4665 Background: Galeterone is an oral steroid analog that suppresses prostate cancer growth by inhibiting CYP17, blocking androgen receptor and reducing androgen receptor levels. Methods: Open label, multicenter dose-finding study assessing the safety, pharmacokinetics and clinical effect of escalating doses of galeterone in chemotherapy naïve CRPC patients (pts). Pts were enrolled in cohorts from 650-2,600mg of galeterone daily for 12 wks. Study also explored effects of food supplement and scheduling. Pts remained on study until disease progression or dose limiting toxicity. Results: Pt characteristics included median age 69 (47-92), median PSA 24 (6-200), and 46.9% with metastases. 36 of 49 pts completed 12 wks of study with early discontinuation for toxicity (6), progression (5), or withdrawal of consent (2). Maximal tolerated dose was not reached. The frequency of AEs was 58% grade 1, 30% grade 2, 8% grade 3 and 1% grade 4. Transient LFT elevations were seen in 15 men (5 with suspected or confirmed Gilberts). There was no trend for increasing toxicity with dose escalation and no PK difference in Gilberts pts. 9 SAEs were reported with one considered related to galeterone (rhabdomyolysis with acute renal failure in the context of high dose statin use). Overall 11/49 pts (22%) demonstrated >50% PSA decline and an additional 13/49 (26%) had 30-50% declines. Partial response by RECIST was seen in 2 pts. Consistent with lyase inhibition, increased corticosteroids and suppressed androgens were seen with dose escalation. Analysis of limited plasma collected 4 - 30 hours after dosing showed high interpatient variability with no consistent relationship to dose or time after dosing. Conclusions: Galeterone was well tolerated in CRPC pts and demonstrated clinical activity. Galeterone is being reformulated with additional PK and phase II trials planned. [Table: see text]
Purpose: The safety, efficacy and pharmacokinetics of LA-2585, a new 6-month subcutaneous depot of leuprolide acetate (Atrix Laboratories, Fort Collins, Colorado) were investigated in patients with prostate cancer.Materials and Methods: In this 12-month, open label, multicenter study 111 patients with adenocarcinoma of the prostate were administered 45.0 mg LA-2585 subcutaneously once every 6 months. The primary efficacy parameter was serum testosterone 50 ng/dl or less. Leuprolide acetate pharmacokinetics were analyzed in a subset of 28 patients.Results: Of the 111 enrolled patients 103 (93%) completed the 12-month study. Eight patients withdrew due to nonmedical reasons in 1, disease progression in 5 and cardiovascular disease in 2. By day 28, 108 of the 109 remaining patients (99%) achieved testosterone suppression, while 1 who never attained suppression was withdrawn at day 85. Mean time to castrate suppression was 21.2 days (median 21). At study completion 102 of 103 patients (99%) were below medical castrate testosterone levels of 50 ng/dl (mean +/- SE 12.3 +/- 2.1 ng/dl) with 91 of 103 (88%) at less than 20 ng/dl. Mean luteinizing hormone decreased from 6.98 +/- 0.48 mIU/ml at baseline to 0.23 +/- 0.14 mIU/ml at month 12. Luteinizing hormone was consistently below 1 mIU/ml. Mean prostate specific antigen decreased 97% from 39.8 +/- 21.5 ng/ml at baseline to 1.2 +/- 0.3 ng/ml at 12 months. No clinically significant flare reactions were observed. The most common treatment related adverse event was mild to moderate hot flashes.Conclusions: LA-2585 (45.0 mg depot) consistently produced and maintained safe and effective serum testosterone suppression with total serum testosterone well below the medical castrate level of less than 50 ng/dl.
Objective: The safety, efficacy, and pharmacokinetics of monthly subcutaneous injections of a new leuprolide acetate (LA) depot formulation were investigated in patients with advanced prostate cancer.Methods: The 2-part, 6-month (168-day), open-label, multicenter study enrolled male patients diagnosed with adenocarcinoma of the prostate (Jewett stage C or D). LA-2500 7.5-mg (a new subcutaneous depot formulation containing 7.5 mg of LA) injections were administered at monthly (28-day) intervals. The primary efficacy parameter was total serum testosterone level. A breakthrough response was defined as a single testosterone measurement >50 ng/dL after achieving castration testosterone levels. Testosterone was isolated from sera by alumina column chromatography and measured by radioimmunoassay (RIA). LA was purified by solid-phase extraction and high-performance liquid chromatography and was then quantitated by RIA.Results: One hundred seventeen of the 120 enrolled patients completed the 6-month study. Three patients withdrew for reasons not related to treatment. LA had a mean (SD) maximal concentration of 26.3 (12.6) ng/mL at 4.66 (1.44) hours and was detected for a mean of 37 days (range, 28-49 days). By day 28, 94.1% (112/119) of the patients achieved medical castration (serum testosterone less than or equal to50 ng/dL). By day 42, 100.0% (118/118) of the patients remaining in the study had serum testosterone levels less than or equal to50 ng/dL and 97.5% (115/118) had levels less than or equal to20 ng/dL. At study completion, the mean (SD) serum testosterone level was 6.12 (4.3) ng/dL (range, 3.0-27.0 ng/dL). No breakthrough or acute-on-chronic responses were reported throughout the study. From baseline to month 6, mean (SD) luteinizing hormone level decreased from 8.0 (7.3) mIU/mL to 0.09 (0.1) mIU/mL, and mean (SD) prostate-specific antigen level decreased from 32.9 (86.3) ng/mL to 3.2 (12.0) ng/mL. Treatment-related adverse events were reported by 74.2% (89/120) of patients, the most common being hot flashes (56.7%).Conclusion: This 6-month, open-label, noncontrolled study showed LA-2500 7.5-mg depot was well tolerated and maintained testosterone suppression (less than or equal to50 ng/dL) in the patients completing the study without any testosterone breakthrough responses.
No AccessJournal of UrologyClinical Urology: Case Report1 Oct 1996Vesical Keratolith: Dense Keratinous Material Mimicking a Bladder Stone J. Chandler Williams, Alan R. Schned, and Stephen N. Rous J. Chandler WilliamsJ. Chandler Williams More articles by this author , Alan R. SchnedAlan R. Schned More articles by this author , and Stephen N. RousStephen N. Rous More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)65614-3AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Vesical Keratolith: Dense Keratinous Material Mimicking a Bladder Stone." The Journal of Urology, 156(4), p. 1440 References 1 : Urothelial neoplasms: pathologic anatomy. In: . New York: Churchill Livingstone1989: 719. chapt. 17. Google Scholar 2 : Keratinizing desquamative squamous metaplasia of the upper urinary tract: leukoplakia-cholesteatoma. J. Urol.1982; 127: 631. Link, Google Scholar 3 : Congenital keratinizing desquamative squamous epithelium of the entire urinary tract. J. Urol.1991; 146: 423. Abstract, Google Scholar Departments of Surgery (Section of Urology) and Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.© 1996 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 156Issue 4October 1996Page: 1440 Advertisement Copyright & Permissions© 1996 by American Urological Association, Inc.MetricsAuthor Information J. Chandler Williams More articles by this author Alan R. Schned More articles by this author Stephen N. Rous More articles by this author Expand All Advertisement PDF downloadLoading ...
