717P - Gemcitabine combined with the mTOR inhibitor temsirolimus (CCI-779) in patients with inoperable or metastatic pancreatic cancer (HE 3/07). A phase I...

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Anticancer agents
Pancreatic Cancer
Therapy
Biological Therapy
Presenter Vasilios Karavasilis
Authors V. Karavasilis1, G. Pentheroudakis2, J. Sgouros1, S.T. Dimoudis3, I. Varthalitis1, E. Samantas4, G. Fountzilas3
  • 1Data Office, Hellenic Cooperative Oncology Group, 11524 - Athens/GR
  • 2Oncology Secretariat B Building Ground Floor, Hellenic Cooperative Oncology Group, 11524 - Athens/GR
  • 3Medical Oncology Clinic, Hellenic Cooperative Oncology Group, 11524 - Athens/GR
  • 4Hellenic Cooperative Oncology Group, 11524 - Athens/GR

Abstract

Aim

To investigate the feasibility of the gemcitabine (G) and mTOR inhibitor temsirolimus (T) combination and define the maximum tolerated dose (MTD) in patients with inoperable or metastatic pancreatic cancer (MPC).

Methods

Eligible patients with histologically confirmed inoperable or MPC were entered into the trial. Available biopsy material for subsequent translational research analysis was mandatory for inclusion in the study. G was given bi-weekly and T was administered on a weekly basis. Each cycle consisted of four consecutive weeks of treatment. First dose level was set at G 800 mg/m2 and T 10 mg. G was escalated in increments of 200 mg/m2 and T in increments of 5 mg.

Results

A total of 30 patients [16M/14F, median age: 63y, PS: 1 (63%)] were enrolled for the pre-planned six dose levels. Up to date, 80 complete cycles of treatment were delivered. Four patients did not complete the first cycle due to rapid disease progression and were therefore replaced. Another patient was found ineligible and was replaced, as well. Ten patients received four or more cycles of treatment. MTD was not achieved and the study was terminated at the sixth dose level of G 1000 mg/m2 and T 25 mg. Dose-limiting toxicity (DLT) was thrombocytopenia of grade 4, which occurred at the first dose level. Non-DLT grade III toxicities were neutropenia (9 patients), abnormal liver biochemistry (8 patients) and fatigue (1 patient). Toxicities below the grade III level were mild, the most predominant being anemia, neutropenia, raised liver function tests and fatigue. Two patients at the final level of G 1000 mg/m2 and T 25 mg are still on treatment. This dose is the recommended dose for phase II evaluation. With regard to response, two partial responses were documented and 11 patients had stable disease.

Conclusion

Combination of G and T is feasible in patients with inoperable or MPC with manageable side effects. The activity of this combination is currently investigated in a recently initiated phase II study.

Disclosure

All authors have declared no conflicts of interest.