Biomedical subjects

J G Posada

Publications and source records attributed to J G Posada.

5 recordsLinked to original sources

PubMed1986

Amsacrine-associated cardiotoxicity: an analysis of 82 cases.

Amsacrine is an antileukemia drug being widely used in North America, Europe, Australia, and New Zealand. In the initial clinical trials, patients treated with amsacrine developed occasional instances of acute cardiac arrhythmias and cardiomyopathy. We review and analyze the features of cardiac abnormalities associated with amsacrine in 82 patients, 27 of whom have not been previously reported. The rest have been reported in the literature, but we have included a large amount of additional information about these patients in our analysis. We conclude that amsacrine-related cardiac events are less common than those related to anthracycline chemotherapeutic agents. Manifestations of such toxicity include ECG abnormalities, ventricular and atrial arrhythmias, sudden death, and congestive heart failure. There is little or no cumulative dose effect. Hypokalemia may be a risk factor for development of serious tachyarrhythmias, but such problems can occur despite a normal serum potassium level. Amsacrine appears to affect depolarization and repolarization of the heart, but the mechanism is unknown.

Adolescent↗

PubMed1985

The cyclophosphamide, hexamethylmelamine, 5 fluorouracil (CHF) regimen in the treatment of advanced and recurrent ovarian cancer.

Fifty-one patients with advanced ovarian carcinoma were treated with a combination of cyclophosphamide, hexamethylmelamine, and 5-fluorouracil, CHF. Compared to the hexamethylmelamine, cyclophosphamide, methotrexate, and 5-fluorouracil (Hexa-CAF) regimen, the omission of methotrexate in CHF did not detract from its antitumor activity and it was well tolerated with only mild to moderate toxicity. The CHF combination was as effective as Hexa-CAF and was particularly active in patients who had nonmeasurable/residual disease, classified as less than 2 cm in its greatest diameter at the initiation of chemotherapy. In future studies, CHF should be prospectively compared to other combination using Adriamycin and cis-platinum that with extended use can cause renal and cardiac damage in long-term survivors.

Adult↗

PubMed1984

Anaphylactic reactions to diaziquone.

Diaziquone, an aziridinylbenzoquinone currently in phase II-III trials, is an alkylating agent, the major toxic effect of which is myelosuppression. We report here on six cases of hypersensitivity attributable to diaziquone. In five patients an acute reaction characterized by hypotension, bronchospasm, and urticaria was observed. In one patient a delayed urticarial rash was noted. Resolution was rapid in all patients but one, who responded to standard treatment over a period of hours. No reaction was fatal. Approximately 2000 patients have been treated with diaziquone in clinical trials sponsored by the National Cancer Institute. It is suggested that the reaction may not be to the drug itself but to the vehicle (dimethylacetamide) in which diaziquone is formulated. Studies to elucidate the relative contribution of drug and vehicle are warranted.

Aged↗

PubMed1983

Diaziquone (AZQ).

Diaziquone is an aziridinylbenzoquinone with properties suggestive of an alkylating agent. The drug has shown broad antitumor activity against numerous transplantable murine tumors including curative activity against several intracerebrally implanted tumors. Parent diaziquone appears to have a t1/2 beta of approximately 30 min. The drug is rapidly and widely distributed to tissues as evidenced by a t1/2 alpha of approximately 1-3 min and a volume of distribution exceeding that of total body water. In addition, it rapidly penetrates the central nervous system, reaching peak concentrations (30-50%) of corresponding plasma levels) in approximately one hour. Diaziquone is rapidly and extensively metabolized by the liver. Diaziquone is a potent marrow suppressive agent inducing significant degrees of leukopenia, granulocytopenia, and thrombocytopenia in humans. Thrombocytopenia is often severe. Although myelosuppression is for the most part dose related, many patients had significant toxicity even at lower doses. Most investigators have attributed this to the extent of prior therapy. Diaziquone demonstrates a very steep dose-response relationship. Myelosuppression was the dose-limiting toxicity in all phase I trials. No nonhematologic dose-limiting toxicity has been identified to date. In phase I and preliminary phase II trials, diaziquone has demonstrated activity against primary brain tumors. Little activity has been seen in other tumor categories. It should be noted, however, that all studies to date have been carried out in heavily pretreated patients. Because of the broad spectrum of antitumor activity in experimental murine tumors, the lack of nonhematologic dose-limiting toxicity, the ability of this drug to attain significant levels in the central nervous system, and the activity of the drug in primary brain tumors, further studies examining its role in the management of patients with cancer are warranted. These studies should be conducted in patients who have had little or no prior therapy in order to better evaluate the efficacy of the drug.

Animals↗

PubMed1983

Nephrotoxicity of semustine.

Semustine is an investigational cancer chemotherapeutic agent in widespread use. This agent has now been documented to produce nephrotoxicity and renal failure with long-term administration. We collected 29 cases of semustine nephrotoxicity from the literature and six unpublished cases brought to the attention of the National Cancer Institute. Using these 35 cases as a data base, we have analyzed the incidence, dose and treatment duration relationships, clinical and histologic manifestations, and clinical course of semustine nephrotoxicity. In addition, we discuss the possible mechanisms of this nephrotoxicity based upon ongoing laboratory work. We conclude that there is a high risk of severe nephrotoxicity from semustine when the cumulative dose exceeds 1200 mg/m2 and that there may be considerable delay in onset of the renal dysfunction.

Animals↗