Abstract
Purpose
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.
Methods
Folic acid and vitamin B12 were given orally for ˃1 week before pemetrexed administration. The primary end-point was onset of a grade ≥3 neutropenia ratio (50 % of threshold expression ratios; an expectation expression ratio of 21 %; α, 0.05; β, 0.1). Blood concentration of folic acid and homocysteine which are markers of vitamin B12 deficiency were also examined (UMIN000003180).
Results
A total of 25 cases were registered from February 2010 to July 2014. The ratio of grade ≥3 neutropenia was 36 % (95 % CI 22–52 %). Grade ≥3 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.
Conclusion
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.
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Acknowledgments
This study was supported by the Clinical Research Fund of Tokyo Metropolitan Government. We acknowledge the contributions of Tetsu Shinkai, Hiroaki Okamoto, and Koichi Minato in their capacity as the members of the Data and Safety Monitoring Board.
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Author YT is the employees of MSD KK. Author Y.H has received honoraria from Elli Lilly. The other authors declare that they have no conflict of interest.
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Takagi, Y., Hosomi, Y., Nagamata, M. et al. 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. Cancer Chemother Pharmacol 77, 559–564 (2016). https://doi.org/10.1007/s00280-015-2954-x
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DOI: https://doi.org/10.1007/s00280-015-2954-x