Purpose: 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.
Methods: 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).
Results: 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.
Conclusions: 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.