Joe Burchenal and the birth of combination chemotherapy

Abstract

SummaryWhen Joe Burchenal started studying medicine at the University of Pennsylvania in 1934, antibiotics had not been discovered and the survival of patients diagnosed with acute leukaemia was <4 months. By the time he retired in 1983, 58% of children with acute lymphoblastic leukaemia survived 5 years with the majority being cured of their disease. His early work in infectious diseases and antimicrobials equipped him well, both clinically and scientifically. The approach to developing antibiotics to conquer previously incurable infection was an inspiration and model for his pioneering work when searching for drugs with activity against cancer. Trials of sequential and then combination chemotherapy followed. Success in treating lymphoid malignancies in children led him to develop treatment regimens for other more resistant cancers, and as an advocate of collaborative working he introduced multimodal therapy to tackle bulky or metastatic cancers, replacing inevitable relapse with a chance of true cure.

Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia

“…The folate analog methotrexate (MTX) and the thio-substituted purine analog 6-mercaptopurine (6MP) became pioneering anticancer agents more than half a century ago, when first Farber et al1 and then Burchenal2,3 demonstrated that such drugs can induce temporary remissions in childhood leukemia. Soon cure became the goal,4,5 and through a series of trials it was shown that the chance of long-term remission of childhood acute lymphoblastic leukemia (ALL) was significantly improved, when patients received several years of postremission maintenance therapy with daily 6MP and weekly MTX 4–8.…”

The 2015 AACR Joseph H. Burchenal Memorial Award for Outstanding Achievement in Clinical Cancer Research

“…Although small successes were seen with this chemotherapy regimen, these researchers were encouraged to experiment with other combinatorial chemotherapies for the treatment of solid tumors. Dr. Burchenal and Herbert Oettengen, along with 14 other scientists, received the 1972 Albert Lasker Award for Medical Research for their contributions to the treatment of Burkitt lymphoma (2,3).…”