| 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. | |
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MedLine Citation:
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PMID: 9610696 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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H Okamoto; A Nagatomo; H Kunitoh; H Kunikane; K Watanabe |
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Publication Detail:
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Type: Clinical Trial; Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cancer Volume: 82 ISSN: 0008-543X ISO Abbreviation: Cancer Publication Date: 1998 Jun |
Date Detail:
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Created Date: 1998-06-11 Completed Date: 1998-06-11 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0374236 Medline TA: Cancer Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 2166-72 Citation Subset: AIM; IM |
Affiliation:
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Division of Respiratory Medicine, Yokohama Municipal Citizen's Hospital, Yokohama City, Kanagawa, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Antineoplastic Combined Chemotherapy Protocols / therapeutic use* Camptothecin / administration & dosage, adverse effects, analogs & derivatives*, pharmacokinetics Carboplatin / administration & dosage*, adverse effects, pharmacokinetics Carcinoma, Non-Small-Cell Lung / drug therapy*, mortality Female Granulocyte Colony Stimulating Factor, Recombinant / administration & dosage*, adverse effects Humans Lung Neoplasms / drug therapy*, mortality Male Middle Aged |
| Chemical | |
Reg. No./Substance:
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0/Granulocyte Colony Stimulating Factor, Recombinant; 100286-90-6/irinotecan; 41575-94-4/Carboplatin; 7689-03-4/Camptothecin |
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