NEW YORK (Reuters Health) Jul 12 - Chemotherapy given in conjunction with regional hyperthermia produces good response rates in children and adolescents with refractory or recurrent germ-cell tumors, German researchers report.
"This protocol allows clinicians to provide a long-term cure for most of these patients with poor prognosis," they say in their paper in The Lancet Oncology published online July 1.
The finding comes from a non-randomized, single-institution, phase 2 study, but as an editorialist notes, a randomized trial would be difficult given the rarity of such cases.
The lead author of the study, Dr. Rudiger Wessalowski, at Heinrich-Heine-University Dusseldorf, Germany, and his colleagues, note that while children with malignant germ-cell tumors have a good prognosis, more than 10% of such cases are resistant to treatment. Research has therefore focused on new salvage strategies, including the use of hyperthermia.
Hyperthermia increases cellular uptake of cisplatin and can overcome cisplatin resistance, the authors explain, "rendering cisplatin effective in patients after primary treatment failure."
The team treated 44 patients with refractory or recurrent non-testicular germ-cell tumors with three or four course of cisplatin, etoposide, and ifosfamide (PEI), plus simultaneous microwave-induced regional deep hyperthermia at a target intratumoral temperature of 41-43�C. Once residual tumor resection was possible, the patients then received one or two more PEI-hyperthermia treatments plus radiotherapy if resection was incomplete.
Among 35 evaluable patients, 30 (86%) achieved complete or partial remission, the investigators report, and overall survival at five years was 72%. "This salvage rate is unmatched by all other reports on recurrent childhood malignant germ-cell tumours," they point out.
Regarding safety, myelotoxic effects were similar to those experienced with other intensive chemotherapy regimens used to treat childhood cancers, the authors found. During hyperthermia treatment (all done with sedation), mild skin inflammation occurred in five patients and no severe skin burns were noted. Seven patients reported grade 1 pain in the treated area.
"These encouraging results for local tumour control, which is essential for a long-term cure, strongly suggest that the use of microwave-induced regional deep hyperthermia at temperatures of 41-43�C in combination with standard platinum-based chemotherapy should be introduced soon after initial treatment failure," Dr. Wessalowski and colleagues conclude. "This regimen has the potential to become a first-line treatment for tumours with locally difficult characteristics."
In his editorial, Dr. Thomas A. Olson of Emory University in Atlanta, Georgia, wonders whether the strategy can be readily adopted by other pediatric centers. "The essential element in hyperthermia is temperature control," he writes, "and until appropriate thermal dosimetry methods are developed and widespread, this procedure might be restricted to a small number of centres."
SOURCE: http://bit.ly/15e2GL1
Lancet Oncol 2013.
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