Venous Thromboembolism and Weight Changes in Veteran Patients Using Megestrol Acetate as an Appetite Stimulant Brandon LaMarr, PharmD, BCPS; and Russell Crawford, BPharm, BCOP These study investigators sought to answer the question whether patients treated with megestrol acetate at a local VA health care system have a greater incidence of venous thromboembolism than that seen in the general population. norexia and cachexia are occur in any patient, they are com- to thrombogenic processes associated associated with a variety of monly seen in patients with cancer with the disease and its treatments.9-11 diseases, including cancer, and AIDS. Cachexia in patients with The overall prevalence of VTE in pa- A acquired immunodeficiency cancer can be due to decreased ca- tients taking MA is unclear, as studies syndrome (AIDS), congestive heart loric intake (possibly due to causes have focused on single diseases such failure, chronic obstructive pulmo- such as gastrointestinal tumors or as cancer or AIDS. The MA prescrib- nary disease, liver disease, end-stage chemotherapy-induced nausea and ing information cautions against use renal disease, and endocrine abnor- vomiting), an increased metabolic in patients with a history of venous malities such as hyperthyroidism, state, or the production of proin- thromboembolic disease, but the adrenal insufficiency, and diabetes flammatory mediators such as inter- prevalence and degree of risk are not mellitus.1 Anorexia has also been leukin-1, interleukin-6, and tumor stated.12 For this reason, many of the shown to be associated with the necrosis factor-α. AIDS-related ca- studies evaluating the efficacy of MA aging process.2 Loss of appetite, lean chexia can be caused by a hyper- have excluded patients with a history muscle mass, and adipose tissue is metabolic state, secondary infection, of VTE. associated with physical weakness medications, or gastrointestinal dis- While the risk for VTE in patients as well as decreases in quality of life, turbances.7 with cancer is firmly established, the sense of well-being, and level of func- Many randomized trials have de- risk in patients who use MA is less tionality.3,4 In addition to health detri- termined the safety, efficacy, and ideal clear. Patients with cancer who use ments, the visual and social effects of dose of megestrol acetate (MA) when MA potentially share many of the physical wasting can be emotionally used for appetite stimulation. These same thrombogenic mechanisms, in- distressing to both patients and their studies have often been small and cluding increased levels of clotting family or caregivers.5 have produced inconclusive results factors as well as decreased levels of Increased metabolic needs and de- due to the short life expectancies of anticoagulant proteins. Oberhoff and creased appetite play important roles the study population, as well as the colleagues evaluated the effects of in disease-related wasting.6 Changing many confounding variables that MA on coagulation in patients with social conditions, psychiatric prob- exist among a generally very sick and gynecologic and breast cancers and lems, and use of medications may heterogeneous patient population. found no evidence of thrombogenic also contribute to changes in appe- Uncertainty regarding the optimal potential.13 Contrasting this, a study tite, weight, and nutritional status. dosing and possible thrombogenic ef- by Kropsky and colleagues found a While anorexia and cachexia may fects of MA remain. 6-fold increased incidence of deep The average annual incidence of vein thrombosis (DVT) in elderly pa- Dr. LaMarr is a clinical inpatient pharmacist at the venous thromboembolism (VTE) tients who live in nursing homes and Southern Arizona VA Health Care System in Tucson, in the general population is about take MA.14 Arizona. Mr. Crawford is a clinical pharmacist in he- 0.1%.8 Patients with cancer are at a The purpose of this study was to motology/oncology and PGY2 Oncology Residency Program Director also at the Southern Arizona VA 4 to 7 times greater risk of VTE than evaluate the safety and efficacy of MA Health Care System in Tucson, Arizona. patients without cancer, mainly due for patients in the Southern Arizona OCTOBER 2012 • FEDERAL PRACTITIONER • 31 Venous Thromboembolism VA Health Care System (SAVAHCS). It was anticipated that data regarding 350 the safety and efficacy of MA for ap- petite stimulation generated by this 300 chart review would serve to optimize future use of MA in this veteran pop- 250 ulation. The primary objective of the 200 study was to determine the incidence of VTE in all patients using MA for 150 appetite stimulation. Secondary out- mg/d comes included evaluations of (1) the 100 effects of MA on weight, including rate of response to treatment (defined 50 by the percentage of patients main- 0 taining