A Phase I/IIa Study of DHP107, a Novel Oral Paclitaxel Formulation, in Patients with Advanced Solid Tumors or Gastric Cancer.

Abstract

Lessons Learned.Ideally, patients should have access to an oral formulation of paclitaxel, as well as an intravenous formulation, to allow development of regimens exploring alternate schedules and to avoid reactions to Cremophor EL (BASF Corp., Ludwigshafen, Germany, https://www.basf.com).DHP107 is a novel oral paclitaxel formulation that is a tolerable and feasible regimen for patients with gastric cancer, with data suggesting efficacy similar to that of intravenous paclitaxel.Background.We evaluated the maximum tolerated dose (MTD) of DHP107, a novel oral paclitaxel formulation, and the efficacy and safety of the agent in patients with advanced solid tumors.Patients and Methods.Phase I study: cohorts of 3–6 patients with advanced solid tumors received escalating DHP107 doses. Phase IIa study: patients with measurable advanced gastric cancer received DHP107, 200 mg/m2 b.i.d., on days 1, 8, and 15 every 4 weeks. Pharmacokinetics, safety, and efficacy were analyzed.Results.Phase I: 17 patients received a dose‐escalating regimen of DHP107, 150–250 mg/m2 b.i.d. Dose‐limiting toxicities were neutropenia and febrile neutropenia. The MTD (recommended dose) for phase IIa was 200 mg/m2 b.i.d. Phase IIa: 11 patients with measurable advanced gastric cancer in whom first‐line therapy failed received DHP107 (MTD). Three confirmed partial responses were observed. Median progression‐free survival of gastric cancer patients (n = 16) treated at the MTD was 2.97 (95% confidence interval, 1.67–5.40) months (Fig. 1). The most frequent grade 3/4 adverse events were neutropenia (35.3%) and leukopenia (17.6%) at the MTD (phase I and IIa combined; n = 17).Conclusion.DHP107 showed good antitumor efficacy and was tolerable. The MTD (200 mg/m2 b.i.d.) is recommended for use in further studies comparing DHP107 with standard intravenous paclitaxel therapy.