Two phase III Children’s Oncology Group studies found that augmenting therapy with additional drugs improves outcomes for children with a high-risk form of Wilms tumour.

These patients have a specific chromosomal abnormality associated with poorer prognosis.

In prior research, such patients had four-year relapse-free survival rates of 74.9% for stage I/II disease and 65.9% for stage III/IV disease.

In the new studies, augmented therapy increased the rates to 83.9% for stage I/II and 91.5% for stage III/IV disease.

“Tailoring therapy to match each patient’s risk for relapse has been a major focus of paediatric oncology. For cancers with a low risk of recurrence, we strive to decrease therapy and minimise exposure to potentially toxic agents. On the other hand, we want to augment the therapy for those patients who are at higher risk of relapse so that we can hopefully increase the chance for cure,” said lead study author David B. Dix, MD, a physician at the British Columbia Children’s Hospital in Vancouver, Canada.

“Our study is an example of successful augmentation of therapy for a higher risk group. We were very encouraged to see that augmentation of therapy can overcome the negative influence of a biologic marker in children with Wilms tumour.”

Wilms tumour is a rare form of kidney cancer that mainly affects children under the age of five years.

About 500 new cases are diagnosed in North America every year.

This study focused on children with so-called favourable histology Wilms tumour, which accounts for 75% of childhood renal cancers.

Of those, about 5-6% of have a chromosome abnormality in the tumour that is known as loss of heterozygosity (LOH) on chromosomes 1p and 16q.

Researchers previously found that patients with LOH 1p and 16q have a higher risk of relapse.

In the studies, LOH 1p and 16q was detected in 35 patients with stage I/II disease and 52 with stage III/IV disease.

For patients with stage I/II disease, the standard therapy (vincristine/dactinomycin chemotherapy) was augmented with the addition of doxorubicin.

Patients with stage III/IV disease received Regimen M: the standard therapy (vincristine/dactinomycin/doxorubicin and radiation therapy) was augmented with 4 cycles of outpatient cyclophosphamide/etoposide.

At a median follow-up of 3.6 years, the four-year relapse-free survival rates were 83.9% for stage I/II disease and 91.5% for stage III/IV disease.

When comparing these rates to outcomes with standard treatment regimens (75% for early stage disease and 66% for late-stage disease), these studies suggest that augmentation of therapy markedly improves outcomes for patients with advanced disease.

Given the small numbers in the study sample, the benefit is less clear for patients with lower stage disease but suggestive of an improved outcome.

Overall, the treatment was well tolerated.

For stage I/II patients, augmented therapy was not associated with any significant short term increase in side effects.

For stage III/IV patients, the most common severe side effect of Regimen M was suppression of bone marrow function, occurring in 60% of patients; however, the side effect was manageable.

According to the authors, Regimen M substantially reduces the number of patients who would otherwise have to undergo very intensive relapse therapy.

However, the regimen is predicted to be associated with some risk of reduced fertility.

The authors recommend a clear discussion with families regarding the risks and benefits of augmented therapy for these higher risk patients with LOH.

Testing for LOH 1p and 16q is available at the Children’s Oncology Group Biopathology Center at Nationwide Children’s Hospital in Columbus, Ohio, and several other centers across North America.

Source: ASCO