Cancer Chemother Pharmacol (1995) 36:356-359 9 Springer-Verlag 1995 SHORT COMMUNICATION C. M. Camaggi 9E. Strocchi 9A. Martoni 9C. Zamagni N. Cacciari 9G. Robustelli della Cuna 9L. Pavesi M. Tedeschi 9A. Silva 9E Pannuti Pharmacokinetic evaluation of two different formulations of megestrol acetate in patients with advanced malignancies Received: 18 August 1994 / Accepted: 31 January 1995 Abstract The bioequivalence of two megestrol acetate formulations, 160-mg "tablets" and 160-mg "sachets," was investigated in a single-dose, open-label, balanced- for-sequence cross-over study involving 12 advanced-can- cer patients. The observed plasma megestrol-acetate time course obtained with both formulations was consistent with the literature data. The main source of variability in the pharmacokinetic parameters was intersubject variability; drug formulation played only a minor (and nonsignificant) role. The width of the 90% confidence interval of the area- under-the-curve (AUC) ratio (sachets: tablets) computed according to Schuirmann (0.9-1.4) was mainly due to the presence of a single outlier, showing an AUC ratio of 2.7. The trend to higher bioavailability of the new formulation was not significant, especially as compared with the dose- response data reported in the literature. Key words Megestrol acetate 9 Pharmacokinetics 9 Bioequivalence 15, 21]. The response rate is equivalent to that reported for tamoxifen, another hormonal agent widely used in treat- ment of breast cancer [16]. The weight gain associated with the use of megestroI acetate may be beneficial in patients who also have cancer anorexia. Several randomized, pla- cebo-controlled trials demonstrate that megestrol acetate therapy improves appetite and food intake in such patients [5, 11]. Data regarding the use of megestrol acetate in the treatment of cachexia related to human immunodeficiency virus (HIV) infection also indicate its effectiveness in treating HIV-related anorexia and cacbexia [9, 14]. From the compliance point of view, in advanced neo- plastic patients it is easier to give liquid formulations rather than tablets and capsules. Thus, a new 160-mg "sachet" formulation has been developed; the aim of the present study was to determine the bioequivalence of the new oral formulations of megestrol acetate relative to the commer- cially available 160-mg "tablets.". Introduction Megestrol acetate is widely used in the palliative treatment of advanced breast cancer and endometrial cancer because of its clinical efficacy and excellent safety profile. In single- agent therapy, the average overall response rate to meges- trol acetate therapy in advanced breast cancer is 30% [12, C. M. Camaggi (~) 9 E. Strocchi Dipartimento di Chimica Organica, Laboratorio ANT di Farmacocinetica e Metabolismo, Universitfi di Bologna, Viale Risorgimento 4, 1-40136 Bologna, Italy A. Martoni 9 C. Zamagni 9 N. Cacciari 9 E Pannuti Divisione di Oncologia, Ospedale S. Orsola-Malpighi, Bologna, Italy G. Robustelli della Cuna 9 L. Pavesi Divisione di Oncologia Fondazione Clinica del Lavoro, Pavia, Italy M. Tedeschi 9 A. Silva Boehringer Mannheim Italia, Monza, Italy Patients and methods Patients The subjects of this study were 12 advanced-cancer patients with normal hepatic and renal function who were aged between 40 and 70 years, had a performance status (Karnofski) of >70% and a body weight of 45-90 kg, and were within _+10% of normal for height and body frame. The characteristics of the patients are described in Table 1. The exclusion criteria were concomitant treatment with cytostatics, corticosteroids, or other hormonal therapies; concomitant treatment with phenobarbital or any other metabolic inducer drug; positive anamnesis for thrombosis, hypertension, diabetes, or cardiovascular disease; any of the following parameters higher than 25% of the upper normal range: SGOT, SGPT, serum bilirubin, blood urea nitrogen (BUN), and serum creatinine; serum albumin levels lower than 25% of the lowest normal range; and the receipt of an investigationaI drug within 30 days of the study. Drugs The megestrol acetate tablets used as a reference in this study are commercially available as Megestil 160-rag tablets, obtained from