Hormonal Therapy

Prostate Cancer continued High Activity Rhenium-186 HEDP with Autologous Peripheral Blood Stem Cell Rescue: A Phase I Study in Progressive Hormone Refractory Prostate Cancer Metastatic to Bone O’Sullivan JM, McCready VR, Flux G, et al. Br J Cancer. 2002;86:1715–1720. Rhenium-186 (186Re) combined with the bisphosphonate hydroxyethylidene diphosphonate (HEDP) has previously been shown to produce response rates ranging from 30% to 80%, with a mean duration of response of 7 weeks, in patients with bone pain secondary to metastatic prostate cancer.9 These study authors postulated that by increasing the administered activity of 186Re-HEDP, palliation benefits may be maximized. In order to prevent major bone marrow toxicity, autologous peripheral blood stem cell rescue (PBSCR) was used in all patients. The feasibility and toxicity of high activities of 186Re-HEDP (2500–5000 MBq) followed 14 days later by the return of PBSCR was tested in a phase I trial that enrolled 25 patients with androgen-independent prostate cancer metastatic to bone. Activity-limiting toxicity (grade 3/4 hematologic toxicity) occurred in 2 of the 6 patients who received 5000 MBq. A prostate-specific antigen (PSA) reduction of 50% or greater lasting at least 4 weeks was demonstrated in 20% of the patients (n = 5), and the actuarial survival at 1 year was 54%. These results are encouraging in that the authors have shown that administered activities of 5000 MBq of 186Re-HEDP with PBSCR are feasible and produce a PSA response (mean duration, 3.5 months). The authors have commenced a phase II trial to further evaluate the response rates. References 1. 2. 3. 4. 5. 6. 7. 8. 9. Carlin BI, Andriole GL. The natural history, skeletal complications, and management of bone metastases in patients with prostate carcinoma. Cancer. 2000;88:2989–2994. Scher HI, Chung LW. Bone metastases: improving the therapeutic index. Semin Oncol. 1994;21:630–656. Gotkas S, Crawford ED. Optimal hormonal therapy for advanced prostatic carcinoma. Semin Oncol. 1999;26:162–173. Diamond T, Campbell J, Bryant C, Lynch W. The effects of combined androgen blockade on bone turnover and bone mineral densities in men treated for prostate carcinoma. Cancer. 1998;83:1561–1566. Hortobagyi GN, Theriault RL, Porter L, et al. Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. N Engl J Med. 1996;335:1785–1791. Djulbegovic B, Wheatley K, Ross J, et al. Bisphosphonates in multiple myeloma. Cochrane Database Syst Rev. 2002;(3):CD003188. Clarke NW, McClure J, George NJ. Morphometric evidence for bone resorption and replacement in prostate cancer. Br J Urol. 1991;68:74–80. Garnero P, Buchs N, Zekri J, et al. Markers of bone turnover for the management of patients with bone metastases from prostate cancer. Br J Cancer. 2000;82:858–864. Maxon HR 3rd, Schroder LE, Hertzberg VS, et al. Rhenium-186(Sn)HEDP for treatment of painful osseous metastases: results of a double-blind crossover comparison with placebo. J Nucl Med. 1991;32:1877–1881. 206 VOL. 5 NO. 3 2003 REVIEWS IN UROLOGY Hormonal Therapy Androgen Replacement and Quality of Life Reviewed by Jacob Rajfer, MD The David Geffen School of Medicine at UCLA and Division of Urology, Harbor-UCLA Medical Center, Los Angeles, CA [Rev Urol. 2003;5(3):206–207] © 2003 MedReviews, LLC onsiderable attention is being paid to the quality of life as men age—and why not? As men age, they still want to remain productive, active and, of course, healthy. Unfortunately, it seems that nature is cruel. For men, this cruelty starts immediately after college, when they begin to notice, ever so subtly, that the refractory period between their erectile events increases. As men enter their forties, they begin to notice that their erections have started to change, such that the erections may not be as rigid as they once were or do not seem to last as long. Some men even begin to lose that “every moment’s interest in sex" that seems to define their persona during youth. This change in sexuality, coupled with the other phenotypic evidence of aging, such as losing one’s hair and increasing one’s waistline, begs the question—what’s next? As most men who have already traveled that road know so well, it does not get any better. What men also have to look forward to with aging is an increasing sense of lethargy, occasional bouts of memory failure, recognition of no longer being a Samson, and, sometimes, depression. Yes, they can become grumpy, overweight, old men. These aforementioned symptoms and signs are referred to as andropause or androgen deficiency of the aging man (ADAM). As men age, their testosterone levels—particularly their free testosterone levels—decrease. There are many reasons for this but, suffice it to say, this does occur in many men. If these symptoms of aging result from a decrease in testosterone levels, it makes sense that such men may benefit from exogenous androgen treatment. Many men opt for this treatment when confronted with their midlife changes because the evidence suggests that many of these afflictions of aging are ameliorated with androgen replacement. C Urologic Oncology Prostate-Specific Antigen Changes in Hypogonadal Men Treated with Testosterone Replacement Urologic Oncology Gerstenbluth RE, Maniam PN, Corty EW, Seftel AD. J Androl. 