Convection-enhanced delivery of paclitaxel for the treatment of recurrent malignant glioma: a Phase I/II clinical study

View More View Less
  • 1 Department of Neurosurgery, Advanced Technology Center, Division of Radiology, Institute of Oncology, and Institute of Pathology, The Chaim Sheba Medical Center, Tel Hashomer; and Department of Neurosurgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

Object. A minority of patients with recurrent glioblastomas multiforme (GBMs) responds to systemic chemotherapy. The authors investigated the safety and efficacy of intratumoral convection-enhanced delivery (CED) of paclitaxel in patients harboring histologically confirmed recurrent GBMs and anaplastic astrocytomas.

Methods. Fifteen patients received a total of 20 cycles of intratumoral CED of paclitaxel. The patients were observed daily by performing diffusion-weighted (DW) magnetic resonance (MR) imaging to assess the convective process and routine diagnostic MR imaging to identify the tumor response. Effective convection was determined by the progression of the hyperintense signal within the tumor on DW MR images, which corresponded to a subsequent lytic tumor response displayed on conventional MR images. Of the 15 patients, five complete responses and six partial responses were observed, giving a response rate of 73%. The antitumor effect was confirmed by one biopsy and three en bloc resections of tumors, which showed a complete response, and by one tumor resection, which demonstrated a partial response. Lack of convection and a poor tumor response was associated with leakage of the convected drug into the subarachnoid space, ventricles, and cavities formed by previous resections, and was seen in tumors containing widespread necrosis. Complications included transient chemical meningitis in six patients, infectious complications in three patients, and transient neurological deterioration in four patients (presumably due to increased peritumoral edema).

Conclusions. On the basis of our data we suggest that CED of paclitaxel in patients with recurrent malignant gliomas is associated with a high antitumor response rate, although it is associated with a significant incidence of treatment-associated complications. Diffusion-weighted MR images may be used to predict a response by demonstrating the extent of convection during treatment. Optimization of this therapeutic approach to enhance its efficacy and reduce its toxicity should be explored further.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

Address reprint requests to: Zvi Ram, M.D., Department of Neurosurgery, Tel-Aviv Sourasky Medical Center, 6 Weizman Street, Tel-Aviv 64239, Israel. email: zviram@tasmc.health.gov.il.
  • 1.

    Basser PJ, , Mattiello J, & LeBihan D: MR diffusion tensor spectroscopy and imaging. Biophys J 66:259267, 1994 Basser PJ, Mattiello J, LeBihan D: MR diffusion tensor spectroscopy and imaging. Biophys J 66:259–267, 1994

    • Search Google Scholar
    • Export Citation
  • 2.

    Bobo RH, , Laske DW, & Akbasak A, et al: Convection-enhanced delivery of macromolecules in the brain. Proc Natl Acad Sci USA 91:20762080, 1994 Bobo RH, Laske DW, Akbasak A, et al: Convection-enhanced delivery of macromolecules in the brain. Proc Natl Acad Sci USA 91:2076–2080, 1994

    • Search Google Scholar
    • Export Citation
  • 3.

    Bouvier G, , Penn RD, & Kroin JS, et al: Direct delivery of medication into a brain tumor through multiple chronically implanted catheters. Neurosurgery 20:286291, 1987 Bouvier G, Penn RD, Kroin JS, et al: Direct delivery of medication into a brain tumor through multiple chronically implanted catheters. Neurosurgery 20:286–291, 1987

    • Search Google Scholar
    • Export Citation
  • 4.

    Brem H, , Mahaley MS Jr, & Vick NA, et al: Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas. J Neurosurg 74:441446, 1991 Brem H, Mahaley MS Jr, Vick NA, et al: Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas. J Neurosurg 74:441–446, 1991

    • Search Google Scholar
    • Export Citation
  • 5.

