Stabilization of disease progression by hydroxyurea in patients with recurrent or unresectable meningiomas

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  • 1 Department of Medicine, Princess Margaret Hospital, and the University of Toronto; Division of Neurosurgery, Department of Surgery, Toronto Western Hospital and the University of Toronto; Departments of Medical Oncology and Neurology, London Regional Cancer Centre and the University of Western Ontario, London, Ontario, Canada; Department of Neurology, New Jersey Neuroscience Institute, Edison, New Jersey; and Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York
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Object. The management of certain meningiomas of the skull base and those involving the dural venous sinuses remains a challenge. In recent reports it has been suggested that hydroxyurea chemotherapy can cause regression of unresectable and recurrent meningiomas. The authors report their experience in using hydroxyurea for the treatment of patients with recurrent or unresectable meningiomas.

Methods. Hydroxyurea was administered at a dosage of approximately 20 mg/kg/day to 11 women and nine men (median age 59 years, range 31–75 years) with recurrent or unresectable intracranial meningiomas (12 basal, two parasagittal, and six multiple). In 16 patients the meningiomas were benign, in three they had atypical features, and in one the meningioma was malignant. All patients had measurable residual disease. Four patients with benign meningiomas had previously received radiotherapy (two were treated with conventional fractionated radiotherapy and two with stereotactic radiosurgery), three with atypical meningiomas received conventional fractionated radiotherapy, and the one with a malignant meningioma received conventional radiotherapy with additional stereotactic radiosurgery. Tumor enlargement was documented in all patients on neuroimages obtained before initiation of hydroxyurea therapy.

All patients were evaluable for response to therapy. In 12 patients with benign meningiomas, the disease had stabilized on neuroimages obtained posttreatment (median duration of treatment 122 weeks, range 8–151 weeks), and two of these showed clinical improvement. One patient with a benign meningioma experienced a minor partial response that was noted after 39 weeks of treatment and was confirmed on neuroimaging and clinical evaluations. In three others with benign meningiomas, progression was confirmed on neuroimages obtained after 41, 55, and 66 weeks, respectively; the 1-year freedom from progression rate was 0.93 (standard error 0.07) in patients with benign meningiomas. In three patients with atypical meningiomas, the tumors had progressed on neuroimages obtained after 12, 19, and 45 weeks, respectively. In the patient with a malignant meningioma, progression was confirmed on neuroimages obtained at 24 weeks. Hydroxyurea has been reasonably well tolerated, although one patient discontinued therapy because of moderate myelosuppression.

Conclusions. Although tumor regression appears uncommon, these results indicate that hydroxyurea may arrest progression of unresectable or recurrent benign meningiomas.

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Contributor Notes

Address reprint requests to: Warren P. Mason, M.D., Princess Margaret Hospital, Suite 18–717, 610 University Avenue, Toronto, Ontario, M5G 2M9 Canada. email: warren.mason@uhn.on.ca.
  • 1.

    Bernstein M, , Villamil A, & Davidson G, et al. : Necrosis in a meningioma following systemic chemotherapy. Case report. J Neurosurg 81:284287, 1994 Bernstein M, Villamil A, Davidson G, et al: Necrosis in a meningioma following systemic chemotherapy. Case report. J Neurosurg 81:284–287, 1994

    • Search Google Scholar
    • Export Citation
  • 2.

    Black P: Meningiomas. Neurosurgery 32:643657, 1993 Black P: Meningiomas. Neurosurgery 32:643–657, 1993

  • 3.

    Chamberlain MC: Adjuvant combined modality therapy for malignant meningiomas. J Neurosurg 84:733736, 1996 Chamberlain MC: Adjuvant combined modality therapy for malignant meningiomas. J Neurosurg 84:733–736, 1996

    • Search Google Scholar
    • Export Citation
  • 4.

    Elford HL: Effect of hydroxyurea on ribonucleotide reductase. Biochem Biophys Res Commun 33:129135, 1968 Elford HL: Effect of hydroxyurea on ribonucleotide reductase. Biochem Biophys Res Commun 33:129–135, 1968

    • Search Google Scholar
    • Export Citation
  • 5.

