Phase I-II trial of concurrent capecitabine and oxaliplatin with preoperative intensity-modulated radiotherapy in patients with locally advanced rectal cancer.
OBJECTIVE
To identify the maximal tolerated dose level of preoperative intensity-modulated radiotherapy combined with capecitabine and oxaliplatin and to evaluate the efficacy.


METHODS
Patients with rectal T3-T4 and/or N0-N+ rectal cancer received capecitabine 825 mg/m(2) twice daily Monday through Friday and oxaliplatin 60 mg/m(2) intravenously on Days 1, 8, and 15, concurrently with intensity-modulated radiotherapy. The radiation dose was increased in 5.0-Gy steps in cohorts of 3 patients starting from 37.5 Gy in 15 fractions (dose level [DL] 1). DL2 and DL3 were designed to reach 42.5 Gy in 17 fractions and 47.5 Gy in 19 fractions, respectively.


RESULTS
No dose-limiting toxicity was observed at DL1 or DL2. Of the 3 patients treated at DL3, 1 presented with Grade 3 diarrhea, which was considered a dose-limiting toxicity, and 3 additional patients were added. Of the 6 patients treated at DL3, no new dose-limiting toxicities were observed, and DL3 was identified as the recommended dose in this study. Eight additional patients were treated at 47.5 Gy. Grade 2 proctitis was the most frequent adverse event (40%); Grade 3 diarrhea occurred in 2 patients (10%). All patients underwent surgery, and 17 patients (85%) underwent R0 resection. Four patients (20%) presented with a histologic response of Grade 4, 11 (55%) with Grade 3+, 2 (15%) with Grade 3, and 2 patients (10%) with Grade 2.


CONCLUSIONS
The maximal tolerated dose in this study was 47.5 Gy. The high rates of pathologic response of Grade 3+ and 4 must be confirmed through the accrual of new patients in the Phase II study.
Aristu
José Javier
JJ
Service of Radiation Oncology, Department of Oncology, Clínica Universitaria, University of Navarre, Pamplona, Spain. jjaristu@unav.es
Arbea
Leire
L
Rodriguez
Javier
J
Hernández-Lizoain
José Luis
JL
Sola
Jesús Javier
JJ
Moreno
Marta
M
Azcona
Juan Diego
JD
Díaz-González
Juan Antonio
JA
García-Foncillas
Jesús Miguel
JM
Martínez-Monge
Rafael
R
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D011300:Preoperative Care / Q000379:methods*; D020266:Radiotherapy, Conformal / Q000379:methods*; D012004:Rectal Neoplasms / Q000628:therapy*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil