 'targeted' agents for the treatment of gastrointestinal cancers.
Authors: Jaffer A Ajani; Miguel B Fodor; Sergei A Tjulandin; Vladimir M Moiseyenko; Yee Chao; Sebastiao Cabral Filho; Alejandro Majlis; Sylvie Assadourian; Eric Van Cutsem Journal: J Clin Oncol Date: 2005-08-20 Impact factor: 44.544
Authors: Y Seium; R Stupp; T Ruhstaller; P Gervaz; G Mentha; M Philippe; A Allal; C Trembleau; J Bauer; R Morant; A D Roth Journal: Ann Oncol Date: 2005-04-07 Impact factor: 32.976
Authors: Anna D Wagner; Wilfried Grothe; Johannes Haerting; Gerhard Kleber; Axel Grothey; Wolfgang E Fleig Journal: J Clin Oncol Date: 2006-06-20 Impact factor: 44.544
Authors: G Masi; G Allegrini; S Cupini; L Marcucci; E Cerri; I Brunetti; E Fontana; S Ricci; M Andreuccetti; A Falcone Journal: Ann Oncol Date: 2004-12 Impact factor: 32.976
Authors: Eric Van Cutsem; Vladimir M Moiseyenko; Sergei Tjulandin; Alejandro Majlis; Manuel Constenla; Corrado Boni; Adriano Rodrigues; Miguel Fodor; Yee Chao; Edouard Voznyi; Marie-Laure Risse; Jaffer A Ajani Journal: J Clin Oncol Date: 2006-11-01 Impact factor: 44.544
Authors: Herbert Hurwitz; Louis Fehrenbacher; William Novotny; Thomas Cartwright; John Hainsworth; William Heim; Jordan Berlin; Ari Baron; Susan Griffing; Eric Holmgren; Napoleone Ferrara; Gwen Fyfe; Beth Rogers; Robert Ross; Fairooz Kabbinavar Journal: N Engl J Med Date: 2004-06-03 Impact factor: 91.245
Authors: David Cunningham; Naureen Starling; Sheela Rao; Timothy Iveson; Marianne Nicolson; Fareeda Coxon; Gary Middleton; Francis Daniel; Jacqueline Oates; Andrew Richard Norman Journal: N Engl J Med Date: 2008-01-03 Impact factor: 91.245
Authors: M Ychou; F Viret; A Kramar; F Desseigne; E Mitry; R Guimbaud; J R Delpero; M Rivoire; F Quénet; G Portier; B Nordlinger Journal: Cancer Chemother Pharmacol Date: 2007-09-28 Impact factor: 3.333
Authors: Daniel J Sargent; Claus Henning Köhne; Hanna Kelly Sanoff; Brian M Bot; Matthew T Seymour; Aimery de Gramont; Ranier Porschen; Leonard B Saltz; Philippe Rougier; Christopher Tournigand; Jean-Yves Douillard; Richard J Stephens; Axel Grothey; Richard M Goldberg Journal: J Clin Oncol Date: 2009-03-02 Impact factor: 44.544
Authors: Y Chao; K H Yeh; C J Chang; L T Chen; T Y Chao; M F Wu; C S Chang; J Y Chang; C Y Chung; W Y Kao; R K Hsieh; A L Cheng Journal: Br J Cancer Date: 2004-08-02 Impact factor: 7.640