PHASE-II TRIAL OF CHLOROQUINOXALINE SULFONAMIDE (CQS) IN PATIENTS WITH STAGE-III AND STAGE-IV NON-SMALL-CELL LUNG-CANCER

Purpose: Chloroquinoxaline sulfonamide (CQS) was one of the first agen ts identified by the human tumor colony-forming assay (HTCFA) as posse ssing antitumor activity in non-small-cell lung cancer (NSCLC). Prior phase I studies had suggested that plasma concentrations equivalent to those showing efficacy in the HTCFA could be reliably attained in hum ans. This phase II study assessed the antitumor activity of CQS while using an adaptive control pharmacokinetic modelling system to attain t argeted plasma levels of this novel compound. Methods: A group of 20 p atients with stage III or IV NSCLC received CQS as a 1-h weekly infusi on at an initial dose of 2 g/m(2). In all patients, 24-h plasma concen trations of CQS were measured. Patients with levels <100 mu g/ml had d ose increases determined by their 24-h levels and pharmacokinetic para meters obtained from two prior phase I trials of this agent. These ind ividuals had 24-h CQS levels repeated after their second weeks' treatm ent and doses were readjusted if the target concentration was not reac hed. Antitumor response assessment was made every 6 weeks. Results: Of the 20 patients, 18 attained the target plasma concentration, and 16 of these achieved this initially or with just one dose adjustment. No major objective antitumor responses were observed (major response rate 0%, 95% CI 0-17%). CQS was well tolerated with hypoglycemia being the most clinically significant toxicity. Conclusions: When given on this schedule CQS is inactive in NSCLC despite the fact that the target co ncentration was achieved in 90% of patients. The ability of the HTCFA to identify active agents remains unproved.