Annals of Oncology Advance Access published online on June 16, 2008
Annals of Oncology, doi:10.1093/annonc/mdn166
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction
1 Semmelweis University, Budapest, Hungary
2 Wielkopolskie Centrum Onkologii Poznan, Poznan, Poland
3 Catholic University of Sacred Heart, Rome, Italy
4 Estonian Oncology Center, Tallinn, Estonia
5 Hacettepe University Medical Faculty Institute of Oncology, Sihhiye, Ankara, Turkey
6 III Med. Klinik, Munich, Germany
7 Markusovszky County Hospital, Szombathely, Markusovszky, Hungary
8 Ege University Medical School, Izmir, Turkey
9 Pfizer, New York, NY, USA
10 Institut Claudius Regaud, Toulouse, France
* Correspondence to: Dr Roland Bugat, Département de Médecine, Institut Claudius Regaud, 20 rue du Pont St Pierre, 31052 Toulouse Cedex 3, France. Tel: +33-5-61-42-41-19; Fax: +33-5-61-42-46-20; E-mail: bugat{at}icr.fnclcc.fr
Background: We aimed to establish the superiority (or noninferiority if superiority was not achieved) in terms of time to progression (TTP) of irinotecan/5-fluorouracil (IF) over cisplatin/5-fluorouracil (CF) in chemonaive patients with adenocarcinoma of the stomach/esophagogastric junction.
Patients and methods: Patients received either IF: i.v. irinotecan 80 mg/m2 30 min, folinic acid 500 mg/m2 2 h, 5-fluorouracil (5-FU) 2000 mg/m2 22 h, for 6/7 weeks or CF: cisplatin 100 mg/m2 1–3 h, with 5-FU 1000 mg/m2/day 24 h, days 1–5, every 4 weeks.
Results: In all, 333 patients were randomized and treated (IF 170, CF 163). Patient characteristics were balanced except more IF patients had Karnofsky performance status 100%. TTP for IF was 5.0 months [95% confidence interval (CI) 3.8–5.8] and 4.2 months (95% CI 3.7–5.5) for CF (P = 0.088). Overall survival (OS) was 9.0 versus 8.7 months, response rate 31.8% versus 25.8%, time to treatment failure (TTF) 4.0 versus 3.4 months for IF and CF, respectively. The difference in TTF was statistically significant (P = 0.018). IF was better in terms of toxic deaths (0.6% versus 3%), discontinuation for toxicity (10.0% versus 21.5%), severe neutropenia, thrombocytopenia and stomatitis, but not diarrhea.
Conclusion: IF did not yield a significant TTP or OS superiority over CF, and the results of noninferiority of IF were borderline. However, IF may provide a viable, platinum-free front-line treatment alternative for metastatic gastric cancer.
cisplatin, 5-fluorouracil, gastric, irinotecan, phase III
Received for publication November 21, 2006. Revision received November 30, 2007. Revision received January 18, 2008. Accepted for publication March 20, 2008.