Outcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy

A children's oncology group phase I/II study

Regina I. Jakacki, Peter C. Burger, Tianni Zhou, Emiko J. Holmes, Mehmet Kocak, Arzu Onar, Joel Goldwein, Minesh Mehta, Roger J. Packer, Nancy Tarbell, Charles Fitz, Gilbert Vezina, Joanne Hilden, Ian F. Pollack

Research output: Contribution to journalArticle

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Abstract

Purpose: We evaluated the feasibility of administering carboplatin as a radiosensitizer during craniospinal radiation therapy (CSRT) to patients with high-risk medulloblastomas (MBs) and supratentorial primitive neuroectodermal tumors, and we report the outcome in the subset with metastatic (M+) MB.Patients and Methods: After surgery, patients received 36 Gy CSRT with boosts to sites of disease. During radiation, patients received 15 to 30 doses of carboplatin (30-45 mg/m 2/dose), along with vincristine (VCR) once per week for 6 weeks. Patients on regimen A received 6 months of maintenance chemotherapy (MC) with cyclophosphamide and VCR. Once the recommended phase II dose (RP2D) of carboplatin was determined, cisplatin was added to the MC (regimen B).Results: In all, 161 eligible patients (median age, 8.7 years; range, 3.1 to 21.6 years) were enrolled. Myelosuppression was dose limiting and 35 mg/m 2/dose x 30 was determined to be the RP2D of carboplatin. Twenty-nine (36%) of 81 patients with M+ MB had diffuse anaplasia. Four patients were taken off study within 11 months of completing radiotherapy for presumed metastatic progression and are long-term survivors following palliative chemotherapy. Excluding these four patients, 5-year overall survival ± SE and progression-free survival ± SE for M+ patients treated at the RP2D on regimen A was 82% ± 9% and 71% ± 11% versus 68% ± 10% and 59% ± 10% on regimen B (P = .36). There was no difference in survival by M stage. Anaplasia was a negative predictor of outcome.Conclusion: The use of carboplatin as a radiosensitizer is a promising strategy for patients with M+ MB. Early progression should be confirmed by biopsy.

Original languageEnglish (US)
Pages (from-to)2648-2653
Number of pages6
JournalJournal of Clinical Oncology
Volume30
Issue number21
DOIs
StatePublished - Jul 20 2012

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Medulloblastoma
Carboplatin
Radiotherapy
Anaplasia
Maintenance Chemotherapy
Vincristine
Primitive Neuroectodermal Tumors
Radiation Dosage
Survival
Cyclophosphamide
Cisplatin
Disease-Free Survival
Survivors
Radiation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Outcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy : A children's oncology group phase I/II study. / Jakacki, Regina I.; Burger, Peter C.; Zhou, Tianni; Holmes, Emiko J.; Kocak, Mehmet; Onar, Arzu; Goldwein, Joel; Mehta, Minesh; Packer, Roger J.; Tarbell, Nancy; Fitz, Charles; Vezina, Gilbert; Hilden, Joanne; Pollack, Ian F.

In: Journal of Clinical Oncology, Vol. 30, No. 21, 20.07.2012, p. 2648-2653.

