Early development of castrate resistance varies with different dosing regimens of luteinizing hormone releasing hormone agonist in primary hormonal therapy for prostate cancer.

OBJECTIVES: Luteinizing hormone releasing hormone (LHRH) agonist therapy is one of the mainstays of prostate cancer treatment. Three dosing regimens currently exist: calendar-based, intermittent, and a testosterone (T)-based (T-based) regimen. We investigated the differences in development of early castrate resistance rates between these different regimens. METHODS: We evaluated 1617 patients with prostate cancer who received LHRH-agonist monotherapy in the Kaiser Permanente Southern California Cancer Registry between January 2003 and December 2006. Patients who had undergone surgery and/or radiation were excluded. Patients were grouped according to their dosing regimen: calendar-based, intermittent dosing, and T-based. Cox proportional hazard-regression analysis was used to estimate the hazards ratio (HR) for treatment failure. RESULTS: A total of 692 patients who received an LHRH agonist as primary monotherapy for prostate cancer fit our criteria. Calendar-based dosing was used in 325 patients; 252 received T-based dosing and 115 received intermittent dosing. On multivariate analysis controlling for demographic and prostate cancer-related variables, the T-based dosing group showed a significantly lower relative risk of treatment failure (HR = 0.65, P = .02). The intermittent-dosing group trended toward a lower risk treatment failure (HR = 0.80, P = .3). Among the variables analyzed, only a Gleason score >8 (HR = 2.05, P = .01) and a pretreatment prostate-specific antigen >20 (HR = 2.00, P <.01) were associated with a higher risk of treatment failure. CONCLUSIONS: During the time period studied, T-based and intermittent dosing regimen of LHRH agonist had lower rates of early castrate resistance compared with standard calendar dosing, based on measurements for early androgen resistance.

Maggot therapy for problematic wounds: uncommon and off-label applications.

OBJECTIVE: To identify off-label uses for maggot therapy that may be worthy of further clinical evaluation. DESIGN: Clinician surveys and invitations to submit unusual and off-label uses of maggot therapy. SETTING: All levels of inpatient, outpatient, extended care, and home care. PARTICIPANTS: More than 350 clinicians known to use maggot therapy were invited to participate in the survey. Twelve returned the survey. MAIN OUTCOME MEASURE: Indications for maggot therapy other than simple debridement of wounds listed on product labeling. MAIN RESULTS: A total of 544 wounds were treated by the 12 respondents; 131 (24%) were rare or off-label applications, including stimulation of epithelialization in clean but nonhealing wounds; disinfection, odor, and drainage control; determination of tissue viability; debridement of acute burns, necrotic tumors, and ischemic ulcers; and debridement of unusual sites (ie, glans penis, joints, pleural space, and peritoneal cavity). Noted drawbacks included the time and effort needed to train personnel and convince administrators of the need for treatment. CONCLUSION: Medicinal maggots are frequently being used as an adjunct to other methods of surgical and nonsurgical wound care and often for off-label indications, including debridement, disinfection, and stimulation of healing. Further study is warranted to evaluate the efficacy and safety of maggot therapy for these indications, and better education is needed for administrative and clinical staff to make maggot treatment more accessible.

Determining dosing intervals for luteinizing hormone releasing hormone agonists based on serum testosterone levels: a prospective study.

