Gemcitabine Combined with the mTOR Inhibitor Temsirolimus in Patients with Locally Advanced or Metastatic Pancreatic Cancer. A Hellenic Cooperative Oncology Group Phase I/II Study.

Autor: Karavasilis V; Department of Medical Oncology, Papageorgiou Hospital, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. karavasv@auth.gr., Samantas E; Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece., Koliou GA; Section of Biostatistics, Hellenic Cooperative Oncology Group, Athens, Greece., Kalogera-Fountzila A; Department of Radiology, AHEPA Hospital, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece., Pentheroudakis G; Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece., Varthalitis I; Oncology Department, General Hospital of Chania, Crete, Greece., Linardou H; First Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece., Rallis G; Department of Medical Oncology, Papageorgiou Hospital, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece., Skondra M; Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, Athens, Greece., Papadopoulos G; Department of Radiology, AHEPA Hospital, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece., Papatsibas G; Oncology Department, University General Hospital of Larissa, Larissa, Greece., Sgouros J; Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece., Goudopoulou A; Department of Pharmacovigilance, Hellenic Cooperative Oncology Group, Athens, Greece., Kalogeras KT; Translational Research Section, Hellenic Cooperative Oncology Group, Athens, Greece.; Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece., Dervenis C; First Department of Surgery, General Hospital Konstantopouleio Agia Olga, Athens, Greece., Pectasides D; Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, Athens, Greece., Fountzilas G; Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece.; Aristotle University of Thessaloniki, Thessaloniki, Greece.
Jazyk: angličtina
Zdroj: Targeted oncology [Target Oncol] 2018 Dec; Vol. 13 (6), pp. 715-724.
DOI: 10.1007/s11523-018-0605-y
Abstrakt: Background: The prognosis of patients with advanced pancreatic cancer is dismal, and there is a need for novel and effective treatments.
Objectives: Tο determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of a novel gemcitabine (G) and temsirolimus (T) combination (phase I) and estimate the 6-month progression-free survival (PFS) in patients treated with the T + G combination (phase II).
Patients and Methods: Eligible patients with histologically confirmed inoperable or metastatic pancreatic carcinoma (MPC) were entered into the trial. G was given bi-weekly and T weekly in a 4-week cycle. The first dose level was set at G 800 mg/m 2 and T 10 mg. G was escalated in increments of 200 mg/m 2 and T in increments of 5 mg until DLT was reached, and the recommended dose was used for the phase II part.
Results: Thirty patients were enrolled in the phase I component at the pre-planned six dose levels; one bilirubin DLT of grade III occurred at the first dose level. The MTD was established as the approved doses of both drugs. Fifty-five patients were entered into the phase II component. Median relative dose intensities administered in the first cycle were 0.75 for T and 0.99 for G. Grade 3-4 hematological toxicities were recorded in 87.3% of patients. The most common non-hematological adverse events were metabolic disorders (81.8%) followed by gastrointestinal disorders (63.6%). Median PFS was 2.69 months (95% CI 1.74-4.95) and median OS was 4.95 months (95% CI 3.54-6.85), while the 6-month PFS rate was 30.9%.
Conclusions: Combination of G and T is feasible in patients with locally advanced or MPC with manageable side effects, but lacks clinical efficacy. The study was registered in the Australian New Zealand Clinical Trials Registry (ACTRN12611000643976).
Databáze: MEDLINE
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