Phase I Study of Preoperative Chemoradiation With S-1 and Oxaliplatin in Patients With Locally Advanced Resectable Rectal Cancer

Journal Article · Tue Mar 01 00:00:00 EST 2011 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2009.11.037· OSTI ID:21491636

Hong, Yong Sang; Lee, Jae-Lyun ^[1]; Park, Jin Hong; Kim, Jong Hoon ^[2]; Yoon, Sang Nam; Lim, Seok-Byung; Yu, Chang Sik ^[3]; Kim, Mi-Jung; Jang, Se-Jin ^[4]; Lee, Jung Shin ^[1]; Kim, Jin Cheon ^[3]

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1. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)
2. Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)
3. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)
4. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

Purpose: To perform a Phase I study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients with locally advanced rectal cancer, to determine the maximum tolerated dose and the recommended dose. Methods and Materials: Radiotherapy was delivered to a total of 45 Gy in 25 fractions and followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of a fixed dose of oxaliplatin (50 mg/m{sup 2}/week) on Days 1, 8, 22, and 29 and escalated doses of S-1 on Days 1-14 and 22-35. The initial dose of S-1 was 50 mg/m{sup 2}/day, gradually increasing to 60, 70, and 80 mg/m{sup 2}/day. Surgery was performed within 6 {+-} 2 weeks. Results: Twelve patients were enrolled and tolerated up to Dose Level 4 (3 patients at each dose level) without dose-limiting toxicity. An additional 3 patients were enrolled at Dose Level 4, with 1 experiencing a dose-limiting toxicity of Grade 3 diarrhea. Although maximum tolerated dose was not attained, Dose Level 4 (S-1 80 mg/m{sup 2}/day) was chosen as the recommended dose for further Phase II studies. No Grade 4 toxicity was observed, and Grade 3 toxicities of leukopenia and diarrhea occurred in the same patient (1 of 15, 6.7%). Pathologic complete responses were observed in 2 of 15 patients (13.3%). Conclusions: The recommended dose of S-1 was determined to be 80 mg/m{sup 2}/day when combined with oxaliplatin in preoperative CRT, and a Phase II trial is now ongoing.

• OSTI ID: 21491636
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 79, Issue 3; Other Information: DOI: 10.1016/j.ijrobp.2009.11.037; PII: S0360-3016(09)03578-0; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
• Country of Publication: United States
• Language: English

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62 RADIOLOGY AND NUCLEAR MEDICINE
ANTINEOPLASTIC DRUGS
COMBINED THERAPY
DIARRHEA
FRACTIONATED IRRADIATION
LEUKOPENIA
NEOPLASMS
RADIATION DOSES
RECTUM
TOXICITY
BODY
DIGESTIVE SYSTEM
DISEASES
DOSES
DRUGS
GASTROINTESTINAL TRACT
HEMIC DISEASES
IMMUNE SYSTEM DISEASES
INTESTINES
IRRADIATION
LARGE INTESTINE
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