Author of

• 12592

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  P3.10 - Poster Session 3 - Chemotherapy (ID 210)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12622

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    P3.10-030 - A Phase II study of Pemetrexed/Carboplatin for Previously Untreated Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer: Analysis of the correlation between the Anti-Tumor Efficacy/Toxicity and SNPs of MTHFR. (ID 1822)

    09:30 - 09:30  |  Author(s): T. Kasai
    • Abstract

    Background
    Previous studies investigating a combination of Pemetrexed (P)/Carboplatin (C) showed promising efficacy in the treatment of non-squamous (Sq) non-small cell lung cancer (NSCLC). However, there is no sufficient data of biomarkers. In the present study, we determined the efficacy and toxicity of 6 cycles of P/C for previously untreated patients with advanced non-Sq NSCLC. In addition, we investigated the correlation between the anti-tumor efficacy/toxicity and single nucleotide polymorphisms (SNPs) of the methylenetetrahydrofolate reductase (MTHFR).

    Methods
    Eligibility criteria were no prior chemotherapy, StageIIIB without any indications for radiotherapy or IV, non-Sq NSCLC patients, performance status (PS) 0-1, age <76 yrs, and adequate hematological, hepatic, and renal function. Patients received 6 cycles of P (500mg/m[2])/C (AUC6) on day 1, repeated every 3 weeks. Primary end-point was the assessment of tumor response rate measured by RECIST criteria. The SNPs of the MTHFR gene were analyzed from the genomic DNA extracted from the peripheral blood cells drawn prior to the chemotherapy.

    Results
    Thirty-nine patients (pts) were enrolled and all pts evaluable for toxicity and response. Male/Female: 30/9; PS 0/1: 11/28; median age 62(45-75); Path: adeno 37(95%), NSCLC unclassified 2(5%); EGFR mutation: positive 2(5%), negative 35(90%), unknown 2(5%). Evaluations of responses were 1CR, 17PR, 16SD, 5PD (response rate 46.2%). The median progression free survival time (PFS) was 6.8 months, and the median survival time (MST) was 18.1 months. Grade 3/4 toxicities in the first cycle included: leukopenia(3/1), anemia(1/1), thrombocytopenia(4/2), neutropenia(2/1), and AST/ALT elevation(2/0). SNPs of the MTHFR at codon 677 were examined in 28 pts. MTHFR genotypes were as follows: C677C; 8 cases, C677T; 14 cases and T677T; 6 cases. Response rates and disease control rates of MTHFR codon677 genotypes were as follows: C677C (50%/75%), C677T (36%/79%) and T677T (50%/100%). Median PFS and MST of MTHFR codon677 genotypes were as follows: C677C; 4.8/7.6 months, C677T; 6.4/20.6 months and T677T; 6.9/18.5 months. Although there were no significant differences of PFS and overall survival between MTHFR genotypes, those of C677C subjects were shorter as compared to the others.

    Conclusion
    In patients with previously untreated advanced non-Sq NSCLC, P/C appears to be well tolerated and demonstrates encouraging activity. PFS and overall survival of the MTHFR C677C subjects were shorter than those of the C677T or T677T subjects, while the disease control rate of the T677T subjects was higher than that of the C677C or C677T subjects.