A phase II trial of CI-958 in patients with hormone-refractory prostate cancer.
OBJECTIVE
To assess the antitumor activity of the benzothiopyranoindazole CI-958 ¿5-[(2-aminomethyl)amino]-2-[2-(diethylamino)ethyl]-2H- [l]benzothiopyrano[4,3,2-cd]-indazol-8-ol trihydrochloride¿ in hormone-resistant prostate carcinoma, using an intravenous dose of 700 mg/m(2) every 3 weeks.


METHODS
Patients eligible for this study had advanced prostate carcinoma that had failed hormonal treatment. Changes in an initially elevated prostate-specific antigen (PSA) level and regression of objectively measurable disease were used as response criteria.


RESULTS
All 33 patients enrolled were evaluated. Of 30 with elevated PSA levels, 6 had a >50% decline maintained for >30 days; response durations ranged from 105 to 623 days. Eleven patients had objectively measurable disease; two had partial responses (lasting 316 and 461 days) consisting of shrinkage of retroperitoneal nodes and of masses surrounding the rectum and bladder. The survival of all responding patients ranged from 366 days to 709 days and the median survival of all patients was 12 months (range 1-23 + months). Neutropenia was common, but thrombocytopenia was not. Nonhematologic side effects included nausea, vomiting, anorexia, asthenia, and chills, but were usually mild. The drug caused phlebitis when given into peripheral veins and central venous administration is recommended. No consistent reductions in cardiac function were documented by sequential assessment of left ventricular ejection fractions.


CONCLUSIONS
CI-958 has modest but definite antitumor activity in hormone-resistant prostate carcinoma. Its toxicities include neutropenia, nausea, vomiting, anorexia, asthenia, chills and phlebitis.
Woolley
P V
PV
University of Pittsburgh Cancer Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Freiha
F S
FS
Smith
D C
DC
Carlson
L
L
Hofacker
J
J
Quinn
N
N
Grove
W
W
Trump
D L
DL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007191:Indazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018579:Patient Selection; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D014057:Tomography, X-Ray Computed; D017211:Treatment Failure
D000970:Antineoplastic Agents; D007191:Indazoles; C054558:ledoxantrone; D017430:Prostate-Specific Antigen