PURPOSE: Long acting luteinizing hormone releasing hormone agonists are the predominant form of androgen suppression in the treatment of prostate cancer with the goal of maintaining castrate levels of testosterone. Current dosing of luteinizing hormone releasing hormone agonists does not include monitoring the end organ response of serum testosterone. Recent evidence suggests standard dosing regimens fail to achieve castrate levels of testosterone in some patients while in other patients testosterone can remain at castrate levels longer than the manufacturer recommended dosing interval. We prospectively evaluated patients with prostate cancer receiving luteinizing hormone releasing hormone agonist hormonal therapy to determine the length of time that serum testosterone remains at or below castrate levels. MATERIALS AND METHODS: A 3-month dose of 22.5 mg leuprolide was administered to all patients as a first dose followed by a second dose 3 months later. Serum testosterone and prostate specific antigen were measured prospectively before starting hormonal therapy, after the first dose (12 weeks) and again following the second dose (24 weeks) to assess if castrate levels of testosterone (50 ng/dl or less) had been reached. At 24 weeks if patient serum testosterone was 50 ng/dl or less, then 22.5 mg leuprolide were not administered, and serum testosterone and prostate specific antigen were checked monthly. When serum testosterone was greater than 50 ng/dl a subsequent dose of 22.5 mg leuprolide was given. Serum testosterone and prostate specific antigen were then checked 3 months later and monthly thereafter until testosterone was greater than 50 ng/dl. Thus, the time that testosterone remained at castrate levels could be accurately established. RESULTS: From February 2003 to August 2005, 42 patients were treated in this manner with a median followup of 18 months (range 10 to 30). Average patient age was 77 years. Median Gleason grade was 7 (range 6 to 9). Median pretreatment prostate specific antigen was 15.1 ng/ml (range 0.6 to 433) and median posttreatment prostate specific antigen was 0.74 (less than 0.1 to 120). The median dosing interval was 6 months (range 5 to 12). Three patients had an increase in prostate specific antigen while receiving treatment despite castrate levels of testosterone. No patient required more frequent dosing than every 5 months. CONCLUSIONS: Testosterone based luteinizing hormone releasing hormone agonist therapy makes empirical sense. It represents continuous androgen ablation based on the patient physiological end point, namely testosterone. Early data suggest that using serum testosterone to guide luteinizing hormone releasing hormone dosing is safe, efficacious and cost-effective. By following end organ response, patients receive individualized care and more accurate androgen suppression therapy.

Intravenous urography in evaluation of asymptomatic microscopic hematuria.

BACKGROUND AND PURPOSE: In 2001, the American Urologic Association Best Practice Policy Panel recommended CT or intravenous urography (IVU) over ultrasonography as the initial imaging modality in patients with asymptomatic microhematuria. We here present results of a study initiated many years ago and completed prior to 2001 that provides information pertinent to the use of IVU as the initial imaging modality for such patients. PATIENTS AND METHODS: This study compared the results of IVU and ultrasonography in patients 40+ years of age who were referred to a single urology department for evaluation of microscopic hematuria between 1994 and 2000. There were 290 patients who agreed to participate by undergoing ultrasonography in addition to IVU; 247 completed both tests. There were 81 men and 166 women with a mean age of 56.4 years (range 40-86 years). Thirty patients (12%) were smokers. RESULTS: A renal lesion or mass suggestive of tumor was found in 8 patients (3.2%); 3 patients had this finding on the IVU examination and 5 on ultrasonography. None of the patients had such a lesion/mass on both examinations. Two patients with suspect lesions were ultimately found to have renal-cell carcinoma. Both of the patients with renal cancer had a suspect lesion on the ultrasound examination but not on the contemporaneous IVU. CONCLUSION: Intravenous urography may miss lesions/masses that lead to a diagnosis of upper-tract neoplasia.

Reversible infertility in a man with 21-hydroxylase deficiency congenital adrenal hyperplasia.

OBJECTIVE: To report a case of an azoospermic man diagnosed with 21-hydroxylase deficiency congenital adrenal hyperplasia who successfully conceived with intrauterine insemination (IUI) after hormonal and clomiphene citrate (CC) treatment. DESIGN: Case report. SETTING: Outpatient practice and academic hospital. PATIENT(S): A 32-year-old azoospermic man who presented for evaluation of male factor infertility. INTERVENTION(S): Semen analysis, ultrasonography, endocrinologic assays, hormonal treatment, CC, and IUI. MAIN OUTCOME MEASURE(S): Semen analysis demonstrating increased sperm count and motility, ultrasonography demonstrating persistent nodules in bilateral testes, endocrinologic assays demonstrating elevated FSH and LH after CC treatment. RESULT(S): Successful intrauterine pregnancy after IUI using the patient's sperm. CONCLUSION(S): Clomiphene citrate treatment in addition to hormonal manipulation in azoospermic patients with congenital adrenal hyperplasia can be successful in improving sperm count and motility to allow for successful conception using IUI. The presumed adrenal rests in the testes may not involute after adrenal suppression.