Carboplatin plus pemetrexed for platinum-pretreated, advanced non-small cell lung cancer: A retrospective study with pharmacogenetic evaluation

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. Crinò

Research output: Contribution to journalArticle

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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-naïve, 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 (26-78), 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 3-4 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.

Original languageEnglish
Pages (from-to)1405-1412
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume68
Issue number6
DOIs
Publication statusPublished - Dec 2011

Fingerprint

Pemetrexed
Pharmacogenetics
Carboplatin
Platinum
Non-Small Cell Lung Carcinoma
Retrospective Studies
Polymorphism
Cells
Nucleotides
Genes
Disease control
Toxicity
Disease-Free Survival
Blood
Single Nucleotide Polymorphism
Survival
Therapeutics
Neutropenia

Keywords

  • Carboplatin
  • Disease relapse
  • Non-small cell lung cancer
  • Pemetrexed
  • Salvage chemotherapy
  • Single nucleotide polymorphisms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

Carboplatin plus pemetrexed for platinum-pretreated, advanced non-small cell lung cancer : A retrospective study with pharmacogenetic evaluation. / Metro, Giulio; Chiari, R.; Mare, M.; Giannarelli, D.; Tofanetti, F. R.; Minotti, V.; Ferraldeschi, M.; Giuffrida, D.; Marcomigni, L.; Bennati, C.; Fischer, M. J.; Meacci, M.; Bellavita, R.; Pistola, L.; Ludovini, V.; Crinò, L.

In: Cancer Chemotherapy and Pharmacology, Vol. 68, No. 6, 12.2011, p. 1405-1412.

Research output: Contribution to journalArticle

Metro, G, Chiari, R, Mare, M, Giannarelli, D, Tofanetti, FR, Minotti, V, Ferraldeschi, M, Giuffrida, D, Marcomigni, L, Bennati, C, Fischer, MJ, Meacci, M, Bellavita, R, Pistola, L, Ludovini, V & Crinò, L 2011, 'Carboplatin plus pemetrexed for platinum-pretreated, advanced non-small cell lung cancer: A retrospective study with pharmacogenetic evaluation', Cancer Chemotherapy and Pharmacology, vol. 68, no. 6, pp. 1405-1412. https://doi.org/10.1007/s00280-011-1632-x
Metro, Giulio ; Chiari, R. ; Mare, M. ; Giannarelli, D. ; Tofanetti, F. R. ; Minotti, V. ; Ferraldeschi, M. ; Giuffrida, D. ; Marcomigni, L. ; Bennati, C. ; Fischer, M. J. ; Meacci, M. ; Bellavita, R. ; Pistola, L. ; Ludovini, V. ; Crinò, L. / Carboplatin plus pemetrexed for platinum-pretreated, advanced non-small cell lung cancer : A retrospective study with pharmacogenetic evaluation. In: Cancer Chemotherapy and Pharmacology. 2011 ; Vol. 68, No. 6. pp. 1405-1412.
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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{\"i}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 (26-78), 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 3-4 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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T2 - A retrospective study with pharmacogenetic evaluation

AU - Metro, Giulio

AU - Chiari, R.

AU - Mare, M.

AU - Giannarelli, D.

AU - Tofanetti, F. R.

AU - Minotti, V.

AU - Ferraldeschi, M.

AU - Giuffrida, D.

AU - Marcomigni, L.

AU - Bennati, C.

AU - Fischer, M. J.

AU - Meacci, M.

AU - Bellavita, R.

AU - Pistola, L.

AU - Ludovini, V.

AU - Crinò, L.

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N2 - Purpose: In the present study, the combination of carboplatin (CBDCA) plus pemetrexed (PMX) for the treatment of patients with platinum-pretreated, pemetrexed-naïve, 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 (26-78), 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 3-4 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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