Temozolomide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: a report from the Children's Oncology Group.

An open-label phase II study (ACNS0126) testing the efficacy of chemoradiotherapy with temozolomide (TMZ) followed by adjuvant TMZ was conducted by the Children's Oncology Group. During the period from July 6, 2004 through September 6, 2005, 63 children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) were enrolled in the study. All patients received TMZ at a dosage of 90 mg/m(2)/day for 42 days to a dose of 59.

Temozolomide in the treatment of high-grade gliomas in children: a report from the Children's Oncology Group.

To determine whether temozolomide is an active agent in the treatment of children with high-grade astrocytomas and whether survival is influenced by the expression of the O6-methylguanine-methyltransferase gene (MGMT) in these patients. In the Children's Oncology Group study ACNS0126, 107 patients with a diagnosis of anaplastic astrocytoma (AA), glioblastoma multiforme (GBM), or gliosarcoma were enrolled. All patients underwent concomitant chemoradiotherapy with temozolomide, followed by adjuvant chemotherapy with temozolomide.

Extended phase I evaluation of vincristine, irinotecan, temozolomide, and antibiotic in children with refractory solid tumors.

Background: The combination of irinotecan, temozolomide, and vincristine is appealing because of potentially synergistic mechanisms of action and non-overlapping toxicities. This phase I study was designed to determine the toxicity and maximum tolerated dose (MTD) of escalating daily protracted doses of irinotecan given in this combination. With extended accrual, we more fully explored the toxicity of multiple courses at the MTD.

Two new patients with Curry-Jones syndrome with trichoblastoma and medulloblastoma suggest an etiologic role of the sonic hedgehog-patched-GLI pathway.

Curry-Jones syndrome (OMIM #601707) is a rare multiple malformation disorder of unknown etiology, associated with brain and skull abnormalities, polysyndactyly, and defects of the eyes, skin and gastrointestinal tract. We report on two new cases of Curry-Jones syndrome with previously unreported features, including benign and malignant neoplasms. The first patient had typical features of Curry-Jones syndrome as well as multiple intra-abdominal smooth muscle hamartomas and trichoblastoma of the skin.

Risk determinants for catheter-associated blood stream infections in children and young adults with cancer.

Background: Catheter-associated blood stream infections (CABSI) are frequent complications encountered with cancer treatment. In order to understand which factors might predispose to CABSIs in children and young adults, we evaluated risk for infection in association with tumor type, catheter type, and setting of occurrence.

Methods: All pediatric oncology patients having a central venous catheter (CVC) with a tunneled external (TE) or totally implantable design (TID) were prospectively followed for the occurrence of a CABSI for 12 months.

Successful treatment of an unresectable choroid plexus carcinoma in a patient with Li-Fraumeni syndrome.

Choroid plexus carcinoma (CPC) is an uncommon central nervous system tumor requiring complete surgical excision for favorable outcome. The authors report the successful treatment of a 2-year-old patient with widely disseminated CPC and Li-Fraumeni syndrome. Following a partial resection of the tumor the patient received chemotherapy consisting of cyclophosphamide, etoposide, and carboplatin.

Clinically evident venous thromboembolic events in children with brain tumors.

We evaluated the incidence and significance of central venous access device dysfunction and symptomatic major thrombosis in 253 pediatric patients with brain tumors. Central venous access device dysfunction was a common complication (28.4%) and was associated with major thrombosis development and a reduced overall survival rate.

Early neuro-otologic effects of three-dimensional irradiation in children with primary brain tumors.

Purpose: Central nervous system (CNS) irradiation can cause sensorineural hearing loss. The relationship between the dose to the cochlea and the development of hearing loss is unknown. Conformal radiation therapy (CRT) techniques facilitate accurate cochlear dosimetry.

Phase 2 study of idarubicin in pediatric brain tumors: Pediatric Oncology Group study POG 9237.

Idarubicin (IDA), the 4-demethoxy analog of daunomycin, has had significant cytotoxicity in many malignancies. In previous reports, the alcohol metabolite of IDA, 4-demethoxydaunorubicinol (idarubicinol, or IDOL), had cytotoxic activity and the ability to penetrate the blood-brain barrier. For this reason, the Pediatric Oncology Group conducted a Phase 2 trial of IDA for children with recurrent or progressive brain tumors.

Population pharmacokinetics of temozolomide and metabolites in infants and children with primary central nervous system tumors.

Purpose: To construct a population pharmacokinetic model for temozolomide (TMZ), a novel imidazo-tetrazine methylating agent and its metabolites MTIC and AIC in infants and children with primary central nervous system tumors.

Methods: We evaluated the pharmacokinetics of TMZ and MTIC in 39 children (20 boys and 19 girls) with 132 pharmacokinetic studies (109 in the training set and 23 in the validation set). The median age was 7.

Survival and functional outcome of children with hypothalamic/chiasmatic tumors.

Background: The management of children with hypothalamic (H) and/or chiasmatic (C) tumors remains controversial. We evaluated the impact of clinical and neuroimaging parameters and primary therapy on overall (OS) and progression-free (PFS) survival and on neuroendocrine and neurocognitive outcome in children with H and/or C tumors.

Methods: Records were reviewed for 73 children with H and/or C tumors treated at St.

Altered irinotecan pharmacokinetics in pediatric high-grade glioma patients receiving enzyme-inducing anticonvulsant therapy.

Purpose: The purpose of this study was to determine the effect of enzyme-inducing anticonvulsants (EIAs) on the disposition of irinotecan and metabolites in pediatric patients with high-grade glioma.

Experimental Design: Pediatric patients with newly diagnosed high-grade glioma were enrolled on this study between March 1999 and February 2001. During course 1, irinotecan was administered as a 60-min i.

Influence of tumor grade on time to progression after irradiation for localized ependymoma in children.

Purpose: To investigate the influence of histologic grade on progression-free survival (PFS) after irradiation (RT) for pediatric patients with localized ependymoma.

Methods And Materials: Fifty patients with localized ependymoma (median age 3.6 years, range 1-18 years at the time of RT) were treated with RT between December 1982 and June 1999.

Preliminary results from a Phase II trail of conformal radiation therapy for pediatric patients with localised low-grade astrocytoma and ependymoma.

Purpose: To estimate the local control and patterns of failure for pediatric patients with low-grade astroglial tumors (LGA) and ependymoma (EP) treated with three-dimensional conformal radiation therapy (CRT) using an anatomically defined clinical target volume (CTV).

Methods And Materials: From an ongoing, prospective Phase II trial initiated in July 1997, 102 pediatric patients with LGA (n = 38) and EP (n = 64) have been treated with CRT using an anatomically defined CTV extending 1.0 cm beyond the gross tumor volume and a 0.

Phase I study of combination topotecan and carboplatin in pediatric solid tumors.

Purpose: We conducted a phase I trial of escalating doses of topotecan (TOPO) in association with a fixed systemic exposure of carboplatin (CARBO) with or without granulocyte colony-stimulating factor (G-CSF) in children.

Patients And Methods: Two separate cohorts of patients (pts) with solid tumors were studied: (A) pts with refractory or recurrent disease and (B) pts with no prior myelosuppressive therapy or newly diagnosed tumors for which there was no standard chemotherapy. CARBO was given on day 1 at an area under the curve of 6.