New chemotherapy regimen prolongs survival in difficult-to-treat childhood brainstem gliomas

Sep 26 2007

Childhood brainstem gliomas (BSGs) are rare but can be very difficult to treat successfully and they tend to have poor survival rates.

However, a team of Spanish researchers have found that a chemotherapy regimen of irinotecan and cisplatin (I/C) produced rapid clinical responses and shrank the tumours by more than 20 percent in all six children enrolled in a clinical trial.

Dr Jaume Mora told the European Cancer Conference (ECCO 14) in Barcelona today (Tuesday) that this was the first time that such a response had been achieved in children with high grade gliomas, while in low grade gliomas the response was comparable with the best achieved by other chemotherapies. All six children were still alive at one year, although the disease had progressed in three children with the most life-threatening tumours. The usual average survival rate for BSGs is between 4-15 months.

Dr Mora, who is head of the department of paediatric oncology at Hospital Sant Joan de Deu, Barcelona, Spain, explained: “The main treatment for BSGs is radiotherapy. Surgery is not really an option because of the way the tumour is situated in life-threatening anatomical structures situated in the brain stem. However, for children the long-term adverse consequences of radiotherapy have meant that doctors have looked to clinical trials to see if chemotherapy could be substituted for radiotherapy. However, most of these trials have failed; at present, many centres use radiation therapy for high-grade gliomas and diffuse intrinsic pontine tumours, the deadliest of all BSGs. For low-grade gliomas in children few combination regimens have shown significant changes in the long-term natural history of this disease: vincristine and carboplatin is the current protocol and was pioneered by the Duke's University group in the USA. The Italians have tested cisplatin and VP-16 with very good results for low-grade gliomas.”

BSGs are rare, but are amongst the commonest cancers to occur in children aged between about six and ten years old. The cause is unknown and the survival rates are poor: high-grade BSGs (diffuse and non-diffuse intrinsic tumours) are uniformly fatal, while children with low-grade gliomas have a more prolonged survival.

Dr Mora and his team enrolled six children out of 22 with BSGs in their trial. Four children had high-grade gliomas (two diffuse and two non-diffuse) and two had low-grade, mid-brain tumours. Irinotecan and cisplatin was given once a week for four weeks for a total of four cycles. Children with the high-grade tumours were also given anti-angiogenic therapy (bevacizumab) and radiotherapy.

Dr Mora said: “All patients had complete and rapid clinical responses to the I/C regimen. Remarkably, the I/C regimen achieved a reduction in tumour size greater than 20 percent in all the children at the end of the therapy, including those with the worst BSGs, the intrinsic diffuse BSGs. No chemotherapy has ever achieved this grade of early response in high-grade BSGs.”

Between nine and twelve months after the therapy, three of the high-grade tumours started to progress again.

Dr Mora said: “This early response is promising but the high-grade patients eventually progress regardless of the maintenance therapy we have given them. We need to rethink these results and find out how to consolidate better these initial responses.”

The other 16 children with BSGs had received different treatments by the start of the trial and they made up the historical cohort. After an average of 25 months, ten of them (65 percent) were still alive. These results cannot be compared directly with the results from the clinical trial but give an indication of how difficult it is to prolong survival for this disease.

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