or gaining weight relative All patients Patients HIV/AIDS Patients with no can- to baseline) and average change in with cancer cer or HIV/AIDS weight; (2) the effects of MA on nu- Figure 1. Average daily MA dose by diagnosis. tritional status, including changes in MA = megestrol acetate. prealbumin and albumin levels while on treatment; (3) effects of MA dose dispensed at SAVAHCS for MA that ically effective, this dosage range was (low, medium, or high) on efficacy also contained the term appetite in categorized as high.12 By default, the (change in weight, rate of response) the directions to identify patients for range of doses > 100 mg and < 400 in all patients and among subgroups whom MA was dispensed and refilled mg was categorized as medium. by diagnosis (cancer, human immu- at least once. This method served to nodeficiency virus [HIV]-positive, ensure that an adequate trial period Statistics and noncancer/non-HIV-positive); of at least 30 days on MA was given. Statistical analyses on the secondary (4) comparison of VTE rates in all Searching retrospectively beginning endpoints assessed the effects of dose patients and among subgroups by di- September 1, 2008, a chart review on efficacy and VTE within diagnosis agnosis in patients treated with MA; was performed on the most recent categories as well as on comparisons and (5) effects of MA dose on VTE 100 patients treated with MA identi- of VTE incidence among diagnoses. incidence among patients with vary- fied in the prescription record search The chi-squared test was used for the ing doses. who met the previously mentioned efficacy analyses and compared the It was hypothesized that patients criteria. The reviews stopped once percentages of patients who main- treated with MA would have an in- 100 patients were identified. Patients tained or gained weight at different cidence of VTE greater than the ob- aged < 20 years or aged > 89 years dose levels with the different diagno- served rate in the general population were excluded. Patients who, on fur- ses. A one-way analysis of variance of 0.1% per year. It was also hypoth- ther review, were not using MA for was performed comparing the aver- esized that patients with cancer who appetite stimulation, were also ex- age changes in weight at different used MA would exhibit a higher rate cluded. dose levels with the different diagno- of VTE than those patients without In order to define the safest and ses as well as the incidences of VTE cancer. most effective doses of MA, the ef- among the different diagnoses. fects of low, medium, and high doses MeThodS of MA on VTE incidence and weight Results Prior to initiating this study, full in- maintenance were analyzed. Doses A total of 145 charts were reviewed stitutional review board approval < 100 mg are rarely studied, perhaps with 45 charts excluded. Reasons for was requested and obtained. A retro- because of their accepted lack of effi- exclusion included MA use for hot spective chart review was performed cacy.15 For this reason, doses < 100 mg flashes (37 charts), aged > 89 years (4 for patients using MA as an appetite were categorized as low. Since charts), gynecologic issues (3 charts), stimulant. Electronic medication re- product labeling states that doses and lack of any data relating to stud- cords were searched for prescriptions > 400 mg have been shown to be clin- ied endpoints (1 chart). Nine charts 32 • FEDERAL PRACTITIONER • OCTOBER 2012 Venous Thromboembolism Table 1. Demographic data Table 2. Incidence of VTE Treatment courses (N) 111 Subgroup VTEs (N) Incidence Average age 70 years All patients 3 2.7% Male 96% Patients with cancer 3 7.3% Patients with cancer 37% Patients on 2 5.9% P atients with HIV/ 4% high-dose MA AIDS Patients on 1 1.7% P atients with no 59% low-dose MA cancer or HIV/AIDS MA = megestrol acetate; VTE = venous thromboembolism. Table 3. Rates of response to treatment All patients Patients with Patients with Patients with no cancer HIV/AIDS cancer or HIV/AIDS P atients on 73% 71% 100% 73% high-dose MA P atients on 59% 50% N/A 64% medium-dose MA P atients on 65% 58% 100% 66% low-dose MA MA = megestrol acetate. documented more than 1 treatment 2). This resulted in a total overall When those patients who lost weight course with MA in the same patient incidence of VTE of 2.7%. All VTEs while on MA were excluded from with 2 charts documenting 3 sepa- occurred in patients with cancer lead- analysis, these effects became even rate MA courses. Each course was ing to an incidence of VTE of 7.3% more dramatic (Table 5). analyzed independently. In total, 111 in this subgroup. VTE occurred in 2 Albumin and prealbumin levels treatment courses with MA for ap- patients on high-dose MA and 1 pa- were not frequently measured in this petite stimulation were included in tient on low-dose MA resulting in an group.