Depletion of l-ascorbic acid alternating with its supplementation in the treatment of patients with acute myeloid leukemia or myelodysplastic syndromes

作者：Park Chan H^*; Kimler Bruce F; Yi Seong Yoon; Park Se Hoon; Kim Kihyun; Jung Chul Won; Kim Sun Hee; Lee Eun Ryung; Rha Miyong; Kim Seonwoo; Park Mary H; Lee Sook J; Park Hye K; Lee Mark H; Yoon Sung Soo; Min Yoo Hong; Kim Bong Seog; Kim Jeong A; Kim Won Seog

来源：European Journal of Haematology, 2009, 83(2): 108-118.

DOI：10.1111/j.1600-0609.2009.01252.x

• cancer
• clonogenic assay
• vitamin C

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.

• 出版日期2009-8