    Chang SM, , Kuhn JG, & Rizzo J, et al: Phase I study of paclitaxel in patients with recurrent malignant glioma: a North American Brain Tumor Consortium report. J Clin Oncol 16:21882194, 1998 Chang SM, Kuhn JG, Rizzo J, et al: Phase I study of paclitaxel in patients with recurrent malignant glioma: a North American Brain Tumor Consortium report. J Clin Oncol 16:2188–2194, 1998

    • Search Google Scholar
    • Export Citation
  • 6.

    Cheson BD: Clinical trials referral resource. Update on taxol trials. Oncology (Huntingt) 7:63, 66–67, 1993 Cheson BD: Clinical trials referral resource. Update on taxol trials. Oncology (Huntingt) 7:63, 66–67, 1993

    • Search Google Scholar
    • Export Citation
  • 7.

    Debinski W: Local treatment of brain tumors with targeted chimera cytotoxic proteins. Cancer Invest 20:801809, 2002 Debinski W: Local treatment of brain tumors with targeted chimera cytotoxic proteins. Cancer Invest 20:801–809, 2002

    • Search Google Scholar
    • Export Citation
  • 8.

    Donelli MG, , Zucchetti M, & D'Incalci M: Do anticancer agents reach the tumor target in the human brain? Cancer Chemother Pharmacol 30:251260, 1992 Donelli MG, Zucchetti M, D'Incalci M: Do anticancer agents reach the tumor target in the human brain? Cancer Chemother Pharmacol 30:251–260, 1992

    • Search Google Scholar
    • Export Citation
  • 9.

    Fetell MR, , Grossman SA, & Fisher JD, et al: Preirradiation paclitaxel in glioblastoma multiforme: efficacy, pharmacology, and drug interactions. New Approaches to Brain Tumor Therapy Central Nervous System Consortium. J Clin Oncol 15:31213128, 1997 Fetell MR, Grossman SA, Fisher JD, et al: Preirradiation paclitaxel in glioblastoma multiforme: efficacy, pharmacology, and drug interactions. New Approaches to Brain Tumor Therapy Central Nervous System Consortium. J Clin Oncol 15:3121–3128, 1997

    • Search Google Scholar
    • Export Citation
  • 10.

    Gudbjartsson H, , Maier SE, & Mulkern RV, et al: Line scan diffusion imaging. Magn Reson Med 36:509519, 1996 Gudbjartsson H, Maier SE, Mulkern RV, et al: Line scan diffusion imaging. Magn Reson Med 36:509–519, 1996

    • Search Google Scholar
    • Export Citation
  • 11.

    Jordan MA, , Toso RJ, & Thrower D, et al: Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations. Proc Natl Acad Sci USA 90:95529556, 1993 Jordan MA, Toso RJ, Thrower D, et al: Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations. Proc Natl Acad Sci USA 90:9552–9556, 1993

    • Search Google Scholar
    • Export Citation
  • 12.

    Kroin JS, & Penn RD: Intracerebral chemotherapy: chronic microinfusion of cisplatin. Neurosurgery 10:349354, 1982 Kroin JS, Penn RD: Intracerebral chemotherapy: chronic microinfusion of cisplatin. Neurosurgery 10:349–354, 1982

    • Search Google Scholar
    • Export Citation
  • 13.

    Lieberman DM, , Laske DW, & Morrison PF, et al: Convection-enhanced distribution of large molecules in gray matter during interstitial drug infusion. J Neurosurg 82:10211029, 1995 Lieberman DM, Laske DW, Morrison PF, et al: Convection-enhanced distribution of large molecules in gray matter during interstitial drug infusion. J Neurosurg 82:1021–1029, 1995

    • Search Google Scholar
    • Export Citation
  • 14.

    Mardor Y, , Roth Y, & Lidar Z, et al: Monitoring response to convection-enhanced taxol delivery in brain tumor patients using diffusion-weighted magnetic resonance imaging. Cancer Res 61:49714973, 2001 Mardor Y, Roth Y, Lidar Z, et al: Monitoring response to convection-enhanced taxol delivery in brain tumor patients using diffusion-weighted magnetic resonance imaging. Cancer Res 61:4971–4973, 2001

    • Search Google Scholar
    • Export Citation
  • 15.

