Alladi Ramakrishnan Hall

Clinical Pharmacology Approaches to Improvement of Outcomes in Oncology in Low and Middle Income Countries

Vikram Gota

Professor, ACTREC, Tata Memorial Centre, Mumbai

Despite the advancements in almost every aspect of cancer therapeutics, there are numerous untouched, unmet and unexplored problems in day-to-day cancer care. These problems exist because they are either rare (orphan) or limited to a section of society or populace with limited means, so that there is no financial incentive for drug manufactures to invest in research and development to mitigate these problems. The onus of finding solutions under these circumstances will rest with academic institutions. The solution could lie in either optimizing the use (dose/frequency) of existing drugs and/or develop novel indigenous drugs and formulations to bridge the ‘therapy’ gap. The department of clinical pharmacology at ACTREC, Tata Memorial Centre has taken up this responsibility in a limited way for the last 15 years. I will discuss three scenarios in which my department has played a critical role providing solutions for unmet medical needs.

The first situation is in the setting of bone marrow transplantation, wherein, a complication called graft versus host disease (GvHD) severely compromises the transplant outcomes as it is associated with high mortality and morbidity. Drugs for the prophylaxis and treatment of GvHD exist, but have high failure rates. Besides, the treatment is extremely expensive and beyond the reach of a majority of transplant recipients. I will discuss our efforts at developing a novel herbal drug for this condition and the ongoing clinical trials at our centre.

The second situation is related to treatment o acute lymphoblastic leukemia in very young children. I will discuss the development of a liquid formulation of a drug called 6-mercaptopurine which is available only in the US and Europe. The pharmacokinetic modelling done to identify the optimal dose will also be discussed. The advantage of the liquid formulation over the existing solid dosage form and consequently its impact on ALL outcomes will be elaborated.

Finally, malnutrition is a huge problem among Indian children with cancer. The cancer outcomes in malnourished children is decidedly inferior compared to their well nourished counterparts. I will discuss the results of our ongoing clinical and non-clinical studies, and the proposed pharmacokinetic-pharmacodynamic modelling to optimize the dose of chemotherapeutic drugs used in this condition.