A randomized phase II study of pomegranate extract for men with rising PSA following initial therapy for localized prostate cancer.

BACKGROUND: Pomegranate juice has been associated with PSA doubling time (PSADT) elongation in a single-arm phase II trial. This study assesses biological activity of two doses of pomegranate extract (POMx) in men with recurrent prostate cancer, using changes in PSADT as the primary outcome. METHODS: This randomized, multi-center, double-blind phase II, dose-exploring trial randomized men with a rising PSA and without metastases to receive 1 or 3 g of POMx, stratified by baseline PSADT and Gleason score. Patients (104) were enrolled and treated for up to 18 months. The intent-to-treat (ITT) population was 96% white, with median age 74.5 years and median Gleason score 7. This study was designed to detect a 6-month on-study increase in PSADT from baseline in each arm. RESULTS: Overall, median PSADT in the ITT population lengthened from 11.9 months at baseline to 18.5 months after treatment (P < 0.001). PSADT lengthened in the low-dose group from 11.9 to 18.8 months and 12.2 to 17.5 months in the high-dose group, with no significant difference between dose groups (P = 0.554). PSADT increases >100% of baseline were observed in 43% of patients. Declining PSA levels were observed in 13 patients (13%). In all, 42% of patients discontinued treatment before meeting the protocol-definition of PSA progression, or 18 months, primarily due to a rising PSA. No significant changes occurred in testosterone. Although no clinically significant toxicities were seen, diarrhea was seen in 1.9% and 13.5% of patients in the 1- and 3-g dose groups, respectively. CONCLUSIONS: POMx treatment was associated with ≥ 6 month increases in PSADT in both treatment arms without adverse effects. The significance of this on-study slowing of PSADT remains unclear, reinforcing the need for placebo-controlled studies in this patient population.

Urologic complications of high-dose chemotherapy and bone marrow transplantation.

OBJECTIVE: This study reviews the incidence and management of cyclophosphamide-induced hemorrhagic cystitis in a group of patients who received high-dose chemotherapy and bone marrow transplantation. METHODS: The records of 217 consecutive patients undergoing bone marrow transplantation were reviewed. The incidence, degree, and management of hematuria in this group of pancytopenic and immunocompromised patients were recorded. RESULTS: Despite prophylaxis, cystitis developed in 58 of these 217 patients (27%). In 12 patients (6%) the cystitis was severe. These patients had gross hematuria, clot retention, and drop in hematocrit necessitating blood transfusion. These patients were managed with continuous bladder irrigation, alum irrigation, and when less aggressive approach was unsuccessful, with intravesical formalin instillation. Alum irrigation was used in 5 patients, and was successful in only 1 patient. Six patients required intravesical formalin instillation to control the hematuria. Formalin solution 2-5% was instilled initially. When lower-concentration formalin failed, 5-10% formalin was used progressively. CONCLUSIONS: Patients with bone marrow transplantation in whom severe hemorrhagic cystitis develops should be managed aggressively early. Intravesical formalin appears to be the most effective regimen in controlling profuse, persistent hematuria.

Unusual primary prostatic malignancies.

Atypical prostatic cancer is defined as any malignancy of prostatic origin, excluding the common acinar prostatic adenocarcinoma. These atypical prostate cancers account for less than 5 percent of all prostatic malignancies. Because atypical prostatic malignancies occur rarely, little is known about their biologic behavior. To date, no large series of patients have been reported, and specific treatment protocols have yet to be defined. Herein we describe 5 new cases of atypical prostatic cancer. By reporting the occurrence of new cases, we believe a better understanding of the natural history of these lesions will emerge.