CASE STUDY
Eliminate Clinical Adverse Effects: Reduce diarrheal toxicity
Combination therapies are expected to greatly improve the treatment of cancer; however, there are concerns that toxic effects can also be amplified. Careful consideration of the combinations and dose regimens may help to maximize efficacy while minimizing toxicity. In addition, nonclinical studies that reveal the mechanisms of toxicity allow clinicians to develop specific strategies to counteract any adverse effects. A publication by Roche in Molecular Cancer Therapeutics has shed new light on the mechanisms by which anti-HER2/3 combination therapies can cause diarrhea.1
Outline of the diarrheal toxicity
In this study, experiments in human fresh gastrointestinal tissue, conducted at REPROCELL (Biopta), helped to elucidate the mechanism by which a combination of two therapies (the investigational anti-HER3 therapy, lumretuzumab and the approved anti-HER2 therapy pertuzumab) caused diarrhea during a recent clinical trial for treatment of breast cancer. Chronic diarrhea narrowed the therapeutic window to such an extent that further clinical development was stopped.