David Richard Newell

Clinical Studies with the p-Carboxyl Dimethyl Phenyl Triazene CB10-277

Analogue development is one of the undoubted success stories of cancer chemotherapy. For example, there are many analogues of the original nitrogen mustard HN2; methotrexate is an analogue of the earlier drug aminopterin; epirubicin is a less cardiotoxic analogue of doxorubicin and carboplatin is a platinum complex which, unlike cisplatin, lacks significant nephrotoxicity. Although DTIC (dacarbazine) does not come into the same class as the above groups of compounds, either in terms of its spectrum or level of activity, it is deemed to be a useful drug. Thus DTIC remains one of the most active single agents for the treatment of malignant melanoma. It is also used in the management of lymphoma and sarcoma although, since DTIC is part of drug combinations in these latter diseases, its exact contribution to therapeutic success is difficult to evaluate.

Clinical-Study and Pharmacokinetics of Lonidamine in Advanced Non-Small Cell Lung-Cancer

THERE IS an urgent need for more effective medical treatment against non-small cell lung cancer (NSCLC). Platinum-containing chemotherapy regimens have produced response rates of 30-40% in patients with advanced NSCLC [l, 21 but the duration of response is short and survival benefit debatable [3, 41. Against this background the use of new agents in phase II trials is reasonable and allows a better evaluation of a new drug. Lonidamine is a substituted indazole carboxylic acid derivative which induced mitochondrial damage and inhibited anaerobic glycolysis in vitro [S] and has shown phase I/II antitumour activity [681. We evaluated lonidamine in 10 patients with advanced NSCLC, none of whom had received chemotherapy. The median age was 55 (range 34-66) years, and there were 7 male and 3 female patients, all with performance status WHO grade 0 or 1. Lonidamine was started at 75 mg three times a day, increasing over 7 days to 600 mg daily in divided doses and then reducing to 400 mg daily in divided doses in those patients experiencing unpleasant toxicity at higher doses. No objective responses were seen. 1 patient had a minor regression of a pleural effusion. Median duration of treatment was 74 (range 31-146) days and treatment was discontinued because of non-haematological toxicity (myalgia, testicular pain) in 4 patients and progressive disease in 6 patients. No haematological or metabolic toxicity was seen. Details of toxicity are in