A phase I dose escalation study to evaluate safety and tolerability of cabazitaxel (Cbz) as a single agent in patients (pts) with advanced gastric adenocarcinoma who have failed prior chemotherapy (CT) regimens (GASTANA).

Abstract

141 Background: Cbz showed antitumor activity in a CT-resistant human gastric cancer xenograft model. The Phase I GASTANA study aimed to determine the safety profile of Cbz in pts with advanced gastric adenocarcinoma who failed prior CT regimens. Methods: Asian pts with metastatic gastric adenocarcinoma failing 2 prior CT regimens received Cbz (single agent, Day 1 of every 3-week cycle) in a standard 3+3 dose escalation design. Dose levels (DL) were 20 mg/m2 (DL 1), 25 mg/m2 (DL 2) and 15 mg/m2 (DL -1). Treatment continued until disease progression or unacceptable toxicity. Prophylactic G-CSF was not permitted at cycle 1. Results: Fifteen pts were evaluable for dose-limiting toxicities (DLTs) at cycle 1. All pts were heavily pretreated (median of 2 prior anticancer regimens), and 11 had prior taxane exposure.At DL 1, no DLTs occurred in any of the first 3 pts. At DL 2, 4 pts were enrolled as 1 pt discontinued prematurely, with only 1 DLT (Grade [Gr] 4 febrile neutropenia [FN]) observed. However, all 4 pts at DL 2 experienced FN, and so 3 more pts were enrolled at DL 1 to further explore safety at this lower DL. Two DLTs (Gr 4 neutropenia > 7 days) occurred in these additional 3 pts. In response, DL -1 was opened, with no DLTs observed in the 6 pts enrolled. The median numbers of cycles were 5 (DL 1), 1.5 (DL 2) and 3 (DL -1). Frequent Gr 3/4 toxicities (safety population, N = 16) included neutropenia (63%) and FN (38%). Best overall responses included 1 partial response (6.3%; DL -1) and 8 stable disease (50%). Conclusions: Due to the unexpectedly high incidence of neutropenia-related complications compared with pts with other cancer types, a further Phase II study of Cbz was put on hold pending further data in pts with gastric cancer. The frequent occurrence of neutropenic complications with Cbz in this study may be attributed in part to the heavily pretreated nature of the pts and the accumulated toxicity of prior taxane therapy. Also, prophylactic G-CSF use after cycle 1 was not mandatory in pts with dose interruptions due to neutropenia, which may have increased the rate of neutropenic complications in subsequent cycles. Clinical trial information: NCT01497964.