title: Prospective multicenter phase II study of irinotecan as third-line therapy in metastatic colorectal cancer and progression after bolus and infusional 5-fluorouracil.
abstract: Irinotecan has proven anti-tumor activity as induction treatment in combination with 5-fluorouracil (5-FU) or as second-line treatment after 5-FU in patients with metastatic colorectal cancer. The aim of the present phase II study was to evaluate irinotecan as third-line chemotherapy in patients with colorectal cancer after sequential treatment with bolus 5-FU followed by an infusional 5-FU regimen. Patients pretreated with bolus 5-FU/folinic acid and the infusional 5-FU/folinic acid regimen were treated with 350 mg/m irinotecan i.v. once every 3 weeks in a multicenter phase II study. Tumor size was measured every cycle and treatment with irinotecan was continued until the occurrence of progressive disease or unacceptable toxicity. A total of 50 pretreated patients were included. Of the 45 evaluable patients, 13.3% [n=6, 95% confidence interval (CI) 5.1-26.8] attained a response (complete/partial response) to treatment lasting 5.6 months (95% CI 4.2-6.3) and in four patients response has been confirmed (8.9%, 95% CI 2.5-21.2). Disease stabilization was noted in 51.1% of the patients (n=23, 95% CI 35.8-66.3). The median duration of response/disease stabilization was 4.2 months (95% CI 3.2-6.0). Median overall survival was 7.9 months (95% CI 6.1-11.1), corresponding to a calculated 1-year survival of 28.3% (95% CI 15.2-41.3). Severe neutropenia occurred in 14% (n=7) and anemia grade III in 6% of the patients (n=3). The most frequent non-hematological toxicity grade III/IV related to treatment was diarrhea in 24% of the patients (n=12), followed by vomiting in 8% (n=4) and constipation as well as infection in two patients each (4%) (evaluable n=50). We conclude single-agent irinotecan is an effective and well-tolerable treatment in pretreated patients with metastatic colorectal cancer after failure of bolus and infusional 5-FU/folinic acid regimens. Elderly patients had the same probability to respond.
authors.affiliation: Abt. Hämatologie/Onkologie/Immunologie/Rheumatologie, Medizinische Klinik II, Eberhard-Karls-Universität, Tübingen, Germany; Krankenhaus Nordwest, Frankfurt, Germany. joerg.hartmann@med.uni-tuebingen.de
authors.forename: Joerg Thomas
authors.initials: JT
authors.lastname: Hartmann
authors.forename: Karin
authors.initials: K
authors.lastname: Oechsle
authors.forename: Elke
authors.initials: E
authors.lastname: Jäger
authors.forename: Hans Edgar
authors.initials: HE
authors.lastname: Reis
authors.forename: Cornelie
authors.initials: C
authors.lastname: Haag
authors.forename: Norbert
authors.initials: N
authors.lastname: Niederle
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Wilke
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Pflüger
authors.forename: Salah Al
authors.initials: SA
authors.lastname: Batran
authors.forename: Thomas
authors.initials: T
authors.lastname: Büchele
authors.forename: Ralf D
authors.initials: RD
authors.lastname: Hofheinz
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin