Abstract |
Revision surgery for loosened hip prostheses is a heavy burden for elderly patients with comorbidity. As an alternative to surgery we performed a study to stabilize the prosthesis by percutaneous cement injection after removing inflammatory tissue with an intraarticular virus-directed enzyme prodrug approach. Twelve elderly patients with debilitating pain from a loosened hip prosthesis were included in a phase 1 dose-escalating clinical study. The patients were admitted to the hospital for 10 days for an intraarticular vector and prodrug injection, and subsequently for a percutaneous bone cement injection. This paper reports the adverse and serious adverse events of the study. After prodrug injection 9 of 12 patients had gastrointestinal adverse events ( nausea, vomiting, and diarrhea), and 8 patients had hepatic adverse events (rise in aspartate aminotransferase and alanine aminotransferase). Five patients developed anemia (World Health Organization grade 1 or 2) from hematomas after cement injection. There were four serious adverse events in the first 6 months after vector injection, but these were not related to gene therapy as judged by an independent safety committee. There was no dose-limiting toxicity. However, the extensive comorbidity in these patients makes it difficult to fully establish the safety of the approach in this small and heterogeneous patient population.
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Authors | Jolanda J de Poorter, Rob C Hoeben, Willem R Obermann, Tom W J Huizinga, Rob G H H Nelissen |
Journal | Human gene therapy
(Hum Gene Ther)
Vol. 19
Issue 10
Pg. 1029-38
(Oct 2008)
ISSN: 1557-7422 [Electronic] United States |
PMID | 18956951
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Aziridines
- Escherichia coli Proteins
- Prodrugs
- tretazicar
- NfsB protein, E coli
- Nitroreductases
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Topics |
- Adenoviridae
- Aged
- Aged, 80 and over
- Antineoplastic Agents
(administration & dosage, adverse effects)
- Arthroplasty, Replacement, Hip
- Aziridines
(administration & dosage, adverse effects)
- Escherichia coli Proteins
- Female
- Genetic Therapy
(adverse effects)
- Genetic Vectors
(administration & dosage, adverse effects)
- Hip Prosthesis
(adverse effects)
- Humans
- Male
- Nitroreductases
- Pain Management
- Prodrugs
(administration & dosage, adverse effects)
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