Mithramycin treatment of malignant hypercalcaemia.

Medical Memoranda MnWLJOUL 167 I would like to thank Dr. A. Brown for permission to publish this report and for helpful advice and criticism. My thanks are also due to Dr. George McDonald, who carried out the iliac crest biopsy. Mithramycin is an antibiotic with anti-tumour activity similar to actinomycin D. Hypocalcaemia has been reported following its use (Brown and Kennedy, 1965), and it has been suggested that it should be given in the emergency treatment of hyper-calcaemia, particularly when associated with malignant disease (Parsons et al., 1967; Baum, 1967). We report the findings in a patient with malignant hypercalcaemia treated in this way. CASE REPORT In 1963 a 47-year-old woman underwent a left radical mastec-tomy, followed by radiotherapy, for a stage 3 anaplastic carcinoma of the breast. In 1965 secondary deposits in the thoracic and lumbar spine and pelvis were treated with bilateral oophorectomy, local radiotherapy, androgens (fluoxymesterone and nandrolone), and prednisolone for eight months. In January 1967 further irradiation of the pelvis and upper femora was necessary. In May 1967 she was readmitted with severe pain in the lower back and legs, having been confined to bed since January and requiring opiates for control of her pain. On this admission her serum calcium was 7.7 mg, 100 ml. and serum phosphorus 3.4 mg./l00 ml. She was given blood transfusion and prednisolone, 30 mg. daily. As the pain was not relieved prednisolone was replaced after two weeks by intramuscular long-acting synthetic 86-' corticotrophin (depot-tetracosactrin), 1 mg. on alternate days (Besser et al., 1967). The pain rapidly disappeared and within a month she was mobilized and discharged, able to walk without sticks. In September 1967, after four days of nausea, vomiting, and headache, she was found to have hypercalcaemia and was readmitted.-trace of protein, no glycosuria, bacteriologically sterile. The dose of depot-tetracosactrin was increased to 2 mg. on alternate days, but nevertheless the serum calcium rose to 16.0 mg./100 ml. Therefore mithramycin was administered. Two doses were given on consecutive days: 25 pg./kg. (1.8 mg.) was infused intravenously over eight hours in 1 litre of 5 % dextrose on each day. There was a rapid fall in serum calcium and magnesium and in urinary calcium and phosphate excretion (see Chart), and a smaller falk