A PHASE-I TRIAL OF HYPOXOSIDE AS AN ORAL PRODRUG FOR CANCER-THERAPY -ABSENCE OF TOXICITY

Objective. To assess the toxicity of hypoxoside taken orally by 24 pat ients with lung cancer. Design. Open study with patients taking 1 200 - 3 200 mg standardised Hypoxis plant extract (200 mg capsules) per da y divided in 3 doses in order to maintain metabolite blood levels near 100 mu g/ml. Participants and setting. Patients with histologically p roven squamous, large-cell or adenocarcinoma were hospitalised initial ly at the radiation oncology ward, Karl Bremer Hospital, Bellville, W. Cape, Thereafter they returned every 2 weeks for full clinical examin ations. Methods. Routine biochemical and haematological measurements w ere done, Patients underwent regular full clinical examinations includ ing radiographs and computed tomography scanning according to the disc retion of the principal investigator. Results. Nineteen patients on hy poxoside therapy survived for an average of 4 months with progression of their primary tumours and metastases, while 5 survived for more tha n a year, One of them survived for 5 years and histological examinatio n of the primary lesion showed absence of cancer. No toxic effects, in clinical examinations or biochemical or haematological measurements, were found that could be ascribed to the ingestion of hypoxoside. Only one occasion of possible drug intolerance, with anxiety, nausea, vomi ting and diarrhoea, was noted. Conclusion. The absence of toxicity war rants further investigation of hypoxoside as an oral prodrug, especial ly in patients with slow-growing necrotising tumours that are inoperab le and have high concentrations of beta-glucuronidase and sulphatase a s well as a high sensitivity for rooperol.