Naoki Uemura1, Shohei Kikuchi1, Yasushi Sato2, Hiroyuki Ohnuma1, Koichi Okamoto2, Hiroshi Miyamoto2, Masahiro Hirakawa1, Tamotsu Sagawa3, Koshi Fujikawa3, Yasuo Takahashi3, Toshinori Okuda4, Shinya Minami4, Minoru Takahashi5, Tetsuro Okamoto6, Kohichi Takada1, Koji Miyanisi1, Tetsuji Takayama2, Junji Kato7. 1. Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-Ku, Sapporo, 060-8543, Japan. 2. Department of Community Medicine for Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan. 3. Department of Gastroenterology, Hokkaido Cancer Center, Sapporo, Japan. 4. Department of Gastroenterology, Oji General Hospital, Tomakomai, Japan. 5. Department of Gastroenterology, Sapporo Kyoritsu-Gorinbashi Hospital, Sapporo, Japan. 6. Department of Gastroenterology, Kiyota Hospital, Sapporo, Japan. 7. Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-Ku, Sapporo, 060-8543, Japan. jkato@sapmed.ac.jp.
Abstract
PURPOSE: Triplet therapy using docetaxel, cisplatin, and S-1 (DCS) against unresectable gastric cancer as previously reported by us showed high clinical efficacy, with a 87.1% total response rate; however, it also showed a high incidence of grade 3/4 toxicity. With the aim of reducing toxicities, we conducted a phase II study of modified DCS (mDCS), using a reduced dose of docetaxel, and evaluated the clinical efficacy and adverse events of this regimen. METHODS: Patients with unresectable gastric cancer received chemotherapy with S-1 (40 mg/m2 b.i.d) on days 1-14, and docetaxel (50 mg/m2) plus cisplatin (60 mg/m2) on day 8 every 3 weeks. The primary endpoint was the response rate (RR). Overall (OS) and progression-free survival (PFS), and toxicities were also evaluated. RESULTS: Forty-nine patients were enrolled from November 2011 to April 2014, and 43 were eligible. The overall RR was 79.1%, including two cases of a complete response (4.7%), and 32 cases of a partial response (74.4%). Nine cases had stable disease (20.9%) but none showed progressive disease. Of the 43 cases, 15 cases (34.9%) underwent curative conversion surgery. The median PFS was 350 days (95% CI 240-416 days) and median OS was 722 days (95% CI 411 days-not reached). Grade 3/4 neutropenia developed in 79.1%, and febrile neutropenia in 34.9%, of patients. Non-hematological grade 3/4 adverse events were anorexia (25.6%), nausea (4.7%), and diarrhea (9.3%). CONCLUSION: Modified DCS therapy showed high clinical efficacy sufficient enough to attempt conversion therapy against unresectable gastric cancer. Modified DCS showed fewer toxicities, but careful management of these is still essential.
PURPOSE: Triplet therapy using docetaxel, cisplatin, and S-1 (DCS) against unresectable gastric cancer as previously reported by us showed high clinical efficacy, with a 87.1% total response rate; however, it also showed a high incidence of grade 3/4 toxicity. With the aim of reducing toxicities, we conducted a phase II study of modified DCS (mDCS), using a reduced dose of docetaxel, and evaluated the clinical efficacy and adverse events of this regimen. METHODS:Patients with unresectable gastric cancer received chemotherapy with S-1 (40 mg/m2 b.i.d) on days 1-14, and docetaxel (50 mg/m2) plus cisplatin (60 mg/m2) on day 8 every 3 weeks. The primary endpoint was the response rate (RR). Overall (OS) and progression-free survival (PFS), and toxicities were also evaluated. RESULTS: Forty-nine patients were enrolled from November 2011 to April 2014, and 43 were eligible. The overall RR was 79.1%, including two cases of a complete response (4.7%), and 32 cases of a partial response (74.4%). Nine cases had stable disease (20.9%) but none showed progressive disease. Of the 43 cases, 15 cases (34.9%) underwent curative conversion surgery. The median PFS was 350 days (95% CI 240-416 days) and median OS was 722 days (95% CI 411 days-not reached). Grade 3/4 neutropenia developed in 79.1%, and febrile neutropenia in 34.9%, of patients. Non-hematological grade 3/4 adverse events were anorexia (25.6%), nausea (4.7%), and diarrhea (9.3%). CONCLUSION: Modified DCS therapy showed high clinical efficacy sufficient enough to attempt conversion therapy against unresectable gastric cancer. Modified DCS showed fewer toxicities, but careful management of these is still essential.
Entities:
Keywords:
Gastric cancer; Phase II study; Triplet chemotherapy