Jin Jing, Li Ye-Xiong, Wang Jin-Wan, Wang Wei-Hu, Liu Yue-Ping, Wang Kai, Fang Hui, Zhou Zhi-Xiang, Zhou Ai-Ping, Yu Zi-Hao
Department of Radiation Oncology, Cancer Hospital/Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Int J Radiat Oncol Biol Phys. 2008 Nov 1;72(3):671-7. doi: 10.1016/j.ijrobp.2008.01.057. Epub 2008 May 1.
A Phase I study was conducted to determine the maximal tolerated dose and the dose-limiting toxicity (DLT) of oxaliplatin (OXA) combined with capecitabine and radiotherapy as adjuvant treatment in patients with operable rectal cancer.
A total of 21 patients with Stage II or III rectal adenocarcinoma after curative surgery were treated with radiotherapy to a total dose of 50 Gy in 5 weeks. OXA was administered at a dosage of 40 (n = 6), 50 (n = 3),60 (n = 3), 70 (n = 3), or 80 mg/m(2) (n = 6) once a week for 2 weeks (first cycle) followed by a second cycle after a 7-day break. Capecitabine at a fixed dose of 1,300 mg/m(2)/d was administered orally at the same schedule as for OXA. DLT was defined as Grade 3 or 4 hematologic and nonhematologic toxicity.
Grade 1-3 leukopenia, diarrhea, and nausea/vomiting were the most common toxic side effects, and most were Grade 1-2. A DLT was first observed in 1 of 3 patients at 40 mg/m(2) (Grade 3 diarrhea) but was not observed in the next 3 patients at the same level or in patients who received a dose level of 50-70 mg/m(2). At 80 mg/m(2), DLT occurred in 3 of 6 patients (1 Grade 4 leukopenia and 2 Grade 3 diarrhea).
OXA combined with a fixed dose of capecitabine at 625 mg/m(2) twice daily by mouth plus radiotherapy in the adjuvant setting was tolerable and clinically feasible. The maximal tolerated dose of OXA in this setting was 80 mg/m(2), comparable to the maximal tolerated dose of OXA in the neoadjuvant setting.
开展一项I期研究，以确定奥沙利铂（OXA）联合卡培他滨及放疗作为可手术直肠癌患者辅助治疗时的最大耐受剂量和剂量限制性毒性（DLT）。
共有21例II期或III期直肠癌患者在根治性手术后接受放疗，5周内总剂量达50 Gy。奥沙利铂剂量为40（n = 6）、50（n = 3）、60（n = 3）、70（n = 3）或80 mg/m²（n = 6），每周1次，共2周（第1周期），7天休息后进行第2周期。卡培他滨固定剂量为1300 mg/m²/d，口服给药时间与奥沙利铂相同。DLT定义为3级或4级血液学和非血液学毒性。
1 - 3级白细胞减少、腹泻和恶心/呕吐是最常见的毒副作用，多数为1 - 2级。在40 mg/m²剂量组的3例患者中有1例首次出现DLT（3级腹泻），但在相同剂量水平的接下来3例患者或接受50 - 70 mg/m²剂量水平的患者中未观察到。在80 mg/m²剂量组，6例患者中有3例出现DLT（1例4级白细胞减少和2例3级腹泻）。
在辅助治疗中，奥沙利铂联合每日2次口服625 mg/m²的固定剂量卡培他滨及放疗是可耐受的且临床可行。在此情况下奥沙利铂的最大耐受剂量为80 mg/m²，与新辅助治疗中奥沙利铂的最大耐受剂量相当。
