Randomized Phase II Trial of S-1 versus S-1 Plus Oxaliplatin (SOX) in Patients with Gemcitabine Refractory Pancreatic Cancer

ABSTRACT Background Gemcitabine (Gem) monotherapy or Gem-based combination therapy is used as standard first-line therapy for advanced pancreatic cancer (PC). There is no consensus on second-line therapy in patients (pts) with disease progression (PD) after Gem-based therapy. The addition of oxaliplatin (L-OHP) to 5-FU/LV, however, yielded a significant improvement in overall survival (OS) and progression-free survival (PFS) in a second-line setting in the CONKO 003 trial. As S-1, an oral fluoropyrimidine derivative, is commonly used to treat advanced PC rather than 5-FU/LV in Japan, we conducted a randomized phase II trial to evaluate the efficacy and safety of S-1 plus L-OHP (SOX) compared with S-1 alone in a second-line setting. Material and methods The inclusion criteria were as follows: 1) histologically or cytologically proven pancreatic adenocarcinoma or adenosquamous carcinoma; 2) confirmed PD after Gem treatment; 3) ECOG PS, 0-1; 4) measurable metastatic lesion based on RECIST criteria; 5) age ≥ 20 years. Patients were randomized to receive either S-1 (80/100/120 mg/day based on BSA, po, d1-28, q6w; Arm A) or SOX (L-OHP 100 mg/m2, iv, d1 plus S-1 80/100/120 mg/day based on BSA, po, d1-14, q3w; Arm B). The primary endpoint was PFS to detect the superiority of Arm B over Arm A. Results Of a total of 271 pts enrolled between January 2009 and July 2010, 264 were eligible (130 randomized to Arm A and 134 to Arm B). Median PFS in Arm A and B was 2.8 and 3.0 months, respectively (HR= 0.838; 95% CI, 0.649-1.082; P = 0.1795) with a median follow-up time of 12.6 months. Median OS in Arm A and B was 7.0 and 7.5 months, respectively (HR = 1.031; 95% CI, 0.791-1.344; P = 0.8235) with a median follow-up time of 13.8 months. Response rate (RR) was 11.5% in Arm A (15/130; 95% CI, 6.6-18.3) and 20.9% in Arm B (28/134; 95% CI, 14.4-28.8)(P = 0.0395). The incidences of grade 3/4 toxicities were as follows: neutropenia (11.4% and 14.0%), thrombocytopenia (3.8% and 9.8%), anorexia (11.4% and 12.5%), diarrhea (4.5% and 5.1%) and nausea (3.0% and 9.8%) in Arm A and B, respectively. Both regimens were tolerable. Conclusions Although SOX showed an advantage in RR, it provided no significant improvement in PFS or OS compared with S-1 alone. Disclosure T. Okusaka: The study detailed in the abstract was funded by a pharmaceutical company. S. Ohkawa: The study detailed in the abstract was funded by a pharmaceutical company. H. Isayama: The study detailed in the abstract was funded by a pharmaceutical company. A. Fukutomi: The study detailed in the abstract was funded by a pharmaceutical company. K. Yamaguchi: The study detailed in the abstract was funded by a pharmaceutical company. M. Ikeda: The study detailed in the abstract was funded by a pharmaceutical company. A. Funakoshi: The study detailed in the abstract was funded by a pharmaceutical company. M. Nagase: The study detailed in the abstract was funded by a pharmaceutical company. S. Nakamori: The study detailed in the abstract was funded by a pharmaceutical company. Y. Hamamoto: The study detailed in the abstract was funded by a pharmaceutical company.