The Safety and Tolerability of Intravenous ASA404 When Administered in Combination with Docetaxel (60 or 75 mg/m2) in Japanese Patients with Advanced or Recurrent Solid Tumors

Objective: This Phase I study was carried out to assess the safety, tolerability, pharmacokinetics and preliminary efficacy of the flavonoid tumor-vascular disrupting agent ASA404 (vadimezan) in combination with docetaxel in Japanese patients with advanced or recurrent solid tumors. Methods: Nine Japanese patients were given ASA404 (1800 mg/m(2)) plus two doses of docetaxel, 60 or 75 mg/m(2), administered every 3 weeks. Results: Dose-limiting toxicity of Grade 3 febrile neutropenia was observed in one patient during Cycle 1 at Level 2 of ASA404 (1800 mg/m(2)) and docetaxel (75 mg/m(2)) treatment. The most frequently reported adverse events were neutropenia, fatigue, alopecia, decreased appetite, constipation and injection site pain. These adverse events were mainly Grade 1 or 2 in severity and, with the exception of injection site pain, were typically associated with docetaxel therapy. A partial response was observed in one patient, and five patients (55.6%) exhibited stable disease. Overall, the study demonstrated that ASA404 has an acceptable tolerability profile when combined with docetaxel at doses up to 75 mg/m(2) in Japanese patients with advanced solid tumors. Conclusions: The study supports the enrollment of Japanese patients in the Phase III study (ATTRACT-2) of ASA404 in combination with docetaxel for the second-line treatment of advanced non-small cell lung cancer. Clinicaltrials.gov identifier: NCT01285453