    Goldsmith BJ, , Wara WM, & Wilson CB, et al. : Postoperative irradiation for subtotally resected meningiomas. A retrospective analysis of 140 patients treated from 1967 to 1990. J Neurosurg 80:195201, 1994 Goldsmith BJ, Wara WM, Wilson CB, et al: Postoperative irradiation for subtotally resected meningiomas. A retrospective analysis of 140 patients treated from 1967 to 1990. J Neurosurg 80:195–201, 1994

    • Search Google Scholar
    • Export Citation
  • 6.

    Goodwin JW, , Crowley J, & Eyre HJ, et al. : A phase II evaluation of tamoxifen in unresectable or refractory meningiomas: a Southwest Oncology Group study. J Neurooncol 15:7377, 1993 Goodwin JW, Crowley J, Eyre HJ, et al: A phase II evaluation of tamoxifen in unresectable or refractory meningiomas: a Southwest Oncology Group study. J Neurooncol 15:73–77, 1993

    • Search Google Scholar
    • Export Citation
  • 7.

    Grunberg S: Role of antiprogestational therapy for meningiomas. Hum Reprod 9 (Suppl 1):202207, 1994 Grunberg S: Role of antiprogestational therapy for meningiomas. Hum Reprod 9 (Suppl 1):202–207, 1994

    • Search Google Scholar
    • Export Citation
  • 8.

    Grunberg SM, , Rankin C, & Townsend J, et al. : Phase III double-blind randomized placebo-controlled study of mifepristone (RU) for the treatment of unresectable meningioma. Proc Am Soc Clin Oncol 20:56a, 2001 (Abstract) Grunberg SM, Rankin C, Townsend J, et al: Phase III double-blind randomized placebo-controlled study of mifepristone (RU) for the treatment of unresectable meningioma. Proc Am Soc Clin Oncol 20:56a, 2001 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 9.

    Grunberg SM, & Weiss MH: Lack of efficacy of megestrol acetate in the treatment of unresectable meningioma. J Neurooncol 8:6165, 1990 Grunberg SM, Weiss MH: Lack of efficacy of megestrol acetate in the treatment of unresectable meningioma. J Neurooncol 8:61–65, 1990

    • Search Google Scholar
    • Export Citation
  • 10.

    Herken R, , Merker HJ, & Krowke R: Investigation of the effect of hydroxyurea on the cell cycle and the development of necrosis in the embryonic CNS of mice. Teratology 18:103118, 1978 Herken R, Merker HJ, Krowke R: Investigation of the effect of hydroxyurea on the cell cycle and the development of necrosis in the embryonic CNS of mice. Teratology 18:103–118, 1978

    • Search Google Scholar
    • Export Citation
  • 11.

    Hoshino T, , Nagashima T, & Murovic JA, et al. : Proliferative potential of human meningiomas of the brain. A cell kinetics study with bromodeoxyuridine. Cancer 58:14661472, 1986 Hoshino T, Nagashima T, Murovic JA, et al: Proliferative potential of human meningiomas of the brain. A cell kinetics study with bromodeoxyuridine. Cancer 58:1466–1472, 1986

    • Search Google Scholar
    • Export Citation
  • 12.

    Kaba SE, , DeMonte F, & Bruner JM, et al. : The treatment of recurrent unresectable and malignant meningiomas with interferon alpha-2B. Neurosurgery 40:271275, 1997 Kaba SE, DeMonte F, Bruner JM, et al: The treatment of recurrent unresectable and malignant meningiomas with interferon alpha-2B. Neurosurgery 40:271–275, 1997

    • Search Google Scholar
    • Export Citation
  • 13.

    Kennedy BJ: Hydroxyurea therapy in chronic myelogenous leukemia. Cancer 29:10521056, 1972 Kennedy BJ: Hydroxyurea therapy in chronic myelogenous leukemia. Cancer 29:1052–1056, 1972

    • Search Google Scholar
    • Export Citation
  • 14.

    Kennedy BJ, & Yarbro JW: Metabolic and therapeutic effects of hydroxyurea in chronic myeloid leukemia. JAMA 195:10381043, 1966 Kennedy BJ, Yarbro JW: Metabolic and therapeutic effects of hydroxyurea in chronic myeloid leukemia. JAMA 195:1038–1043, 1966

    • Search Google Scholar
    • Export Citation
  • 15.

