Phase II study of high-dose medroxyprogesterone acetate in advanced malignant melanoma

It has been shown that a small number of patients with advanced malignant melanoma (MM) respond to additive hormonal treatments such as the anti-oestrogen tamoxifen (Karakousis et al., 1980). Receptor studies have shown that the expression of significant amounts of oestrogen receptors is rare in MM. However, glucocorticoid receptors are a common finding (Hawkins et al., 1980; Bhakoo et al., 1981; Bojar et al., 1982). The observation that medroxyprogesterone acetate (MPA) binds to the glucocorticoid receptor in the same way as dexamethasone, led to a phase II study to assess the therapeutic relevance of the high glucocorticoid receptor levels in MM. Eighteen outpatients with histologically confirmed MM and measurable and progressive lesions, who were not amenable to curative surgery were treated with high-dose MPA. The patients had a performance status according to the Karnofsky index above or at 70%. The characteristics of patients are shown in Table I. All patients received 1 g MPA per day as intramuscular injection on days 1-10 and 200 mg MPA t.i.d. orally thereafter. This treatment schedule was adapted from a treatment schedule for advanced breast cancer and yields MPA serum levels well above 100 ng ml(Miller et al., 1985). Treatment was continued as long as disease stabilisation or remission was achieved. The criteria for response were as follows. Tumour progression was defined as an increase of tumour size of more than 25% of any measurable lesion or the appearance of new lesions. Partial response was defined as a reduction of tumour size of more than 50% of every measurable lesion without appearance of new lesions. Complete response was defined as disappearance of all measurable lesions. All patients were evaluable for response. Duration of treatment ranged from 13 days to 10 months (median 50 Table I Pretreatment characteristics of patients