Abstract 1742
Background
In Japan, gemcitabine based chemotherapy has been a standard regimen as one of the first-line treatment for unresectable pancreatic cancer. FOLFIRINOX was introduced in the second-line treatment for the gemcitabine-refractory pancreatic cancer of patients with an ECOG performance status score of 0 or 1. However, FOLFIRINOX requires close monitoring and must be limited to patients with good performance status because of significant toxicity. Further FOLFIRINOX requires a central veins port, and a trouble such as the port infection may occur. Therefore, it is difficult to administer FOLFIRINOX as second-line treatment. The first time in the world, we introduced IRISOX which substituted S-1 for fluorouracil and leucovorin in the second-line treatment. We aimed to evaluate the tolerance, safety, and clinical efficacy of IRISOX in the second-line treatment for the gemcitabine-refractory pancreatic cancer in a phase 1 study.
Methods
The primary objective was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of IRISOX. The study was designed in accordance with a standard 3 + 3 method. Patients received 2-week cycles of treatment. Irinotecan was administered as an intravenous infusion at 100, 120, or 150 mg/m2 on day 1, S-1 was administered orally at 80 mg/m2 twice daily for 7 days, and oxaliplatin was administered as an intravenous infusion at 85 mg/m2 on day 1.
Results
Among the 12 patients enrolled, dose-limiting toxicity was observed in a patient at level 1 (irinotecan 100 mg/ m2 on day 1, S-1 80 mg/m2 twice daily, and oxaliplatin 85 mg/m2 on day 1) , and in two patients at level 2 (irinotecan 120 mg/ m2 on day 1, S-1 80 mg/m2 twice daily, and oxaliplatin 85 mg/m2 on day 1). The MTD was established as level 2. The RD was established as level 1. The most common grade 3-4 toxicity was neutropenia (33.3 %). The overall response rate was 9.0 %. The overall disease control rate was 45.4 %.
Conclusions
Based on the present results, the RD was determined as level 1 (irinotecan 100 mg/ m2 on day 1, S-1 80 mg/m2 twice daily, and oxaliplatin 85 mg/m2 on day 1). IRISOX was well tolerated and showed antitumor efficacy in the second-line treatment for the gemcitabine-refractory pancreatic cancer in a phase 1 study.
Clinical trial identification
UMIN000022964.
Legal entity responsible for the study
Kitasato University School of Medicine, Japan.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4162 - ODM-207 - a novel BET bromodomain inhibitor with antitumor activity in nonclinical models of ER+ breast cancer
Presenter: Anu Moilanen
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3747 - HER2-positive breast cancer resistance to trastuzumab is associated with metabolic switch.
Presenter: Roman Dubianski
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
4688 - Combination treatment with the PARP inhibitor niraparib and chemotherapeutics in a preclinical model of KRAS/BRAF mutated colorectal cancer cell lines across the four Consensus Molecular Subtypes.
Presenter: Pietro Paolo Vitiello
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
498 - Exosomal microRNA-32-5p induces multidrug resistance in hepatocellular carcinoma via the PI3K/Akt pathway.
Presenter: Xiao Fu
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3731 - Effect of the polymorphism rs2470893 of the CYP1A1 gene on ovarian and endometrial cancer in Mediterranean women
Presenter: Judith Begona Ramirez Sabio
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1215 - Cisplatin in NIPEC or HIPEC?
Presenter: Ivan Alvovsky
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2738 - Matrix metalloproteinase-mediated regulation of programmed-death ligand in the human head and neck squamous cell carcinoma microenvironment
Presenter: MARIKO HIRAI
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
2190 - Trametinib synergizes with dexamethasone in KRAS-mutant myeloma cell lines through modulation of NDRG1 and induction of apoptosis
Presenter: Priya Sriskandarajah
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
4482 - Functional inhibition of TGF-_ in colorectal cancer cells and its interaction with AXL receptor
Presenter: Davide Ciardiello
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
624 - Isoform-specific AKT Inhibition Differentially Affects Cell Functions in Pancreatic Adenocarcinoma
Presenter: Hugo Arasanz
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract