Phase I/II trial of irinotecan plus high-dose 5-fluorouracil (TTD regimen) as first-line chemotherapy in advanced colorectal cancer
| Autor: | Linda Pronk, Javier Sastre, Eduardo Díaz-Rubio, E. Aranda, Alfredo Carrato, M Balcells, F. Ribera, Eugenio Marcuello, M. A. Gómez, Albert Abad, B. Masutti, A. Cervantes |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male medicine.medical_specialty Colorectal cancer medicine.drug_class medicine.medical_treatment Irinotecan Gastroenterology Antimetabolite Cohort Studies Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Aged Chemotherapy Dose-Response Relationship Drug business.industry Combination chemotherapy Hematology Middle Aged medicine.disease Surgery Regimen Treatment Outcome Oncology Fluorouracil Toxicity Camptothecin Female business Colorectal Neoplasms medicine.drug |
| Zdroj: | Annals of oncology : official journal of the European Society for Medical Oncology. 15(4) |
| ISSN: | 0923-7534 |
| Popis: | Background We conducted a phase I/II study of weekly irinotecan [30 min intravenous (i.v.) infusion] combined with 5-fluorouracil (5-FU 3 g/m2 weekly 48 h i.v. infusion, TTD regimen) as first-line chemotherapy for patients with advanced colorectal cancer (CRC). Patients and methods The maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) in the treatment of gastrointestinal solid tumors (in phase I), and the antitumor activity and toxicity of the recommended phase I dose (in phase II) were determined. Results Diarrhea was the DLT, and irinotecan 80 mg/m2 plus 5-FU 3 g/m2 was the recommended phase I dose. In phase II, the confirmed response rate was 44% [95% confidence interval (CI) 29% to 59%] and the median overall survival was 23.8 months. However, grade 3/4 diarrhea affected 59% of patients and led to withdrawal of three patients. A second cohort of patients studied using the same schedule but with a reduced 5-FU starting dose of 2.25 g/m2 showed improved tolerance (the incidence of grade 4 diarrhea decreased from 28% to 11% and overall grade 3/4 diarrhea to 56%, with no patient withdrawals) but the confirmed response rate was 28% (95% CI 14% to 45%) and median overall survival was 17.2 months. Conclusions We found weekly irinotecan 80 mg/m2 plus TTD regimen (5-FU 2.25 g/m2 given as 48-h i.v. infusion) to be a feasible and active combined chemotherapy for the first-line treatment of advanced colorectal cancer. |
| Databáze: | OpenAIRE |
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