Phase I Trial of Antibody-Directed Enzyme Prodrug Therapy in Colorectal Cancer
Author Information
Author(s): Francis R J, Sharma S K, Springer C, Green A J, Hope-Stone L D, Sena L, Martin J, Adamson K L, Robbins A, Gumbrell L, O'Malley D, Tsiompanou E, Shahbakhti H, Webley S, Hochhauser D, Hilson A J, Blakey D, Begent R H J
Primary Institution: Cancer Research UK Targeting and Imaging Group, Department Oncology, Royal Free and University College Medical School, University College London
Hypothesis
Can antibody-directed enzyme prodrug therapy (ADEPT) effectively target and treat advanced colorectal carcinoma without the need for a clearing antibody?
Conclusion
The study found that while the treatment did not result in objective responses, it was well tolerated and showed potential for future use with improved targeting systems.
Supporting Evidence
- Three patients had stable disease at day 56.
- Patients' quality of life was not adversely affected during the trial.
- The maximum tolerated dose of ZD2767P was reached at 15.5 mg m−2.
- Myelosuppression limited dose escalation.
- Immunogenicity was observed in all but one patient.
Takeaway
Doctors tried a new way to treat cancer using special drugs that work only at the tumor site, but they didn't see big improvements in patients' conditions.
Methodology
Twenty-seven patients were treated with ADEPT in a dose-escalating phase I trial, assessing toxicity and pharmacokinetics.
Potential Biases
The immunogenicity of the antibody-enzyme conjugate may limit repeated use in patients.
Limitations
The study had no objective responses and limited tumor localization of the antibody-enzyme conjugate.
Participant Demographics
The median age of participants was 56 years, with 21 males and 6 females.
Digital Object Identifier (DOI)
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