Faculty Bibliography

The literature is briefly summarized as to how several nutrients affect immune function, susceptibility to infection, and cancer susceptibility or progression. Nutritional deficiencies can impair immunity and so influence susceptibility to infectious agents, including ones that are common and relatively virulent in acquired immune deficiency syndrome (AIDS) patients. A variety of nutrients affect several of the immune functions that are defective in human immunodeficiency virus (HIV)-infected individuals. For example, beta-carotene increased the number of CD4+ cells; vitamin E decreased the number of CD8+ cells and increased the CD4+/CD8+ ratio; vitamin D decreased the CD4+/CD8+ ratio; and iron increased the number of peripheral lymphocytes in humans receiving supplementation. Furthermore, nutritional deficiencies can influence gastrointestinal function, while infectious diseases can influence nutrient requirements by altering the efficiency of absorption and the rate of tissue metabolism. Malnutrition, depressed serum zinc levels, and intestinal nutrient malabsorption have been found in AIDS patients. The above findings suggest that dietary manipulations might diminish the immune defects in HIV infection and enhance resistance to opportunistic infections. However, dietary alterations in immune defects are generally not well quantified and may be small relative to the magnitude of the defects observed in AIDS patients. Because conflicting or adverse effects have been reported for some nutrients, recommendations for dietary supplementation in HIV-infected individuals are premature and possibly hazardous. Further studies are much needed to relate dietary nutrient intakes to clinical outcomes

One hundred seventeen patients with mycosis fungoides were treated with topical mechlorethamine hydrochloride. The probability of achieving a clinically apparent remission within 2 years of therapy was 75.8% in patients with stage I disease, 44.6% in patients with stage II disease, and 48.6% in patients with stage III disease. Patients with stage I disease achieved complete remission sooner (median, 6.5 months) than patients with stage II (median, 41.1 months) or stage III (median, 39.1 months) disease. The median time to relapse was 44.5 months. Sixty-eight patients (58.1%) developed a delayed hypersensitivity reaction, but only one patient had to discontinue therapy as a consequence. No appreciable differences were seen in the probability to achieve complete remission or time to complete remission as stratified by gender, substage, or the development of a delayed hypersensitivity reaction. Survival analysis revealed that the probability of surviving at 5 years was 89% for all patients. These findings compare favorably with results with other treatments for early stage mycosis fungoides

Studies in animals suggest that the bispiperazinedione ICRF-187 can prevent the development of dose-related doxorubicin-induced cardiac toxicity. In a randomized trial in 92 women with advanced breast cancer, we compared treatment with fluorouracil, doxorubicin, and cyclophosphamide (FDC), given every 21 days, with the same regimen preceded by administration of ICRF-187 (FDC + ICRF-187). Patients were withdrawn from the study when cardiac toxicity developed or the cancer progressed. The mean cumulative dose of doxorubicin tolerated by patients withdrawn from study was 397.2 mg per square meter of body-surface area in the FDC group and 466.3 mg in the FDC + ICRF-187 group (no significant difference). Eleven patients on the FDC + ICRF-187 arm received cumulative doxorubicin doses above 600 mg per square meter, whereas one receiving FDC was able to remain in the study beyond this dose. Antitumor response rates were similar (FDC vs. FDC + ICRF-187, 3 vs. 4 complete responses; 17 vs. 17 partial responses; and 9.3 vs. 10.3 months to disease progression). Although myelosuppression was slightly greater in the FDC + ICRF-187 group, the incidence of fever, infections, alopecia, nausea and vomiting, or death due to toxicity did not differ between the groups. Cardiac toxicity was evaluated by clinical examination, determination of the left ventricular ejection fraction by multigated nuclear scans, and endomyocardial biopsy. In comparisons of the FDC group with the FDC + ICRF-187 group, clinical congestive heart failure was observed in 11 as compared with 2 patients; the mean decrease in the left ventricular ejection fraction was 7 vs. 1 percent when the cumulative dose of doxorubicin was 250 to 399 mg per square meter (P = 0.02), 16 vs. 1 percent at 400 to 499 mg (P = 0.001), and 16 vs. 3 percent at 500 to 599 mg (P = 0.003); and the Billingham biopsy score was 2 or more in 5 of 13 patients undergoing biopsy vs. none of 13 (P = 0.03). We conclude that ICRF-187 offers significant protection against cardiac toxicity caused by doxorubicin, without affecting the antitumor effect of doxorubicin or the incidence of noncardiac toxic reactions

All randomized controlled trials of adjuvant therapy of colorectal cancer, published up to December 1986 in English, were reviewed. Eight trials compared radiotherapy groups with control groups in rectal cancer (3062 patients), and 17 trials compared chemotherapy groups with control groups in colorectal cancer (6791 patients). The results of trials testing radiotherapy or chemotherapy were combined. Fluorouracil-containing regimens resulted in a small benefit of therapy in terms of overall survival, with a mortality odds ratio of 0.83 in favor of therapy (95% confidence interval, 0.70 to 0.98). All other combinations of trials failed to show statistically significant differences between treated and control patients, even though the odds of death tended to be slightly lower in treated patients, especially those with rectal tumors. Some overall survival benefit from adjuvant therapy cannot be excluded, but it is likely small. Such small benefit, if real, would be far from negligible in a common case of malignancy with long survival expectancy. Trials much larger than those published up to now are needed