Pediatrics Xagena

Children and adolescents with refractory or recurrent non-testicular malignant germ-cell tumours: regional deep hyperthermia for salvage treatment

Although the survival of children and adolescents with malignant germ-cell tumours has improved greatly in recent years, the outcome remains poor for those with refractory or recurrent malignant germ-cell tumours.
A study has determined whether objective tumour response could be achieved in patients with refractory or recurrent malignant germ-cell tumours with PEI-regional deep hyperthermia as salvage treatment.

Patients with refractory or recurrent non-testicular malignant germ-cell tumours after standard Cisplatin-based chemotherapy were treated prospectively with PEI chemotherapy ( Cisplatin 40 mg/m2, delivered intravenously on days 1 and 4; Etoposide 100 mg/m2, intravenously on days 1-4; and Ifosfamide 1800 mg/m2, intravenously on days 1-4 ) plus simultaneous 1-h regional deep hyperthermia ( 41-43°C ) on days 1 and 4.
Patients received three to four treatment courses at 21-day intervals until residual tumour resection was possible; they subsequently received one or two additional courses of PEI-regional deep hyperthermia.
Local radiotherapy was given for incompletely resected tumours.
Chemotherapy and hyperthermia toxic effects were assessed using WHO grading.

The primary endpoint was the proportion of patients who had an objective response as assessed with RECIST ( Response Evaluation Criteria in Solid Tumors ) version 1.0 guidelines.
Secondary endpoints were the event-free survival and overall survival after 5 years.

44 patients aged 7 months to 21 years ( median 2 years 7 months ) with refractory or recurrent malignant germ-cell tumours ( 9 patients with poor response, 23 patients with first relapse, 12 patients with multiple relapses ) were included in this study.

Researchers identified 34 yolk sac tumours, eight embryonal carcinomas, one choriocarcinoma, and one dysgerminoma by histology analysis.

Of the 35 patients who had sufficient clinical and radiographical data available for response assessment, 30 ( 86% ) had an objective response to treatment ( 16 patients had complete remission and 14 had partial remission ).

Five-year event-free survival was 62%, and 5-year overall survival was 72%. The median follow-up of surviving patients was 82 months ( range 9-195 ).

WHO grade 3-4 neutropenia and thrombocytopenia occurred in all 181 chemotherapy cycles. Granulocytopenic fever, which required intercurrent hospital admission, was noted in 29 ( 66% ) of 44 patients after 53 ( 29% ) of 181 courses.
Five patients experienced treatment-related grade-3 acute renal toxic effects.

A multimodal strategy integrating PEI-regional deep hyperthermia and tumour resection with or without radiation can successfully treat children and adolescents with refractory or recurrent malignant non-testicular germ-cell tumours.
The long-term prognosis of patients with poor response or after first relapse was almost similar to those receiving first-line treatment. ( Xagena )

Wessalowski R et al, The Lancet Oncology 2013; 843-852