Phase II study of S-1 on alternate days plus bevacizumab in patients aged ≥ 75 years with metastatic colorectal cancer (J-SAVER)
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Alternate-day administration of S-1 is thought to reduce toxicities. This phase II study evaluated S-1 on alternate days combined with bevacizumab as first-line treatment for elderly patients with metastatic colorectal cancer.
Patients and methods
Eligible patients had histologically proven colorectal adenocarcinoma, measurable metastatic lesions, age ≥ 75 years, Eastern Cooperative Oncology Group performance status ≤ 1, no previous chemotherapy, and refused oxaliplatin- or irinotecan-containing regimens. Patients received 40 mg, 50 mg, or 60 mg (body surface area ≤ 1.25 m2, > 1.25 to ≤ 1.50 m2, or > 1.50 m2, respectively) of S-1 twice orally on Sunday, Monday, Wednesday, and Friday every week. Bevacizumab (7.5 mg/kg) was administered every 3 weeks. The primary endpoint was progression-free survival.
Of 54 enrolled patients, 50 patients were evaluated for efficacy and 53 for safety. The median age was 79 years (range 75–88 years). The median progression-free survival was 8.1 months (95% confidence interval (CI) 6.7–9.5 months). The median overall survival was 23.1 months (95% CI 17.4–28.8 months). The response rate was 44% (95% CI 30.2–57.8%), and the disease control rate was 88% (95% CI 79.0–97.0%). Grade 3 or higher hematologic, non-hematologic, and bevacizumab-related adverse events occurred in 9%, 11%, and 25% of patients, respectively. The most common grade 3 and 4 treatment-related adverse events were hypertension (11%), nausea (6%), fatigue (6%), anemia (6%), and proteinuria (6%). Only 6 patients discontinued treatment due to adverse events.
S-1 on alternate days combined with bevacizumab showed better tolerability and comparable survival compared with the results of similar studies.
KeywordsBevacizumab Colorectal cancer Elderly Fluoropyrimidine S-1
We are grateful to Kentaro Yamazaki, Takako E. Nakajima, and Takehiro Oikawa for their important contributions to this study as part of the Data and Safety Monitoring Committee and Miss Mizuki Aida for data management. The participating investigators are as follows: T. Masuishi and T. Eto (Tsuchiura Kyodo General Hospital); S. Yoshida, Y. Ito, and M. Shimoyamada (National Hospital Organization Mito Medical Center); T. Murashita (Ryugasaki Saiseikai Hospital); H. Satake (Kobe City Medical Center General Hospital); M. Chikakiyo (Tokushima Prefecture Naruto Hospital); T. Fujita and S. Mori (JCHO Ritsurin Hospital); A. Soeda and M. Kobayashi (Tsukuba Memorial Hospital); J. Higashijima and T. Nakao (Tokushima University); M. Inukai and Y. Suzuki (Kagawa University); M. Goto (Ibaraki Prefectural Central Hospital and Cancer Center). This work is supported by the NPO Tsukuba Cancer Clinical Trial Group. We would like to thank Editage (www.editage.jp) for English language editing.
Compliance with ethical standards
Conflict of interest
MS received a research funding from Chugai, Taiho, CSL Behring, MSD, Astelllas, AbbVie, Eisai, Ono, TSUMURA, Coviklen Japan, Johnson&Johnson, Takeda, Novartis, Bayer Yakuhin, and Merck Serono; KA received research funding from Taiho, Hisamitsu, and MSD; AT received honoraria from Chugai and Taiho; TN received research funding from Taiho; IH received honoraria and research funding from Taiho and Chugai. All other authors declare no potential conflicts of interest.
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