Phase I study of suramin combined with doxorubicin in the treatment of androgen-independent prostate cancer.
In this study, we determined the maximum tolerated plasma concentration of suramin (within the predetermined study target range) when combined with doxorubicin in the treatment of androgen-independent prostate cancer. Twenty-four patients received suramin dosages based on proportional adjustment of the steady-state plasma suramin concentration to achieve the targeted plasma concentrations of 50-100, 101-150, 151-200, or 201-250 microg/ml. Doxorubicin (20 mg/m2) was administered i.v. over 24 h at weekly intervals. Suramin was given i.v. over 2 h twice weekly. Patients received treatment until dose-limiting toxicity or disease progression. Side effects similar to those reported for suramin and doxorubicin administered as individual agents were observed. Dose-limiting motor neuropathy developed in three patients (13%). Twelve of 24 evaluable patients (50%; 95% confidence interval, 28-71%) and 6 of 10 evaluable patients (60%; 95% confidence interval, 26-88%) had a >50% decrease of prostate-specific antigen and measurable lesions, respectively. The maximum tolerated plasma level of suramin when combined with doxorubicin was 151-200 microg/ml. Future studies on suramin combined with doxorubicin or other agents could be performed using a fixed dosing scheme with a targeted suramin steady-state plasma concentration of 200 microg/ml.
Tu
S M
SM
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Pagliaro
L C
LC
Banks
M E
ME
Amato
R J
RJ
Millikan
R E
RE
Bugazia
N A
NA
Madden
T
T
Newman
R A
RA
Logothetis
C J
CJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D004064:Digestive System / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D006321:Heart / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D012867:Skin / Q000187:drug effects; D013498:Suramin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D016896:Treatment Outcome
D013498:Suramin; D004317:Doxorubicin