nsc-366140 and Uterine-Cervical-Neoplasms

The Gynecologic Oncology Group performed a phase II study to determine the response rate to pyrazoloacridine (PZA) in patients with advanced, persistent or recurrent squamous carcinoma of the cervix.. PZA was administered intravenously over 3 h every 3 weeks. A dose of 760 mg/m(2) was given to the first 11 patients and was reduced to 560 mg/m(2) for subsequent patients. The dose reduction was undertaken because of unexpected severe neutropenia among the initial patients.. Among 24 evaluable patients, 21 of whom had prior chemotherapy, there was one, brief, complete response (4.2%) and no partial responses. The major toxicity was neutropenia.. PZA at the dose and schedule employed, has insignificant activity in this population.

Topics: Acridines; Adult; Aged; Carcinoma, Squamous Cell; Drug Administration Schedule; Enzyme Inhibitors; Female; Humans; Infusions, Intravenous; Intercalating Agents; Middle Aged; Neutropenia; Nucleic Acid Synthesis Inhibitors; Pyrazoles; Remission Induction; Salvage Therapy; Treatment Outcome; Uterine Cervical Neoplasms; Vomiting

The Gynecologic Oncology Group performed a Phase II study to determine the response rate of Pyrazoloacridine (PZA) in patients with advanced, persistent or recurrent squamous carcinoma of the cervix.. PZA was administered at a dose of 750 mg/m2 intravenously over three hours every three weeks.. Among 21 evaluable patients, there were no complete and one (4.2%) partial response. The major toxicities were hematologic.. PZA at the dose and schedule employed has insignificant activity in this population.

Topics: Acridines; Adult; Aged; Antineoplastic Agents; Carcinoma, Squamous Cell; Female; Humans; Middle Aged; Pyrazoles; Treatment Outcome; Uterine Cervical Neoplasms

To determine the maximum-tolerated doses (MTDs), principal toxicities, and pharmacologic behavior of pyrazoloacridine (PZA), a novel DNA intercalator with a unique mechanism of action, on single- and multiple-dosing schedules.. PZA was administered on a single-dosing schedule as a 1- to 3-hour infusion and on a multiple-dosing schedule as a 1-hour infusion daily for 5 days to cancer patients at doses ranging from 400 to 935 mg/m2 and 40 to 180 mg/m2/d every 3 weeks, respectively.. On the single-dosing 1-hour schedule, CNS toxicity, characterized by neuropsychiatric and neuromotor effects, prompted prolongation of the infusion duration to 3 hours and led to a study of PZA on a multiple-dosing schedule. Both measures resulted in lower incidence of CNS toxicity. Neutropenia was the principal toxicity and precluded dose escalation to levels greater than 750 mg/m2 on the single-dosing (3-hour) schedule and 150 mg/m2/d x 5 (total dose, 750 mg/m2) on the multiple-dosing schedule. Thrombocytopenia, anemia, and nonhematologic effects occurred less frequently. Responses were observed in several patients with platinum- and taxane-refractory ovarian carcinoma; antitumor activity was also noted in patients with cervical and colorectal carcinomas. Significant intraindividual variability characterized by the presence of multiple drug peaks and troughs was observed in the pharmacologic studies. The maximal PZA concentrations achieved in both studies exceeded drug concentrations associated with significant cytotoxicity in preclinical studies and correlated with the occurrence of CNS toxicity.. Neutropenia is the dose-limiting toxicity on both schedules and 750 mg/m2 and 150 mg/m2/d are the recommended starting doses of PZA on single- and multiple-dosing schedules, respectively, for minimally pretreated patients in phase II studies; slightly lower doses are recommended for more heavily pretreated subjects. The favorable toxicity profile of PZA and its antitumor activity in several refractory tumors warrant broad phase II evaluations of this agent.

Topics: Acridines; Adult; Aged; Antineoplastic Agents; Central Nervous System; Colorectal Neoplasms; DNA, Neoplasm; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Intercalating Agents; Male; Middle Aged; Neutropenia; Ovarian Neoplasms; Pyrazoles; Remission Induction; Uterine Cervical Neoplasms