2002;23:922-926. Late Relapse of Germ-Cell Tumor Like any medication, testosterone has certain side effects. Most troubling to physicians is whether exogenous androgen treatment induces the development of prostate cancer, because this cancer is an androgen-dependent tumor. Many investigators have addressed this issue in the past. Recently, Gerstenbluth and colleagues revisited this question in a study of 54 patients, with a mean age of 60 years, who received exogenous intramuscular androgen treat- Reviewed by Hyung L. Kim, MD, Ken-Ryu Han, MD, Arie S. Belldegrun, MD, FACS A DRE and baseline PSA test should be performed prior to initiating androgen therapy. ment and were followed for a mean of 30 months with digital rectal examinations (DREs) and prostate-specific antigen (PSA) tests. From a mean baseline of 1.86 ng/mL, PSA level rose to a mean of 2.82 ng/mL in these patients. In 6 patients, however, PSA rose to a level above 4.0 ng/mL; all 6 patients underwent prostate biopsy, and only 1 showed histologic evidence of prostate cancer. The results of this study reinforce what most urologists should be doing today when a patient is placed on exogenous androgen treatment; that is, a DRE and baseline PSA test should be performed prior to initiating androgen therapy. A repeat PSA test should be done at 6 weeks to 3 months and every 6 months thereafter while the patient is receiving testosterone therapy. DREs should be performed semiannually during treatment. Any suspicious changes in the DRE or PSA level warrant a biopsy. If the biopsy is positive, androgen therapy should be withheld and appropriate therapy for the cancer entertained. If the biopsy is negative, informed consent should be provided to the patient describing the benefits and risks of continuing the androgen therapy, because prostate biopsy is not 100% sensitive in detecting prostate cancer. In instances in which the patient has benefited clinically from the androgen replacement, it is often possible to continue androgen treatment and repeat a biopsy within 3 to 6 months. In many men, treatment with androgen therapy has led to a marked improvement in quality of life, and the urologist should play a leading role in the diagnosis and treatment of andropause. Department of Urology, The David Geffen School of Medicine at UCLA, Los Angeles, CA [Rev Urol. 2003;5(3):207–208] © 2003 MedReviews, LLC erm-cell tumors represent the most common cancer in men aged 15 to 35 years. They account for approximately 95% of all testicular cancers, and their management represents one of the success stories of modern medicine. Today, approximately 90% of men diagnosed with testicular cancer are ultimately cured of their disease.1 What is particularly impressive is that, with the use of cisplatin-based chemotherapy, 70% to 80% of patients with metastatic disease achieve complete remission. Most patients who relapse after primary treatment present with recurrent disease within 2 years of initial therapy; however, 2% to 3% present with late relapse. In a retrospective analysis, Dr David George and colleagues describe the clinical characteristics and preliminary molecular data in patients with late relapse of germ-cell tumor treated at the University of Indiana. G Update on Late Relapse of Germ Cell Tumor: A Clinical and Molecular Analysis George DW, Foster RS, Hromas RA, et al. J Clin Oncol. 2003;21:113–122. This study reports on 83 patients who were identified between 1993 and 2000 with relapse of germ-cell tumor more than 2 years after initial treatment. Most patients presented with relapse more than 5 years after initial therapy. The median time to relapse was 7 years. Of the 49 patients treated by surgical resection, 43 were rendered disease-free by surgery, and 20 patients (41%) remained free of additional recurrences. Of the 32 patients treated with chemotherapy, only 6 were rendered disease-free, and 5 patients (16%) remained free of additional recurrences. Of these 5 patients, 3 were naïve to chemotherapy. Of the 32 patients treated with chemotherapy for recurrent disease, 18 were disease-free after successful postchemotherapy resection of residual lesions. VOL. 5 NO. 3 2003 REVIEWS IN UROLOGY 207