Journal
EUROPEAN JOURNAL OF HAEMATOLOGY
Volume 83, Issue 2, Pages 108-118Publisher
WILEY-BLACKWELL PUBLISHING, INC
DOI: 10.1111/j.1600-0609.2009.01252.x
Keywords
cancer; clonogenic assay; vitamin C
Categories
Funding
- NCI/USDHHS [RO1 CA20717]
- Research Career Development Award [KO4 CA00534]
- Jin Yang and Huons Pharmaceutical companies
- Kyunggi High School 51st Alumni Cancer Research Support Group
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Purpose: l-ascorbic acid (LAA) modifies the in vitro growth of leukemic cells from similar to 50% of patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). To test the hypothesis that depletion of LAA, alternating with supplementation to prevent scurvy, would provide therapeutic benefit, a single-arm pilot trial was conducted (ClinicalTrials.gov identifier: NCT00329498). Experimental results: During depletion phase, patients with refractory AML or MDS were placed on a diet deficient in LAA; during supplementation phase, patients received daily intravenous administration of LAA. An in vitro assay was performed pretherapy for LAA sensitivity of leukemic cells from individual patients. Results: Of 18 patients enrolled, eight of 16 evaluable patients demonstrated a clinical response. Responses were obtained during depletion (four patients) as well as during supplementation (five patients) but at a pharmacologic plasma level achievable only with intravenous administration. Of nine patients for whom the in vitro assay indicated their leukemic cells were sensitive to LAA, seven exhibited a clinical response; compared with none of six patients who were insensitive to LAA. Conclusions: The clinical benefit, along with a conspicuous absence of significant adverse events, suggests that further testing of LAA depletion alternating with pharmacologic dose intravenous supplementation in patients with these and other malignancies is warranted.
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