Efficacy and tolerance of LV5FU2-carboplatin chemotherapy in patients with advanced pancreatic ductal adenocarcinoma after failure of standard regimens.

Abstract

Chemotherapy options in patients with advanced pancreatic ductal adenocarcinoma (PDAC) after failure of standard chemotherapies are limited. We aimed to report the efficacy and safety of the leucovorin and 5-fluorouracil (LV5FU2) and carboplatin combination in this setting. We performed a retrospective study including consecutive patients with advanced PDAC who received LV5FU2-carboplatin between 2009 and 2021 in an expert center. We measured overall survival (OS) and progression-free survival (PFS), and explored associated factors using Cox proportional hazard models. In all, 91 patients were included (55% male, median age 62), with a performance status of 0/1 in 74% of cases. LV5FU2-carboplatin was mainly used in third (59.3%) or fourth line (23.1%), with three (interquartile range: 2.0-6.0) cycles administered on average. The clinical benefit rate was 25.2%. Median PFS was 2.7 months (95% CI: 2.4-3.0). At multivariable analysis, no extrahepatic metastases (p = 0.083), no ascites or opioid-requiring pain (p = 0.023), <2 prior treatment lines (p < 0.001), full dose of carboplatin (p = 0.004), and treatment initiation >18 months after initial diagnosis (p < 0.001) were associated with longer PFS. Median OS was 4.2 months (95% CI: 3.48-4.92) and was influenced by the presence of extrahepatic metastases (p = 0.058), opioid-requiring pain or ascites (p = 0.039), and number of prior treatment lines (0.065). Prior tumor response under oxaliplatin did not impact either PFS or OS. Worsening of preexisting residual neurotoxicity was infrequent (13.2%). The most common grade 3-4 adverse events were neutropenia (24.7%) and thrombocytopenia (11.8%). Although the efficacy of LV5FU2-carboplatin appears limited in patients with pretreated advanced PDAC, it may be beneficial in selected patients.