1326 - Phase II trial of carboplatin and pemetrexed as first-line chemotherapy for non-squamous non-small cell lung cancer and correlation between the effi...

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Anticancer agents
Translational Research
Non-small-cell lung cancer
Basic Principles in the Management and Treatment (of cancer)
Biological therapy
Presenter Yuka Fujita
Authors Y. Fujita1, H. Yokouchi2, S. Fujiuchi3, T. Harada4, M. Harada5, K. Takamura6, S. Oizumi7, H. Isobe8, H. Akita9, M. Nishimura7
  • 1National Hospital Organization Asahikawa Medical Center, 0708644 - Asahikawa/JP
  • 2Department Of Pulmonary Medicine, Fukushima Medical University Hospital, Fukushima/JP
  • 3Department Of Respiratory Medicine, National Hospital Organization Asahikawa Medical Center, 0708644 - Asahikawa/JP
  • 4Hokkaido Social Insurance Hospital, Sapporo/JP
  • 5Department Of Pulmonary Disease, National Hospital Organization Hokkaido Cancer Center, Sapporo/JP
  • 6First Department Of Medicine, Hokkaido P.W.F.A.C Obihiro-Kosei General Hospital, Obihiro/JP
  • 7First Department Of Medicine, Hokkaido university School of Medicine, Sapporo/JP
  • 8Department Of Medical Oncology And Respiratory Medicine, KKR Sapporo Medical Center, Sapporo/JP
  • 9Department Of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo/JP



The importance of biomarkers is increasing in individualized treatment strategy for cancer patients (pts). We evaluated the efficacy and safety of carboplatin (CBDCA) and pemetrexed (PEM) in Japanese pts with non-squamous non-small cell lung cancer (NSCLC), and single nucleotide polymorphisms (SNPs) associated with PEM metabolism were also analyzed to investigate their relationship with efficacy or toxicity.

Patients and methods

Eligible pts had a performance status 0 or 1, aged from 20 to 74 years, chemotherapy-naïve stage IIIB/IV non-squamous NSCLC, and adequate organ function. Pts received CBDCA at a dose targeting an area under the concentration-time curve of 5 and 500 mg/m2 PEM every 3 weeks. More than 3 cycles was considered as completion of treatment. Peripheral blood was drawn for SNPs analyses of thymidylate synthase gene (TS) and methylenetetrahydrofolate reductase gene (MTHFR) in pts with consent for the biomarker study.


Forty-one pts (28 men, 13 women; median age 63 years, range 43 - 73), with 39 adenocarcinomas and 2 large cell carcinomas, were enrolled and SNPs were analyzed in 37 pts. The median follow-up time was 16.1 months and the median number of treatment cycle was 4 (range 1 - 6). The completion rate was 80.5% (33 pts). All pts were assessable for response; the overall response rate (RR) was 36.6% and disease control rate (DCR) was 85.4%. Median progression-free survival (PFS) and overall survival (OS) were 4.6 months (138 days: 95%C.I.; 107-168) and 16.1 months (483 days: 95%C.I.; 180-786), respectively. Grade 3 or 4 hematologic toxicities included anemia (34.1%), neutropenia (29.3%), leukopenia (19.5%) and thrombocytopenia (17.1%). Grade 3 or 4 non-hematologic toxicities included anorexia (7.3%) and nausea (4.9%). No treatment-related death was observed. Although the SNPs had no relation to PFS, OS, RR nor hematologic toxicity, the variable number of tandem repeat (VNTR) of the TS significantly correlated with anemia (p = 0.047) and thrombocytopenia (p = 0.038).


The efficacy of this regimen seems even better than previously reported, and with acceptable toxicities. VNTR of the TS has the possibility of being a predictive factor of anemia and thrombocytopenia for this regimen.


All authors have declared no conflicts of interest.