Vitamin Supplementation in NSCLC Patients on Pemetrexed Based Chemotherapy

Chemotherapy Regimen:

All patients will receive pemetrexed and cisplatin in doses of 500 mg and 65 mg, respectively, per square meter of body surface area each on day 1 of a 3-week cycle. Patients with contraindications to administration of cisplatin, those who are intolerant to cisplatin, or develop grade 3 or 4 adverse events from cisplatin will be given carboplatin in combination with pemetrexed. Carboplatin will be given at a dose calculated to produce an area under the concentration-time curve (AUC) of 5.0mg/mL/min. Dose modifications of either pemetrexed or the platinum agent or both will be done in case of significant change in PS or toxicity from or intolerance to dose administered in the previous cycle.

Supplementation:

• Folic acid (FA) supplementation will be given to all patients orally in the dose of 5 ml (1000 μg) once daily of VITCOFOL (FDC Limited, Mumbai, India) pediatric formulation, which contains 200 μg FA/ml of the preparation. Patients will be instructed to measure the prescribed dose using a 5 ml plastic syringe containing markings at every 0.5 ml. Patients will also be instructed not to take any additional multivitamin supplements. In addition to FA supplementation, all patients will also be started simultaneously on oral iron (ferrous sulphate 200 mg twice a day). Once initiated, both FA and ferrous sulphate will be given on a daily basis and continued throughout the duration of chemotherapy and for at least 3 weeks beyond the last cycle.
• Vitamin B12 supplementation will be given to all patients intramuscularly in the dose of 1000 μg along with each cycle of chemotherapy (maximum of six doses during the study period).

Inclusion criteria

• Locally advanced or metastatic (Stage IIIB/IV) NSCLC and Stage III A NSCLC, not scheduled for upfront surgical resection
• Nonsquamous histology (including adenocarcinoma)
• At least one unidimensionally measurable lesion, according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.0), or at least one nonmeasurable lesion that was assessable using conventional techniques or a spiral computed tomography scan
• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• No previous chemotherapy for advanced disease and no previous targeted molecular therapy
• Adequate liver and renal function;
• Previous radiation therapy is permitted if completed >4 weeks before enrollment and the patient has recovered from any treatment-related toxicity.

Exclusion criteria

• Hemoglobin value < 9gm/dl
• Required erythropoiesis stimulating agents or blood transfusions in the recent past (4 months)
• Symptomatic untreated brain metastasis
• Any previous malignancy
• Concurrent use of any other tumor therapy
• Active infection or a serious concomitant disorder
• Inability to interrupt nonsteroidal anti-inflammatory agents
• Inability or unwillingness to take folic acid, vitamin B12, or dexamethasone supplementation
• Pregnancy or breast feeding