JOURNAL ARTICLE
MULTICENTER STUDY

Pharmacogenetic study of patients with advanced non-small cell lung cancer (NSCLC) treated with second-line pemetrexed or pemetrexed-carboplatin

Marcello Tiseo, Elisa Giovannetti, Carmelo Tibaldi, Andrea Camerini, Francesco Di Costanzo, Fausto Barbieri, Jacobus A Burgers, Andrew Vincent, Godefridus J Peters, Egbert F Smit, Andrea Ardizzoni
Lung Cancer: Journal of the International Association for the Study of Lung Cancer 2012, 78 (1): 92-9
22889494

PURPOSE: To correlate candidate polymorphisms affecting pemetrexed and carboplatin activity with clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated in second-line with pemetrexed or pemetrexed plus carboplatin.

METHODS: Functional polymorphisms in thymidylate synthase (TS), reduced folate carrier (RFC), gamma-glutamyl hydrolase (GGH), methylenetetrahydrofolate reductase (MTHFR) and xeroderma pigmentosum group D (XPD) genes were evaluated in 208 patients either treated within randomized phase II trials NVALT-7 and GOIRC-02.2006, comparing second-line pemetrexed with pemetrexed plus carboplatin, or with the same regimens outside of these trials. Univariate and multivariate analyses correlated genotyping data with response, clinical benefit, toxicity, progression-free (PFS) and overall survival (OS) using Pearson-χ2 test, log-rank test and Cox proportional hazards model.

RESULTS: Patients harboring the MTHFR-T667T variant had significantly longer PFS (5.4 versus 3.4 months; p=0.012) and OS (16.4 versus 8.5 months; p=0.026) than patients with CC-CT genotypes. No correlation was observed for other polymorphisms, except for XPD-Gln751Gln, which was associated with shorter PFS (p=0.021) and OS (p=0.044) in the subgroup of patients treated with pemetrexed plus carboplatin. Multivariate analysis confirmed the independent prognostic significance of MTHFR-C677T both in risk of disease progression (CC-CT genotypes hazard ratio [HR] 1.94, 95%CI 1.15-3.28; p=0.012) and of death (HR 2.00, 95% CI 1.12-3.54; p=0.018).

CONCLUSIONS: MTHFR-C667T polymorphisms appear to predict survival differences in pemetrexed-treated NSCLC. These results should be validated in larger and adequately designed prospective studies using pemetrexed.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
22889494
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"