A double blind placebo controlled trial of medroxyprogesterone acetate (MPA) in cancer cachexia

Abstract

Summary Patients with breast cancer treated with MPA often report an improvement in appetite. Similar appetite stimulation is seen in patients treated with some corticosteroids, but MPA has a potential advantage over these drugs in that it does not exert a catabolic effect. MPA (100 mg tds orally) has therefore been compared with placebo in 60 patients with advanced malignant disease. Twenty-one patients in the MPA group and 20 in the placebo group were receiving chemotherapy. Patients were treated for 6 weeks and were assessed at weeks 0, 3 and 6 for appetite, energy, mood and pain using visual analogue scales. Nutritional status was assessed by the measurement of serum proteins and anthropometrics. Karnofsky score was recorded as a measure of performance status.There was a significant improvement in appetite in the MPA group between weeks 0 (pre-study) and 3 (P = 0.0002) and 0 and 6 (P = 0.015). There was no significant improvement in appetite in the placebo group. Supporting this finding was the significant increase in serum thyroid binding pre-albumin and retinol binding protein in the MPA group between weeks 0 and 3 and 0 and 6 (P = 0.023 and P = 0.039 respectively). These two parameters showed no significant change in the placebo group Anorexia is a debilitating symptom commonly experience by cancer patients (Theologides, 1977). It is a component of protein-energy malnutrition which is associated with a poor prognosis, reduced response to anti-neoplastic therapy and a reduced quality of life (Holmes & Dickerson, 1987). In a study of 126 cancer patients receiving chemotherapy or radiotherapy Padilla et al. reported that appetite and the ability to eat were the most important factors in the physical aspects of the patients' quality of life. These factors were more important in determining quality of life than the ability to work, physical strength or sexual satisfaction (Padilla, 1986). The background to this often profound loss of appetite and the weight loss that accompanies cancer is complex and agreement on the underlying mechanism has not been reached (Bernstein & Symundi, 1980). Psychological, emotional or physiological factors due to the disease and treatment may initiate or worsen anorexia, but as the disease progresses it is usually the cancer itself that is the main cause of the anorexia (Theologides, 1977 (Goodinson, 1987a). More recently a number of studies have investigated the use of biochemical testing in nutritional assessment, with particular reference to plasma proteins (Mullen & Torosian, 1981;Inglebleek et al., 1975;Carpentier et al., 1982;Ota et al., 1985;Thean et al., 1988;Weisberg, 1983). Those (Aitken, 1969). As an instrument they allow a measurement of changes in subjective feelings within individual patients over a set time. These scales have been validated for reliability, between subject reliability, test-retest reliability and validity by Silverstone (1982).

Medroxyprogesterone acetate inhibits interleukin 6 secretion from KPL-4 human breast cancer cells both in vitro and in vivo: a possible mechanism of the anticachectic effect

“…However, the results of a recent clinical trial suggest that this adverse effect results in improvement of the anorexia and bodyweight loss induced in patients by cytotoxic agents (Tominaga et al, 1994). Moreover, MPA has been used as an anticachectic agent for patients with non-breast malignancies in a clinical trial (Downer et al, 1993). A similar clinical trial has been conducted using another synthetic progestin, megestrol acetate (Gebbia et al, 1996).…”

“…It has been reported, however, that concomitant administration of MPA reduces the nausea and anorexia induced by the administration of cytotoxic agents, and subsequently reverses bodyweight loss (Tominaga et al, 1994). Based on these findings, a clinical trial using MPA as an anticachectic agent has been undertaken in patients with various malignancies which are not hormone responsive (Downer et al, 1993).…”

Mechanisms Behind Illness-Induced Anorexia

“…Improvement of appetite by treatment with medroxyprogesterone acetate did not result in weight gain in patients with malignant cancer [123] and it was shown that most of the weight gain seen in that study was due to increase of adipose tissue and water [124]. The changes in metabolism and tissue catabolism in cancer patients are extensive (see [125]), but the cause leading to the metabolic changes as well as the cause of appetite suppression are poorly understood.…”

What We Have Learned about Cachexia in Gastrointestinal Cancer

“…Studies using medroxyprogesterone acetate have also been associated with a significant increase in appetite together with increases in serum thyroid binding prealbumin (transthyretin) and retinal binding protein without any concomitant changes in body weight, functional performance status, or anthropometric measurements [80,83]. On the other hand, a controlled multicenter study comparing medroxyprogesterone with a placebo demonstrated significantly approved appetite and body weight (but not quality of life) in the experimental group versus the control group in advanced-stage, non-hormone sensitive cancer [80,84].…”