Phase II study of pyrazoloacridine in patients with advanced colorectal carcinoma.
OBJECTIVE
Pyrazoloacridine (PZA) is an acridine derivative selected for clinical development because of broad preclinical antitumor activity and solid tumor selectivity. Phase I evaluations with PZA have demonstrated predictable toxicity and suggested clinical efficacy. A phase II trial in patients with previously untreated advanced colorectal cancer was conducted.


METHODS
PZA was administered at a dose of 750 mg/m2 intravenously over 3 h every 21 days to patients who received a total of 31 courses of PZA.


RESULTS
In 15 patients evaluable for response, no responses were observed (0% response rate, 95% confidence interval 0-22%). Toxicity to PZA consisted of myelosuppression and neurotoxicity that was treatment-limiting in several instances.


CONCLUSIONS
PZA at this dose and schedule of administration is inactive in patients with colorectal cancer.
Zalupski
M M
MM
Karmanos Cancer Institute, Department of Medicine, Wayne State University, Detroit, MI 48201, USA.
Philip
P A
PA
LoRusso
P
P
Shields
A F
AF
D000166:Acridines / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000556:secondary; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D012449:Safety; D016896:Treatment Outcome
D000166:Acridines; D000970:Antineoplastic Agents; D011720:Pyrazoles