Homoharringtonine: a phase I evaluation

Summary Homoharringtonine is one of several Cephalotaxine esters which have shown experimental antineoplastic activity as well as anti-leukemia effects in patients in China. In a Phase I trial of homoharringtonine administered daily × 5 by bolus intravenous injection, the dose limiting toxicity was hypotension and the maximum tolerated dose was 3.5 mg/m²/d × 5. Evidence of drug induced cardiac irritability with resulting ventricular and atrial dysrhythmias was seen. Minimal myelosuppression was seen at this dose. Treatment of patients by 5 day continuous intravenous (rather than bolus) infusion resulted in more pronounced myelosuppression and clinically significant but tolerable hypotension. Significant reduction of white blood cell and platelet counts occurred at a dose of 3.5 mg/m²/day. Further investigations of the hypotensive and cardiac effects of homoharringtonine and Phase II trials using continuous infusion are indicated.     

Phase I evaluation of piperazinedione in patients with advanced cancer.

The effects of iv administered piperazinedione were studied in 28 evaluable adult and eight evaluable pediatric patients with advanced cancer. Piperazinedione produced predictable myelosuppression of moderate degree at dosages of 3--3.5 mg/m2/day X 5 days by iv injection. When given in this manner, nausea and vomiting did not occur. Single iv doses of 10--15 mg/m2 produced mild-to-moderate nausea and vomiting and mild myelosuppression. Thrombocytopenia was more severe than leukopenia in both schedules. The drug produced comparable dose-related effects in adults and children. Although no therapeutic response was observed in the adults, a partial remission of 6 months' duration was seen in one child with Hodgkin's disease.     

Treatment of advanced and recurrent ovarian carcinoma with cyclophosphamide, doxorubicin, and cisplatin

Forty-seven patients with primary advanced (N = 37) or recurrent ovarian carcinoma (N = 10) completed a 12-month course of CAP chemotherapy or developed progressive disease while on therapy and were evaluated. All patients were treated between August 1, 1977 and August 1, 1982. Cyclophosphamide 400 mg/m2, Adriamycin (doxorubicin) 40 mg/m2, and cisplatin 60 mg/m2, were administered every 4 weeks intravenously. After 8 courses the cisplatin was stopped. The patients then received 500 mg/m2 of cyclophosphamide and 50 mg/m2 of Adriamycin. At the cumulative dose of 450 mg/m2, the Adriamycin was stopped and cyclophosphamide was given at 1 g/m2 alone until the patient had received a total of 12-13 courses from the initiation of the chemotherapy protocol. The cardiac, renal, and hematopoetic toxicity of the regimen was mild to moderate. The median survival of the entire study population was 32 months. The median survival of the patients with primary disease was 36 months. The median survival of patients with recurrent disease was 20 months. There was a significant difference in median survival based on size of the largest lesion prior to initiation of chemotherapy. There was no difference in median survival based on tumor grade or comparing Stage III to Stage IV tumors. The most important aspects of the study appeared to be the length of the median survival of the patients, the fact that all patients who were complete responders and who were considered to have no evidence of disease, have been documented by second look, and the success of secondary treatment after second-look procedures revealed persistent tumor. The authors additionally report the use of weight change as an indicator of tumor response, and the importance of the pelvic examination complimented by fine-needle aspiration in following the course of these patients.     

Noninvasive ambulatory blood pressure monitoring in patients with recently detected systemic hypertension

Noninvasive ambulatory blood pressure monitoring and Doppler echocardiography were used in a recent study evaluating persons aged 18 to 50 years who were initially found to have mild hypertension by casual blood pressure determination. Ambulatory blood pressure recordings were performed on a day of usual activity in 54 subjects; a subgroup of 24 patients had evaluation of left ventricular dimensions and diastolic filling patterns by Doppler echocardiography. Average ambulatory systolic pressures of 42% of subjects were greater than or equal to 130 mm Hg. Only 35% had average diastolic pressures greater than or equal to 85 mm Hg, and 57% had either systolic or diastolic pressures greater than or equal to 130/85 mm Hg. Correlation between casual and ambulatory pressures was not significant. No subject had left ventricular hypertrophy determined by echocardiography. Abnormal left ventricular diastolic filling was noted in 38% of those patients with average ambulatory pressures greater than or equal to 130/85 mm Hg, but in no patients with average pressures less than 130/85 mm Hg (p less than 0.05). These results suggest that ambulatory blood pressure monitoring may be a specific method for detecting those patients with mild hypertension who may have early and potentially reversible cardiac abnormalities.