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. Issue 13 (2nd March 2019)

• Record Type: Journal Article
• Authors: Singh, Navneet; Baldi, Milind; Kaur, Jyotdeep; Muthu, Valliappan; Prasad, Kuruswamy T.; Behera, Digambar; Bal, Amanjit; Gupta, Nalini; Kapoor, Rakesh
• Is Part Of: Cancer. Volume 125:Issue 13(2019)
• Page Start: 2203
• Page End: 2212
• Publication Date: 2019-03-02
• Subjects: chemotherapy -- folic acid -- hematologic toxicity -- pemetrexed -- supplementation; Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.32028
• Languages: English
• ISSNs: 0008-543X

Abstract

Abstract : Background: Vitamin B12 and folic acid (FA) supplementation (B12‐FAS) reduces hematologic toxicity with pemetrexed‐based chemotherapy (PEM). However, the basis for recommending 1 week of B12‐FAS before PEM initiation has never been proven in a randomized trial. Methods: An open‐label, randomized trial (PEMVITASTART; clinicaltrials.gov identifier NCT02679443) was conducted to compare hematologic toxicity between patients with locally advanced/metastatic nonsquamous non–small cell lung cancer who initiated PEM after 5 to 7 days of B12‐FAS (delayed arm [DA]) versus those who received B12‐FAS simultaneously (≤24 hours) with PEM initiation (immediate arm [IA]). Every 3 weeks, all enrolled patients received pemetrexed (500 mg/m 2 ) AND either cisplatin (65 mg/m 2 ) OR carboplatin (area under the curve = 5.0 mg/mL per minute) on day 1 for a maximum of 6 cycles. Supplementation consisted of oral FA 1000 μg daily and intramuscular vitamin B12 1000 μg every 3 weeks. The primary outcome was any grade of hematologic toxicity and secondary outcomes included grade 3/4 hematologic toxicity, the relative dose intensity delivered, and changes in serum levels of B12/FA/homocysteine. Results: Of 161 patients (IA, n = 81; DA, n = 80) recruited, 150 (IA, n = 77; DA, n = 73) received ≥1 cycle and were included in a modified intention‐to‐treat analysis. Baseline anemia prevalence was 34.7% (IA, 32.5%; DA, 37%; P = .56). The incidence of any grade anemia, leukopenia, neutropenia, and thrombocytopenia was 87% versus 87.7% ( P = .90), 37.7% versus 28.8% ( P = .25), 20.8% versus 15.1% ( P = .36), and 31.2% versus 16.4% ( P = .04), respectively, in the IA and DA, respectively. Grade 3/4 cytopenias and median relative dose intensities delivered (pemetrexed, 93.5%; platinum, 91%) were similar in both arms. After cycle 3 (compared with baseline), serum homocysteine levels were lower, whereas FA and B12 levels were higher. In the DA, serum FA and B12 levels on day 1 of cycle 1 (after 5‐7 days of B12‐FAS) were significantly higher than at baseline, but homocysteine levels were similar. Conclusions: Simultaneous B12‐FAS initiation with a pemetrexed‐platinum doublet chemotherapy regimen is feasible and does not lead to enhanced hematologic toxicity. Serum homocysteine levels are unaffected by 5 to 7 days of B12‐FAS. Abstract : The basis for starting vitamin B12 and folic acid supplementation 1 week before initiating pemetrexed‐based chemotherapy with the objective of reducing hematologic toxicity has never been proven in a randomized trial. Results from the PEMVITASTART randomized trial reported herein demonstrate that the simultaneous initiation of vitamin B12 and folic acid supplementation with pemetrexed‐platinum chemotherapy is feasible and does not lead to enhanced hematologic toxicity in patients with nonsquamous non–small cell lung cancer.