Reducing Adjuvant Chemo Safe, Effective for Children with Resected Hepatoblastoma

Results from a recent phase 3 clinical trial demonstrate that reducing the dose of ototoxic agents is safe and effective for children with hepatoblastoma resected at diagnosis (Lancet Oncol. 2019 Apr 8. Epub ahead of print).

“Hepatoblastoma treatment with curative intent requires surgical resection, but only about a third of newly diagnosed patients with hepatoblastoma have resectable disease at diagnosis,” said Howard M. Katzenstein, MD, Nemours Children's Specialty Care and Wolfson Children's Hospital, Jacksonville, Florida, and colleagues.

“Patients who have upfront resection typically receive a total of 4-6 cycles of adjuvant chemotherapy post-surgery, with the combination of cisplatin, fluorouracil, and vincristine,” they continued.

Seeking to determine whether event-free survival (EFS) could be maintained with 2 cycles of adjuvant chemotherapy in children with hepatoblastoma who underwent complete resection at diagnosis, Dr Katezenstein and his co-investigators conducted a multi-center, Children's Oncology Group study.

Between May 18, 2010, and May 28, 2014, a total of 51 patients aged <21 years were enrolled into a low-risk cohort based on Evans surgical stage, tumor histology, and levels of α-fetoprotein at diagnosis.

Within 42 days of undergoing resection, these patients were given cisplatin, fluorouracil, and vincristine across 2 cycles spanning 21 days each. The primary end point of the study was investigator-assessed EFS, which was analyzed 6 years post-enrollment.

Ultimately, 49 patients were considered evaluable for safety and activity. Follow-up for these patients lasted for a medium time frame of 42 months. Their 4- and 5-year EFS rates were 92% (95% CI, 79-97) and 88% (95% CI, 72-95), respectively.

Bile leaks occurred in 2 (4%) patients, and febrile neutropenia, decreased neutrophil count, infections, and diarrhea were the most frequently reported grade 3-4 adverse events, occurring in 7 (14%), 3 (6%), 4 (8%), and 4 (8%) patients, respectively. Only 1 (2%) patient had ototoxicity.

Of 3 patients whose cancer relapsed, 1 (2%) died because of the disease; in addition, 2 (4%) patients died in clinical remission after discontinuing therapy. Pneumonia and bacterial sepsis 1 year after therapy led to the death of 1 patient, and another patient died from unrelated causes 57 months after completing therapy. No treatment-related deaths were reported.

“Minimal postoperative chemotherapy with two cycles of cisplatin, fluorouracil, and vincristine can ensure disease control in patients with hepatoblastoma resected at diagnosis. Our results show that dose reduction of ototoxic agents is a safe, effective treatment for these children,” Dr Katzenstein and colleagues concluded.—Hina Khaliq