Association of Graded Folic Acid Supplementation and Total Plasma Homocysteine Levels With Hematological Toxicity During First-line Treatment of Nonsquamous NSCLC Patients With Pemetrexed-based Chemotherapy

Abstract

Prevalence of elevated tpHcy levels posttreatment as compared with baseline was reduced significantly with FAS. Among ns-NSCLC patients treated with pemetrexed and with FAS of 400 to 1000 μg daily, HTox was not associated with either baseline tpHcy levels or with graded baseline FAS.

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

“…ICDs ≥7 days occurred only in approximately 10% of patients and were similar in the 2 arms. However, this was less than our previous observation of approximately 20% in a mixed histology cohort that received several different chemotherapy regimens and in the previous retrospective study on first‐line pemetrexed chemotherapy . Although it was not one of the prespecified outcomes of the current trial, we also observed a trend toward higher objective radiologic responses in the IA.…”

“…The reason for a relatively lower rate of grade 3/4 cytopenias (other than anemia) may be related to the use of a lower dose of cisplatin (65 mg/m 2 is the standard followed at our center) as well as use of the highest permissible FAS (1000 μg daily) . However, the pemetrexed and carboplatin doses are similar to those followed in routine practice globally as well as in other randomized trials.…”

“…This trial was designed as a superiority trial based on the null hypothesis that the delayed (standard) approach to FA and B12 supplementation was superior to the immediate (experimental) approach. The calculation was based on incidence rates observed with the delayed approach in the registration trial and with the immediate approach in our observational study . We chose incidence rates of anemia (the most common cytopenia) observed in both of the above studies .…”

“…Nonetheless, chemotherapy remains the backbone of treatment for advanced/metastatic ns‐NSCLC, in which predictive molecular biomarkers for upfront targeted therapy (epidermal growth factor receptor [ EGFR ] and v‐Raf murine sarcoma viral oncogene homolog B1 [ BRAF ] mutations; anaplastic lymphoma kinase [ ALK ] and ROS proto‐oncogene 1 [ ROS1 ] rearrangements) and upfront immunotherapy (monoimmunotherapy) (programmed death ligand 1 [PD‐L1] expression ≥50%) either have not been assessed or are absent . In this context, pemetrexed is the preferred drug to be used as a component of platinum‐based doublet chemotherapy for patients with ns‐NSCLC . It is also the preferred chemotherapeutic agent for patients with malignant mesothelioma .…”

Plasma homocysteine levels and hematological toxicity in NSCLC patients after the first cycle of pemetrexed under folate supplementation

“…The Homocysteine Lowering Trialists' Collaboration reported that a maximum reduction of 90% in the plasma homocysteine level can be achieved with 0.4 mg of folic acid per day [14]. Recently, Singh et al [15] reported that hematological toxicity was not associated with plasma homocysteine levels before folate supplementation during first-line treatment of nonsquamous NSCLC patients with pemetrexed-based chemotherapy. Therefore, treatment with 0.5 mg of folic acid is possibly sufficient for most patients.…”