For a growing number of diseases (e.g. AML, CML, MM, and NHL), combination therapies are being employed, due in part to their superior efficacy compared to monotherapies and because initial clinical trials with new drugs are often given in combination with standard of care drugs. There are a number of publications that cite the benefits of combination therapy over monontherapy, but this type of treatment often comes with increased toxicity.[1,2] While combining multiple agents is often beneficial for disease progression, the adverse effects may be unexpected and difficult to predict.
To assess additive or synergistic toxicity, we can perform assays on either normal or diseased bone marrow using combinations of compounds. Additionally, a protective effect by one compound can also be detected using these multi-compound assays.This figure demonstrates inhibition of CFU-GM with combination therapies as compared to single agents.
R.Z. Orlowski et. al.,J. Clin. Oncol. 2007 (Sept 1); 25(25): 3892-901.
"Randomized Phase III Study of Pegylated Liposomal Doxorubicin Plus Bortezomib Compared With Bortezomib Alone in Relapsed or Refractory Multiple Myeloma: Combination Therapy Improves Time to Progression"
C.K. Min et. al.,
Jpn Clin. Oncol. 2007 (Dec); 37(12): 961-8. "Bortezomib in combination with conventional chemotherapeutic agents for multiple myeloma compared with bortezomib alone"