Phase I study of preoperative chemoradiotherapy with sequential oxaliplatin and irinotecan with S-1 for locally advanced rectal cancer.

Abstract:

:The present study designed a novel preoperative chemoradiotherapy (CRT) with sequential oxaliplatin and irinotecan with S-1 for locally advanced rectal cancer (LARC). This phase I study evaluated the maximum tolerated dose and recommended dose (RD) of oxaliplatin following irinotecan with S-1. Patients with clinical stage T3 or 4 or involvement of the regional nodes and no evidence of distant metastases were treated with fixed doses of S-1 (80 mg/m2/day) on days 1-5, 8-12, 15-19, 22-27 and 29-33, and irinotecan (40 mg/m2/day) on days 1 and 8, followed by oxaliplatin on days 22 and 29. The dose of oxaliplatin was initially 40 mg/m2 (level 1) with a predefined dose escalation schedule. The radiation dose was 1.8 Gy/fraction to a total dose of 45 Gy. A total of 9 patients were enrolled in the present study and 7 patients completely received CRT with this study protocol. The maximum tolerated dose for oxaliplatin was 50 mg/m2 (level 2). Three of four patients experienced dose-limiting toxicity (grade 3 diarrhea) in oxaliplatin phase of level 2 dose. The RD of oxaliplatin was 40 mg/m2 (level 1 dose). In addition, 2 patients had pathological CR (28.5%). Novel preoperative CRT with sequential oxaliplatin and irinotecan with S-1 for LARC resulted in acceptable toxicity and promising efficacy. However, the RD of oxaliplatin was lower than in previous CRT studies that combined oxaliplatin with S-1. To administer higher oxaliplatin, we have planned a phase I trial of preoperative CRT with sequential oxaliplatin followed by irinotecan with S-1 for LARC.

journal_name

Oncol Lett

journal_title

Oncology letters

authors

Fujikawa H,Toiyama Y,Inoue Y,Omura Y,Ide S,Kitajima T,Yasuda H,Okugawa Y,Okita Y,Yoshiyama S,Hiro J,Kobayashi M,Ohi M,Araki T,Kusunoki M

doi

10.3892/ol.2019.10028

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

3930-3936

issue

4

eissn

1792-1074

issn

1792-1082

pii

OL-0-0-10028

journal_volume

17

pub_type

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