Aaron R. Rausen

Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma

Preclinical models show sequence‐dependent synergy with the combination of temozolomide and irinotecan, and a Phase I trial has demonstrated the combination to be tolerable and active in children with relapsed solid tumors. Because responses were seen in patients with Ewing sarcoma (ES) on that trial, additional patients were treated with this combination following study completion.

Treatment of Metastatic Ewing's Sarcoma or Primitive Neuroectodermal Tumor of Bone: Evaluation of Combination Ifosfamide and Etoposide—A Children's Cancer Group and Pediatric Oncology Group Study

PURPOSE One hundred twenty patients with metastatic Ewings sarcoma or primitive neuroectodermal tumor (PNET) of bone were entered onto a randomized trial evaluating whether the addition of ifosfamide and etoposide to vincristine, doxorubicin, cyclophosphamide, and dactinomycin improved outcomes. METHODS Thirty-two patients had metastases to lungs only, 12 patients had metastases to bone marrow or bones only, 64 patients had metastases in multiple sites, and five patients had metastases in other sites; seven patients could not be assessed precisely. Treatment comprised 9 weeks of chemotherapy before local control and 42 weeks of chemotherapy; thereafter, regimen A consisted of vincristine 2 mg/m(2), cyclophosphamide 1,200 mg/m(2), and either doxorubicin 75 mg/m(2) or dactinomycin 1.25 mg/m(2). Regimen B consisted of regimen A alternating every 3 weeks with ifosfamide 1,800 mg/m(2)/d for 5 days and etoposide 100 mg/m(2)/d for 5 days. RESULTS Patients treated on regimen B did not have significantly better survival than those treated on regimen A. The event-free survival (EFS) and survival (S) at 8 years were 20% (SE, 5%) and 32% (SE, 6%), respectively, for those treated on regimen A and 20% (SE, 6%) and 29% (SE, 6%), respectively, for those treated on regimen B. Patients who had only lung metastases had EFS and S of 32% (SE, 8%) and 41% (SE, 9%), respectively, at 8 years. There were six toxic deaths (5%), four from cardiac toxicity and two from sepsis (four treated on regimen B and two treated on regimen A). Two had second malignant neoplasms. CONCLUSION Adding ifosfamide and etoposide to standard therapy does not improve outcomes of patients with Ewings sarcoma or PNET of bone with metastases at diagnosis.

Treatment of metastatic Ewing sarcoma/primitive neuroectodermal tumor of bone: Evaluation of increasing the dose intensity of chemotherapy—a report from the Children's Oncology Group†

The outcome for patients with Ewing sarcoma family of tumors (ESFTs) of bone with metastases at diagnosis remains poor despite new approaches to treatment. We evaluated whether a dose‐intensity chemotherapy regimen improved survival for patients with ESFTs of bone with metastases at diagnosis.

Chemotherapy for Eye Cancer

Chemotherapy has been used to treat a multitude of eye cancers. We attempted to review the role of chemotherapy in the treatment of ocular, adnexal, and orbital malignancies by conducting an extensive search of the medical literature. Unfortunately, the published reports typically contain few patients with limited follow-up, precluding definitive recommendations. For most eye cancers, multicenter trials will offer the potential to gather the numbers of patients required to determine the clinical utility of chemotherapy.

Chemotherapy For Retinoblastoma: A Current Topic

Retinoblastoma is the most common primary intraocular tumour in children, with an incidence of 1 in 15 000 live births. Treatment strategies for retinoblastoma have gradually evolved over the past few decades. There has been a trend way from enucleation (removal of the eye) and external beam radiation therapy toward focal ‘conservative’ treatments. Every effort has been made to save the child’s life with preservation of eye and sight, if possible.Primary enucleation continues to be the commonly used method of treatment for retinoblastoma. It is employed in situations where eyes contain large tumours, long standing retinal detachments, neovascular glaucoma and suspicion of optic nerve invasion or extrascleral extension. Most of these eyes either have or are expected to have no useful vision. Radiation therapy continues to be an effective treatment option for retinoblastoma. However, external beam radiotherapy has unfortunately been associated with secondary non-ocular cancers in the field of radiation (primarily in children carrying the RB-1 germline mutation). Ophthalmic plaque brachytherapy has a more focal and shielded radiation field, and may carry less risk. Unfortunately, its applicability is limited to small to medium-sized retinoblastomas in accessible locations. Cryotherapy and transpupillary thermotherapy (TTT) have been used to provide control of selected small tumours. TTT is an advanced laser system adapted to the indirect ophthalmoscope which provides flexible nonsurgical treatment for small retinoblastomas.Recent research in the treatment of retinoblastoma has concentrated on methods of combining chemotherapy with other local treatment modalities (TTT, radiotherapy, cryotherapy). This approach combines the principle of chemotherapeutic debulking in paediatric oncology with conservative focal therapies in ophthalmology. Termed chemoreduction, intravenous or subconjunctival chemotherapy is used to debulk the initial tumour volume and allow for focal treatment with TTT, cryotherapy and plaque radiotherapy. Cyclosporin has been added to the chemotherapy regimen in several centres.Other clinical settings where chemotherapy is considered are situations where the histopathology suggests a high risk for metastatic disease and where there is extraocular extension. There is no consensus that chemotherapy is needed when choroidal invasion is observed on histopathology. However, in patients where the retinoblastoma is noted beyond the cut end of the optic nerve or if there is disruption of the sciera with microscopic invasion of the orbital tissue, treatment has been helpful. Systemic and intrathecal chemotherapy with local and cranial radiotherapy has improved the survival of these patients. Most recently, the use of new chemotherapy modalities with haematopoietic stem cell rescue or local radiotherapy has increased the survival of patients with distant metastasis. Nevertheless, the prognosis of patients with central nervous system involvement is still poor.