Rationale and Design of PEMVITASTART—An Open-label Randomized Trial Comparing Simultaneous Versus Standard Initiation of Vitamin B 12 and Folate Supplementation in Nonsquamous, Non–Small-cell Lung Cancer Patients Undergoing First-line Pemetrexed-based Chemotherapy

Timing of folic acid/vitamin B12 supplementation and hematologic toxicity during first‐line treatment of patients with nonsquamous non–small cell lung cancer using pemetrexed‐based chemotherapy: The PEMVITASTART randomized trial

“…PEMVITASTART was an open‐label, parallel‐arm, randomized trial for which newly diagnosed, chemotherapy‐naive patients with cytologically or histopathologically proven ns‐NSCLC at the authors’ institute (a tertiary care referral center) who were planned for upfront pemetrexed‐platinum doublet chemotherapy were screened for enrolment . Eligible patients had to be aged ≥18 years, had to have ns‐NSCLC histology with locally advanced or metastatic disease (stage IIIB/IV according to the seventh edition of the International Association for the Study of Lung Cancer TNM staging system), and had to have at least 1 unidimensionally measurable lesion (according to the Response Evaluation Criteria in Solid Tumors), an Eastern Cooperative Oncology Group performance status from 0 to 2, adequate bone marrow and organ function, and no previous systemic (chemotherapy or targeted molecular) therapy.…”

“…The primary outcome was incidence of any grade hematologic toxicity (anemia, leukopenia, neutropenia, or thrombocytopenia according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0) in the 2 arms during the study period. Secondary outcomes included the incidence of grade 3/4 hematologic toxicity, the receipt of supportive care (mean number of doses per patient of G‐CSF, ESAs, and erythrocyte transfusions), the relative dose intensity (RDI) delivered of pemetrexed and platinum, the number of intercycle delays (ICDs), and changes in serum levels of FA, B12, and homocysteine . For the latter, blood samples were drawn from patients in both treatment arms at baseline; whereas, for patients in the DA, an additional sample was taken on day 1 of the first cycle of chemotherapy (after 5‐7 days of vitamin supplementation).…”

“…For the purpose of this study (assessment of primary and secondary endpoints), patients were followed for at least 3 weeks beyond completion of pemetrexed‐platinum doublet chemotherapy (average, 18 weeks). Radiologic responses were assessed according to the Response Evaluation Criteria in Solid Tumors (version 1.0) after 4 cycles of chemotherapy had been received or earlier if clinically indicated . The study was approved by the institutional ethics committee, and informed consent was obtained from all patients before enrollment.…”

“…We previously conducted a retrospective analysis of a large cohort of 111 patients with advanced/metastatic ns‐NSCLC who received treatment with a pemetrexed‐platinum doublet and an immediate approach of vitamin supplementation and observed that the rates of grade 3/4 toxicity were comparable to those observed in the registration trial and in other published studies with similar patient numbers . In the current open‐label, randomized trial (PEMVITASTART; clinicaltrials.gov identifier NCT02679443) being reported herein, we compared immediate initiation versus delayed initiation (after 5‐7 days of supplementation) of pemetrexed‐platinum chemotherapy …”

“…4,[14][15][16][17] In the current openlabel, randomized trial (PEMVITASTART; clinicaltrials.gov identifier NCT02679443) being reported herein, we compared immediate initiation versus delayed initiation (after 5-7 days of supplementation) of pemetrexedplatinum chemotherapy. 18…”