Ishihara Soichiro, Matsusaka Satoshi, Kondo Keisaku, Horie Hisanaga, Uehara Keisuke, Oguchi Masahiko, Murofushi Keiko, Ueno Masashi, Mizunuma Nobuyuki, Shinbo Taijyu, Kato Daiki, Okuda Junji, Hashiguchi Yojiro, Nakazawa Masanori, Sunami Eiji, Kawai Kazushige, Yamashita Hideomi, Okada Tohru, Ishikawa Yuichi, Nakajima Toshifusa, Watanabe Toshiaki
Department of Surgical Oncology, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Department of Gastroenterology, Cancer Institute Hospital, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan.
Radiat Oncol. 2015 Jan 23;10:24. doi: 10.1186/s13014-015-0333-8.
The objective of this phase I study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of preoperative chemoradiotherapy (CRT) with S-1 plus oxaliplatin in patients with locally advanced rectal cancer.
Patients received radiotherapy in a total dose of 50.4 Gy in 28 fractions. Concurrent chemotherapy consisted of a fixed oral dose of S-1 (80 mg/m(2)/day) on days 1-5, 8-12, 22-27, and 29-33, plus escalated doses of oxaliplatin as an intravenous infusion on days 1, 8, 22, and 29. Oxaliplatin was initially given in a dose of 40 mg/m(2)/week to three patients. The dose was then increased in a stepwise fashion to 50 mg/m(2)/week and the highest dose level of 60 mg/m(2)/week until the MTD was attained.
Thirteen patients were enrolled, and 12 received CRT. Dose-limiting toxicity (DLT) occurred in two of six patients (persistent grade 2 neutropenia, delaying oxaliplatin treatment by more than 3 days) at dose level 3; there were no grade 3 or 4 adverse events defined as DLT. The RD was 60 mg/m(2)/week of oxaliplatin on days 1, 8, 22, and 29. Twelve patients underwent histologically confirmed R0 resections, and two out of six patients (33%) given dose level 3 had pathological complete responses.
The RD for further studies is 80 mg/m(2) of S-1 5 days per week plus 60 mg/m(2) of oxaliplatin on days 1, 8, 22, and 29 and concurrent radiotherapy. Although our results are preliminary, this new regimen for neoadjuvant chemoradiotherapy is considered safe and active.
This trial was registered with Clinicaltrials.gov (identifier: NCT01227239 ).
本I期研究的目的是确定S-1联合奥沙利铂用于局部晚期直肠癌患者术前放化疗（CRT）的最大耐受剂量（MTD）和推荐剂量（RD）。
患者接受总量为50.4 Gy、分28次的放疗。同步化疗包括在第1 - 5天、8 - 12天、22 - 27天和29 - 33天口服固定剂量的S-1（80 mg/m²/天），并在第1天、8天、22天和29天静脉输注递增剂量的奥沙利铂。最初3例患者接受的奥沙利铂剂量为40 mg/m²/周。然后剂量逐步增加至50 mg/m²/周，最高剂量水平为60 mg/m²/周，直至达到MTD。
13例患者入组，12例接受了CRT。在剂量水平3时, 6例患者中有2例发生剂量限制性毒性（DLT）（持续性2级中性粒细胞减少，奥沙利铂治疗延迟超过3天）；没有定义为DLT的3级或4级不良事件。RD为第1天、8天、22天和29天奥沙利铂60 mg/m²/周。12例患者接受了组织学确认的R0切除，在接受剂量水平3的6例患者中有2例（33%）达到病理完全缓解。
进一步研究的RD为每周5天80 mg/m²的S-1加第1天、8天、22天和29天60 mg/m²的奥沙利铂及同步放疗。尽管我们的结果是初步的，但这种新的新辅助放化疗方案被认为是安全且有效的。
本试验在Clinicaltrials.gov注册（标识符：NCT01227239）
