Megestrol acetate in advanced, progressive, hormone-insensitive cancer. Effects on the quality of life: a placebo-controlled, randomised, multicentre trial¹

Abstract

A randomised double-blind placebo-controlled multicentre trial was performed to investigate the effects of megestrol acetate (MA) on the quality of life (QoL), appetite, weight and survival of patients with advanced, incurable, hormone-insensitive cancer. QoL was assessed at the start of treatment and at 4, 8 and 12 weeks, using the EORTC-QLQ-C30 instrument. 255 patients were randomised to 320 mg of MA daily or placebo for 12 weeks. 244 patients were assessable at baseline, 190 at 4 weeks (placebo 94; MA 96), 150 at 8 weeks (placebo 69; MA 81) and 112 at 12 weeks (placebo 55; MA 57). A beneficial effect of MA on appetite loss was observed at week 4 (P<0.0001) and possibly at week 8 (P=0.058). Further weight loss during treatment was significant only in the placebo group. In the first 8 weeks, changes in mean global QoL were small and similar in both groups. By 12 weeks the decrease in mean global QoL was more pronounced in the MA group (P=0.028), which was related to a deterioration in physical function, while psychosocial function was not affected. Survival was not affected by MA, and side-effects were mild. The results show that MA has a beneficial effect on appetite and that it may retard weight loss with no adverse impact on survival and with mild toxicity. However, MA does not appear to improve global QoL as measured by the EORTC QLQ-C30.

Introduction

Cachexia and weight loss1, 2are important factors contributing to the impaired quality of life of cancer patients, and more than 50% of cancer patients have cachexia at death3, 4. In several controlled studies, treatment with corticosteroids resulted in an improvement in symptoms and the quality of life5, 6, 7, 8. Cyproheptadine has a mild stimulating effect on appetite[9], and metoclopramide is useful in patients with delayed gastric emptying[10]. Other treatments have not been successful11, 12, 13.

Megestrol acetate (MA) and medroxyprogesterone acetate often cause weight gain as a side-effect in the endocrine treatment of advanced breast cancer[14]and prostate cancer[15]. Thus, MA has been tried as a treatment for cancer-related cachexia/anorexia, and uncontrolled studies16, 17have shown that this treatment resulted in an increase in appetite and weight.

In an early controlled study, Bruera and associates[18]randomised 40 patients in a double-blind cross-over trial to 480 mg of MA a day versus placebo for 7 days. Appetite, subjective energy level, triceps skinfold measurement and calf circumference improved significantly on treatment with MA. Loprinzi and associates[19]randomised 133 patients into a group treated with 800 mg of MA a day or a group on placebo. Patients assigned to the MA group reported improved appetite and food intake more often. A weight gain of 15 lb or more above the baseline was found in 16% of patients on MA compared with 2% in the placebo group.

To investigate the effects of MA on the quality of life (QoL), appetite, weight and survival, we conducted a double-blind, randomised, multicentre placebo-controlled trial of MA in patients with advanced-stage, incurable, progressive, hormone-insensitive cancer. The primary end-point for the study was QoL. Secondary end-points were survival, weight and side-effects. General aims were to collect data on QoL and study the performance of the QoL instrument.