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The role of glutamine in the treatment of oncological (3/4)

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(3/4) The role of glutamine in the treatment of oncological

Glutamine and chemotherapy

Cytotoxic chemotherapy often causes intestinal damage manifested as an inflammation of the intestinal mucosa and oral cavity (Mucositis, stomatitis, enterocolitis). The diversity of these symptoms may prevent dose escalation or reduction of its force.Been recognized numerous beneficial effects of glutamine administration in inflammatory bowel disease induced by chemotherapy. These effects are the improvement of nutritional status, reduced damage to the intestine, reduced the degree of bacterial dysbiosis, reduced toxicity and longer survival of the organism (27.28). Additional studies showed that administration of glutamine can enhance the therapeutic effect of methotrexate, as well as reduce the mortality rate (29.30).

Skubitz and Anderson published a pilot study describing the effect of glutamine in chemotherapy-induced mucositis.
Chemotherapeutic agents used in this study, a doxorubicin (12x), etoposyd (2x), ifosfomid (1x), carboplatin (1x). Patients were treated twice a day Glutamine in solution for 28 days. The authors demonstrated a significant reduction in both the degree of mucosal inflammation as well as during its duration.

Subjectively - patients feel that mucosal inflammation was
less burdensome, as well as better was the quality of life. The same authors
continued randomized, cross-examination, double-blind
sample of 24 patients receiving chemotherapy. Served
chemotherapeutics are CAD, VAdrC, IA, CDDPAdr or MTX.Patients
received for 14 days for a solution of glutamine or glycine. Results
confirmed findings from earlier pilot studies: reduction
degree and duration of mucositis in the group supplemented
glutamine. The authors conclude that patients who had previously
suffering from mucositis while receiving doxorubicin or
methotrexate may feel a special improvement as a result of administration
glutamine (31.32).

In a similar study in adult patients with AML (Acute Leukemia
Myelogenous) chemotherapy Muscaritoli et al. discovered
decreased duration and severity of diarrhea, as well as important
reduction in demand for parenteral nutrition with oral
supplementation with glutamine (33).
Glutamine supplementation was also studied in patients undergoing
bone marrow transplantation. Ziegler et al. observed in
randomized, double-blind study of the effect of parenteral
administration of glutamine in 45 adult patients. Both groups received
lasting an average of four weeks parenteral nutrition. Group
Experimental received TPN (parenteral nutrition kit)
enriched with glutamine at a dose of 0.57 g / kg / d (about 30-40g / d). Group
The control preparation received an identical calorie, content
nitrogen, but without glutamine. Groups supplemented with glutamine was characterized
a lesser rate of infection and bacterial colonization, the better
balance of nitrogen and 19% shorter hospitalization. Schloerb et al.
observed a reduction of 5.8 day hospital stay in the same
designed study observing the effect of glutamine supplementation on
bone marrow transplant (34.35).

The most recent studies, Schloerb et al. in a randomized
double-blind study of oral and parenteral supplementation
glutamine in 66 patients after bone marrow transplantation showed a reduction in
need for TPN and possible improvements in survival in these patients,
who received glutamine (36).
Glutamine has also been studied in terms of reducing parenteral
toxicity of chemotherapy. In a controlled study at the University of
Arkansas, a study on rats demonstrated that glutamine administered
improved survival of animals fed a lethal (deadly) and
sublethal (slightly less than lethal) dose of cyclophosphamide. Only
20% of the group supplemented with glycine, survived a dose of 450mg/kg in
compared to 100% survival in the group, which was administered glutamine.
Glutamine supplementation also maintained the proper level
glutathione in the heart of reducing cardiotoxicity (37).

Another direction of scientific interest is to determine what
can play the role of glutamine in enhancing the effects of chemotherapy
by reducing the poisoning of the body. Klimberg et al. found that
rats treated with methotrexate and glutamine were 45% pure
tumor reduction compared to the group, which was administered methotrexate and
glycine. Further studies of these investigators have shown increased levels
methotrexate in the tumor after 24 and 48 hours, the group of rats
supplementation with glutamine compared to the group receiving diet
without glutamine. The authors drew the hypothesis that elevated
glutamine resulted in an increase in poliglutaminianu methotrexate, which
resulted in increased drug retention within the tumor (41,42,43).

Rubio et al. presented a threefold increase in the amount of methotrexate
tumors in rats treated with glutamine for 48 hours before
intraperitoneal injection of methotrexate. The same group of researchers reported
also a first phase of the study, nine patients with inflammatory
breast cancer treated with glutamine and with increasing doses of methotrexate
and doxorubicin. There have been reported on the toxicity of glutamine or
the toxicity associated with chemotherapy. One patient had slight
inflammation of the mucous membranes and intestines. The average survival was 35 months

Literature Cited:
26) VS Klimberg, Glutamine Enhances Oral radiosensitivity in rat
sarcoma, presented at The Society of Surgical Oncology, Houston,
Texas, 1994
27) Rombeau, A Review of the Effects of Glutamine-Enriched diets on
experimentally induced enterocolitis, JPEN 14 100S-105S supplement
28) AD Fox et al, Effect of glutamine supplemented enteral diet on
methotrexate induced enterocolitis, JPEN 12:325-331,1988
29) Klimberg VS et al, Does glutamine Facilitate chemotherapy while
Reducing toxicity? Surg Forum 42:16-18,1991
30) Klimberg VS et al, Effect of dietary glutamine on Supplemental
methotrexate concentration in tumors, Arch Surg 127:1317-1322,1992
31) Skubitz K, Anderson P, Oral glutamine to Prevent chemotherapy
induced stomatitis: a pilot study, J Lab Clin Med 127:223-228,1996
32) Anderson P et al, Oral glutamine reduces the duration and severity
of stomatitis after cytotoxic cancer chemotherapy,
Cancer ,83:1433-1439, 1998
33) Muscariotol M et al, Oral glutamine in the prevention of
chemotherapy-induced gastrointestinal toxicity, E Journal Cancer
34) Ziegler T, et al, Clinical and metabolic efficacy of
glutamine-supplemented parenteral nutrition after bone marrow
transplantation, Ann Intern Med 116:821-828,1992
35) Schloerb PR et al, TPN with glutamine in bone marrow
transplantation and other clinical applications: a randomized, double
blind study. JPEN 17:407-413,1993
36) Schloerb PR: Oral and parenteral glutamine in bone marrow
transplantation: a randomized, double-blind study, JPEN
37) Klimberg VS et al: Oral glutamine protects against induced Cytoxan
cardiotoxicity and death. Presented at the associaiton of Academic
Surgery: Hershey, PA, 1993
38) Savarese D et al, Glutamine treatment of paclitaxel-induced
myalgias and arthralgias, J Clin Oncology 12:3918-9,1998
39) Boyle FM, et al, Glutamate ameliorates experimental vincristine
neuropathy, J Pharmacol Exp Therap 279:410-415, 1996
40) Boyle FM, et al, Prevention of experimental paclitaxel neuropathy
with glutamate, Proc AACR 37:290,1996
41) Klimberg VS et al, Effect of glutamine on tumor concentrations of
methotrexate, Arch Surg 27:1317, 1992
42) Rouse K et al, Glutamine Enhances selectivity of chemotherapy
through changes in glutathione metabolism. Ann Surg 221:430-431, 1996
43) Rubio IT, et al: Effect of glutamine on methotrexate efficacy and
toxicity, Ann Surg 227:772-780,1998
44) Hall, JC et al, Glutamine. Brit J Surg 83:305-312,1996

tbc ...

MD Piotr Krzysztof Michalak
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The role of glutamine in the treatment of oncological (3/4)

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