Phase II study of oral vitamin B12 supplementation as an alternative to intramuscular injection for patients with non-small cell lung cancer undergoing pemetrexed therapy

A vitamin B12 supplement is required in pemetrexed single agent therapy. Intramuscular administration is the method of choice; however, oral administration is simpler and easier and may be sufficiently effective. We conducted a Phase II study to evaluate the safety of oral administration of vitamin B12 in patients with advanced non-small cell lung cancer who received pemetrexed single agent therapy. Folic acid and vitamin B12 were given orally for E integral 1 week before pemetrexed administration. The primary end-point was onset of a grade a parts per thousand yen3 neutropenia ratio (50 % of threshold expression ratios; an expectation expression ratio of 21 %; alpha, 0.05; beta, 0.1). Blood concentration of folic acid and homocysteine which are markers of vitamin B12 deficiency were also examined (UMIN000003180). A total of 25 cases were registered from February 2010 to July 2014. The ratio of grade a parts per thousand yen3 neutropenia was 36 % (95 % CI 22-52 %). Grade a parts per thousand yen3 non-hematologic toxicity and hematologic toxicity were seen in 20 % (5 cases) and 44 % (11 cases) of patients, respectively. In addition, the homocysteine blood concentration just before the first cycle dosage of pemetrexed was significantly elevated relative to the 2-3 cycle. This study failed to meet its primary endpoint. We could not demonstrate the safety and efficacy of the 1-week vitamin B12 oral administration protocol as compared with intramuscular administration.