Phase I study of oxaliplatin in combination with capecitabine and radiotherapy as postoperative treatment for stage II and III rectal cancer.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Jin
Jing
J
Department of Radiation Oncology, Cancer Hospital/Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Li
Ye-Xiong
YX
Wang
Jin-Wan
JW
Wang
Wei-Hu
WH
Liu
Yue-Ping
YP
Wang
Kai
K
Fang
Hui
H
Zhou
Zhi-Xiang
ZX
Zhou
Ai-Ping
AP
Yu
Zi-Hao
ZH
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000633:toxicity*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000633:toxicity; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000633:toxicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000633:toxicity*; D011725:Pyridines / Q000633:toxicity*; D011878:Radiotherapy / Q000379:methods*; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery
D009944:Organoplatinum Compounds; D011725:Pyridines; C431073:oxiplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil