Depletion of L-ascorbic acid alternating with its supplementation in the treatment of patients with acute myeloid leukemia or myelodysplastic syndromes.
OBJECTIVE
L-ascorbic acid (LAA) modifies the in vitro growth of leukemic cells from approximately 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.
Park
Chan H
CH
Cancer Center and Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. bkimler@kumc.edu
Kimler
Bruce F
BF
Yi
Seong Yoon
SY
Park
Se Hoon
SH
Kim
Kihyun
K
Jung
Chul Won
CW
Kim
Sun Hee
SH
Lee
Eun Ryung
ER
Rha
Miyong
M
Kim
Seonwoo
S
Park
Mary H
MH
Lee
Sook J
SJ
Park
Hye K
HK
Lee
Mark H
MH
Yoon
Sung Soo
SS
Min
Yoo Hong
YH
Kim
Bong Seog
BS
Kim
Jeong-A
JA
Kim
Won Seog
WS
D000328:Adult; D000368:Aged; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000178:diet therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000178:diet therapy* / Q000235:genetics; D011446:Prospective Studies; D018570:Risk Assessment
D001205:Ascorbic Acid