A phase I dose escalation study of continuous oral capecitabine in combination with oxaliplatin and pelvic radiation (XELOX-RT) in patients with locally advanced rectal cancer.
OBJECTIVE
To determine the maximum tolerated dose (MTD) of continuous oral capecitabine plus oxaliplatin and pre-operative pelvic radiotherapy (XELOX-RT).


METHODS
Patients with clinically unresectable rectal cancer or for whom resection with histologically clear (R0) surgical margins was unlikely received continuous capecitabine (500-825 mg/m2 twice daily, 7 days/week), oxaliplatin 2-h intravenous infusion (130 mg/m2 days 1 and 29) and pelvic radiotherapy (Monday-Friday for 5 weeks, total dose 45 Gy in 25 daily 1.8 Gy fractions). The MTD was the capecitabine dose causing dose-limiting toxicities (DLTs; treatment-related grade 3/4 toxicities) in one-third or more of patients treated per dose level.


RESULTS
Eighteen patients received three dose levels. The MTD was capecitabine 825 mg/m2 twice daily: DLTs occurred in two of six patients (grade 3 diarrhoea, rectal pain with local skin reaction). No DLTs occurred in six patients receiving capecitabine 650 mg/m2 twice daily. Grade 3/4 toxicity was rare, with minimal myelosuppression. Although predominantly a dose-finding study, XELOX-RT showed promising activity. Fourteen patients had histologically confirmed R0 resections and five had a pathological complete response.


CONCLUSIONS
The recommended dose for further study is capecitabine 650 mg/m2 twice daily with oxaliplatin and radiotherapy. XELOX-RT showed promising antitumour activity. Further evaluation is underway.
Glynne-Jones
R
R
Mount Vernon Cancer Centre, Northwood, London, UK. rob.glynne-jones@whht.nhs.uk
Sebag-Montefiore
D
D
Maughan
T S
TS
Falk
S J
SJ
McDonald
A C
AC
D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010388:Pelvis / Q000528:radiation effects*; D011300:Preoperative Care; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D015996:Survival Rate
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil