open access: Phase I dose-escalation study of afatinib, an ErbB family blocker, plus docetaxel in patients with advanced cancer, Future Oncology, Future Medicine

 Blogger's Note: of the 31 patients included in this study 14 were ovarian cancer patients

Phase I dose-escalation study of afatinib, an ErbB family blocker, plus docetaxel in patients with advanced cancer, Future Oncology, Future Medicine

Aims:
To determine the maximum tolerated dose (MTD), safety and anti-tumor activity of afatinib combined with docetaxel in advanced cancer. 

Patient demographics
Thirty-one patients were treated and included in all analyses. Baseline demographics are presented in Table 1. The patient population was heavily pretreated; 64.5% had received ≥3 lines of prior chemotherapy and 54.8% had received prior radiotherapy.

Anti-tumor activity

No objective responses were observed during the study. The best overall response was stable disease, which was achieved in 14 (45.2%) of all treated patients. The median duration of stable disease was 82.5 days. Disease stabilization was observed in four of the six patients treated at the MTD. Seven patients completed four treatment cycles.......

Conclusion & future perspective

This study defined an MTD of afatinib of 20 mg/day when given in combination with 75 mg/m² docetaxel on a 3-weekly dosing schedule, involving administration of docetaxel on day 1, followed by daily afatinib on days 2–21. The safety profile of this regimen was manageable. The inability to escalate afatinib to doses achieved in other trials, despite the lack of PK interactions, did not permit recommendation of a possible Phase II dose. A new dose-finding study in a less-heavily pretreated patient population, where the use of GM-CSF is recommended, is currently ongoing