title: A phase II study of capecitabine and irinotecan in combination with concurrent pelvic radiotherapy (CapIri-RT) as neoadjuvant treatment of locally advanced rectal cancer.
abstract: We sought to evaluate the efficacy and safety data of a combination regimen using weekly irinotecan in combination with capecitabine and concurrent radiotherapy (CapIri-RT) as neoadjuvant treatment in rectal cancer in a phase-II trial. Patients with rectal cancer clinical stages T3/4 Nx or N+ were recruited to receive irinotecan (50 mg m(-2) weekly) and capecitabine (500 mg m(-2) bid days 1-38) with a concurrent RT dose of 50.4 Gy. Surgery was scheduled 4-6 weeks after the completion of chemoradiation. A total of 36 patients (median age 62 years; m/f: 27:9) including three patients with local recurrence were enclosed onto the trial. The median distance of the tumour from the anal verge was 5 cm. The main toxicity observed was (NCI-CTC grades 1/2/3/4 (n)): Anaemia 23/9/-/-; leucocytopenia 12/7/7/2, diarrhoea 13/15/4/-, nausea/vomiting 9/10/2/-, and increased activity of transaminases 3/3/1/-. One patient had a reversible episode of ventricular fibrillation during chemoradiation, most probably caused by capecitabine. The relative dose intensity was (median/mean (%)): irinotecan 95/91, capecitabine 100/92). Thirty-four patients underwent surgery (anterior resection n=25; abdomino-perineal resection n=6; Hartmann's procedure n=3). R0-resection was accomplished in all patients. Two patients died in the postoperative course from septic complications. Pathological complete remission was observed in five out of 34 resected patients (15%), and nine patients showed microfoci of residual tumour (26%). After a median follow-up of 28 months one patient had developed a local recurrence, and five patients distant metastases. Three-year overall survival for all patients with surgery (excluding three patients treated for local relapse or with primary metastatic disease) was 80%. In summary, preoperative chemoradiation with CapIri-RT exhibits promising efficacy whereas showing managable toxicity. The local recurrence and distant failure rates observed after a median 28 months are low compared with standard 5-fluorouracil based therapy.
authors.affiliation: Chirurgische Klinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Willeke
authors.forename: K
authors.initials: K
authors.lastname: Horisberger
authors.forename: U
authors.initials: U
authors.lastname: Kraus-Tiefenbacher
authors.forename: F
authors.initials: F
authors.lastname: Wenz
authors.forename: A
authors.initials: A
authors.lastname: Leitner
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
authors.forename: R
authors.initials: R
authors.lastname: Grobholz
authors.forename: A
authors.initials: A
authors.lastname: Willer
authors.forename: G
authors.initials: G
authors.lastname: Kähler
authors.forename: S
authors.initials: S
authors.lastname: Post
authors.forename: R-D
authors.initials: RD
authors.lastname: Hofheinz
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000532:radiotherapy; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery
chemical_list: D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin