Pilot Study of Adding Vincristine, Topotecan, and Cyclophosphamide to Interval-Compressed Chemotherapy in Newly Diagnosed Patients With Localized Ewing Sarcoma: A Report From the Children's Oncology Group.

BACKGROUND: The combination of topotecan and cyclophosphamide is active in relapsed Ewing sarcoma family of tumors (ESFT). The feasibility of adding these agents combined with vincristine (vincristine-topotecan-cyclophosphamide [VTc]) to standard five-drug chemotherapy with vincristine-doxorubicin-cyclophosphamide (VDC) and ifosfamide-etoposide (IE) administered in an interval-compressed (2-week instead of 3-week intervals) schedule was investigated. PROCEDURE: Newly diagnosed patients with localized ESFT < 31 years, with good performance status and adequate organ function were eligible. Seventeen alternating cycles of chemotherapy with VTc, VDC, and IE were administered at 2-week intervals. Local control (LC) of the primary tumor occurred following six cycles. Primary endpoints were the ability to deliver chemotherapy in an interval-compressed schedule, and the rate of grade 3 or greater nonhematologic toxicity and grade 4 hematologic toxicity, which delayed chemotherapy by ≥2 weeks. Secondary endpoints were event-free survival (EFS) and overall survival (OS). RESULTS: Thirty-five patients with a median age of 11 years were enrolled. The mean time to last dose of chemotherapy prior to LC was 12.6 ± 1.4 weeks and 45.5% of patients received intended chemotherapy without any delay prior to LC. There were no toxic deaths or unexpected toxicities. Five-year EFS was 79.6% (95% confidence interval [CI]: 61.8-89.7%) and 5-year OS was 88% (95% CI: 71.4-95.3%). CONCLUSIONS: The addition of VTc to standard therapy was tolerable with sufficient interval compression compared to historical standard 3-week cycles.

Abnormal liver transaminases and conjugated hyperbilirubinemia at presentation of acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood. While hepatitis is a well-known complication during the treatment phase of ALL, the association of abnormal liver biochemistries at initial presentation of leukemia is poorly described. The aim of this study is to examine the prevalence and assess the clinical impact of hepatitis at diagnosis in children with ALL. PROCEDURE: All children diagnosed with ALL at BC Children's Hospital between 2001 and 2006 were included. Charts were reviewed and data recorded to a computerized spreadsheet. Descriptive statistical analyses were performed. RESULTS: One hundred forty-seven ALL patients were identified. Over one third of patients had abnormal liver transaminase values (AST and/or ALT). Of the patients with abnormal transaminases, (52%) had ALT elevations twice the upper limit of normal. Risk factors for elevated transaminases included a high WBC count at diagnosis, older age, bulky disease, and T-cell leukemia. Conjugated hyperbilirubinemia was observed in 3.4% of subjects. Of these cases, 60% received steroids prior to induction chemotherapy and all had rapid resolution of their hyperbilirubinemia to normal levels. CONCLUSIONS: Elevated transaminases are common at initial presentation of ALL and are likely due to hepatic injury from leukemic infiltrates. Conjugated hyperbilirubinemia at presentation may require treatment modification and dose reduction. A short course of steroids prior to initiation of induction chemotherapy appears to result in rapid resolution of the hyperbilirubinemia with subsequent ability to provide full dosing of induction chemotherapy.

Understanding clinical trials in childhood cancer.

Clinical trials in paediatric cancer continue to be a key factor in progress toward better treatment and prognosis. Paediatricians and family physicians may be asked by patients and families for their advice regarding participation in such trials. The significant advances in the success of treatment of paediatric cancer have come, in part, from the high participation rate of patients in such studies. The present article reviews the definitions and goals of phase 1, 2 and 3 trials. A known and trusted physician or paediatrician can be helpful in conjunction with the oncologist in guiding patients and their families and helping them understand the risks and benefits of participation in clinical trials.