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
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/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).
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Adding mTOR inhibitors to gemcitabine-based chemotherapy did not significantly improve clinical activity.
“Combination of these inhibitors with gemcitabine-based chemotherapy also did not yield significant improvement in clinical activity (92, 93).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [92]
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- Authors
- Karavasilis, V., Samantas, E., Koliou, G.-A., Kalogera-Fountzila, A., Pentheroudakis, G., Varthalitis, I., Linardou, H., Rallis, G., Skondra, M., Papadopoulos, G., Papatsibas, G., Sgouros, J., Goudopoulou, A., Kalogeras, K. T., Dervenis, C., Pectasides, D., & Fountzilas, G.
- Affiliations
- Aristotle University of Thessaloniki (GR)
- Hellenic Cooperative Oncology Group (GR)
- University Hospital of Ioannina (GR)
- Chania General Hospital ”St. George” (GR)
- Metropolitan Hospital (GR)
- Hippocration General Hospital (GR)
- University Hospital of Larissa (GR)
- Agia Olga Hospital (GR)
- Corresponding author
- Karavasilis, Vasilios
- ORCID
- Venue
- Targeted Oncology
- Published
- 2018-11-28
- Volume
- 13
- Issue
- 6
- Pages
- 715-724
- ISSN
- 1776-2596 (ISSN-L)
- 1776-260X
- OpenAlex
- W2902345163
- Cited by
- 27
- References
- 30
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 3
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Targeted Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer Inc
- Hellenic Cooperative Oncology Group (HE_R3/07)
- Hellenic Study Group for Metastatic Liver Disease
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Keywords
- gemcitabine, temsirolimus, mTOR inhibitors, pancreatic cancer, metastatic pancreatic cancer, locally advanced pancreatic cancer, combination chemotherapy, maximum tolerated dose, dose-limiting toxicity, progression-free survival, overall survival, hematologic toxicity, metabolic side effects
- MeSH terms
- Gemcitabine, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Deoxycytidine, Female, Humans, Male, Middle Aged, Neoplasm Metastasis, Pancreatic Neoplasms, Sirolimus
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