    Kim JH, , Gelbard AS, & Perez AG: Action of hydroxyurea on the nucleic acid metabolism and viability of HeLa cells. Cancer Res 27:13011305, 1967 Kim JH, Gelbard AS, Perez AG: Action of hydroxyurea on the nucleic acid metabolism and viability of HeLa cells. Cancer Res 27:1301–1305, 1967

    • Search Google Scholar
    • Export Citation
  • 16.

    Kondziolka D, , Levy EI, & Niranjan A, et al. : Long-term outcomes after meningioma radiosurgery: physician and patient perspectives. J Neurosurg 91:4450, 1999 Kondziolka D, Levy EI, Niranjan A, et al: Long-term outcomes after meningioma radiosurgery: physician and patient perspectives. J Neurosurg 91:44–50, 1999

    • Search Google Scholar
    • Export Citation
  • 17.

    Krakoff IH, , Brown NC, & Reichard P: Inhibition of ribonucleotide diphosphate reductase by hydroxyurea. Cancer Res 28:15591565, 1968 Krakoff IH, Brown NC, Reichard P: Inhibition of ribonucleotide diphosphate reductase by hydroxyurea. Cancer Res 28:1559–1565, 1968

    • Search Google Scholar
    • Export Citation
  • 18.

    Lamberts SW, , Tanghe HL, & Avezaat CJ, et al. : Mifepristone (RU 486) treatment of meningiomas. J Neurol Neurosurg Psychiatry 55:486490, 1992 Lamberts SW, Tanghe HL, Avezaat CJ, et al: Mifepristone (RU 486) treatment of meningiomas. J Neurol Neurosurg Psychiatry 55:486–490, 1992

    • Search Google Scholar
    • Export Citation
  • 19.

    Longstreth WT Jr, , Dennis LK, & McGuire VM, et al. : Epidemiology of intracranial meningioma. Cancer 72:639648, 1993 Longstreth WT1 Jr, Dennis LK, McGuire VM, et al: Epidemiology of intracranial meningioma. Cancer 72:639–648, 1993

    • Search Google Scholar
    • Export Citation
  • 20.

    Macdonald DR, , Cascino TL, & Schold SC Jr, et al. : Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:12771280, 1990 Macdonald DR, Cascino TL, Schold SC Jr, et al: Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280, 1990

    • Search Google Scholar
    • Export Citation
  • 21.

    Marks SM, , Whitwell HL, & Lye RH: Recurrence of meningiomas after operation. Surg Neurol 25:436440, 1986 Marks SM, Whitwell HL, Lye RH: Recurrence of meningiomas after operation. Surg Neurol 25:436–440, 1986

    • Search Google Scholar
    • Export Citation
  • 22.

    Milosevic MF, , Frost PJ, & Laperriere NJ, et al. : Radiotherapy for atypical or malignant intracranial meningioma. Int J Radiat Oncol Biol Phys 34:817822, 1996 Milosevic MF, Frost PJ, Laperriere NJ, et al: Radiotherapy for atypical or malignant intracranial meningioma. Int J Radiat Oncol Biol Phys 34:817–822, 1996

    • Search Google Scholar
    • Export Citation
  • 23.

    Miralbell R, , Linggood RM, & de la Monte S, et al. : The role of radiotherapy in the treatment of subtotally resected benign meningiomas. J Neurooncol 37:157164, 1992 Miralbell R, Linggood RM, de la Monte S, et al: The role of radiotherapy in the treatment of subtotally resected benign meningiomas. J Neurooncol 37:157–164, 1992

    • Search Google Scholar
    • Export Citation
  • 24.

    Mirimanoff R, , Dosoretz DE, & Linggood RM, et al. : Meningioma: analysis of recurrence and progression following neurosurgical resection. J Neurosurg 62:1824, 1985 Mirimanoff R, Dosoretz DE, Linggood RM, et al: Meningioma: analysis of recurrence and progression following neurosurgical resection. J Neurosurg 62:18–24, 1985

    • Search Google Scholar
    • Export Citation
  • 25.

