The importance of biomarkers is increasing in individualized treatment strategy for cancer patients. We evaluated the efficacy and safety of carboplatin (CBDCA) and pemetrexed (PEM) in Japanese patients, and single nucleotide polymorphysms (SNPs) associated with PEM metabolism were also analyzed to investigate their relationship with efficacy or toxicity.Patients and methods
Eligible patients had a performance status 0 or 1, aged from 20 to 74 years, chemotherapy-naïve stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC), and adequate organ function. Patients 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 three cycles was considered as completion of treatment. Peripheral blood was drawn for SNPs analyses of thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) genes in patients with consent for the biomarker study.Results
Forty-one patients (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 patients. The median follow-up time was 12.9 months and the median number of treatment cycle was 4 (range 1—6). The completion rate was 80.5% (33 patients). All patients 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 (95% CI 3.6–5.6 months) and 16.1 months (95% CI 8.0–24.2 months), respectively. Grade 3 or 4 hematologic toxic effects included anemia (34.1%), neutropenia (29.3%), leukopenia (19.5%) and thrombocytopenia (17.1%). Grade 3 or 4 non-hematologic toxic effects 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 gene significantly correlated with anemia (P = 0.047) and thrombocytopenia (P = 0.038).Conclusions
The efficacy of this regimen seems even better than previously reported, and with acceptable toxic effects. VNTR of the TS gene has the possibility of being a predictive factor of anemia and thrombocytopenia for this regimen.