Abstract
Background
This phase I study was performed to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose-limiting toxicities (DLTs) of oxaliplatin combined with preoperative chemoradiotherapy with S-1, oxaliplatin, and bevacizumab in locally advanced rectal cancer.
Methods
Eligible patients had a newly diagnosed clinical stage T1–4 N0–3 M0 rectal adenocarcinoma within 12 cm of the anal verge suitable for curative resection. Conformal radiation therapy was given (4 fields, 2 Gy daily fractions, 5 days/week, total dose 40 Gy) with concurrent S-1 (80 mg/m2/day orally, days 1–5, 8–12, 15–19, and 22–26), bevacizumab (90 min continuous intravenous infusion at 5 mg/kg, days 1 and 15), and oxaliplatin (120 min continuous intravenous infusion, days 1, 8, 15, and 22). The initial oxaliplatin dose (40 mg/m2/day) was gradually increased to determine the MTD and RD. Surgery was performed 6 weeks after completion of preoperative chemoradiotherapy.
Results
11 patients were enrolled. The MTD of oxaliplatin was considered to be 60 mg/m2, because three of five patients developed DLTs such as diarrhea and hives. The recommended dose of oxaliplatin was set at 50 mg/m2. Of the patients who received oxaliplatin at ≤ RD, 5 (83.3 %) had a clinical response [four pathological responses and one pathological complete response (Grade 3)].
Conclusions
With this new regimen, the MTD of oxaliplatin was 60 mg/m2, and the RD for phase II studies was 50 mg/m2. This new regimen appears to provide worthwhile outcomes for locally advanced rectal cancer and merits a phase II study.
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Acknowledgments
This study was supported by a grant-in-aid from a cooperative cancer research project between TAIHO Pharmaceutical Co., Ltd., Yakult Co., Ltd. and Chugai Co., Ltd..
Conflict of interest
Drs. Sato, Kurita, Iwata, Yoshikawa, Higashigima, Chikakio, Kashihara, Takasu, Mastumoto, Eto declare no conflict of interest or financial ties. Dr. Shimada declares the following conflict of interest: financial grants from a cooperative cancer research project between TAIHO Pharmaceutical Co., Ltd., Yakult Co., Ltd. and Chugai Co., Ltd..
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Sato, H., Shimada, M., Kurita, N. et al. Phase I trial of neoadjuvant preoperative chemotherapy with S-1, oxaliplatin, and bevacizumab plus radiation in patients with locally advanced rectal cancer. Int J Clin Oncol 20, 543–548 (2015). https://doi.org/10.1007/s10147-014-0733-z
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DOI: https://doi.org/10.1007/s10147-014-0733-z