Phase II trial of pyrazoloacridine as second-line therapy for patients with unresectable or metastatic transitional cell carcinoma.
OBJECTIVE
A phase II trial of pyrazoloacridine (PZA) was conducted to assess its activity and toxicity in patients with advanced transitional cell carcinoma (TCC) refractory to or progressing after one prior cisplatin-, carboplatin- or paclitaxel- based regimen.


METHODS
PZA at a dose of 750 mg/m2 was administered to 14 patients as a three-hour intravenous infusion on day 1 every 21 days. Premedication consisted of lorazepam 0.5-1.0 mg prior to each cycle to alleviate central nervous system toxicity. Reduction of subsequent doses was made for hematologic or central nervous system toxicity.


RESULTS
Among fourteen patients evaluable for response, no responses were observed (0% response rate; 95% confidence interval 0% to 23%). The median duration of survival for all patients was 9 months with a median follow-up of 8.5 months. Toxicity to PZA included grade 3 or 4 neutropenia in 8/14 (57%) and grade 3 or 4 thrombocytopenia in 2/14 (14%). Non-hematologic toxicity was mild.


CONCLUSIONS
PZA at this dose and schedule does not have significant single-agent activity in patients with TCC who have failed one prior regimen.
Dodd
P M
PM
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
McCaffrey
J A
JA
Mazumdar
M
M
Icasiano
E
E
Higgins
G
G
Herr
H
H
Bajorin
D F
DF
D000166:Acridines / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality
D000166:Acridines; D000970:Antineoplastic Agents; D011720:Pyrazoles; C064541:NSC 366140