Feasibility and efficacy of intratumoural delivery of chemotherapeutic drugs in recurrent malignant glial tumours

A. Boiardi, M. Eoli, A. Salmaggi, B. Zappacosta, G. Broggi, L. Fariselli, A. Solari, A. Silvani

Research output: Contribution to journalArticle

Abstract

Chemotherapy for brain tumours has been limited because of difficulty in achieving adequate exposure to the tumour without systemic toxicity. We evaluated a protocol involving delivery of chemotherapy directly into the tumour mass through an Ommaya reservoir in order to improve survival (Mitoxantrone in association with bleomycin). A total of 99 patients bearing malignant glioma sequentially selected according to strict eligibility criteria (72 GBL and 27 AA) entered the study; they were subdivided in homogeneous groups, all treated with the same systemic chemotherapy protocol: 27 GBL (group A) only systemically treated, 20 GBL (group B) treated also locally through the Ommaya reservoir, and 25 GBL (group C) treated with a second operation and locally as group B. Of the AA group, 13/27 were treated locally trough the Ommaya reservoire after repeat surgery. Irradiation was given to fields defined by the enhanced-CT tumour area, plus 2-3 cm margin with a total dose of 60 Gy. Chemotherapy was performed with nitrosoureas and platin compounds. Median overall survival was 27.2 and 26 and 15.5 months, respectively, for groups C, B and A (log rank = 0.1). After tumour recurrence median survival was 16.8 and 12 and 6.6 months, respectively, for groups C and B and A (log rank = 0.001). For the 29 AA the overall survival was 48.5 and 90 months (log rank = 0.03) if treated locally with second tumour debulking. The side effects of local chemotherpy delivery included 8.4% partial seizures, 11.8% migratory headache, and 3% transient focal deficit. Our results stress that a second operation is suitable only if it is a part of a therapetic protocol which includes a loco-regional treatment. The efficacy depends upon its ability to diffuse into brain parenchyma, its uptake into tumour cells and the speed with which it is cleared from the CNS after release. From our results we assume that local delivery of chemotherapy after tumour recurrence possibly extends patient survival but certainly improves the number of long-term survivors.

Original languageEnglish
JournalNeurological Sciences
Volume21
Issue number4 SUPPL.
Publication statusPublished - 2000

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Neuroglia
Pharmaceutical Preparations
Drug Therapy
Survival
Neoplasms
Nitrosourea Compounds
Recurrence
Mitoxantrone
Bleomycin
Reoperation
Brain Neoplasms
Glioma
Headache
Survivors
Seizures
Brain

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Feasibility and efficacy of intratumoural delivery of chemotherapeutic drugs in recurrent malignant glial tumours. / Boiardi, A.; Eoli, M.; Salmaggi, A.; Zappacosta, B.; Broggi, G.; Fariselli, L.; Solari, A.; Silvani, A.

In: Neurological Sciences, Vol. 21, No. 4 SUPPL., 2000.

Research output: Contribution to journalArticle

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abstract = "Chemotherapy for brain tumours has been limited because of difficulty in achieving adequate exposure to the tumour without systemic toxicity. We evaluated a protocol involving delivery of chemotherapy directly into the tumour mass through an Ommaya reservoir in order to improve survival (Mitoxantrone in association with bleomycin). A total of 99 patients bearing malignant glioma sequentially selected according to strict eligibility criteria (72 GBL and 27 AA) entered the study; they were subdivided in homogeneous groups, all treated with the same systemic chemotherapy protocol: 27 GBL (group A) only systemically treated, 20 GBL (group B) treated also locally through the Ommaya reservoir, and 25 GBL (group C) treated with a second operation and locally as group B. Of the AA group, 13/27 were treated locally trough the Ommaya reservoire after repeat surgery. Irradiation was given to fields defined by the enhanced-CT tumour area, plus 2-3 cm margin with a total dose of 60 Gy. Chemotherapy was performed with nitrosoureas and platin compounds. Median overall survival was 27.2 and 26 and 15.5 months, respectively, for groups C, B and A (log rank = 0.1). After tumour recurrence median survival was 16.8 and 12 and 6.6 months, respectively, for groups C and B and A (log rank = 0.001). For the 29 AA the overall survival was 48.5 and 90 months (log rank = 0.03) if treated locally with second tumour debulking. The side effects of local chemotherpy delivery included 8.4{\%} partial seizures, 11.8{\%} migratory headache, and 3{\%} transient focal deficit. Our results stress that a second operation is suitable only if it is a part of a therapetic protocol which includes a loco-regional treatment. The efficacy depends upon its ability to diffuse into brain parenchyma, its uptake into tumour cells and the speed with which it is cleared from the CNS after release. From our results we assume that local delivery of chemotherapy after tumour recurrence possibly extends patient survival but certainly improves the number of long-term survivors.",
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