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Biomedical subjects

R M Goldberg

Publications and source records attributed to R M Goldberg.

8 recordsLinked to original sources

Cancer-associated anorexia and cachexia. Implications for drug therapy.

Anorexia and cachexia are major problems in patients with cancer. Such measures as anti-cancer therapy, dietary counselling or hyperalimentation are not very successful in reversing this phenomenon in the vast majority of cancer patients. Thus, several drugs have been evaluated as agents to ameliorate cancer-associated anorexia/cachexia. Cyproheptadine is an antiserotonergic drug which appears to cause slight appetite stimulation in patients. A randomised clinical trial, however, was unable to demonstrate any weight gain from this agent. Corticosteroids are frequently used in clinical practice for appetite stimulation in patients with advanced malignancies. Supporting this practice, 4 randomised clinical trials showed that corticosteroid medications can stimulate the appetites of advanced cancer patients. However, these studies were not able to show any substantial nonfluid weight gain in treated patients. Megestrol acetate is a progestational agent which appears to be a relatively potent appetite stimulant. Randomised studies in advanced cancer patients have shown both substantial appetite stimulation and improvement in the nonfluid bodyweights of patients receiving this drug. Preliminary evidence also suggests that this drug has antiemetic properties. Several clinical studies are currently ongoing to determine the effect of various doses of megestrol acetate in patients with cancer. Efforts are also ongoing to evaluate both anabolic steroids and hydrazine sulfate as drugs for the treatment of patients with cancer anorexia/cachexia. The preliminary nature of these investigations, however, precludes recommendations for the use of either of these latter 2 drugs in routine clinical practice.

Anorexia

Phase II evaluation of menogaril in patients with advanced cervical carcinoma. A collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic.

Fourteen patients with advanced/recurrent squamous cell carcinoma of the uterine cervix received menogaril, 200 mg/m2 by one hour intravenous infusion at four-week intervals. No objective regressions were observed. Median time to progression was less than two months and median survival was seven months. All patients experienced neutropenia. Platelet toxicity was negligible. Venous irritation and phlebitis occurred at the infusion site in 43% of patients. Menogaril as administered in this protocol is ineffective in treating previously irradiated advanced/recurrent squamous cell carcinoma of the uterine cervix and warrants no further investigation in this disease at the dosage and administration schedule used in this protocol.

Adult

Bolus versus infusion regimens of etoposide and cisplatin in treatment of non-small cell lung cancer: a study of the North Central Cancer Treatment group.

In an effort to test clinically the hypothesis that the duration of cellular exposure to etoposide (VP-16) and cisplatin (CDDP) is an important determinant of cytotoxicity, we performed a phase III randomized trial comparing an outpatient bolus regimen of combined VP-16 and CDDP with a sequential infusion over 72 hours of these same two drugs. All patients had stage IV non-small cell lung cancer, and survival was the primary end point. Of 113 patients randomly allocated to the study, 108 were assessable for response, survival, and toxicity. A major response was observed in 20 (37%) of 54 patients on the bolus regimen and in 16 (30%) of 54 patients receiving infusion therapy. The median time to progression was 61 and 88 days for bolus and infusion therapy, respectively. The median survival time was 148 and 157 days, respectively (P = .71). Study results were not consistent with the possibility that infusion therapy could be associated with a 50% improvement in median survival, i.e. from 5 months to 7 1/2 months. Toxicity was primarily myelosuppression and was significantly greater with the infusion regimen. We conclude that infusion therapy as tested in this protocol with VP-16 and CDDP does not offer any advantage in response rate, time to disease progression, or survival as compared with bolus therapy. In addition, infusion therapy is associated with a greater degree of neutropenia and more treatment-related deaths.

Adult

A clinical trial of biochemical modulation of 5-fluorouracil with N-phosphonoacetyl-L-aspartate and thymidine in advanced gastric and anaplastic colorectal cancer.

A novel sequential administration schedule of PALA (N-phosphonoacetyl-L-aspartate) and thymidine to enhance the cytotoxic effect of 5-fluorouracil (5FU) was tested in 36 patients with advanced gastric cancer and 21 patients with advanced poorly differentiated (anaplastic) colorectal cancer. The potency of 5FU was dramatically increased as indicated by the observation of dose-limiting leukopenia at less than one tenth the maximum tolerated dose of 5FU when given as a single agent by intravenous bolus technique. Twenty-five percent of gastric cancer patients and 33% of colorectal cancer patients experienced an objective tumor response, including three patients with complete response. However, response duration was brief (median, 6 months), and there were four treatment-related fatalities due to severe and unpredictable leukopenia leading to sepsis. Survival was short with a median of 6 months for gastric cancer patients and 3 1/2 months for colorectal cancer patients. We conclude that therapeutic index of 5FU was not improved by the addition of PALA and thymidine in this patient population based on considerations of objective tumor response rate, patient survival, and toxicity.

Adult

Alleviation of cancer anorexia and cachexia: studies of the Mayo Clinic and the North Central Cancer Treatment Group.

Anorexia and cachexia are common clinical problems of many patients with advanced cancer. Approximately 20 years ago, a controlled, clinical study demonstrated that dexamethasone could stimulate appetites of patients with advanced gastrointestinal cancer without causing any apparent effect on patient weight or survival. More recently, two double-blind, placebo-controlled trials investigated cyproheptadine and megestrol acetate in patients with cancer anorexia/cachexia. The first of these studies suggested that cyproheptadine could mildly stimulate appetite without causing any discernible effect on patient weight. Megestrol acetate, on the other hand, can clearly cause an increase in patient-perceived appetite and food intake and can also lead to substantial nonfluid weight gain in a proportion of patients with cancer anorexia/cachexia. Ongoing studies have been designed to better study the appetite-enhancing effects of megestrol acetate. In addition, current studies are evaluating the effect of the drug hydrazine sulfate on the appetite and weight status of patients with advanced lung or colon cancer.

Anorexia

Treatment of acute nonlymphocytic leukemia in the elderly with intermediate high-dose cytosine arabinoside.

Effective treatment of the elderly patients (greater than or equal to 65 years) with acute nonlymphocytic leukemia (ANLL) remains elusive and controversial. In the present study, single-agent Cytosine Arabinoside (ARA-C) was administered at an intermediate dose level (500 mg/m2 intravenously [I.V.] 1-hour infusion q12 hours for 12 doses) to 30 newly diagnosed and previously untreated patients. Complete remission was achieved in seven patients after the initial cycle of treatment, in two patients after retreatment, and in one patient after delayed recovery of his peripheral count over a 6-month period. The toxicity of this schedule was primarily hematologic, and the response rate was in keeping with that reported by other groups using aggressive multiagent regimens.

Age Factors

Laryngeal burns secondary to the ingestion of microwave-heated food.

Thermal injuries to the upper airway are a well-recognized complication of the inhalation of steam and hot gases, but have only rarely been reported to occur in relation to the ingestion of heated foodstuffs. We report the case of an acute laryngeal burn caused by the ingestion of a microwave-heated food product, a previously undescribed complication of ingesting microwave-processed foods.

Acute Disease