Related Experiment Videos
Combination therapy with SCH58500 (p53 adenovirus) and cyclophosphamide in preclinical cancer models
1Tumor Biology, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. loretta.nielsen@spcorp.com
Abstract:
SCH58500 (ACN53) is a replication-deficient, recombinant adenovirus which expresses human p53 tumor suppressor. In preclinical models, SCH58500 has therapeutic efficacy against a wide range of human tumor types containing nonfunctional p53 and it has enhanced activity in combination with many chemotherapeutic drugs. However, the anti-tumor efficacy of SCH58500 combined with the DNA-damaging chemotherapeutic cyclophosphamide has not been previously reported. Cyclophosphamide did not enhance the activity of SCH58500 in three out of four human tumor xenograft models studied. Furthermore, combination therapy with SCH58500 and cyclophosphamide was not any better than single drug treatment in transgenic H-ras mice and in FVB mice bearing syngeneic MidT2-1 tumors. This is in sharp contrast to previous combination studies in these models where SCH58500 had enhanced efficacy when given with the farnesyl protein transferase inhibitor SCH66336, paclitaxel, cisplatin, cisplatin/paclitaxel, or doxorubicin. Further evaluation of this combination is required before it can be recommended for clinical trials in cancer patients.
Insights
SCH58500, a p53 tumor suppressor gene therapy, showed no enhanced anti-tumor activity when combined with cyclophosphamide in preclinical cancer models. Further research is needed before clinical trials of this specific combination therapy.
Area of Science:
- Oncology
- Gene Therapy
- Pharmacology
Background:
- SCH58500 (ACN53) is a recombinant adenovirus expressing human p53, demonstrating therapeutic efficacy in preclinical tumor models with nonfunctional p53.
- SCH58500 has shown enhanced activity in combination with various chemotherapeutic agents.
- The combination of SCH58500 with cyclophosphamide has not been previously investigated.
Purpose of the Study:
- To evaluate the anti-tumor efficacy of SCH58500 in combination with cyclophosphamide.
- To compare the efficacy of this combination therapy against single-agent treatment.
- To assess if cyclophosphamide enhances SCH58500's activity in different preclinical cancer models.
Main Methods:
- Testing SCH58500 and cyclophosphamide combination therapy in human tumor xenograft models.
- Evaluating combination therapy in transgenic H-ras mice and FVB mice with syngeneic MidT2-1 tumors.
- Comparing combination therapy outcomes to single-drug treatments and previous combination studies.
Main Results:
- Cyclophosphamide did not enhance SCH58500 activity in three out of four human tumor xenograft models.
- Combination therapy was not superior to single-agent treatment in transgenic H-ras mice and FVB mice.
- This lack of enhancement contrasts with previous findings where SCH58500 combined with other agents showed improved efficacy.
Conclusions:
- The combination of SCH58500 and cyclophosphamide did not demonstrate synergistic anti-tumor effects in the tested preclinical models.
- Further investigation into this specific combination therapy is warranted before considering clinical trials.
- The efficacy of SCH58500 is dependent on the specific chemotherapeutic agent used in combination.