Nirmala Bhoopalam

Intravenous Zoledronic Acid to Prevent Osteoporosis in a Veteran Population With Multiple Risk Factors for Bone Loss on Androgen Deprivation Therapy

PURPOSE Androgen deprivation therapy for prostate cancer is associated with osteoporosis and increased fracture risk. Previous studies of zoledronic acid demonstrated bone loss prevention in patients initiating androgen deprivation therapy. There are limited data on patients on prolonged androgen deprivation therapy or in Veterans Affairs patients with multiple risk factors for osteoporosis. METHODS We randomized 93 patients with M0 prostate cancer in this placebo controlled trial in the Veterans Affairs health care system. Preplanned strata included 50 patients on androgen deprivation therapy for less than 1 year (stratum 1) and 43 on androgen deprivation therapy for greater than 1 year (stratum 2). In each stratum patients were randomized to 4 mg zoledronic acid intravenously every 3 months for 4 treatments or intravenous placebo. The primary end point was the percent change in bone mineral density at the lumbar spine at 12 months. RESULTS Age, race, body mass index and osteoporosis risk factors were similar for the 2 treatments. Most patients were former smokers, had moderate alcohol intake, were not on calcium/vitamin D supplements and were relatively sedentary at baseline. In stratum 1 spine bone mineral density increased 5.95% in the zoledronic acid arm and decreased 3.23% in the placebo arm (p = 0.0044). In stratum 2 spine bone mineral density increased 6.08% in the zoledronic acid arm and only increased 1.57% in the placebo arm (p = 0.0005). Treatment was well tolerated with minimal impact on renal function. CONCLUSIONS Zoledronic acid improved bone mineral density in patients with M0 prostate cancer on androgen deprivation therapy for 1 year or less, or greater than 1 year. This finding indicates that bisphosphonate therapy remains effective when initiated later in the course of androgen deprivation therapy and is efficacious in Veterans Affairs patients with multiple risk factors for osteoporosis.

A phase I clinical trial of recombinant interleukin-2 by periodic 24-hour intravenous infusions.

Recombinant interleukin-2 (rIL-2) (NSC# 600664; Hoffmann-La Roche, Inc., Nutley, NJ) was studied in a phase I clinical trial in 33 patients with advanced, measureable cancer of the colon or malignant melanoma, Eastern Cooperative Oncology Group (ECOG) performance status O-1, and no prior chemotherapy or radiotherapy. The goal of the study was to identify a dose and schedule of IL-2 to generate maximal immune modulation with tolerable toxicity. Such a regimen might allow the addition of other treatment modalities and/or prolonged treatment duration in later trials. Each patient received IL-2 as a continuous 24-hour infusion once weekly for 4 weeks and then twice weekly for 4 weeks. Five treatment groups received from 10(3) U/m2 to 3 x 10(7) U/m2 per 24-hour infusion. The maximal tolerated dose was 3 x 10(7) U/m2/d twice weekly. Patients treated twice weekly at 1 x 10(7) and 3 x 10(7) U/m2/d had immune modulation in terms of lymphocytosis, eosinophilia, increased natural killer (NK) activity, and elevated numbers of peripheral blood mononuclear cells expressing CD16, OKT10/Leu-17, and Leu-19 surface markers. Endogenous generation of peripheral blood lymphokine-activated killer (LAK) activity was demonstrated by lysis of NK-resistant Daudi targets, in patients treated at 3 x 10(7) U/m2/d. Biochemical and hematological abnormalities were moderate and reversible. Clinical toxicity included hypotension, myalgia, arthralgia, stomatitis, fever, fatigue, nausea, headache, chills, diarrhea, and oliguria at high doses. Cardiovascular toxicity was tolerable for most patients and reversed after IL-2 was stopped. Two of six melanoma patients at 3 x 10(7) U/m2/d achieved partial responses by the end of the eighth week. This IL-2 schedule appears to produce potentially clinically useful immune enhancement with tolerable toxicity.

Hemolytic anemia from ceftriaxone in an elderly patient: a case report.

Hemolytic anemia is uncommon in the general population; however, drug-induced hemolysis is not rare in hospitalized patients. We report a case of unrecognized subacute hemolytic anemia due to ceftriaxone in a geriatric patient requiring multiple blood transfusions before a correct diagnosis could be established.

Androgen deprivation therapy, osteoporosis in prostate cancer: An evaluation of risk factors and patient awareness

4693 Background: Androgen deprivation therapy (ADT) is often used early for treatment of men with prostate cancer (CAP), but recent studies show that ADT can decrease bone mineral density (BMD) and predispose to osteoporotic fractures. Patients on ADT should have DEXA scan to monitor BMD, and counseling about lifestyle modifications and vitamin supplementation to optimize bone health. The purpose of this study was to determine whether this was commonly practiced among a large group of patients receiving ADT at Hines VA hospital. METHODS A retrospective medical record review and telephone survey was conducted to evaluate risk factors for osteoporosis among 184 CAP patients on LHRH agonist therapy (>1 year duration), and to assess whether patients were counseled about lifestyle modifications (exercise, smoking cessation, alcohol moderation), calcium and vitamin D supplementation. RESULTS Chart review was completed in 184 patients and complemented by completed questionnaires in 106 (58%). Mean age 77 years; mean BMI 28; Caucasian 76% and African-American 24%. 7.6% were taking steroids, and 10.9% had a history of fracture(s). Despite only 29% of patients being counseled about calcium or vitamin D, nearly half (47%) were taking these supplements. Conversely, despite 58% of men being counseled about exercise, 42% were sedentary and only 27% routinely exercised. Most men were not currently smoking or consuming alcohol regularly, (12% and 11%, respectively). Only 24% had a DEXA scan. Finally, only 14% remembered any discussion with a physician regarding osteoporosis prior to initiation of ADT. An additional 5% recall osteoporosis counseling on follow-up visits. CONCLUSIONS The majority of patients with CAP undergoing ADT did not receive counseling focused on osteoporosis prevention, despite the prevalence of concurrent risk factors for osteoporosis. Based on this data, we have now developed a brochure to educate our patients on ADT about osteoporosis, and we have organized an osteoporosis prevention and treatment clinic for this vulnerable population. No significant financial relationships to disclose.