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BACKGROUND: A method of augmenting host defenses against bacterial pathogens could result in a decrease in postoperative infections. Given its effects on leukocyte proliferation and function, it is possible that prophylactic granulocyte-macrophage colony-stimulating factor (GM-CSF) could reduce the incidence and severity of infections in high-risk surgical patients. The current study was undertaken to determine the safety and hematologic effects of perioperative GM-CSF. METHODS: Cancer patients undergoing operations with a high risk of postoperative infection were treated perioperatively for 10 days with subcutaneous GM-CSF. Cohorts were treated with GM-CSF at 125 [mu]g/[m.sup.2]/day (12 patients) and 250 [mu]g/[m.sup.2]/day (11 patients). RESULTS: There were no severe or life-threatening toxicities associated with GM-CSF. Mean maximum neutrophil counts during the first 5 postoperative days were 16.3 [+ or -] 9.14 and 24.5 [+ or -] 7.60 at 125 and 250 [mu]g/[m.sup.2], respectively (P = 0.04). Only one wound infection was diagnosed during this study. CONCLUSIONS: GM-CSF may be safely administered perioperatively at doses that augment neutrophil number and function. An ongoing randomized clinical trial will determine the impact of GM-CSF on postoperative infection. Am J Surg. 1996;172:299-302.

Background. Cancer is most common in older age groups, but little information is available with regard to the impact of age on chemotherapy toxicity. This study was undertaken to determine if age is an independent risk factor for 5-fluorouracil (5-FU) toxicity. Methods. Toxicity data from a prospective, randomized, multiinstitution trial of 5-FU-based treatment for advanced colorectal cancer were analyzed. Toxicity for each organ system was graded. Individual organ toxicity proportions were compared using chi-square analysis. A logistic regression was performed using age (younger than 70 years vs. 70 years or older), sex, treatment arm, performance status, and length of therapy as model parameters to predict severe toxicity. Toxicity in 331 patients was analyzed. Results. Advanced age was significantly associated with the occurrence of any severe toxicity (58 vs. 36%, P < 0.001), leukopenia (24 vs. 10%, P < 0.005), diarrhea (24 vs. 14%, P = 0.01), vomiting (15 vs. 5%, P = 0.01), severe toxicity in more than 2 organ systems (10 vs. 3%, P = 0.02), and treatment mortality (9 vs. 2%, P = 0.01). By univariate analysis, age (P < 0.001) and sex (P < 0.0001) were independent predictors of severe toxicity. Twenty-two of 27 women age 70 years or older had severe toxicity. Conclusions. Age 70 years or older and sex are risk factors for severe toxicity from 5-FU-based chemotherapy. Advanced age does not contraindicate the use of this type of chemotherapy, but close monitoring for multiple organ toxicities and vigorous supportive care of those with toxicity are required. Dosing decisions in older patients are difficult and must integrate assessments of organ function, comorbidities, overall physical status, and goals of treatment, in an effort to ensure the best possible outcome for these patients.

As greater numbers of cancer and leukemia patients survive for longer periods, it is becoming more common to see various complications of chemotherapy. Among the most serious of complications is neutropenic enterocolitis. Under normal circumstances, the gut is filled with bacteria which perform an important role in the digestive process. These bacteria are prevented from entering the body by the barrier of the healthy cells lining the intestines and by immune system cells which quickly eat any invading microbes. These normal protective barriers are disrupted in neutropenic enterocolitis. The details of the development of this condition remain poorly understood. Chemotherapy can destroy healthy intestinal cells as well as cancerous cells. It is thought that if the destruction of cells lining the intestine is complicated by neutropenia, a reduction in the protective bacteria-ingesting neutrophil cells, then bacteria from the gut may gain a stronghold in the wall of the intestines perhaps progressing to necrosis (tissue death) and perforation of the intestines. The authors report the cases of 22 patients who received a diagnosis of neutropenic enterocolitis on the basis of their clinical symptoms. A total of 63 percent of these patients died. Some clinicians believe that the best treatment may be the surgical removal of the affected portion of the bowel; this opinion remains quite controversial, however. In the present series of patients, 50 percent of the patients who underwent surgery survived, in contrast to 39 percent of those who did not. While this might appear to support the notion of surgery as the superior treatment, the authors caution that neutropenic enterocolitis is a very heterogeneous condition. In nine cases of patients who were not treated surgically and were later examined at autopsy, four were found to have normal gastrointestinal tracts (indicating the original diagnosis was wrong) and none were found to have perforations or necrosis which spanned the wall of the intestines. it is unlikely that the outcome of these cases would have been any different if surgery had been used in their treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)

Out of about 20,000 diagnosed cases of stomach cancer in 1989, only one quarter are candidates for curative surgery, and only a quarter of these are likely to survive more than five years. A currently accepted chemotherapeutic protocol for gastric cancer consists of 5-fluorouracil, doxorubicin, and mitomycin C, called the FAM regimen. However, the average survival time is still short, and stomach cancer remains the sixth largest cause of cancer deaths in the United States. In preparation for a randomized trial, which could definitively assess the contribution of leucovorin when added to the accepted FAM protocol, the safety and effectiveness of FAM-leucovorin treatment was evaluated in a total of 32 patients with stomach cancer. The estimated average survival time was 11.5 months for all patients, and a response rate of 38 percent was obtained among patients in whom the disease was measurable. These results are not outside the range of what might be expected with FAM alone. Cumulative bone marrow suppression required the limitation of FAM dosage to the point where the 5-fluorouracil component was no longer being administered at the optimum dose. Since the theoretical justification for leucovorin administration is as a possible synergistic boost for 5-fluorouracil, the addition of leucovorin to the FAM protocol is not an effective means of demonstrating whether any such synergism actually takes place. (Consumer Summary produced by Reliance Medical Information, Inc.)