Preoperative chemoradiotherapy with capecitabine and oxaliplatin in locally advanced rectal cancer. A phase I-II multicenter study of the Dutch Colorectal Cancer Group.
BACKGROUND
We studied the maximum tolerated dose (MTD) and efficacy of oxaliplatin added to capecitabine and radiotherapy (Capox-RT) as neoadjuvant therapy for rectal cancer.


METHODS
T3-4 rectal cancer patients received escalating doses of oxaliplatin (day 1 and 29) with a fixed dose of capecitabine of 1000 mg/m(2) twice daily (days 1-14, 25-38) added to RT with 50.4 Gy and surgery after 6-8 weeks. The MTD, determined during phase I, was used in the subsequent phase II, in which R0 resection rate (a negative circumferential resection margin) was the primary end point.


RESULTS
Twenty-one patients were evaluable. In the phase I part, oxaliplatin at 85 mg/m(2) was established as MTD. In phase II, the main toxicity was grade III diarrhea (18%). All patients underwent surgery, and 20 patients had a resectable tumor. An R0 was achieved in 17/21 patients, downstaging to T0-2 in 7/21 and a pCR in 2/21.


CONCLUSIONS
Combination of Capox-RT has an acceptable acute toxicity profile and a high R0 resection rate of 81% in locally advanced rectal cancer. However the pCR rate was low.
Hospers
Geke A
GA
Medical Oncology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands. g.a.p.hospers@int.umcg.nl
Punt
Cornelis J A
CJ
Tesselaar
Margot E
ME
Cats
Annemieke
A
Havenga
Klaas
K
Leer
Jan W H
JW
Marijnen
Corrie A
CA
Jansen
Edwin P
EP
Van Krieken
Han H J M
HH
Wiggers
Theo
T
Van de Velde
Cornelis J H
CJ
Mulder
Nanno H
NH
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000633:toxicity; D000077150:Oxaliplatin; D010147:Pain Measurement; D010315:Particle Accelerators; D011788:Quality of Life; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D012007:Rectum / Q000473:pathology / Q000601:surgery
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil