Biomedical subjects
Publications and source records attributed to F M Muggia.
VM 26 and VP 16-213 are epipodophyllotoxin analogs. This paper presents a comparative analysis of their experimental and clinical features but fails to disclose any significant difference between these drugs. Similar studies with other classes of compounds might help to define some rationale for the development of analogous cytotoxic agents.
Daunomycin, like its anthracycline analog adriamycin, is a cardiotoxic antitumor antibiotic. Reports on 5,613 patients receiving daunomycin were reviewed for cardiotoxicity. Two distinct patterns of cardiotoxicity were defined, congestive heart failure (cardiomyopathy) and electrocardiographic changes. Dose-response curves were constructed using the percent incidence of cardiomyopathy versus the total dose of daunomycin in mg/m2. There was a dose-response relationship between the total dose of daunomycin and the development of cardiomyopathy, both in children and adults. The children seem more susceptible to the drug-induced cardiomyopathy. The electrocardiographic changes in the children and adults did not show a dose-dependent relationship, were present consistently even at the lowest dosage levels, and did not predict for subsequent development of cardiomyopathy. The dose-response curves constructed enable the clinician to judge the relative risk of developing cardiomyopathy at a given total dosage level and allows comparison of the human experience with the experimental animal model data.
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Estramustine phosphate is a nitrogen mustard derivative of estradiol that has been advocated for the treatment of prostatic cancer. The compound was designed with the hope that the estrogen moiety would direct the alkylating moiety to estrogen-dependent malignancies, where the alkylating moiety would be released specifically. Preclinical and clinical data are reviewed to determine to what extent that challenging concept is fulfilled. In addition, we have examined critically the efficacy of this drug for the treatment of prostatic cancer. From available data it appears that there is no evidence that the alkylating moiety of estramustine phosphate is specifically freed in estrogen-dependent tissues. Estramustine phosphate appears to be an active compound with acceptable toxicity in prostatic cancer. However, further clinical trials must be undertaken to clarify the future role of estramustine phosphate in the treatment of prostatic cancer.
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Cis-diamminedichloroplatinum (II) (DDP) leads the series of platinum coordination complexes, a new class of cytotoxic agents. The antitumor and toxic effects of this drug are discussed. It has displayed encouraging results in testicular tumors. The drug's therapeutic effectiveness has also been recognized in a variety of other solid tumors, particularly ovarian, bladder, and head and neck malignancies. Gastrointestinal, renal, audiologic, and relatively minor hematologic toxicities may be encountered, but promising methods have been developed to increase the therapeutic index of DDP.
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A detailed review of the literature was done to define the epidemiology, pathology, clinical features, and treatment of pleural mesothelioma. It appears that pleural mesothelioma accounts for approximately 400 deaths each year in the United States. Asbestos has been definitely implicated in the etiology of this disease. The common clinical features include chest pain, pleural effusion, and radiologic findings of irregular pleural thickening or pleural densities. Therapeutic modalities used in the past have included surgery, radiation therapy, and, more recently, chemotherapy. A combined modality approach to treatment appears more promising.
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Current cooperative group trails in non-Hodgkin's lymphoma have been analyzed for their overall methods and strategies. There has been more frequent application of staging procedures and individualization of protocols for favorable and unfavorable histologies according to the Rappaport classification. Early-stage protocols are evaluating the extent of radiotherapy and the need for chemotherapy as maintenance. In later stages the incorporation of new agents in induction regimens, use of cycle-active agents, development of non-cross-resistant combinations, and use of radiation in bulk disease are being examined. In childhood lymphoma, strategies using both leukemia- or lymphoma-type approaches are being tested. Cooperative group trials should also serve as an extensive repository of data on late effects of treatment and on alterations of the course of the disease for future analysis.
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Twenty-six investigational anticancer drugs formerly supplied by the National Cancer Institute are no longer available due to the lack of requests for their use in clinical trials. This report examines the data on these drugs to determine how well they were clinically evaluated. Generally, the studies are incomplete, and 34% of the compounds have not been studied beyond phase I trials. Clinical pharmacology data were not obtained for most of the drugs. In addition, the information available for drugs that did undergo phase II trials is grossly inadequate and does not permit a confident decision to withdraw them from investigational use. Instances of "hints" of activity and interesting drug properties are cited to stimulate further study. Finally, a list of compounds scheduled for future termination is given within the framework of this analysis to provoke thought toward obtaining more phase II data before these drugs fall into disuse.
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This report describes a de novo development of Kaposi's sarcoma in a Puerto-Rician man 9 months after a cadaveric renal transplant. Progression of the disease was observed despite local irradiation, while the patient remained immunosuppressed with prednisone and azathioprine. This was accompanied by depressed immunologic tests. Discontinuation of azathioprine and addition of chemotherapy (bleomycin and vincristine), while continuing prednisone to maintain functional survival of renal allograft, has led in this patient to regression of extensive cutaneous and suspected pulmonary Kaposi's sarcoma lesions. The possible importance of a depressed immunosurveillance mechanism and activation of latent oncogenic virus by the presence of an allograft in the de novo appearance of Kaposi's sarcoma in transplant recipients is briefly discussed.