Oncology Unscripted with John Marshall, MD: Are You Overdosing Your Patients? Revisiting Dosing Practices

In the latest episode of Oncology Unscripted, Dr. John Marshall addresses critical issues concerning the dosing practices in oncology, particularly questioning the prevailing approach of using maximum tolerated doses. Dr. Mark Ratain, a distinguished pharmacologist from the University of Chicago, joins the conversation to shed light on how dosing practices can be improved to enhance patient outcomes.

Exploring the MARIPOSA Study Dr. Marshall begins by discussing the findings from the MARIPOSA study featured in the New England Journal of Medicine. This study investigated the combination of amivantamab and lazertinib in treating EGFR-mutated non-small cell lung cancer, comparing it to the standard osimertinib. Although the combination showed a slight improvement in progression-free survival, it was associated with a significant increase in grade three toxicities. Dr. Marshall questions whether the minor benefits justify such an increase in adverse effects, prompting a broader discussion on the need for dose optimization.

Historical Context of Dosing Protocols Dr. Marshall reflects on the historical reliance on maximum tolerated doses in oncology, a practice rooted in the early days of chemotherapy where more aggressive dosing was equated with better outcomes. He cites instances, such as the treatment of adjuvant breast cancer with bone marrow transplants based on now-debunked studies, to illustrate the dangers of this approach.

In-depth Discussion with Dr. Mark Ratain Dr. Ratain expands on these concerns, critiquing the ongoing adherence to the “more is better” dosing philosophy despite a lack of scientific justification for many cancers. He introduces Project Optimus, an initiative he is involved with, which aims to push for dose optimization in drug development processes endorsed by the FDA. This project seeks to ensure that new drugs are approved at doses that balance efficacy with minimal toxicity.

Challenging Conventional Dosing with Sotorasib as a Case Study The conversation then shifts to specific examples, such as the recent FDA approval of sotorasib. Dr. Ratain points out that the approved dose was likely higher than necessary, as evidenced by phase studies showing no correlation between higher doses and increased efficacy or plasma concentration. This example highlights the resistance within the pharmaceutical industry and regulatory bodies to reduce doses, often driven by commercial interests.

Advocating for a Paradigm Shift Both experts advocate for a significant paradigm shift in how doses are determined and prescribed in oncology. They argue for a more patient-centric approach that prioritizes quality of life and long-term health outcomes over outdated dosing paradigms. Dr. Ratain emphasizes the importance of ongoing educational efforts and regulatory support to foster this change.

Conclusion This episode of Oncology Unscripted not only highlights the urgent need for reevaluation of dosing strategies in cancer treatment but also serves as a call to action for oncologists, regulators, and the pharmaceutical industry to prioritize safer, more effective patient care through scientifically grounded dosing practices.

For more insights and expert discussions, tune in to Oncology Unscripted or visit www.clinicalcaresolutions.net  for extended coverage and expert interviews on the pressing issues in medical dosing today.