Abstract
The introduction of combination chemotherapeutic regimens for the treatment of childhood leukaemia in the 1960s provided the proof-of-principle that cytotoxic drugs were capable of curing cancer. However, in the four decades since this discovery, the majority of cancers still cannot be cured by chemotherapy. Clinical evidence supports the hypothesis of Goldie and Coldman that treating cancers with all the available effective agents simultaneously provides the greatest chance of eliciting a cure. Unfortunately, for traditional cytotoxic agents with narrow therapeutic indices, lifethreatening toxicity precludes combination chemotherapy regimens employing multiple agents. This review discusses the concept of fixed dose combination chemotherapy with emphasis on capturing therapeutic efficacy described as synergistic as a basis for improving the effectiveness of combination chemotherapy. The use of lipid-based nanotechnologies, focusing on liposomes, as an enabling technology to facilitate the delivery of cytotoxic agents to the tumour site at concentrations and/or drug ratios judged to be synergistic will be discussed. It is envisaged that the development of this model system will be supported by cell-based screening technologies, pharmacokinetic and pharmacodynamic parameters and mathematical models describing therapeutic drug:drug interactions (the Median Effect Principle of Chou and Talalay). Experiments using preclinical models are presented to support the benefits of drug delivery systems as a foundation for fixed dose anticancer drug combinations. The ultimate goal of this research is to prepare a single vial fixed dose combination product that encompasses both traditional cytotoxic agents and new molecularly targeted modalities with optimum therapeutic effects and acceptable toxicity.
Keywords: fixed dose, liposome, combination chemotherapy, median effect principle, cancer
Current Drug Delivery
Title: The Formulation of Lipid-Based Nanotechnologies for the Delivery of Fixed Dose Anticancer Drug Combinations
Volume: 2 Issue: 4
Author(s): Euan C. Ramsay, Nancy D. Santos, Wieslawa H. Dragowska, Janessa J. Laskin and Marcel B. Bally
Affiliation:
Keywords: fixed dose, liposome, combination chemotherapy, median effect principle, cancer
Abstract: The introduction of combination chemotherapeutic regimens for the treatment of childhood leukaemia in the 1960s provided the proof-of-principle that cytotoxic drugs were capable of curing cancer. However, in the four decades since this discovery, the majority of cancers still cannot be cured by chemotherapy. Clinical evidence supports the hypothesis of Goldie and Coldman that treating cancers with all the available effective agents simultaneously provides the greatest chance of eliciting a cure. Unfortunately, for traditional cytotoxic agents with narrow therapeutic indices, lifethreatening toxicity precludes combination chemotherapy regimens employing multiple agents. This review discusses the concept of fixed dose combination chemotherapy with emphasis on capturing therapeutic efficacy described as synergistic as a basis for improving the effectiveness of combination chemotherapy. The use of lipid-based nanotechnologies, focusing on liposomes, as an enabling technology to facilitate the delivery of cytotoxic agents to the tumour site at concentrations and/or drug ratios judged to be synergistic will be discussed. It is envisaged that the development of this model system will be supported by cell-based screening technologies, pharmacokinetic and pharmacodynamic parameters and mathematical models describing therapeutic drug:drug interactions (the Median Effect Principle of Chou and Talalay). Experiments using preclinical models are presented to support the benefits of drug delivery systems as a foundation for fixed dose anticancer drug combinations. The ultimate goal of this research is to prepare a single vial fixed dose combination product that encompasses both traditional cytotoxic agents and new molecularly targeted modalities with optimum therapeutic effects and acceptable toxicity.
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Cite this article as:
Ramsay C. Euan, Santos D. Nancy, Dragowska H. Wieslawa, Laskin J. Janessa and Bally B. Marcel, The Formulation of Lipid-Based Nanotechnologies for the Delivery of Fixed Dose Anticancer Drug Combinations, Current Drug Delivery 2005; 2 (4) . https://dx.doi.org/10.2174/156720105774370294
DOI https://dx.doi.org/10.2174/156720105774370294 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
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