A phase I study of capecitabine, irinotecan, celecoxib, and radiation as neoadjuvant therapy of patients with locally advanced rectal cancer.
OBJECTIVE
We conducted a prospective phase I trial to determine the maximum tolerated dose of capecitabine and irinotecan when used in combination with celecoxib and radiation as preoperative therapy for patients with locally advanced rectal cancer.


METHODS
Patients with histologic diagnosis of adenocarcinoma of distal rectum, evidence of T3/T4 tumor or nodal involvement by endorectal ultrasound/magnetic resonance imaging, any T status where tumor was close to but not involving the sphincter requiring abdominoperineal resection were evaluated by standard phase I methodology. Starting chemotherapy dosage (dose level: 0) was capecitabine 550 mg/m bid, day 1 to 5 every week through out x-ray therapy, irinotecan 30 mg/ m IV on days 1, 8, 22, 29 (no treatment on day 15 and day 36), and celecoxib 400 mg PO bid from day 1 till the last day of radiation. Radiation dosage of 50.4 Gy in 28 fractions was delivered in 5.6 weeks. If no dose limiting toxicity was observed, dose of capecitabine was escalated by 75 mg/m and irinotecan by 5 mg/m. Celecoxib dosage was fixed.


RESULTS
Fourteen patients were accrued. Dose limiting toxicity was observed at level 2 and was primarily hematological and gastrointestinal. Two patients at level 2 developed grade-3 diarrhea and thrombocytopenia and 1 patient at level 2 developed grade 3/4 vomiting, diarrhea and dehydration.


CONCLUSIONS
Recommended dosage for future trials is capecitabine 625 mg/m bid, irinotecan 35 mg/m, and celecoxib 400 mg orally bid in combination with pelvic radiation.
Malik
Imtiaz
I
Loma Linda Oncology Medical Group Inc., 10408 Industrial Circle, Redlands, CA 92354, USA. imtiaz.malik.md@hotmail.com
Hussein
Farabi
F
Bush
David
D
Alqaisi
Munther
M
Bernal
Pedro
P
Byrd
Janet
J
Garberoglio
Carlos
C
D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D000068579:Celecoxib; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003967:Diarrhea / Q000209:etiology; D005242:Fecal Incontinence / Q000209:etiology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005734:Gangrene; D005767:Gastrointestinal Diseases / Q000209:etiology; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011349:Proctitis / Q000209:etiology; D011720:Pyrazoles / Q000008:administration & dosage; D011832:Radiation Injuries / Q000209:etiology; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D013449:Sulfonamides / Q000008:administration & dosage
D011720:Pyrazoles; D011838:Radiation-Sensitizing Agents; D013449:Sulfonamides; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D000068579:Celecoxib; D005472:Fluorouracil; D002166:Camptothecin