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R Jakacki

Publications and source records attributed to R Jakacki.

9 recordsLinked to original sources
PubMed1999

A phase I/II study of carboplatin combined with hyperfractionated radiotherapy for brainstem gliomas.

BACKGROUND: Brainstem gliomas often respond to radiotherapy but long term disease control is exceptional. The concomitant administration of a chemotherapy agent with radiosensitizing properties such as carboplatin may increase the efficacy of radiotherapy. METHODS: A dose escalation schedule of carboplatin was devised to determine the maximum tolerated dose (MTD) of intravenous carboplatin when given on a twice-weekly schedule during a course of hyperfractionated, involved field radiotherapy (100 centigrays [cGy] twice daily to 7200 cGy). The starting dose was 20 mg/m(2) and the dose was increased by 15 mg/m(2) after every 3 patients provided no Grade 3 or 4 (according to the National Institutes of Health Common Toxicity Criteria) toxicity occurred. Magnetic resonance imaging (MRI) scans (brain and spine) were obtained before treatment and at the time of disease progression. Clinical entry criteria included an MRI scan demonstrating a diffuse intrinsic pontine tumor and a typical 2-3-month history of evolving cranial neuropathies and a gait disorder. Biopsy-confirmed evidence of a high grade glioma was required for nonpontine brain stem tumors. RESULTS: A total of 34 patients were enrolled. The median age of the patients was 7.8 years (range, 3.6-15.4 years) and the median prodrome duration was 1.5 months (range, 0.25-36 months). The MTD was 110 mg/m(2) or a total cumulative dose of 1540 mg/m(2) over 7 weeks. The dose-limiting toxicity was hematologic. The median progression free survival was 8 months (range, 0-104+ months) and the overall survival was 12 months (range, 5-104+ months). At last follow-up there were 5 long term survivors (15%) who remained in continuous remission after a mean follow-up period of 79 months (range, 46-104 months). Fifteen of the 29 patients (52%) with recurrence and or disease progression developed leptomeningeal/intraaxial tumor spread beyond the local radiation field. CONCLUSIONS: The cumulative MTD for carboplatin is 1540 mg/m(2) when administered concomitantly with involved field, hyperfractionated radiotherapy in a twice-weekly schedule for 7 weeks. Subsequent Phase II and III clinical trials can be conducted safely at this level.

Adolescent↗
PubMed1998

Treatment of diencephalic syndrome with chemotherapy: growth, tumor response, and long term control.

BACKGROUND: The diencephalic syndrome (DS), which is manifested by progressive emaciation and failure to thrive in an apparently alert, cheerful infant, usually is due to a low grade hypothalamic glioma. Treatment with aggressive surgery and/or radiotherapy is variably successful in controlling disease and may result in severe neurologic sequelae. Chemotherapy recently has been shown to be effective in patients with low grade gliomas of childhood, but it is used infrequently in those with DS. METHODS: The authors evaluated the efficacy of a regimen of carboplatin and vincristine on improving weight, causing tumor shrinkage, and delaying the need for alternative therapies in seven children (ages 9-20 months; median age, 11 months) with DS. Five patients weighed less than the 5th percentile for their age at the start of the study, one weighed within the 10th percentile, and one weighed within the 25th percentile. RESULTS: At follow-up (range, 6-54 months; median, 28 months), the patients' weights had increased by 66-95% (median, 80%). On magnetic resonance imaging, four patients had a >50% reduction in tumor mass, one had a 25-50% reduction, and two had stable disease. In those patients with radiographic response to treatment, weight gain was accomplished with oral feedings in four of five patients, whereas those with stable disease required nasogastric, nasojejunal, or gastrostomy tube supplementation to maintain weight. Disease progression occurred at a median of 24 months after initiation of chemotherapy, and two patients remained free of progressive disease at last follow-up. Five patients were alive a median of 59 months from diagnosis. The need for radiation or other therapies was delayed in six of seven children. Therapy was tolerated without significant toxicities. CONCLUSION: The authors conclude that treatment of DS with a carboplatin and vincristine regimen results in demonstrable weight gain, may result in tumor shrinkage, and in some cases, significantly delays the need for alternative therapies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas.

