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The purpose of this bridging phase I study was to characterize the toxicity, pharmacokinetics, and antitumor effects of a capsule formulation of DRF-1042, a novel camptothecin analog, in refractory solid tumor patients. DRF-1042 was given daily for 5 consecutive days for 2 weeks, repeated every 3 weeks at 81 mg/m2. Adverse events were monitored following NCI-CTC. Blood samples were processed for bioanalysis using a validated high-performance liquid chromatography method. The pharmacokinetics of lactone and total (lactone + carboxylate) forms was determined on days 1 and 12 using a noncompartmental pharmacokinetic method. Pharmacokinetic data with the capsule formulation were compared with previously reported pharmacokinetic parameters with a suspension formulation. Efficacy was evaluated by applying World Health Organization criteria. Six patients received 10 courses of therapy. Thrombocytopenia and diarrhea were dose-limiting toxicities. The upper limit of the area under the curve of DRF-1042 (lactone and total) with the capsule formulation was higher than a suspension formulation at a similar dose on day 1 (lactone: capsule = 8.53 μM·h, suspension = 5.33 μM·h; total: capsule = 393 μM·h, suspension = 176 μM·h) and day 12 (lactone: capsule = 22.1 μM·h, suspension = 6.1 μM·h; total: capsule = 1302 μM·h, suspension = 309 μM·h). The upper limit of the area under the curve of DRF-1042 (lactone and total) was higher under fed conditions (lactone = 15.9 μM·h, total = 605 μM·h) relative to fasted conditions (lactone = 8.53 μM·h, total = 393 μM·h) on day 1. One patient experienced stable disease. The toxicity and pharmacokinetics of the capsule correlated well with the suspension. The recommended phase II dose is 81 mg/m2.