AI Article Synopsis
- The study compares Maximum Tolerated Dose (MTD) and Metronomic Chemotherapy (MC) protocols for temozolomide, aiming to identify optimal chemotherapy regimens.
- A pharmacokinetics/pharmacodynamics model is used to evaluate drug efficacy and toxicity, including myelosuppression caused by temozolomide.
- Findings indicate that the MC regimen can lower toxicity without losing efficacy, while the MTD protocol faces trade-offs between improved efficacy and increased toxicity, paving the way for customized treatment plans.
Article Abstract
Purpose: We compare the Maximum Tolerated Dose (MTD) and Metronomic Chemotherapy (MC) protocols for temozolomide administration. We develop an innovative methodology for characterizing optimal chemotherapy regimens.
Methods: We use a PK/PD model based on Faivre et al. (2013) for the pharmacokinetics of temozolomide, as well as the pharmacodynamics of its efficacy. For toxicity, which is measured by the nadir of the normalized absolute neutrophil count, we formalize the myelosuppression effect of temozolomide with the physiological model of Panetta et al. (2003b). We introduce a multi-criteria tool for comparing protocols along their efficacy and toxicity dimensions.
Results: We show that the toxicity of the MC regimen proposed by Faivre et al. (2013) can greatly be reduced without affecting its efficacy, while the standard MTD protocol efficacy cannot be improved without impairing its toxicity. We also show that for any acceptable toxicity level, the optimal protocol remains closely related to standard MTD.
Conclusions: Overall, our new method enables a rich comparison between protocols along multiple dimensions. We can rank protocols for temozolomide administration. It is a first step toward building optimal individual protocols.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jtbi.2018.02.034 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Results of the Latin American Pediatric Oncology Group (GALOP-2011) Trial for Patients With Localized Ewing Sarcoma: A Multicentric Study of Interval-Compressed Multiagent Chemotherapy.
Pediatr Blood Cancer
January 2025
Department of Clinical Research, Instituto do Câncer Infantil, Porto Alegre, Brazil.
Background: GALOP investigators developed a prospective cooperative protocol for localized Ewing sarcoma (ES) incorporating interval-compressed chemotherapy (VDC/IE, vincristine, doxorubicin, cyclophosphamide/ifosfamide and etoposide). After completing conventional treatment, patients were randomized to 1 year of metronomic chemotherapy (vinblastine and cyclophosphamide).
Methods: Phase III randomized prospective trial.
Metronomic Chemotherapy and Drug Repurposing: Two Sides of an Oncology Coin To Reduce Host and Financial Toxicity.
Cancer Lett
January 2025
Biological Sciences Platform, Sunnybrook Research Institute, Department of Medical Biophysics, University of Toronto, Toronto, Canada.
Linifanib alone and in combination with metronomic chemotherapy is active on cutaneous T-cell lymphoma cells by targeting the AKT/mTOR signaling pathway.
Invest New Drugs
January 2025
Dipartimento Di Ricerca Traslazionale E Delle Nuove Tecnologie in Medicina E Chirurgia, Università Di Pisa, Via Savi 10, 56126, Pisa, Italy.
Cutaneous T-cell lymphomas (CTCLs) are a rare and heterogeneous subset of skin-localized, non-Hodgkin lymphomas. Our aim was to evaluate the in vitro antitumor activity of the multi-kinase inhibitor linifanib, either alone or in combination with metronomic vinorelbine (mVNR) or etoposide (mETO), on CTCL cells. In vitro proliferation assay and Luminex analysis showed that long-term, daily exposure of linifanib significantly inhibited the proliferation of the human CTCL cell line HH, in a concentration-dependent manner (IC = 48.
View Article and Find Full Text PDFDurvalumab and tremelimumab in combination with metronomic oral vinorelbine for recurrent advanced cervical cancer: an open-label phase I/II study.
J Immunother Cancer
January 2025
Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.
Background: The MOVIE phase I/II trial (NCT03518606) evaluated the safety and antitumor activity of durvalumab and tremelimumab combined with metronomic oral vinorelbine in patients with advanced tumors. We present the results of the recurrent advanced cervical cancer cohort.
Methods: Patients received tremelimumab (intravenously, 75 mg, every four weeks (Q4W); four cycles max) plus durvalumab (intravenously, 1,500 mg, Q4W; 26 cycles max) and metronomic oral vinorelbine (40 mg, every three weeks (3QW)) until disease progression.
Mutations in the , , , and Genes and Their Relationship with Resistance to Temozolomide in Patients with High-Grade Gliomas.
Biomedicines
December 2024
Life and Health Sciences Research Group, Graduate School, CES University, Medellín 050021, Colombia.
Introduction: The treatment for patients with high-grade gliomas includes surgical resection of tumor, radiotherapy, and temozolomide chemotherapy. However, some patients do not respond to temozolomide due to a methylation reversal mechanism by the enzyme O-methylguanine-DNA-methyltransferase (MGMT). In patients receiving treatment with temozolomide, this biomarker has been used as a prognostic factor.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!