A Prospective Study of Shortened Vitamin Supplementation Prior to Cisplatin–Pemetrexed Therapy for Non-Small Cell Lung Cancer

Abstract

Background. Prior supplementation with folic acid and vitamin B 12 is required to reduce pemetrexed therapy toxicity; the recommended lead-in time is at least 7 days. On the basis of previous pharmacokinetic and clinical studies, we hypothesized that the lead-in time could be shortened to 24 hours, enabling earlier commencement of standard chemotherapy; thus, we planned the first prospective trial of this regimen. Methods. Patients with advanced nonsquamous non-small cell lung cancer who had not previously received cytotoxic chemotherapy were enrolled. After measurement of homocysteine concentrations, the patients received 1,000 mg of vitamin B 12 by intramuscular injection and began taking 350-500 mg of oral folic acid daily. Starting 24-48 hours after the vitamin B 12 injection, the patients received intravenous 500 mg/m 2 pemetrexed and 75 mg/m 2 cisplatin for 4 cycles at 3

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

“…We observed that immediate initiation of chemotherapy and B12‐FAS was safe. This outcome was reported in previous retrospective analyses and single‐arm studies but was never verified in a randomized trial . The difference in incidence rates for any grade of cytopenia was statistically significant only for thrombocytopenia, which was more frequent in the IA.…”

“…This outcome was reported in previous retrospective analyses and single-arm studies but was never verified in a randomized trial. 12,13 The difference in incidence rates for any grade of cytopenia was statistically significant only for thrombocytopenia, which was more frequent in the IA. However, the 2 groups also differed significantly at baseline for this parameter, with thrombocytopenia present in 8% of patients in the IA and in no patients in the DA at randomization.…”

“…11 Observational and prospective, single-arm studies did not demonstrate any increase in pemetrexed-related toxicity if it was started earlier than the recommended duration of supplementation. 12,13 The delay in pemetrexed-based chemotherapy initiation resulting from a 1-week run-in period related to vitamin supplementation perhaps may be unnecessary and thus avoidable.…”

Efficacies and Adverse Reactions of Modified Vitamin Supplement Programs Before Pemetrexed Chemotherapy as a Second-Line Treatment Against Epidermal Growth Factor Receptor (EGFR) Mutant Wild-Type Lung Adenocarcinoma

“…As for the non-hematologic toxicities, fatigue was still the most common adverse reaction, 31.14% vs 30.97%, P = 0.804; because the antiemetics was routinely prophylacti-pyrimidine nucleotides, the supplements was indispensable during any chemotherapy with antagonist of folic acid [15], and vitamin B12, which involved in the manufacture of marrow erythrocyte, was also need to be supplied exogenously [16].…”

Total Plasma Homocysteine Level Assessment and Timing of Folate/B12 Supplementation Prior to Initiation of Pemetrexed-Based Chemotherapy for Nonsquamous Non-Small Cell Lung Cancer Patients: An Irrelevant Investigation, an Unnecessary Delay, or Both?

“…This letter is in reference to the study by Takagi et al in a recent issue of the journal [1]. The authors assessed total plasma homocysteine (tpHcy) concentrations at baseline in a small cohort of advanced nonsquamous non-small cell lung cancer (NSCLC) patients prior to initiation of chemotherapy (pemetrexed and cisplatin), and then correlation of toxicity profiles with baseline tpHcy levels was assessed [1].…”