A study led by Dr. Doug Hawkins shows that a new chemotherapy protocol greatly reduces side effects for patients with rhabdomyosarcoma.

Findings from a Children’s Oncology Group (COG) clinical trial led by Dr. Doug Hawkins opened the door to a new standard of care for rhabdomyosarcoma (RMS) that reduces harmful side effects of treatment. Hawkins presented the findings and proposed the new standard of care at the 2014 meeting of the American Society of Clinical Oncology (ASCO).

Although only about 350 children are diagnosed with RMS in the United States each year, it’s the most common soft tissue cancer in children. Two-thirds of the patients can be cured with a combination of chemotherapy, radiation and surgery. But chemotherapy increases the risk of infection, infertility and repeated blood transfusions.

In this international clinical trial, Hawkins compared current standard chemotherapy – 14 rounds of vinicristine, dactinomycin and cyclophosphamide (VAC) – to seven rounds of VAC alternating with seven rounds of vinicristine plus irinotecan (VI).

Notably lower side effects

Febrile neutropenia, a condition marked by fever and reduced white blood cell production, is one of the more severe complications of cancer chemotherapy and is often associated with life-threatening infection. The rate of febrile neutropenia with the new VAC/VI therapy ranged from 4% to 8% compared to 9% to 18% with the standard VAC chemotherapy. Red blood cell transfusions ranged from 8% to 9% with VAC/VI versus 26% to 27% with VAC. Platelet transfusions ranged from 6% to 12% versus 30% to 32%.

Infertility data will not be available until study participants – mostly children and adolescents – are older. However, Hawkins expects infertility to decrease because the VAC/VI reduces by 50% each patient’s total dosage of cyclophosphamide, the primary cause of infertility risk.

“Protecting fertility is very important to young people,” Hawkins notes. “Any treatment that can reduce the risk of infertility is a huge benefit.”

The six-year randomized study was built on 15 years of previous research and involved 481 newly diagnosed patients with intermediate-risk RMS at more than 200 sites in the U.S., Canada, Australia and several other countries. The study’s primary goal was to learn whether VAC/VI could improve the current cure rate of 65%.

“We are disappointed we were unable to improve the cure rate,” acknowledges Hawkins, “but we are excited to identify a new therapy that makes treatment more tolerable and improves quality of life – all without reducing the effectiveness of treatment.”

Irinotecan is most often used to treat colorectal cancer in adults, but RMS is primarily a childhood disease. Hawkins and other researchers began studying how to use irinotecan to treat RMS 15 years ago. Laboratory investigations suggested that irinotecan would be a particularly effective treatment for RMS based on empiric trials of the drug in laboratory models of the disease.

The COG will begin another RMS study later this year that will compare VAC/VI to VAC/VI plus temsirolemus, a drug that is currently used to treat advanced kidney cancer. Once again, the goal of the five-year study is to improve the cure rate. Hawkins is not the principal investigator of this study, but will oversee it as leader of the COG’s Soft Tissue Sarcoma Committee.