ObjectiveChemotherapy doses are limited by toxicity to normal tissues. Intravenous glutamine protects liver cells from oxidant injury by increasing intracellular glutathione (GSH) content. The authors hypothesized that supplemental oral glutamine (GLN) would increase the therapeutic index of methotrexate (MTX) by improving host tolerance through changes in glutathione metabolism. The authors examined the effects of oral glutamine on tumor and host glutathione metabolism and response to methotrexate. MethodsThirty-six 300-g Fischer 344 rats were implanted with fibrosarcomas. On day 21 after implantation, rats were randomized to receive isonitrogenous isocaloric diets containing 1 g/kg/day glutamine or glycine (GLY) by gavage. On day 23 after 2 days of prefeeding, rats were randomized to one of the following four groups receiving an intraperitoneal injection of methotrexate (20 mg/kg) or saline (CON): GLN + MTX, GLY + MTX, GLN-CON, or GLY-CON. On day 24, rats were killed and studied for arterial glutamine concentration, tumor volume, tumor, kidney and gut glutaminase activity, and glutathione content (tumor, gut, heart, liver, muscle, kidney, and lung). ConclusionThese data suggest that oral glutamine supplementation will enhance the selectivity of antitumor drugs by protecting normal tissues from and possibly sensitizing tumor cells to chemotherapy treatment-related injury. jected to alternate 12-hour periods of dark/light cycle and given at least 1 week to acclimate to the animal care facilities. During that time, the rats were allowed ad libitum intake of standard rat chow and water. Animals were randomized during the study period to receive isonitrogenous isocaloric chow diets supplemented with 1 g/kg/day elemental GLN or glycine (GLY) by gavage.Tumor Cell ImplantationAfter 1 week of acclimation to the animal care facility and on day 0 of the study, 36 rats were randomized to flank implantation of a 2 X 2 X 2 mm3 of viable methylcholanthrene-induced fibrosarcoma cells. This tumor model has been used previously by the author7"15-'6'20,2' to study tumor host metabolism interaction. This tumor-cell line is fast-growing and locally aggressive, metastasizes rarely, and never regresses spontaneously. Study ProcedureOn day 21 after tumor cell implantation, rats were randomized to receive pair-fed chow diets with supplemental GLN or GLY by gavage. On day 23, after 2 days of prefeeding, rats were randomized to one ofthe following four groups receiving an intraperitoneal injection of MTX (20 mg/kg) or saline (CON): GLN + MTX, GLY + MTX, GLN-CON, or GLY-CON. Each group contained nine rats. On day 24, all rats were weighed and anesthesia was obtained with ketamine (7.5 mg/100 g body weight) and acepromazine (0.1 mg/100 g body weight). Under sterile conditions, a mid-line incision was made, and the rat was heparinized. Arterial blood was withdrawn from the aorta using a 25-gauge needle attached to a 1-mL syringe. Blood was processed for arterial GLN content. The jejunum and kidney were removed and processed for glutaminas...

Because of the retrospective nature of this study and inherent limitations of the SEER database, a large prospective study is needed to further elucidate the relationship between postoperative radiation and survival. However, these data do support the use of adjuvant radiation for patients with high-grade extremity STS measuring >5 cm.

Dose intensification of chemotherapy is thought to increase survival. With recent advances in hemopoietic cell modulators such as granulocyte colony stimulating factor, the limiting toxicity of intensifying chemotherapeutic regimens has become the severity of the associated enterocolitis. In animal models, glutamine protects the host from methotrexate-induced enterocolitis. This study evaluates the effects of a glutamine-supplemented diet on the tumoricidal effectiveness of methotrexate. Sarcoma-bearing Fisher 344 rats (n = 30) were pair-fed an isocaloric elemental diet containing 1% glutamine or an isonitrogenous amount of glycine beginning on day 25 of the study. Rats from each group received two intraperitoneal injections of methotrexate (5 mg/kg) or saline on days 26 and 33 of the study. On day 40, rats were killed, tumor volume and weight were recorded, and tumor glutaminase activity and tumor morphometrics were measured. Blood was taken for arterial glutamine content, complete blood count, and blood culture. The gut was processed for glutaminase activity and synthesis phase of the deoxyribonucleic acid. In rats receiving methotrexate, the tumor volume loss was nearly doubled when glutamine was added to the diet. Significant differences in tumor glutaminase activity and morphometrics were not detected. The toxicity to the host was ameliorated. Significantly increased synthesis phase of deoxyribonucleic acid of the whole jejunum, decreased bacteremia, "sepsis," and mortality were demonstrated. Glutamine supplementation enhances the tumoricidal effectiveness of methotrexate while reducing its morbidity and mortality in this sarcoma rat model.

BACKGROUND:The Surveillance, Epidemiology, and End Results database was analyzed to explore the pathologic extent of disease for clinically localized prostate cancer after radical prostatectomy as well as the use of adjuvant radiation in this population.METHODS:Identified were patients from 2004 to 2006 with clinically staged T1c‐2cNx‐0M0 prostate adenocarcinoma who underwent radical prostatectomy. All patients had complete clinical and pathologic data. The use of postoperative radiation was recorded. Logistic regression analysis was performed to identify unadjusted and adjusted predictors for extraprostatic disease or positive surgical margins and for adjuvant radiation use.RESULTS:A total of 35,642 patients were identified. For those patients with Gleason 7 (4 + 3) and a prostate‐specific antigen (PSA) level of ≥10.1 ng/mL or Gleason 8 to 10 with any PSA level, the rate of organ‐confined disease with negative surgical margins was found to be <50%. Of those with indications for adjuvant radiation, 11.1% received the treatment.CONCLUSIONS:This large population‐based study detailed the risk of extraprostatic extension and positive surgical margins in a broad setting across multiple regions and communities, as well as the use of adjuvant radiation for these patients. As of 2006, 11.1% of patients who had indications for adjuvant radiation received this treatment, providing a useful baseline for future patterns of care studies. Cancer 2010. © 2010 American Cancer Society.