    National Cancer Institute: Common Toxicity Criteria. Bethesda, MD: National Cancer Institute, 1998 National Cancer Institute : Common Toxicity Criteria. Bethesda, MD: National Cancer Institute, 1998

    • Search Google Scholar
    • Export Citation
  • 26.

    Newman SA: Meningiomas: a quest for the optimum therapy. J Neurosurg 80:191194, 1994 Newman SA: Meningiomas: a quest for the optimum therapy. J Neurosurg 80:191–194, 1994

    • Search Google Scholar
    • Export Citation
  • 27.

    Newton H, , Slivka MA, & Stevens C: Hydroxyurea chemotherapy for unresectable or residual meningioma. J Neurooncol 49:165170, 2000 Newton H, Slivka MA, Stevens C: Hydroxyurea chemotherapy for unresectable or residual meningioma. J Neurooncol 49:165–170, 2000

    • Search Google Scholar
    • Export Citation
  • 28.

    Palma L, , Celli P, & Franco C, et al. : Long-term prognosis for atypical and malignant meningiomas: a study of 71 surgical cases. J Neurosurg 86:793800, 1997 Palma L, Celli P, Franco C, et al: Long-term prognosis for atypical and malignant meningiomas: a study of 71 surgical cases. J Neurosurg 86:793–800, 1997

    • Search Google Scholar
    • Export Citation
  • 29.

    Petty AM, , Kun LE, & Meyer GA: Radiation therapy for incompletely resected meningiomas. J Neurosurg 62:502507, 1985 Petty AM, Kun LE, Meyer GA: Radiation therapy for incompletely resected meningiomas. J Neurosurg 62:502–507, 1985

    • Search Google Scholar
    • Export Citation
  • 30.

    Rachlin JR, & Rosenblum ML: Etiology and biology of meningiomas, in Al-Mefty O (ed): Meningiomas. New York: Raven Press, 1991, pp 2237 Rachlin JR, Rosenblum ML: Etiology and biology of meningiomas, in Al-Mefty O (ed): Meningiomas. New York: Raven Press, 1991, pp 22–37

    • Search Google Scholar
    • Export Citation
  • 31.

    Rohringer M, , Sutherland GR, & Louw DF, et al. : Incidence and clinicopathological features of meningioma. J Neurosurg 71:665672, 1989 Rohringer M, Sutherland GR, Louw DF, et al: Incidence and clinicopathological features of meningioma. J Neurosurg 71:665–672, 1989

    • Search Google Scholar
    • Export Citation
  • 32.

    Schrell UM, , Rittig MG, & Anders M, et al. : Hydroxyurea for treatment of unresectable and recurrent meningiomas. I. Inhibition of primary human meningioma cells in culture and in meningioma transplants by induction of the apoptotic pathway. J Neurosurg 86:845852, 1997 Schrell UM, Rittig MG, Anders M, et al: Hydroxyurea for treatment of unresectable and recurrent meningiomas. I. Inhibition of primary human meningioma cells in culture and in meningioma transplants by induction of the apoptotic pathway. J Neurosurg 86:845–852, 1997

    • Search Google Scholar
    • Export Citation
  • 33.

    Schrell UM, , Rittig MG, & Anders M, et al. : Hydroxyurea for treatment of unresectable and recurrent meningiomas. II. Decrease in the size of meningiomas in patients treated with hydroxyurea. J Neurosurg 86:840844, 1997 Schrell UM, Rittig MG, Anders M, et al: Hydroxyurea for treatment of unresectable and recurrent meningiomas. II. Decrease in the size of meningiomas in patients treated with hydroxyurea. J Neurosurg 86:840–844, 1997

    • Search Google Scholar
    • Export Citation
  • 34.

    Taylor BW Jr, , Marcus RB Jr, & Friedman WA, et al. : The meningioma controversy: postoperative radiation therapy. Int J Radiat Oncol Biol Phys 15:299304, 1988 Taylor BW Jr, Marcus RB Jr, Friedman WA, et al: The meningioma controversy: postoperative radiation therapy. Int J Radiat Oncol Biol Phys 15:299–304, 1988

    • Search Google Scholar
    • Export Citation

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