Abstract
Introduction
Glioblastoma (GBM) remains the most aggressive brain tumor; even with current standard of care for newly diagnosed GBM, the majority of patients recur within a year. Therapeutic options are lacking and the development of more effective therapeutic approaches is imperative. Ortataxel, another second-generation taxane, showed to be active in different tumor. It was hypothesize a potential therapeutic activity of ortataxel against glioblastoma and led us to design a phase two study in patients with glioblastoma recurring after surgery and first line treatment.
Patients and methods
A single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma was performed to evaluate the activity of ortataxel in in terms of PFS-6. PFS, overall survival at 9 months (OS-9) after the enrolment, objective response rate (ORR), compliance, tolerability and safety were evaluated as secondary endpoints.
Results
A total of 40 GBM patients were recruited. PFS-6 was 11.4 %: four patients were alive and progression free at 6 months after the enrolment. One additional patient progressed at 5.5 months with the appearance of a new lesion but his clinical status was considered stable and therefore the clinician decided to continue the treatment with ortataxel receiving up to 18 cycles until the further disease progression. All other patients progressed in a range from 1.0 to 5.5 months from the study entry. The median follow-up was 19.9 months (IQR 12.0–32.0). Median PFS was 1.7 months (IQR 1.4–3.8). Regarding the OS-9, 29 patients out of 35 (OS-9 %: 12.8; 95%CI: 21.8–53.8) died before 9 months from the enrolment, in a range from 0.99 to 7.70 months from study enrolment. The best response to treatment was PR in only one patient that was still on treatment when the analysis was performed and SD in 9 patients (29.0%). The most important toxicities were neutropenia, hepatotoxicity and leukopenia that occurred in 5 patients (13.2%), 5 patients (13.2%) and 6 patients (15.8%) respectively.
Conclusion
The finding that two cases responded to the drug for a long time invite us to speculate that ortataxel might be effective in a limited fraction of GBM patients with some peculiar molecular features associated to high sensitivity to the drug.