Research output: Contribution to journalArticle

Jakacki, RI, Burger, PC, Zhou, T, Holmes, EJ, Kocak, M, Onar, A, Goldwein, J, Mehta, M, Packer, RJ, Tarbell, N, Fitz, C, Vezina, G, Hilden, J & Pollack, IF 2012, 'Outcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy: A children's oncology group phase I/II study', Journal of Clinical Oncology, vol. 30, no. 21, pp. 2648-2653. https://doi.org/10.1200/JCO.2011.40.2792
Jakacki, Regina I. ; Burger, Peter C. ; Zhou, Tianni ; Holmes, Emiko J. ; Kocak, Mehmet ; Onar, Arzu ; Goldwein, Joel ; Mehta, Minesh ; Packer, Roger J. ; Tarbell, Nancy ; Fitz, Charles ; Vezina, Gilbert ; Hilden, Joanne ; Pollack, Ian F. / Outcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy : A children's oncology group phase I/II study. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 21. pp. 2648-2653.
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abstract = "Purpose: We evaluated the feasibility of administering carboplatin as a radiosensitizer during craniospinal radiation therapy (CSRT) to patients with high-risk medulloblastomas (MBs) and supratentorial primitive neuroectodermal tumors, and we report the outcome in the subset with metastatic (M+) MB.Patients and Methods: After surgery, patients received 36 Gy CSRT with boosts to sites of disease. During radiation, patients received 15 to 30 doses of carboplatin (30-45 mg/m 2/dose), along with vincristine (VCR) once per week for 6 weeks. Patients on regimen A received 6 months of maintenance chemotherapy (MC) with cyclophosphamide and VCR. Once the recommended phase II dose (RP2D) of carboplatin was determined, cisplatin was added to the MC (regimen B).Results: In all, 161 eligible patients (median age, 8.7 years; range, 3.1 to 21.6 years) were enrolled. Myelosuppression was dose limiting and 35 mg/m 2/dose x 30 was determined to be the RP2D of carboplatin. Twenty-nine (36{\%}) of 81 patients with M+ MB had diffuse anaplasia. Four patients were taken off study within 11 months of completing radiotherapy for presumed metastatic progression and are long-term survivors following palliative chemotherapy. Excluding these four patients, 5-year overall survival ± SE and progression-free survival ± SE for M+ patients treated at the RP2D on regimen A was 82{\%} ± 9{\%} and 71{\%} ± 11{\%} versus 68{\%} ± 10{\%} and 59{\%} ± 10{\%} on regimen B (P = .36). There was no difference in survival by M stage. Anaplasia was a negative predictor of outcome.Conclusion: The use of carboplatin as a radiosensitizer is a promising strategy for patients with M+ MB. Early progression should be confirmed by biopsy.",
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T1 - Outcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy

T2 - A children's oncology group phase I/II study

AU - Jakacki, Regina I.

AU - Burger, Peter C.

AU - Zhou, Tianni

AU - Holmes, Emiko J.

AU - Kocak, Mehmet

AU - Onar, Arzu

AU - Goldwein, Joel

AU - Mehta, Minesh

AU - Packer, Roger J.

AU - Tarbell, Nancy

AU - Fitz, Charles

AU - Vezina, Gilbert

AU - Hilden, Joanne

AU - Pollack, Ian F.

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Y1 - 2012/7/20

N2 - Purpose: We evaluated the feasibility of administering carboplatin as a radiosensitizer during craniospinal radiation therapy (CSRT) to patients with high-risk medulloblastomas (MBs) and supratentorial primitive neuroectodermal tumors, and we report the outcome in the subset with metastatic (M+) MB.Patients and Methods: After surgery, patients received 36 Gy CSRT with boosts to sites of disease. During radiation, patients received 15 to 30 doses of carboplatin (30-45 mg/m 2/dose), along with vincristine (VCR) once per week for 6 weeks. Patients on regimen A received 6 months of maintenance chemotherapy (MC) with cyclophosphamide and VCR. Once the recommended phase II dose (RP2D) of carboplatin was determined, cisplatin was added to the MC (regimen B).Results: In all, 161 eligible patients (median age, 8.7 years; range, 3.1 to 21.6 years) were enrolled. Myelosuppression was dose limiting and 35 mg/m 2/dose x 30 was determined to be the RP2D of carboplatin. Twenty-nine (36%) of 81 patients with M+ MB had diffuse anaplasia. Four patients were taken off study within 11 months of completing radiotherapy for presumed metastatic progression and are long-term survivors following palliative chemotherapy. Excluding these four patients, 5-year overall survival ± SE and progression-free survival ± SE for M+ patients treated at the RP2D on regimen A was 82% ± 9% and 71% ± 11% versus 68% ± 10% and 59% ± 10% on regimen B (P = .36). There was no difference in survival by M stage. Anaplasia was a negative predictor of outcome.Conclusion: The use of carboplatin as a radiosensitizer is a promising strategy for patients with M+ MB. Early progression should be confirmed by biopsy.

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