Neuroblastoma and Sarcomas

Soft tissue sarcomas in adults

These tumours exhibit a wide variety of histologic types and can occur anywhere in the body.

At present, treatment options are surgery, with adjuvant radiation used selectively for high-grade, incompletely resected lesions. Chemotherapy has been shown to be of limited benefit, delaying time to recurrence but not affecting overall survival.

Soft tissue sarcomas in childhood

Soft tissue sarcomas are the fifth most common solid tumour in children under 20 years old, after brain tumours, lymphomas, and carcinomas (mainly thyroid and melanoma). As in adult patients, pediatric patients experience a wide variety of sarcomas. The most common soft tissue sarcoma in children is rhabdomyosarcoma.

Over the past 40 years, advances in the combined use of chemotherapy, surgery, and radiation have markedly improved the survival of rhabdomyosarcoma patients with localized disease from 25% in 1970 to over 70% by 1995.

There remain a number of challenges, however, in treating patients with rhabdomyosarcoma. Metastatic disease is the major predictor of poor outcome and has not been significantly impacted by combination therapy.

Bone sarcomas

Bone sarcomas are the third most common cancer in adolescence, with the two most common types being osteosarcoma and Ewing's sarcoma.

At present treatment options for these tumour types is surgery and chemotherapy is also required to treat micrometastatic disease, which is present but not detectable in most at diagnosis. Radiotherapy is also used as an important treatment for Ewing's sarcoma but osteosarcomas are uniformly resistant to radiation. For localised disease, cure rates with combination therapies are in the range of 60-70%. Patients who present with metastases or multifocal disease have a poor prognosis, with long-term survival rates of less than 25%.

Neuroblastoma

Neuroblastomas are the most common extracranial solid tumours in children under 10 years of age. Median age of diagnosis is 17.3 months, with 40% of patients diagnosed as infants, and 98% by 10 years of age. Long term survival rate of high-risk neuroblastoma is poor.

At present treatment options are high dose chemotherapy, autologous stem cell rescue, and retinoic acid. These have improved survival of high risk neuroblastoma, however survival remains at under 50%.

There is an urgent need for new treatments that are safe and effective for both localised and metastatic sarcomas, and neuroblastoma.

HSV1716 therapy

Non clinical data supports the use of SEPREHVIR^®(HSV1716) in this indication and justifies the commencement of clinical development.

A Phase I dose escalation study of intratumoural SEPREHVIR^® in patients with non-CNS solid tumours, such as neuroblastomas and sarcomas, has been initiated at Cincinnati Children’s Hospital Medical Center under the leadership of Timothy P.Cripe, MD, Ph.D, Chief of Hematology/Oncology at Nationwide Children’s Hospital (Columbus, Ohio) and Associate Professor at Cincinnati Children’s.

The study is investigating single and repeat administration of SEPREHVIR^®(HSV1716) at different dose levels. 

The study has completed recruitment at the first dose level and following review of that data by an independent Data Safety Monitoring Board recruitment is continuing at a higher dose level.

We acknowledge the support provided to this study by Solving Kids Cancer and the FDA Orphan Grant Programme.