Phase II trial of S-1 in combination with gemcitabine for chemo-naïve patients with locally advanced or metastatic pancreatic cancer

Abstract

The combination chemotherapy of S-1 and gemcitabine showed promising antitumor activity and manageable toxicities, and especially for the good performance status patients with unresectable pancreatic cancer.

Randomized phase II study of gemcitabine and S-1 combination versus gemcitabine alone in the treatment of unresectable advanced pancreatic cancer (Japan Clinical Cancer Research Organization PC-01 study)

“…Although the response rate obtained in the current study was lower than that in the previous one-arm phase II trials, the anticancer activity of GS was conWrmed to be stronger than Gem alone [9][10][11][12][13]. Favorable results of GS as to PFS and OS data also encouraged us to plan a large phase III study comparing GS to standard Gem alone.…”

“…On the other hand, randomized comparison of GS and Gem alone was one of the strengths of the current study. The ORR of GS in a previous non-randomized phase II study was extremely high, around 40%, perhaps due to selection bias [9][10][11][12][13]. However, in actual practice, since the response rate is usually below 30%, the PC-01 demonstrated a response rate acceptable to medical oncologists.…”

“…A phase II trial of S-1 alone for PC metastatic to other organ has shown a response rate of 37.5% and a median survival of 9.2 months [7,8]. Moreover, non-randomized phase II trials of a combination of Gem and S-1 (GS) therapy have demonstrated excellent results as to ORR of 44-48% and median survival of 10-12 months [9][10][11][12][13].…”

Phase I/II study of gemcitabine as a fixed dose rate infusion and S-1 combination therapy (FGS) in gemcitabine-refractory pancreatic cancer patients

“…Preclinical studies have demonstrated a synergy between gemcitabine and 5-FU in tumor cell lines, including pancreatic cancer cells [3,23]. S-1 is a fluoropyrimidine, and several phase II studies of S-1 and gemcitabine combination therapy have yielded results that demonstrated a promising activity in chemonaïve advanced pancreatic cancer patients, including a response rate of 32-48% and a median survival times of 7.89-12.5 months [16,18,19,31].…”

Gemcitabine and Oxaliplatin Combination Chemotherapy for Patients with Refractory Pancreatic Cancer

“…Chemotherapy with gemcitabine and S-1, either in combination [13,14,15,16,17,18] or sequential, was approved for the treatment of pancreatic cancer and widely used in clinical practice in Japan [19,20], but there was no standard chemotherapy for patients who are refractory to these two agents. Gemcitabine and oxaliplatin combination therapy in gemcitabine-refractory pancreatic cancer was reported to be well tolerated and active [21,22].…”