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A Phase I/II study of carboplatin combined with hyperfractionated radiotherapy for brainstem gliomas
Author(s) -
Allen Jeffrey,
Siffert Joao,
Donahue Bernadine,
Nirenberg Anita,
Jakacki Regina,
Robertson Patricia,
DaRosso Robert,
Thoron Louisa,
Rosovsky Mark,
Pinto Richard
Publication year - 1999
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19990915)86:6<1064::aid-cncr24>3.0.co;2-1
Subject(s) - medicine , carboplatin , radiation therapy , toxicity , nuclear medicine , chemotherapy , radiology , surgery , cisplatin
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. Cancer 1999;86:1064–9. © 1999 American Cancer Society.