Carboplatin plus pemetrexed for platinum-pretreated, advanced non-small cell lung cancer: a retrospective study with pharmacogenetic evaluation |
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Authors: | Giulio Metro R Chiari M Mare D Giannarelli F R Tofanetti V Minotti M Ferraldeschi D Giuffrida L Marcomigni C Bennati M J Fischer M Meacci R Bellavita L Pistola V Ludovini L Crin?? |
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Institution: | Division of Medical Oncology, Azienda Ospedaliera Santa Maria della Misericordia, Via Dottori 1, 06156 Perugia, Italy. giulio.metro@yahoo.com |
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Abstract: | Purpose In the present study, the combination of carboplatin (CBDCA) plus pemetrexed (PMX) for the treatment of patients with platinum-pretreated, pemetrexed-na?ve, advanced non-small cell lung cancer (NSCLC) was investigated. Also, single nucleotide polymorphisms (SNPs) at the XRCC3, XPD, ERCC1, GARFT, DHFR, and TS genes were investigated. Methods Eighty patients treated with CBDCA/PMX at two Italian institutions were evaluable. Of these, 73 patients had blood samples collected for pharmacogenetic evaluation. Results Overall, the median age was 59?years (26?C78), 59 patients (73.7%) had a performance status of 0, and 34 patients (42.5%) had stage IIIB disease. Thirty-eight patients (47.5%) had responded to prior first-line platinum-based therapy. Study treatment resulted into one complete and 33 partial responses for an overall response rate of 42.5%. The disease control rate was 77.5%. The median progression-free survival (PFS) and overall survival (OS) were 5.8?and 17.4?months, respectively. Responders achieved a significant longer PFS and OS versus non-responders (P?=?0.007 and P?=?0.003, respectively). The only grade 3?C4 adverse event occurring in more than 5.0% of patients was neutropenia (6 patients, 7.5%). No statistically significant association was noted between polymorphisms of the genes analyzed and clinical outcome. Conclusions In patients with platinum-pretreated, advanced NSCLC and favorable clinical prognostic factors, treatment with CBDCA/PMX is associated with a good clinical outcome and toxicity profile. None of the SNPs analyzed was found to be a useful predictor of treatment efficacy. |
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