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Biomedical subjects

W K Murphy

Publications and source records attributed to W K Murphy.

77 records · Page 5Linked to original sources
PubMedDate not supplied

Initial clinical studies with bruceantin.

A phase I clinical study of bruceantin was conducted in 66 patients with various types of advanced solid tumors to evaluate its toxicity and efficacy. The initial dose of 0.2 mg/m2/day x 5 days repeated at 2-week intervals was progressively increased to a maximum dose of 4.5 mg/m2/day. Hypotension was the dose-limiting toxic effect; it was delayed, cumulative, and occurred more often in patients with abnormal pretreatment liver function. Nausea, vomiting, and fever were common at higher doses, and diarrhea, stomatitis, alopecia, paresthesia, and rash were observed in some patients. The hematologic toxicity of bruceantin was moderate at high doses and was manifested mainly as thrombocytopenia; it was more severe in patients with abnormal hepatic and renal functions. No objective tumor regressions were observed. The recommended dose of bruceantin is 3.5 mg/m2/day x 5 days for phase II studies.

Adult↗
PubMedDate not supplied

Phase I clinical evaluation of 2,3-dihydro-1H-imidazo[1,2-b]pyrazole.

2,3-Dihydro-1H-imidazo[1,2-b]pyrazole, a DNA synthesis inhibitor, was given to 25 patients in a phase I study. The drug was administered by rapid iv infusion daily x 5 days at 3-week intervals at doses ranging from 150 to 1500 mg/m2/day. Side effects were observed with doses of greater than or equal to 1000 mg/m2/day and included nausea and vomiting, diarrhea, dark urine, and anemia. At doses of 1500 mg/m2, three patients had evidence of hemolysis (two had hemoglobinuria and one had acute intravascular hemolysis). The hemolysis was severe enough to cause death in one patient and necessitated abandoning further dose escalation. There was minimal or no myelosuppression at any dose level. No objective tumor regression was observed in any of the 16 patients evaluable for response. Further studies are recommended to carefully evaluate the etiology of the hemolysis before proceeding to a phase II trial. It is unlikely that this drug will prove to be useful unless methods for circumventing hemolysis are developed.

Adult↗
PubMedDate not supplied

Phase II evaluation of AMSA in adult sarcomas.

AMSA an acridine derivative, was administered to 35 adults with previously treated advanced sarcomas. Patients with adequate bone marrow reserve received 120-150 mg/m2 of AMSA as a single dose repeated every 3 weeks. Patients with inadequate bone marrow reserve received 100-120 mg/m2 of AMSA. Among 31 evaluable patients, there was one partial response that lasted 6 months in a patient with intra-abdominal malignant fibrous histiocytoma with liver metastases. Thirteen patients had stable disease with a median time to disease progression of 5 months (range, 2-13), while 17 patients demonstrated progressive disease with a median time to disease progression of 2 months (range, 1-3). The median survival time for the 31 evaluable patients in this study was 5 months. The toxic effects were mild and included myelosuppression, nausea and vomiting, fever of unknown origin, and fatigue. At the dose and schedule used in this study, AMSA does not appear to have any significant activity in advanced sarcomas of adults.

Adolescent↗