A phase II study of irinotecan and carboplatin in advanced non-small cell lung cancer with pharmacogenomic analysis: final report.

A phase II study of irinotecan and carboplatin in advanced non-small cell lung cancer with pharmacogenomic analysis: final report. Research Abstract Details 

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A phase II study of irinotecan and carboplatin in advanced non-small cell lung cancer with pharmacogenomic analysis: final report. Abstract Text:

Giancarlo A Pillot,William L Read,Kristin L Hennenfent,Sharon Marsh,Feng Gao,Avinash Viswanathan,Kristopher Cummings,Howard L McLeod,Ramaswamy Govindan,

PURPOSE: We conducted a phase II study of carboplatin and irinotecan in patients with advanced non-small cell lung cancer (NSCLC). In addition, we studied the correlation between certain genotypes of enzymes involved in irinotecan metabolism with efficacy and toxicity. PATIENTS AND METHODS: Patients with stage IIIB, IV, or recurrent NSCLC received a combination of irinotecan and carboplatin every 3 weeks at a dose of 200 mg/m2 and area under the curve of 5. Pharmacogenomic analysis was performed on several genes of interest (ABCB1, CYP3A4*1B, ERCC2, GSTP1, UGT1A1*28, and XRCC1). RESULTS: Forty-two patients enrolled between December 2001 and January 2004. Six patients achieved partial responses (14%), and 19 (45%) had stable disease. The median progression-free survival was 6.9 months. The median overall survival was 11.7 months, with 1-year overall survival of 42%. The most common toxicities were hematologic; grade 3 or 4 neutropenia was experienced by 26 patients (62%) during treatment, and 15 patients (36%) experienced grade 3 or 4 thrombocytopenia. The homozygous UGT1A1*28 (7/7) genotype was associated with grade 4 neutropenia in three of four patients (75%), but only eight out of 30 (27%) with 6/6 or 6/7 genotypes experienced grade 4 neutropenia (p = 0.09). None of the 14 patients with the GSTP1 I105V A/A genotype had a partial response, as opposed to five out of 19 (26%) of those with the G/A or G/G genotypes (p = 0.057). CONCLUSION: The combination of carboplatin and irinotecan is an active combination in NSCLC, with response rates comparable with other platinum-containing doublets. Further studies with irinotecan should incorporate prospective pharmacogenomic analysis to identify markers for response and toxicity.

A phase II study of irinotecan and carboplatin in advanced non-small cell lung cancer with pharmacogenomic analysis: final report. Publishing Authors By Initials

GA Pillot,WL Read,KL Hennenfent,S Marsh,F Gao,A Viswanathan,K Cummings,HL McLeod,R Govindan,

For similar diagnosis: prognosis: treatment outcome research abstracts see: diagnosis: prognosis: treatment outcome research

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A phase II study of irinotecan and carboplatin in advanced non-small cell lung cancer with pharmacogenomic analysis: final report. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of thoracic oncology : official publicatio

VOLUME: 1

Page Numbers: 972-8

Journal Abbreviation:

ISSN: 1556-1380

DAY: 3

MONTH: Nov

YEAR: 2006

A phase II study of irinotecan and carboplatin in advanced non-small cell lung cancer with pharmacogenomic analysis: final report. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101274235

A phase II study of irinotecan and carboplatin in advanced non-small cell lung cancer with pharmacogenomic analysis: final report. Keywords Mesh Terms:

KEYWORDS: Treatment Outcome

MESH TERMS: pathology

Chemical & Substance for Abstract: A phase II study of irinotecan and carboplatin in advanced non-small cell lung cancer with pharmacogenomic analysis: final report. Information

Substance Name: Camptothecin

Registry Number: 7689-03-4

Grant and Affiliation Information for A phase II study of irinotecan and carboplatin in advanced non-small cell lung cancer with pharmacogenomic analysis: final report.

AFFILIATION: Division of Medical Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM63340

ACRONYM: GM

MEDLINETA: J Thorac Oncol

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