Vasilios Karavasilis1, Epaminontas Samantas2, Georgia-Angeliki Koliou3, Anna Kalogera-Fountzila4, George Pentheroudakis5, Ioannis Varthalitis6, Helena Linardou7, Grigorios Rallis8, Maria Skondra9, Georgios Papadopoulos4, George Papatsibas10, Joseph Sgouros2, Athina Goudopoulou11, Konstantine T Kalogeras12,13, Christos Dervenis14, Dimitrios Pectasides9, George Fountzilas13,15. 1. Department of Medical Oncology, Papageorgiou Hospital, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. karavasv@auth.gr. 2. Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece. 3. Section of Biostatistics, Hellenic Cooperative Oncology Group, Athens, Greece. 4. Department of Radiology, AHEPA Hospital, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. 5. Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece. 6. Oncology Department, General Hospital of Chania, Crete, Greece. 7. First Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece. 8. Department of Medical Oncology, Papageorgiou Hospital, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. 9. Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, Athens, Greece. 10. Oncology Department, University General Hospital of Larissa, Larissa, Greece. 11. Department of Pharmacovigilance, Hellenic Cooperative Oncology Group, Athens, Greece. 12. Translational Research Section, Hellenic Cooperative Oncology Group, Athens, Greece. 13. Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece. 14. First Department of Surgery, General Hospital Konstantopouleio Agia Olga, Athens, Greece. 15. Aristotle University of Thessaloniki, Thessaloniki, Greece.
Abstract
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/m2 and T 10 mg. G was escalated in increments of 200 mg/m2 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).
RCT Entities:
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/m2 and T 10 mg. G was escalated in increments of 200 mg/m2 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).
Authors: Miroslav Zavoral; Petra Minarikova; Filip Zavada; Cyril Salek; Marek Minarik Journal: World J Gastroenterol Date: 2011-06-28 Impact factor: 5.742
Authors: Zonera Hassan; Christian Schneeweis; Matthias Wirth; Christian Veltkamp; Zahra Dantes; Benedikt Feuerecker; Güralp O Ceyhan; Shirley K Knauer; Wilko Weichert; Roland M Schmid; Roland Stauber; Alexander Arlt; Oliver H Krämer; Roland Rad; Maximilian Reichert; Dieter Saur; Günter Schneider Journal: Br J Cancer Date: 2018-01-02 Impact factor: 9.075
Authors: Katherine M Bever; Erkut H Borazanci; Elizabeth A Thompson; Jennifer N Durham; Kimberly Pinero; Gayle S Jameson; Amber Vrana; Meizheng Liu; Cara Wilt; Annie A Wu; Wei Fu; Hao Wang; Yafu Yin; Jeffrey P Leal; Ana De Jesus-Acosta; Lei Zheng; Daniel A Laheru; Daniel D Von Hoff; Elizabeth M Jaffee; Jonathan D Powell; Dung T Le Journal: Oncotarget Date: 2020-05-26