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01-12-2014 | Original Article

Phase II trial of carboplatin and pemetrexed as first-line chemotherapy for non-squamous non-small cell lung cancer, and correlation between the efficacy/toxicity and genetic polymorphisms associated with pemetrexed metabolism: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0902

Authors: Kenya Kanazawa, Hiroshi Yokouchi, Xintao Wang, Takashi Ishida, Yuka Fujita, Satoru Fujiuchi, Toshiyuki Harada, Masao Harada, Kei Takamura, Satoshi Oizumi, Ichiro Kinoshita, Yutaka Katsuura, Osamu Honjo, Tetsuya Kojima, Hirotoshi Dosaka-Akita, Hiroshi Isobe, Mitsuru Munakata, Masaharu Nishimura, Hokkaido Lung Cancer Clinical Study Group

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2014

Abstract

Purpose

This phase II study evaluated the response rate (RR) and safety of combination therapy with carboplatin (CBDCA) and pemetrexed (PEM) in Japanese patients with non-squamous non-small cell lung cancer (non-sq NSCLC). Further, the relationship between therapy efficacy/toxicity and genetic polymorphisms associated with PEM metabolism was analyzed.

Methods

Forty-one patients received CBDCA at a dose targeting an area under the concentration–time curve of 5 mg/mL × min and PEM of 500 mg/m² on day 1 every 3 weeks. Single-nucleotide polymorphisms of the thymidylate synthase (TYMS) coding gene, the variable number of tandem repeat (VNTR) in the TYMS, and the methylenetetrahydrofolate reductase (MTHFR) coding gene were analyzed.

Results

The overall RR was 36.6 %. Median progression-free survival and median survival time were 4.7 months [95 % confidence interval (CI) 3.9–5.6 months] and 16.2 months (95 % CI 6.1–26.2 months), respectively. Epidermal growth factor receptor gene mutations were detected in 6 patients (14.6 %). The VNTR in the TYMS significantly correlated with anemia (p = 0.047) and thrombocytopenia (p = 0.038).

Conclusions

This combination therapy was effective and tolerable in patients with advanced non-sq NSCLC. The VNTR in the TYMS appears to be a predictive factor for anemia and thrombocytopenia in patients treated with this regimen.

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Title: Phase II trial of carboplatin and pemetrexed as first-line chemotherapy for non-squamous non-small cell lung cancer, and correlation between the efficacy/toxicity and genetic polymorphisms associated with pemetrexed metabolism: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0902
Authors: Kenya Kanazawa
Hiroshi Yokouchi
Xintao Wang
Takashi Ishida
Yuka Fujita
Satoru Fujiuchi
Toshiyuki Harada
Masao Harada
Kei Takamura
Satoshi Oizumi
Ichiro Kinoshita
Yutaka Katsuura
Osamu Honjo
Tetsuya Kojima
Hirotoshi Dosaka-Akita
Hiroshi Isobe
Mitsuru Munakata
Masaharu Nishimura
Hokkaido Lung Cancer Clinical Study Group
Publication date: 01-12-2014
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2014
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-014-2589-3

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Abstract

Purpose

Methods

Results

Conclusions

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