The optimum treatment of nonresectable low-grade gliomas of childhood remains undecided. There has been increased interest in the use of chemotherapy for young children, but little information concerning the long-term efficacy of such treatment. Seventy-eight children with a mean age of 3 years (range 3 months-16 years) who had newly diagnosed, progressive low-grade gliomas were treated with combined carboplatin and vincristine chemotherapy. The patients were followed for a median of 30 months from diagnosis, with 31 patients followed for more than 3 years. Fifty-eight children had diencephalic tumors, 12 had brainstem gliomas, and three had diffuse leptomeningeal gliomas. Forty-four (56%) of 78 patients showed an objective response to treatment. Progression-free survival rates were 75 +/- 6% at 2 years and 68 +/- 7% at 3 years. There was no statistical difference in progression-free survival rates between children with neurofibromatosis Type 1 and those without the disease (2-year, progression-free survival 79 +/- 11% vs. 75 +/- 6%, respectively). The histological subtype of the tumor, its location, and its maximum response to chemotherapy did not have an impact on the duration of disease control. The only significant prognostic factor was age: children 5 years old or younger at the time of treatment had a 3-year progression-free survival rate of 74 +/- 7% compared with a rate of 39 +/- 21% in older children (p < 0.01). Treatment with carboplatin and vincristine is effective, especially in younger children, in controlling newly diagnosed progressive low-grade gliomas.

Adolescent↗
PubMed1997

Flow cytometric DNA analysis of pediatric intracranial ependymomas.

OBJECTIVE: To examine the clinicopathologic features and perform flow cytometric DNA analysis of pediatric intracranial ependymomas to determine whether any of these parameters were predictors of clinical outcome. METHODS: Flow cytometric DNA analysis was performed on 17 paraffin-embedded tumors from patients aged 7 months to 16 years. RESULTS: Seven cases were aneuploid, while the remaining 10 were diploid. Proliferative fractions varied from 1% to 17%. CONCLUSIONS: No correlation between histologic features such as mitotic activity, cellularity, pleomorphism, vascular proliferation, and length of survival was observed. However, the presence of a diploid DNA stemline, elevated proliferative fraction, or young age were associated with a poor clinical outcome and shortened survival times (P < 0.05). Additional studies of larger patient groups with extended follow-up are necessary to confirm these findings.

Adolescent↗
PubMed1993

Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood.

PURPOSE: This study investigates the response rate to and toxicity of carboplatin and vincristine in children with recurrent low-grade gliomas (LGGs) or patients younger than 60 months with newly diagnosed LGGs. PATIENTS AND METHODS: Twenty-three children with recurrent and 37 children with newly diagnosed LGGs were treated with a 10-week induction cycle of carboplatin and vincristine, followed by maintenance treatment with the same drugs. Patients were evaluated for response to treatment and toxicity. RESULTS: Twelve of 23 (52% +/- 10%; 95% confidence interval [CI], 0.32 to 0.72) assessable children with recurrent disease had an objective response to treatment, which included a greater than 50% reduction in tumor size in seven of 23 (30% +/- 10%; 95% CI, 0.10 to 0.50). Twenty-three of 37 (62% +/- .08; 95% CI, 0.46 to 0.78) of newly diagnosed patients had an objective response, 16 of 37 (43% +/- 0.08%; 95% CI, 0.27 to 0.59) with greater than 50% reduction in tumor size. The majority of those with an objective response had diencephalic tumors (n = 29), but children with thalamic (n = 2), cortical (n = 1), and brain stem (n = 2) LGGs also responded to treatment. Of the 35 patients with objective response to treatment, the maximum response was seen in 25 after completion of induction and in the remaining 10 after two to six cycles of maintenance treatment. Forty-nine of 53 (92% +/- .04%) patients who were stable or improved after induction remain without progressive disease (PD). Hematologic toxicity was common, but resulted in cessation of therapy in only one patient. Six children have been removed from the study because of allergic reactions, which were considered to be carboplatin-associated. CONCLUSION: Carboplatin and vincristine have activity in children with recurrent and newly diagnosed progressive LGGs. Objective responses to treatment after chemotherapy can be seen. This drug regimen is relatively well tolerated, and further studies are indicated to define the role of this combination of drugs in children with newly diagnosed LGGs.

Adolescent↗
PubMed1990

Chondrosarcoma.

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Adolescent↗