A Dose-Finding Study of Irinotecan (CPT-11) plus a Four-Day Continuous 5-Fluorouracil Infusion in Advanced Colorectal Cancer
| العنوان: | A Dose-Finding Study of Irinotecan (CPT-11) plus a Four-Day Continuous 5-Fluorouracil Infusion in Advanced Colorectal Cancer |
|---|---|
| المؤلفون: | John Souglakos, D. Mavroudis, N. Vardakis, Charalambos Kouroussis, Nikos Androulakis, J. Romanos, Athanasios Kotsakis, Michael I. Koukourakis, Kostas Kalbakis, Stelios Kakolyris, V. Georgoulias |
| المصدر: | Oncology. 60:207-213 |
| بيانات النشر: | S. Karger AG, 2001. |
| سنة النشر: | 2001 |
| مصطلحات موضوعية: | Adult, Male, Oncology, endocrine system, Cancer Research, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Rectum, Irinotecan, Advanced colorectal cancer, Dose finding, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, heterocyclic compounds, Infusions, Intravenous, neoplasms, Colonic disease, Aged, Chemotherapy, business.industry, General Medicine, Middle Aged, medicine.disease, digestive system diseases, Surgery, medicine.anatomical_structure, Fluorouracil, Camptothecin, Female, Colorectal Neoplasms, business, medicine.drug |
| الوصف: | Objective: Irinotecan (CPT-11) has shown considerable activity in colorectal cancer, and its combination with 5-fluorouracil (5-FU) represents an attractive approach. A phase I study was conducted to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of CPT-11 in combination with a continuous infusion of 5-FU for 4 days. Methods: Forty-two patients with histologically confirmed metastatic colorectal cancer who had not received prior treatment for advanced disease were enrolled. The patients’ median age was 64 years; 26 (62%) patients were men, and the performance status (WHO) was 0 in 26 (62%) patients, 1 in 15 (36%) and 2 in 1 (2%). Twenty-two (52%) patients had 2 or more metastatic sites. CPT-11 (starting dose 200 mg/m2) was administered as a 30-min intravenous infusion with increments of 50 mg/m2 on day 4. 5-FU (starting dose 400 mg/m2) was administered as a 4-day continuous intravenous infusion with increments of 50 mg/m2 on days 1–4. Treatment was repeated every 4 weeks. Results: The MTD of the combination was found to be 600 mg/m2 for 5-FU and 350 mg/m2 for CPT-11. Neutropenia, febrile neutropenia and delayed diarrhea were the DLTs. Grade 3/4 neutropenia was observed in 22 (13%) out of 169 administered treatment cycles, febrile neutropenia in 7 (4%) and grade 3/4 diarrhea in 20 (12%). Other toxicities were mild. Among 36 patients evaluable for response, partial response was achieved in 8 (22%), stable disease in 12 (33%) and progressive disease in 16 (44%) patients. Responses were mostly seen at the higher dose levels. Conclusions: The combination of a 4-day continuous infusion of 5-FU followed by CPT-11 represents an active and well-tolerated regimen for patients with colorectal cancer. This regimen merits further evaluation in phase II studies. |
| تدمد: | 1423-0232 0030-2414 |
| DOI: | 10.1159/000055320 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4504b36a6f4f4da406b07d46f78e079c https://doi.org/10.1159/000055320 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....4504b36a6f4f4da406b07d46f78e079c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14230232 00302414 |
|---|---|
| DOI: | 10.1159/000055320 |