The NCCN Guidelines Development Program.

The National Comprehensive Cancer Network (NCCN) has begun a program for the development of comprehensive clinical practice guidelines for the management of the most common tumors. The NCCN guidelines reflect a process of consensus that relies on evaluation of the evidence and structured feedback. The guidelines are designed to reflect clinical decision-making, and attempt to deal with the complexity of managing cancer. The initial guidelines effort has yielded eight guidelines for adult cancers and three for pediatric cancers. The guidelines are set up in algorithm format. The NCCN members believe that clinical trials are always an appropriate form of patient management, and that the inclusion of a patient in a clinical trial is preferred at every decision point in the algorithm.

Phase II study of coumarin and cimetidine in patients with metastatic renal cell carcinoma.

Fifty patients with locally advanced or metastatic renal cell carcinoma were treated with coumarin (1,2-benzopyrone) at 100 mg orally daily starting on day 1 and cimetidine 300 mg orally four times a day starting on day 15. When disease progressed, coumarin was escalated to 100 mg orally four times a day. Three patients (6%; 95% confidence interval [Cl], 2% to 17%) achieved a partial response, one of those after dose escalation. In addition, one patient had a minor response, then progressing disease, and again had a minor response after dose escalation. All four responders had nonassessable primary tumors (three had had prior nephrectomy and one a renal angioinfarction). The only major toxicity was renal (37 patients had minor to moderate elevations in serum creatinine level). Immunologic studies (hypersensitivity skin testing, lymphocyte blastogenesis response, number of lymphocytes, T lymphocytes, T helper and T suppressor subsets, and T helper: suppressor ratio), performed before and after therapy, showed a relative lymphopenia and decreased hypersensitivity skin-testing results at baseline, and a general decline over time in the number of T cells and T helper and T suppressor subsets. There was no enhancement in any of the immunologic parameters tested. The response rate was 6%, lower than previously reported; a general immunodeficiency was noted at baseline, and the lymphopenia worsened with progressing disease, unaffected by therapy.

Monitoring antibiotic usage in the hospital.

The authors outline the quality indicators being developed by the Joint Commission on Accreditation of Health Care Organizations to compare hospital performance. The Joint Commission has provided several incentives to encourage antibiotic monitoring based on criteria derived from standard practice, as defined in the literature, and on the clinical judgment of the medical staff. In addition, the drug review process should be continuous and should encompass all areas of drug use in the hospital, including effectiveness in terms of disease outcome as well as cost efficiency. The authors discuss procedures under development in their institution to promote cost efficiency and informed discussion regarding clinical use of antibiotics on the formulary. Microbiology reporting, drug use, requests for nonformulary drugs, and unusual patterns of infection and sensitivities are tracked to identify problem areas and a feedback loop is used to inform the medical staff.

Acquired immune deficiency syndrome and the management of associated opportunistic infections.

Since the spring of 1981, more than 2300 cases of acquired immune deficiency syndrome (AIDS) have been reported from 41 states to the Centers for Disease Control. Cases also have been reported from 20 foreign countries, and reports are increasing at an alarming rate. More than 900 people (approximately 40 percent) have died of this disease. AIDS is characterized by skin test anergy to recall antigens, decreased T-helper subset, and inverted helper T-cell:suppressor T-cell ratios in the peripheral blood. Overt AIDS may be preceded by a prodrome that may last for many months and consists of fever, weight loss, and lymphadenopathy. The immune defect in AIDS permits the development of opportunistic infections caused by a number of organisms, including Pneumocystis carinii, Mycobacterium avium-intracellulare, Toxoplasma gondii, and various fungi. Certain malignancies also are associated with AIDS, in particular, Kaposi's sarcoma. Although the etiology of AIDS is unknown, the causative agent appears to be infectious. Lifestyle factors such as drug use and certain sexual activities may play a role. Currently, epidemiologists and others investigating the syndrome believe that AIDS can spread through sexual contact, blood products, or both. AIDS patients include homosexual males, users of intravenous drugs, immigrants from Haiti, hemophiliacs, female partners of males with AIDS, infants born to mothers who have AIDS, and persons who have received blood products from AIDS patients. Thus far, questions about AIDS outnumber the answers. Intensive research is being conducted to develop a rational approach to the treatment of AIDS and a better understanding of the relationship between the immune defense system and cancer.