A Phase I study of cabazitaxel in patients with advanced gastric cancer who have failed prior chemotherapy (GASTANA)

This Phase I dose-escalation study (GASTANA) evaluated the safety, tolerability, pharmacokinetics and preliminary antitumor activity of cabazitaxel in Asian patients with advanced gastric adenocarcinoma failing two prior chemotherapy regimens. Cabazitaxel safety/tolerability was determined using a standard 3 + 3 dose-escalation design based on dose-limiting toxicities (DLTs) in Cycle 1. Three dose levels (DL) were planned: 20, 25 and 15 mg/m(2) (DL 1, DL 2 and DL -1). Fifteen patients were evaluable for DLTs. At DL 1, no DLTs occurred in three patients. At DL 2, four patients were enrolled (one patient discontinued), with only one DLT observed [Grade 4 febrile neutropenia (FN)]; however, all four patients experienced FN, hence three more patients were enrolled at DL 1 who experienced two DLTs (Grade 4 neutropenia > 7 days). In response, DL -1 was opened, with no DLTs observed in six patients. In the total population (n = 16), frequent Grade 3/4 toxicities included neutropenia (63 %) and FN (38 %), best overall responses included one partial response (6.3 %; DL -1) and eight stable disease (50 %), and median progression-free survival was 83 days. No unexpected safety findings were observed. Significant toxicities included neutropenia and FN, potentially due to patients being heavily pretreated and the accumulated toxicity of prior taxane therapy.