Brief Article
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World J Gastroenterol. Sep 7, 2012; 18(33): 4533-4541
Published online Sep 7, 2012. doi: 10.3748/wjg.v18.i33.4533
FOLFIRI regimen in metastatic pancreatic adenocarcinoma resistant to gemcitabine and platinum-salts
Cindy Neuzillet, Olivia Hentic, Benoît Rousseau, Vinciane Rebours, Léïla Bengrine-Lefèvre, Franck Bonnetain, Philippe Lévy, Eric Raymond, Philippe Ruszniewski, Christophe Louvet, Pascal Hammel
Cindy Neuzillet, Olivia Hentic, Vinciane Rebours, Philippe Lévy, Philippe Ruszniewski, Pascal Hammel, Service de Gastroentérologie-Pancréatologie, Hôpital Beaujon, 100 Boulevard du Général Leclerc, 92110 Clichy La Garenne, AP-HP, France
Cindy Neuzillet, Benoît Rousseau, Léïla Bengrine-Lefèvre, Service d’Oncologie Médicale, Hôpital Saint Antoine, 184 Rue du Faubourg Saint-Antoine, 75012 Paris, AP-HP, France
Franck Bonnetain, Unité de Biostatistique et d’Epidémiologie EA 4184, Centre Georges François Leclerc, 1 Rue du Pr Marion, 21079 Dijon, France
Eric Raymond, Service d’Oncologie Médicale, Hôpital Beaujon, 100 Boulevard du Général Leclerc, 92110 Clichy La Garenne, AP-HP, France
Christophe Louvet, Département d’Oncologie Médicale, Institut Mutualiste Montsouris, 42 Boulevard Jourdan, 75014 Paris, France
Author contributions: Neuzillet C, Louvet C and Hammel P designed the study; Neuzillet C, Hentic O, Rousseau B, Bengrine-Lefèvre L, Lévy P, Raymond E, Ruszniewski P, Louvet C and Hammel P performed the research; Rebours V and Bonnetain F analyzed the data; and Neuzillet C and Hammel P wrote the paper.
Correspondence to: Dr. Pascal Hammel, Service de Gastroentérologie-Pancréatologie, Hôpital Beaujon, 100 Boulevard du Général Leclerc, 92110 Clichy La Garenne, AP-HP, France. pascal.hammel@bjn.aphp.fr
Telephone: +33-1-40875653 Fax: +33-1-42703784
Received: January 6, 2012
Revised: March 16, 2012
Accepted: April 13, 2012
Published online: September 7, 2012
Abstract

AIM: To evaluate the efficacy and safety of the FOLFIRI regimen in patients with metastatic pancreatic adenocarcinoma (PAC) after the failure of gemcitabine and platinum salts.

METHODS: All consecutive patients with histologically confirmed, metastatic PAC and World Health Organization performance status (PS) ≤ 2 received FOLFIRI-1 [irinotecan 180 mg/m2 on day 1 and leucovorin 400 mg/m2 followed by 5-fluorouracil (5-FU) 400 mg/m2 bolus, then 5-FU 2400 mg/m2 as a 46-h infusion, biweekly] or FOLFIRI-3 (irinotecan 100 mg/m2 on day 1 and leucovorin 400 mg/m2, then 5-FU 2400 mg/m2 as a 46-h infusion and irinotecan 100 mg/m2 repeated on day 3, biweekly) after failure of gemcitabine and platinum-based chemotherapies as a systematic policy in two institutions between January 2005 and May 2010. Tumor response, time to progression (TTP), overall survival rate (OS) and grade 3-4 toxicities were retrospectively studied. Subgroup analyses were performed to search for prognostic factors.

RESULTS: Sixty-three patients (52.4% male, median age 59 years) were analyzed. Among them, 42.9% were PS 0, 38.1% were PS 1 and 19.0% were PS 2. Fifty one patients (81.0%) had liver metastases. Before the FOLFIRI regimen, patients had received 1 line (n = 19), 2 lines (n = 39) or 3 lines (n = 5) of chemotherapy. Median TTP obtained with the line before FOLFIRI was 3.9 mo (95% CI: 3.4-5.3 mo). A total of 480 cycles was completed (median: 6 cycles, range: 1-51 cycles). The main reason for discontinuing FOLFIRI was tumor progression (90.3%). Tumor control was achieved in 25 patients (39.7%) (partial response: n = 5, stable disease: n = 20) with FOLFIRI. Median TTP was 3.0 mo (95% CI: 2.1-3.9 mo) and median OS was 6.6 mo (95% CI: 5.3-8.1 mo). Dose adaptation was required in 36 patients (57.1%). Fifteen patients (23.8%) had grade 3-4 toxicities, mainly hematological (n = 11) or digestive (n = 4). Febrile neutropenia occurred in 3 patients. There was no toxic death. PS 2 was significantly associated with poor TTP [hazard ratio (HR): 16.036, P < 0.0001] and OS (HR: 4.003, P = 0.004).

CONCLUSION: The FOLFIRI regimen had an acceptable toxicity and an interesting efficacy in our study, limited to patients in good condition (PS 0-1).

Keywords: Pancreatic cancer, Pancreatic adenocarcinoma, Metastases, Chemotherapy, 5-fluorouracil, Irinotecan, Camptothecin, FOLFIRI regimen