Population-based maximum tolerated dose of irinotecan and carboplatin.
Oncology (Williston Park)
; 17(7 Suppl 7): 11-6, 2003 Jul.
Article
em En
| MEDLINE
| ID: mdl-12886868
ABSTRACT
A novel schema of intrapatient dose escalation was applied to determine a population-based maximum tolerated dose (pMTD) for irinotecan (CPT-11, Camptosar) and carboplatin (Paraplatin) in a phase I trial. A total of 74 patients with advanced solid tumors were enrolled with the following characteristics men/women, 46/28; median age, 61 years; 51 patients with and 23 patients without prior chemotherapy; performance status of 0-1 (93%) and 2 (7%). Patients were started at dose level 1 with irinotecan at 200 mg/m2, and carboplatin at an area under the concentration-time curve (AUC) of 5 mg/mL x min, administered every 21 days. Depending on degree of toxicity observed, the dose for each patient in each subsequent cycle was determined according to a predetermined schema of dose levels. Individual maximum tolerated dose (iMTD) was determined for each patient. The pMTD was defined as the highest dose level for which the incidence of dose-limiting toxicity occurred in less than 33% of the patient population. The most common dose-limiting toxicity included neutropenia (58%), thrombocytopenia (15%), diarrhea (8%), and nausea/emesis (7%). The iMTD ranged from dose level-3 (irinotecan at 100 mg/m2 and carboplatin at an AUC of 4) to dose level 5 (irinotecan at 350 mg/m2 and carboplatin at AUC 6). The pMTD was determined to be dose level-1 and 1 for previously chemotherapy-treated and--untreated patients, respectively. Fifty-nine patients were assessable for response. Of note, a response rate of 40% was observed in 15 patients with relapsed small-cell lung cancer previously treated with platinum-based therapy. We recommend dose level 1 of irinotecan (200 mg/m2) and carboplatin (AUC 5) for chemotherapynaive patients, and dose level-1 of irinotecan (150 mg/m2) and carboplatin (AUC 5) for chemotherapy-treated patients in phase II trials.
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Base de dados:
MEDLINE
Assunto principal:
Camptotecina
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Protocolos de Quimioterapia Combinada Antineoplásica
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Dose Máxima Tolerável
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article