FOLFIRI regimen in metastatic pancreatic adenocarcinoma resistant to gemcitabine and platinum-salts

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/m(2) on day 1 and leucovorin 400 mg/m(2) followed by 5-fluorouracil (5-FU) 400 mg/m(2) bolus, then 5-FU 2400 mg/m(2) as a 46-h infusion, biweekly] or FOLFIRI-3 (irinotecan 100 mg/m(2) on day 1 and leucovorin 400 mg/m(2), then 5-FU 2400 mg/m(2) as a 46-h infusion and irinotecan 100 mg/m(2) 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: 5-fluorouracil; Camptothecin; Chemotherapy; FOLFIRI regimen; Irinotecan; Metastases; Pancreatic adenocarcinoma; Pancreatic cancer.

Figure 1

Time to progression (A) and overall survival (B) from the beginning of FOLFIRI for the 63 patients. TTP: Time to progression; OS: Overall survival.

Figure 2

Subgroup analysis according to the World Health Organization performance status. A: Time to progression (TTP) according to World Health Organization (WHO) performance status (PS). B: Overall survival (OS) according to WHO PS.