    Morrison PF, , Laske DW, & Bobo H, et al: High-flow microinfusion: tissue penetration and pharmacodynamics. Am J Physiol 266:R292R305, 1994 Morrison PF, Laske DW, Bobo H, et al: High-flow microinfusion: tissue penetration and pharmacodynamics. Am J Physiol 266:R292–R305, 1994

    • Search Google Scholar
    • Export Citation
  • 16.

    Nierenberg D, , Harbaugh R, & Maurer LH, et al: Continuous intratumoral infusion of methotrexate for recurrent glioblastoma: a pilot study. Neurosurgery 28:752761, 1991 Nierenberg D, Harbaugh R, Maurer LH, et al: Continuous intratumoral infusion of methotrexate for recurrent glioblastoma: a pilot study. Neurosurgery 28:752–761, 1991

    • Search Google Scholar
    • Export Citation
  • 17.

    Ohata K, & Marmarou A: Clearance of brain edema and macromolecules through the cortical extracellular space. J Neurosurg 77:387396, 1992 Ohata K, Marmarou A: Clearance of brain edema and macromolecules through the cortical extracellular space. J Neurosurg 77:387–396, 1992

    • Search Google Scholar
    • Export Citation
  • 18.

    Rand RW, , Kreitman RJ, & Patronas N, et al: Intratumoral administration of recombinant circularly permuted interleukin-4-pseudomonas exotoxin in patients with high-grade glioma. Clin Cancer Res 6:21572165, 2000 Rand RW, Kreitman RJ, Patronas N, et al: Intratumoral administration of recombinant circularly permuted interleukin-4-pseudomonas exotoxin in patients with high-grade glioma. Clin Cancer Res 6:2157–2165, 2000

    • Search Google Scholar
    • Export Citation
  • 19.

    Reulen HJ, , Graham R, & Spatz M, et al: Role of pressure gradients and bulk flow in dynamics of vasogenic brain edema. J Neurosurg 46:2435, 1977 Reulen HJ, Graham R, Spatz M, et al: Role of pressure gradients and bulk flow in dynamics of vasogenic brain edema. J Neurosurg 46:24–35, 1977

    • Search Google Scholar
    • Export Citation
  • 20.

    Rosenberg GA, , Kyner WT, & Estrada E: Bulk flow of brain interstitial fluid under normal and hyperosmolar conditions. Am J Physiol 238:F42F49, 1980 Rosenberg GA, Kyner WT, Estrada E: Bulk flow of brain interstitial fluid under normal and hyperosmolar conditions. Am J Physiol 238:F42–F49, 1980

    • Search Google Scholar
    • Export Citation
  • 21.

    Sendelbeck SL, & Urquhart J: Spatial distribution of dopamine, methotrexate and antipyrine during continuous intracerebral microperfusion. Brain Res 328:251258, 1985 Sendelbeck SL, Urquhart J: Spatial distribution of dopamine, methotrexate and antipyrine during continuous intracerebral microperfusion. Brain Res 328:251–258, 1985

    • Search Google Scholar
    • Export Citation
  • 22.

    Terzis AJ, , Thorsen F, & Heese O, et al: Proliferation, migration and invasion of human glioma cells exposed to paclitaxel (Taxol) in vitro. Br J Cancer 75:17441752, 1997 Terzis AJ, Thorsen F, Heese O, et al: Proliferation, migration and invasion of human glioma cells exposed to paclitaxel (Taxol) in vitro. Br J Cancer 75:1744–1752, 1997

    • Search Google Scholar
    • Export Citation
  • 23.

    Walter KA, , Cahan MA, & Gur A, et al: Interstitial taxol delivered from a biodegradable polymer implant against experimental malignant glioma. Cancer Res 54:22072212, 1994 Walter KA, Cahan MA, Gur A, et al: Interstitial taxol delivered from a biodegradable polymer implant against experimental malignant glioma. Cancer Res 54:2207–2212, 1994

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 817 273 16
Full Text Views 246 49 0
PDF Downloads 159 28 0
EPUB Downloads 0 0 0