Safety and Efficacy of Cabazitaxel in Advanced Gastric Adenocarcinoma: A Phase I Dose-Escalation Study

Strategic Insights -

A Phase I dose-escalation study, known as GASTANA, has evaluated the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of cabazitaxel in Asian patients with advanced gastric adenocarcinoma who have failed two prior chemotherapy regimens. The study revealed that 15 patients were evaluable for dose-limiting toxicities, with one patient experiencing a Grade 4 febrile neutropenia. Despite this, the study concluded that significant toxicities included neutropenia and febrile neutropenia, potentially due to patients being heavily pretreated and the accumulated toxicity of prior taxane therapy.

Key Takeaways:

  • The study involved 15 patients with advanced gastric adenocarcinoma who had failed two prior chemotherapy regimens.
  • The study evaluated the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of cabazitaxel at three dose levels: 20, 25, and 15 mg/m² (DL 1, DL 2, and DL -1).
  • At DL 1, three patients had no dose-limiting toxicities, while at DL 2, one patient experienced a Grade 4 febrile neutropenia.
  • The most frequent Grade 3/4 toxicities were neutropenia (63%) and febrile neutropenia (38%).
  • The study reported a partial response in one patient (6.3%) and stable disease in eight patients (50%).
  • The median progression-free survival was 83 days.
  • The study concluded that significant toxicities included neutropenia and febrile neutropenia due to the accumulated toxicity of prior taxane therapy.
  • Cabazitaxel showed non-significant antitumor activity, with one patient experiencing a partial response.

Statistics:

  • 15 patients were evaluable for dose-limiting toxicities.
  • 63% of patients experienced Grade 3/4 neutropenia.
  • 38% of patients experienced Grade 3/4 febrile neutropenia.
  • 50% of patients had stable disease.
  • 6.3% of patients experienced a partial response.
  • Median progression-free survival was 83 days.

Sources:

  • A Phase I study of cabazitaxel in patients with advanced gastric cancer who have failed prior chemotherapy (GASTANA). Cancer Chemotherapy and Pharmacology, 2015;75(2):309-318.
  • Sanofi, Kerry Center, Shanghai 200040, People's Republic of China.