Reduced, Compressed Chemotherapy Fails in Pediatric Germ Cell Tumors

Event-free survival (EFS) was not maintained in children and adolescents with intermediate-risk malignant germ cell tumors (MGCTs) when cisplatin-based chemotherapy was reduced from four to three cycles and compressed from 5 to 3 days per cycles, according to the results of a Children’s Oncology Group study published in the Journal of Clinical Oncology.

“We thus recommend that four cycles should remain the standard treatment when cisplatin, etoposide, and bleomycin (PEb) is used in the treatment of childhood MGCTs,” wrote Furqan Shaikh, MD, of the Hospital for Sick Children in Toronto, and colleagues.

Children with MGCT have EFS rates exceeding 90% when treated with standard chemotherapy; however, they often experience significant dose-dependent toxicities. Therefore, Shaikh and colleagues conducted this phase III study to determine if a 4-year EFS rate of 92% could be maintained with a reduction in standard chemotherapy from four to three cycles and a compression of therapy from 5 days to 3 days per cycle.

The study included 210 patients enrolled from 2003 to 2011. Boys up to age 15 and girls up to age 21 could be included. The most common tumor type was ovary (59%), followed by testes (22%), and extragonadal (19%). The majority of patients were female (71%).

Among these patients, the 4-year EFS rate was 89% (95% CI, 83%–92%), and the 4-year overall survival rate was 97%. The researchers wrote that “the reduction in chemotherapy to three compressed cycles of PEb for children with intermediate-risk MGCT resulted in an EFS rate that was less than targeted.”

In a secondary analysis, the researchers compared outcomes for patients with newly diagnosed disease with those of a matched cohort of patients treated in prior Children’s Oncology Group studies. Among the 181 patients with newly diagnosed disease, the 4-year EFS rate was 87% compared with 92% for the 92 comparable children in the historical cohort.

A subgroup analysis showed that EFS at 4 years was significantly associated with stage of disease. The EFS for patient with stage I disease was 100%; for stage II, 92%; stage III, 85%; and stage IV, 54%; P < .001).

The authors noted that some patient subgroups had excellent EFS rates when treated with the reduced/compressed chemotherapy regimen, including patients with stage I and II extragonadal tumors (4-year EFS rate, 100%). Patients with stage I gonadal tumors who recurred after surgery alone also showed good response with the compressed treatment schedule (4-year EFS rate, 97%). “These patients typically had minimal residual disease evidenced by microscopic positive margins or rising tumor markers; therefore, reduced therapy may have been sufficient to achieve remission,” the researchers wrote.

The researchers noted that since the study was not powered for subgroup comparisons, these results should be considered hypothesis generating only.