Progress in complementary and alternative medicine: contribution of the National Institutes of Health and the Food and Drug Administration.

Since the creation of the Office of Alternative Medicine (OAM) at the National Institutes of Health (NIH), progress has been made in the evaluation and, where appropriate, the clinical and scientific acceptance of "complementary and alternative" medicine (CAM). This progress is due in part to initiatives jointly conducted by the NIH and the U.S. Food and Drug Administration (FDA). In particular, advances in the evaluation and acceptance of two CAM practices, acupuncture and botanical medicine, have resulted from ongoing cooperation between the two agencies. The legalization of the use of acupuncture needles in 1996 came as a result of a workshop sponsored by the OAM with the participation of the FDA, which explored key regulatory issues. Prompted by similar regulatory issues, as well as by the initiation of NIH-funded research projects, the OAM sponsored an international symposium to examine the evidence for and the role of botanical medicine in the United States. This conference generated a series of workshops sponsored by the Drug Information Association in conjunction with NIH and FDA, which explored the scientific, regulatory, and policy issues of heterogeneous botanical products. These efforts resulted in the initiation of a large randomized multicenter clinical trial (sponsored by the National Institute of Mental Health) of the botanical, St. John's wort, for the treatment of depression, and the formation of internal working groups within the FDA that are drafting a guidance policy for the development of botanicals as drugs in the United States. This document is expected to be available in the near future.

Effects of intravenous hyperalimentation during treatment in patients with small-cell lung cancer.

One hundred nineteen patients were entered onto a randomized trial of the role of intravenous hyperalimentation (IVH) in patients with small-cell lung cancer. IVH was given during the first 30 days of induction chemotherapy to 54 patients. IVH did not effect any improvement in response or survival from therapy. In view of the lack of benefits from IVH, an analysis was made of the toxicities suffered by the 54 patients receiving IVH as well as any effects IVH might have made on chemotherapy-induced toxicity. Toxicities observed included mechanical difficulties with the catheter leading to temporary or permanent discontinuation of the IVH (11 patients), subclavian vein thrombosis (one patient), sepsis in nine patients v none of the 62 control patients, fluid overload (27 patients), hyponatremia (25 patients), and hyperglycemia requiring insulin (13 patients). Patients receiving IVH had higher granulocyte counts on days 14 and 21 of the first cycle of chemotherapy. Analysis shows that this difference is likely caused by fever and infection associated with IVH rather than any nutritional effect on granulopoiesis. In this population of patients, IVH had significant complications but did not ameliorate chemotherapy-induced toxicity and it did not effect any clinical benefit. Future studies of adjunctive nutritional therapy must consider the significant risk in this older population and must limit IVH volume or exclude patients with even mild compromise in cardiovascular functions. Further, any new trial must have a significant rationale for adjunctive use to justify the potential risks.

Production of and response to interleukin-2 by cultured T cells: effects of lithium chloride and other putative modulators.

Immunomodulating substances may be useful as host-modifying adjuvants in patients receiving immunosuppressive therapies or as probes for studying the immune system. Detection of interleukin-2 (IL-2) is possible via a microassay, enabling investigation of the effects of immunomodulating agents on T cell production of and response to IL-2 in vitro. Four such agents were examined: lithium chloride, Bestatin, Azimexon, and muramyl dipeptide (MDP). All four agents increased the response of cultured T cells to IL-2 over control populations supplied with IL-2 alone. Lithium chloride, Bestatin, and MDP enhanced the production of IL-2 in standard mixed lymphocyte cultures over control cultures receiving media alone. These results suggest that several immunomodulators may produce their effects by the modulation of IL-2 or other lymphokines. Additionally, microassay systems may prove useful as probes to elucidate the function of putative immunoregulatory substances.

The effect of intravenous hyperalimentation on the dietary intake of patients with small cell lung cancer. A randomized trial.

In a randomized trial of 119 patients with small cell cancer of the lung, the effects of a 30-day course of central intravenous hyperalimentation (IVH) on dietary intake were evaluated. All patients underwent the same aggressive chemotherapy and radiation therapy; 57 patients received IVH and 62 served as controls. Median caloric intake prior to antineoplastic therapy was less than 1.2 times basal energy expenditure, below the maximum necessary to maintain weight. While receiving IVH, patients had increased caloric and protein intake. Once the IVH was stopped, oral intake was transiently depressed and thereafter similar to control patients. Baseline nutritional parameters, age, sex, and immediate toxicity from chemotherapy did not predict subsequent caloric insufficiency. Direct estimation of dietary intake is likely the most valuable measure in selecting patients who will need adjunctive nutritional support.

Effect of adjuvant central iv hyperalimentation on the survival and response to treatment of patients with small cell lung cancer: a randomized trial.

The effect of central iv hyperalimentation (IVH) as an adjunct to aggressive antineoplastic therapy for small cell carcinoma of the lung was evaluated in a randomized trial with 119 evaluable patients. IVH was given over a 28-day period with higher caloric and protein intake for patients nutritionally depleted on entry in the study; all patients were escalated in caloric and protein intake to maximize nutritional repletion. Combination chemotherapy and radiation therapy induced a 45.5% complete response rate and an overall response rate of 92.8%. Median survival for patients with limited disease was 18 months; median survival for patients with extensive disease was 11 months. Patients randomized to receive IVH did not have a better response rate (P = 0.97) or survival (P = 0.78) than control patients. IVH did not significantly alter the survival for patients who at baseline had greater than 5% pretreatment weight loss, low caloric intake, decreased serum albumin, or reduced total iron-binding capacity. Significantly more febrile episodes were seen in IVH patients than in control patients (P less than 0.001). Short-term IVH to patients with this malignancy who are capable of enteral alimentation cannot be routinely recommended as adjunctive therapy.

Micronutrient requirements of cancer patients.

Several major factors may influence the micronutrient requirements of the patient with cancer. These factors include the metabolic state of the malignancy and its effects on host metabolism, the catabolic effects of antineoplastic therapy, and other physiologic stresses commonly associated with the treatment of cancer, i.e., surgery, fever and infection. Although the nutritional importance of vitamins, minerals and trace elements is recognized, the optimal daily dose that will preserve lean body mass without enhancing tumor growth, is not known. Recommended Dietary Allowances (RDAs), where established, are based on populations with nonmalignant diseases. However, supplementation with vitamins, minerals, and certain trace elements is recommended for the cancer patient who requires prolonged parenteral support, since clinically relevant deficiency states have been described. The effect of malignancy on the metabolism of several of these micronutrients (iron, ascorbic acid, alpha tocopherol, selenium, zinc, copper) is discussed.

Serum folate and vitamin B12 levels in patients with small cell lung cancer.

Serum folate and vitamin B12 levels were evaluated in 80 patients with small cell lung cancer at diagnosis and during therapy over a 30-week period. Approximately one half of the patients were randomized to receive hyperalimentation. Folate and vitamin B12 intake was adequate without parenteral nutrition in these cancer patients. Serum folate and Vitamin B12 levels did not correlate with disease extent. At the initiation of therapy, serum folate declined with increasing weight loss. During therapy, the intake of folate was adequate to maintain a normal serum folate despite marked weight loss.