Single and combined supplementation of glutamine and n-3 polyunsaturated fatty acids on host tolerance and tumour response to 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11)/5-fluorouracil chemotherapy in rats bearing Ward colon tumour.
Prior reports suggest that during irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin; CPT-11) chemotherapy in laboratory rats, the anti-tumour efficacy and diarrhoea toxicity could be modulated by n-3 PUFA and glutamine, respectively. We further examined how these two dietary elements, when provided individually and in combination, would affect the efficacy of a cyclical regimen of CPT-11/5-fluorouracil (5-FU), an accepted combination regimen for colorectal cancer. Prior to initiating chemotherapy, diets enriched either with glutamine (2 %, w/w total diet) or n-3 PUFA (0.88 %, w/w total diet) alone, inhibited Ward colon tumour growth (P < 0.05). These diets also completely or partially normalized the changes in peripheral leucocyte counts associated with the tumour-bearing state (e.g. neutrophil proportion/concentration and lymphocyte proportion). During chemotherapy, either glutamine- or n-3 PUFA-enriched diet enhanced tumour chemo-sensitivity, and reduced body weight loss, anorexia and muscle wasting (v. animals fed control diet, P < 0.05). Surprisingly, providing both glutamine and n-3 PUFA together did not confer a greater benefit on tumour inhibition either in the presence or absence of chemotherapy; individual benefits associated with single treatments, particularly in respect to host nutritional status (i.e. body weight, food intake and muscle weight) and immune (peripheral leucocyte counts) features were instead partially or completely lost when these two nutrients were combined. These results draw into question the common assumption that there are additive or synergistic benefits of combinations of nutrients, which are beneficial on an individual basis, and suggest that co-supplementation with glutamine and n-3 PUFA is not indicated during chemotherapy with CPT-11 and 5-FU.
Xue
Hongyu
H
Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, Canada.
Le Roy
Séverine
S
Sawyer
Michael B
MB
Field
Catherine J
CJ
Dieleman
Levinus A
LA
Baracos
Vickie E
VE
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D001835:Body Weight; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D003131:Combined Modality Therapy; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D005973:Glutamine / Q000627:therapeutic use*; D007108:Immune Tolerance; D000077146:Irinotecan; D007958:Leukocyte Count; D009752:Nutritional Status; D051381:Rats; D011916:Rats, Inbred F344; D017211:Treatment Failure; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000972:Antineoplastic Agents, Phytogenic; D015525:Fatty Acids, Omega-3; D005973:Glutamine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin