A phase I clinical and pharmacologic study of a carboplatin and irinotecan regimen combined with recombinant human granulocyte-colony stimulating factor in the treatment of patients with advanced nonsmall cell lung carcinoma.
Cancer
; 82(11): 2166-72, 1998 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-9610696
ABSTRACT
BACKGROUND:
This Phase I study was designed to determine the toxicity and efficacy of a carboplatin and irinotecan (CPT-11) regimen with recombinant human granulocyte colony-stimulating factor (rhG-CSF) support for patients with advanced nonsmall cell lung carcinoma.METHODS:
Treatment consisted of carboplatin administered intravenously (i.v.) on Day 1 plus CPT-11 i.v. on Days 1, 8, and 15. The carboplatin dose was calculated using Calvert's formula, where the target area under the plasma concentration versus the time curve (AUC) was 5 or 6 mg x min/mL. rhG-CSF (2 microg/kg) was administered daily, except on Days 1, 8, and 15, until the leukocyte count exceeded 20,000/mm3 (10,000/mm3 after Day 16). Cycles were repeated every 4 weeks. Groups entered the trial at escalating CPT-11 and carboplatin dose levels of 60 mg/m2 and 5 mg x min/mL, 70/5 and 60/6.RESULTS:
Twenty-one patients were enrolled in this study, of whom 20 were assessable for toxicity and therapeutic efficacy. Two of 6 patients experienced Grade 4 diarrhea at the 70/5 dose level, suggesting that this was the maximum tolerated dose (MTD). However, the 60/6 dose level was included because toxicities were very mild at the 60/5 dose level. At the 60/6 dose level, 1 of 6 patients experienced severe, life-threatening toxicity. Therefore, subsequent dose escalation was stopped and the study terminated. There were 7 responses (35%) among the 20 patients. At the 60/6 dose level (n=5), the observed carboplatin AUC after aiming for a target AUC of 6 was 5.9+/-0.9 mg x min/mL, as expected, although the AUCs of both CPT-11 and its active metabolite, SN-38, were lower than expected.CONCLUSIONS:
The recommended doses for Phase II studies are 60 mg/m2 of CPT-11 and a target AUC of 5 mg x min/mL for carboplatin, plus rhG-CSF. The combination of AUC-based carboplatin and CPT-11 with rhG-CSF support appears to be an active regimen in the treatment of patients with NSCLC.
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Base de dados:
MEDLINE
Assunto principal:
Camptotecina
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Protocolos de Quimioterapia Combinada Antineoplásica
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Carboplatina
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Fator Estimulador de Colônias de Granulócitos
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Carcinoma Pulmonar de Células não Pequenas
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Neoplasias Pulmonares
Limite:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article