Book contents
- Frontmatter
- Contents
- Acknowledgments
- List of abbreviations
- 1 Introduction: gene transfer lost in translation
- 2 What is gene transfer?
- 3 Safety, values, and legitimacy: the protean nature of risk in translational trials
- 4 Taming uncertainty: risk and gene-transfer clinical research
- 5 Succor or suckers? Benefit, risk, and the therapeutic misconception
- 6 Looking backward: a model of value for translational trials
- 7 The chasm: the ethics of initiating first-in-human clinical trials
- 8 Tropic of cancers: gene transfer in resource-poor settings
- 9 Great Expectations and Hard Times: expectation management in gene transfer
- 10 Something in the sight adjusts itself: conclusions
- Epilogue
- Index
6 - Looking backward: a model of value for translational trials
Published online by Cambridge University Press: 28 January 2010
- Frontmatter
- Contents
- Acknowledgments
- List of abbreviations
- 1 Introduction: gene transfer lost in translation
- 2 What is gene transfer?
- 3 Safety, values, and legitimacy: the protean nature of risk in translational trials
- 4 Taming uncertainty: risk and gene-transfer clinical research
- 5 Succor or suckers? Benefit, risk, and the therapeutic misconception
- 6 Looking backward: a model of value for translational trials
- 7 The chasm: the ethics of initiating first-in-human clinical trials
- 8 Tropic of cancers: gene transfer in resource-poor settings
- 9 Great Expectations and Hard Times: expectation management in gene transfer
- 10 Something in the sight adjusts itself: conclusions
- Epilogue
- Index
Summary
Introduction
In 2000, Lancet published results of a phase 1 study testing augmerosen in volunteers receiving the standard chemotherapy dacarbazine for melanoma. Augmerosen belongs to a class of genetic therapies – called antisense agents – that work by blocking expression of specific genes. In this case, the target was BCL-2, which prevents cells that have sustained DNA damage from undergoing “cell suicide.” The idea of the study, then, was to use augmerosen to release the genetic “brake” on cell suicide so that tumor cells would die after chemotherapy.
The study results were favorable: augmerosen combined with the chemotherapy drug dacarbazine proved safe even at the highest dose tested, with no volunteers developing life-threatening and/or unanticipated toxicities. In addition, six of the fourteen volunteers showed tumor shrinkage, and for two others, tumors stopped growing. In one figure, numerous thick, pigmented growths crowd a volunteer's forearm before the start of treatment; after, the tumors are reduced to a series of small moles. Whereas patients treated for advanced melanoma might typically live another five months, these study volunteers survived a median of twelve.
The study was valuable in the way phase 1 studies are typically valuable. According to one authoritative source, “the primary purposes of classic phase I studies are to investigate toxicity of organ systems involved, establish an optimalbiological dose, estimate pharmacokinetics, and assess tolerability and feasibility of the treatment. Secondary purposes are to assess evidence for efficacy, investigate the relation between pharmacokinetics and pharmacodynamics of the drug, and targeting.
- Type
- Chapter
- Information
- Gene Transfer and the Ethics of First-in-Human ResearchLost in Translation, pp. 89 - 109Publisher: Cambridge University PressPrint publication year: 2009
- 1
- Cited by