In 1916, Albert Einstein predicted the existence of gravitational waves. It took almost 100 years and the construction of the Laser Interferometer Gravitational-Wave Observatory (LIGO) to show that he was right. In 2015, a brilliant team of researchers detected gravitational ripples that had been generated by the collision of two black holes about 1.3 billion years ago.
What can we learn from this amazing achievement? First, science requires patience – major breakthroughs rarely happen overnight. Second, the most important steps forward are often not immediately obvious.
To commemorate its 50th anniversary in 2014, the American Society of Clinical Oncology (ASCO) polled its members to identify the top five advances in oncology. The top winner of this friendly competition was the development of a cure for Hodgkin’s lymphoma by means of combination chemotherapy. But the story behind the cure reveals the importance of continuous innovation – stepwise advances in research and discovery that build on each other to create sea changes in the oncology standard of care.
On its timeline of major milestones in cancer progress, ASCO pins this cure for Hodgkin’s lymphoma to 1965, while acknowledging that the original regimen has since been continuously improved to become more effective and less toxic.
Dr. Vincent DeVita Jr., a key player in the development of this first cure for Hodgkin’s lymphoma, vividly describes the intense work and struggles that led to this advance in his recent book, The Death of Cancer.
Inspired by previous work in childhood leukemia, Dr. DeVita and his colleague, Dr. Jack Moxley, devised the first protocol for combination chemotherapy in Hodgkin’s lymphoma using four drugs: cyclophosphamide, vincristine, methotrexate, and prednisone (MOMP). The initial trial showed promise. New insights into the biology of Hodgkin’s lymphoma – including a better understanding of the rate at which Hodgkin’s lymphoma cells divide and how bone marrow recovers from exposure to toxic drugs – then led Drs. DeVita and Moxley to adjust the dose and schedule of MOMP and replace methotrexate with procarbazine. They called the new regimen MOPP. In the first trial of MOPP, 80 percent of patients experienced a complete disappearance of their cancer. As long as 40 years later, 60 percent of these patients never experienced a recurrence.
Despite Drs. DeVita and Moxley’s successes in treating Hodgkin’s lymphoma, many other physicians were at first unable to reproduce their results. The reason proved to be seemingly minor deviations from the intended protocol: dose modifications to reduce toxicity, substitutions with similar drugs and changes to the treatment schedule. The failures of these amended protocols underscore the need to precisely adjust treatments to maximize their effectiveness. In the decades since the original MOPP protocol was developed, numerous additional innovations have brought the cure rate of Hodgkin’s lymphoma to more than 75 percent today.
MOPP and its successors have had a remarkable impact on the lives of patients with Hodgkin’s lymphoma. The ripples of Drs. DeVita and Moxley’s brilliant ideas a half century ago are still being felt, and the long-term benefit of their treatments on the survival of Hodgkin’s patients are still being measured.
The story of the MOPP regimen’s continuous and stepwise development is not unique among cancer treatments.
To boost our ability to keep track of all the individual steps necessary to advance progress against cancer, PACE (Patient Access to Cancer care Excellence), a global initiative that encourages innovation in cancer treatment and care, recently developed a new tool called the PACE Continuous Innovation Indicators (CII). We now use this instrument to systematically assess progress against 12 solid tumors and better understand how clinical cancer research moves forward over time.
Time and again, analyses of CII data reveal the same pattern: progress does not happen overnight. In fact, each so-called “milestone” of cancer progress represents the sum of many individual contributions, collaborative research studies and an enormous amount of skilled work.
The ASCO members who voted in the competition were right to acknowledge Drs. DeVita and Moxley’s tedious work with their gold medal. By fostering and accelerating this continuous process, oncologists create value for patients today that holds the promise to create ripples in the fabric of our universe felt far into the future.
The author is the lead developer and researcher of the PACE (Patient Access to Cancer Care Excellence) Continuous Innovation Indicators—the first ever evidence-based, customizable, online tool to visualize progress achieved against cancer. Her scientific work has resulted in more than 30 peer-reviewed publications. Paddock received her postdoctoral training at the National Institute of Mental Health, her Ph.D. in Neuroscience from Karolinska Institute, and her undergraduate training (Cand. Med.) at Heidelberg University in Germany.