Correspondence to: Federico Bozzetti, M.D., Ist Naz per lo Studio e la Cura dei Tumori, Via Venizian, 1 20133 Milan, Italy.
I would like to comment briefly on the issue raised by Dr. Wheeler (1) with reference to the review by Tisdale (2) on the use of hydrazine sulfate for the treatment of patients with cancer cachexia.
The point, in my opinion, is not whether or not hydrazine sulfate was effective in the clinical trials reported by the authors but whether its use in that context was appropriate. We know, in fact, that 1) cancer patients have an increased glucose synthesis from lactate, alanine, and glycerol and 2) energy metabolism of human cancer cells mainly relies on glucose (3-6). Hydrazine sulfate is a gluconeogenic blocking agent that selectively starves tumor cells by interrupting the cycle of tumor energy gain and host energy deprivation at the enzymatic level of phosphoenol pyruvate-carboxykinase, thus preventing glucose formation from lactate and amino acids.
It seems obvious that if patients have a regular diet (as in the reported clinical trials), the intake of glucose with the diet is enough to maintain the energy metabolism of the cancer cells and to decrease or at least partially compensate the host for the shift of energy from the host tissue to the cancer cells due to the increased gluconeogenesis.
It is not surprising that, in such conditions, hydrazine sulfate proved to be ineffective. The efficacy of hydrazine sulfate should be tested when patients are given a complete but otherwise glucose-free diet (consequently, tumor energy metabolism is only supported by the endogenous production of glucose).
This nutritional approach may be taken because the brain, which is the main consumer of glucose (110-145 g/24 hours) switches to ketone body utilization after a short period of starvation. Moreover, the brain is able to directly use glycerol, whereas the tumor tissue cannot due to the very low activity of glycerokinase.
This approach is the hypothesis that we are currently testing, with good preliminary results with respect to tolerance and feasibility of an intravenous complete glucose-free nutritional regimen plus hydrazine sulfate (7).
REFERENCES
1 Wheeler BM. Re: Biology of cachexia [letter]. J Natl Cancer Inst 1997;90:628.
2
Tisdale MJ. Biology of cachexia. J Natl Cancer Inst1997
;89:1763-73.
3 Burt ME, Norton JA, Brennan M. The human tumor-bearing limb: an ex vivo model. Surgery 1980;87:128-32.[Medline]
4 Greschner M, Saeger HD, Barth H, Leweling H, Holm E. Balances of energy-yielding substrates across malignant gastric tumors in man. Clin Nutr 1991;10 Suppl:12.
5 Hagmuller E, Kollmar HB, Gunther HJ, Holm E, Trede M. Protein metabolism in human colon carcinomas: in vivo investigations using a modified tracer technique with L-[1-13C] leucine. Cancer Res 1995;55:1160-7.[Abstract]
6 Holm E, Hagmuller E, Staedt U, Schlickeiser G, Gunther HJ, Leweling H, et al. Substrate balances across colonic carcinomas in humans. Cancer Res 1995;55:1373-8.[Abstract]
7 Bozzetti F, Cozzaglio L, Gavazzi C, Brandi S, Bonfanti G, Lattarulo M, et al. Total nutritional manipulation in humans: report of a cancer patient. Clin Nutr 1996;15:207-9.
This article has been cited by other articles in HighWire Press-hosted journals:
![]() |
||||
|
Oxford University Press Privacy Policy and Legal Statement |