Phase II trial of pyrazoloacridine in recurrent platinum-sensitive ovarian cancer: a Gynecologic Oncology Group study.
OBJECTIVE
Acridine compounds are believed to exhibit anti-cancer cytotoxic effects because of interactions with both DNA and RNA. Pyrazoloacridine (PZA) (NSC No. 366140) is a 9-methoxyacridine compound that has demonstrated activity in some patients with solid tumors. The Gynecologic Oncology Group (GOG) performed a phase II trial of PZA to determine the response rate of this agent in patients with recurrent platinum-sensitive ovarian cancer.


METHODS
Patients with recurrent ovarian cancer who experienced a progression-free interval of greater than 6 months after response to platinum-based chemotherapy are defined as platinum sensitive by the GOG and were eligible for this trial. PZA was administered at a dose of 750 mg/m2 intravenously over 3 h every 3 weeks.


RESULTS
Among 42 evaluable patients, there was 1 (2.4%) complete response and 9 (21.5%) partial responses, including 1 patient who had a partial response after 10 courses of treatment. The major toxicity was neutropenia; severe thrombocytopenia was infrequent.


CONCLUSIONS
PZA demonstrates moderate activity in this chemotherapy-sensitive population, with manageable hematologic toxicity. Due to its unique mechanism of action and preclinical activity against hypoxic and noncycling cells, PZA should be considered for evaluation in combination with other active agents.
Plaxe
Steven C
SC
Department of Gynecologic Oncology, University of California at San Diego, San Diego, California 92103, USA.
Blessing
John A
JA
Bookman
Michael A
MA
Creasman
William T
WT
D000166:Acridines / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*
D000166:Acridines; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011720:Pyrazoles; C064541:NSC 366140