Combination 5-fluorouracil, folinic acid and cisplatin (LV5FU2-CDDP) followed by gemcitabine or the reverse sequence in metastatic pancreatic cancer: final results of a randomised strategic phase III trial (FFCD 0301)

Abstract

PurposeGemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma. Although the 5-fluorouracil (5FU), folinic acid and cisplatin combination (LV5FU2-CDDP) is an option, the optimal order of the regimens must be determined. The first strategic phase III trial comparing LV5FU2-CDDP followed by gemcitabine versus gemcitabine followed by LV5FU2-CDDP was conducted.MethodsPatients with metastatic pancreatic adenocarcinoma, performance status (PS) 0–2, without prior chemotherapy were randomly assigned (1:1) to receive either LV5FU2-CDDP followed by gemcitabine at disease progression or toxicity (Arm A), or the opposite sequence (Arm B). 202 patients had to be included and 170 deaths had to be observed to detect an expected improvement in median overall survival (OS) from 6.5 to 10 months in Arm A (two-sided α = 5% and β = 20%).Results202 patients were included (Arm A, 102; Arm B, 100). Median age, male/female ratio, PS 0–1 and previous surgery were similar in the two arms. After a median follow-up of 44 months, median OS in Arm A was 6.6 months versus 8.0 months in Arm B (p = 0.85). Median progression-free survival was similar between Arms A and B. More grade 3/4 toxicities were observed when LV5FU2-CDDP was administered as a first-line treatment compared with gemcitabine: 79% versus 64% (p = 0.018).ConclusionThis trial did not show any strategic advantage to using LV5FU2-CDDP as a first-line treatment and suggests that gemcitabine remains the standard first-line treatment. Sixty-one per cent of patients were able to receive a second line of chemotherapy.

Phase II study of palliative S-1 in combination with cisplatin as second-line chemotherapy for gemcitabine-refractory pancreatic cancer patients

“…It is difficult to conduct a clinical trial for second-line chemotherapy in advanced pancreatic cancer due to the rapidly progressive nature of the general condition and the lack of agents active in pancreatic cancer. However, it has been reported that 55-60% of patients had a relatively good PS following the failure of first-line therapy; thus, physicians should consider second-line therapy in such patients (14).…”

5-Fluorouracil/Leucovorin Combined with Irinotecan and Oxaliplatin (FOLFIRINOX) as Second-Line Chemotherapy in Patients with Metastatic Pancreatic Adenocarcinoma

“…A significant percentage of MPA patients (about 60%) progressing after gemcitabine-based chemotherapy are still in relatively good clinical condition and may require a second and even a third line of therapy [18]. However, a standard treatment for patients resistant to gemcitabine has not been established to date.…”

5-Fluorouracil/Leucovorin Combined with Irinotecan and Oxaliplatin (FOLFIRINOX) as Second-Line Chemotherapy in Patients with Advanced Pancreatic Cancer Who Have Progressed on Gemcitabine-Based Therapy

“…According to the NCCN Clinical Practice Guidelines in Oncology (version 2.2012) [13], the regimen includes capecitabine, 5-fluorouracil (5-FU)/leucovorin/oxaliplatin [9] and capecitabine/oxaliplatin [10] as options. However, after the failure of a gemcitabine-based first-line chemotherapy, there is no accepted active standard second-line treatment of benefit, even if a considerable percentage of patients display good functional condition and a relatively low tumor burden [14,15]. …”