Phase I study of intraarterial mitomycin-c for recurrent intracerebral tumors

  • David J. Stewart
  • Zvonimir Grahovac
  • Michael T. Richard
  • Brien Benoit
  • Jean A. Maroun
  • Herman Hugenholtz
  • Neville Russell
  • Jean Dennery
  • Eric Peterson
  • Brian Luke
  • Enrique G. Ventureyra
  • André Girard
  • Harry S. Hopkins
Chapter

Abstract

Seventeen patients with intracerebral neoplasms were treated with intra-arterial mitomycin-c 7.5–18 mg/m2 at 6–9 week intervals. Most were heavily pretreated. Three of 8 evaluable patients with brain metastases, a single patient with a primitive neuroectodermal tumor, and 0 of 6 with glioblastomas responded to treatment. The activity of this regimen to date has been impressive considering the patient population treated. Neurological and ocular toxicity were dose-limiting. We recommend a mitomycin-c dose of 15 mg/m2 every 6–9 weeks for further studies.

Keywords

Brain Metastasis Internal Carotid Artery Vertebral Artery Cranial Irradiation Primitive Neuroectodermal Tumor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. 1.
    Fenstermacher J, Cowles A: Theoretic Limitations of Intracarotid Infusions in Brain Tumor Chemotherapy. Cancer Treat Rep 61: 519–526, 1977PubMedGoogle Scholar
  2. 2.
    Chen HAG, Gross J: Intra-arterial Infusion of Anticancer Drugs: Theoretic Aspects of Drug Delivery and Review of Responses. Cancer Treat Rep 64: 31–40, 1980PubMedGoogle Scholar
  3. 3.
    Collins J: Phamracologic Rationale for Regional Drug Delivery. J Clin Oncol 2: 498–504, 1984PubMedGoogle Scholar
  4. 4.
    Stewart DJ, Benjamin RS, Zimmerman S, Caprioli RM, Wallace S, Chuang V, Calvo III D, Samuels M, Bonura J, Loo TL: Clinical Pharmacology of Intra-arterial Cis-diammine Dichloroplatinum (II). Cancer Research 43: 917–920, 1983PubMedGoogle Scholar
  5. 5.
    Stewart DJ: Novel Modes of Chemotherapy Administration. Rosenblum ML, Wilson CB (eds). Progress in Experimental Brain Tumor Research. S Kargel Med & Scientific Publishers. Basel/Switzerland. Vol 28, pp 32–50, 1984Google Scholar
  6. 6.
    Ensminger W, Gyves J: Clinical Pharmacology of Hepatic Arterial Chemotherapy. Semin Oncol 10: 176–182, 1983PubMedGoogle Scholar
  7. 7.
    Stewart DJ, Benjamin RS, Luna M, Seifert WE, Loo TL: Human Tissue Distribution of Platinum After Cis-diamminedichloroplatinum. Cancer Chemother & Pharm 10: 51–54, 1982Google Scholar
  8. 8.
    Stewart DJ, Leavens M, Maor M, Feun L, Luna M, Bonura J, Caprioli R, Loo TL, Benjamin RS: Human Central Nervous System Distribution of Cis-Diamminedichloroplatinum and Use as a Radiosensitizer in Malignant Brain Tumors. Cancer Research 2: 2474–2479, 1982Google Scholar
  9. 9.
    Levin V, Kabra P, Freeman-Dove M: Pharmacokinetics of intra-carotid Artery 14C-BCNU in the Squirrel Monkey. J Neurosurg 48: 587–593, 1978PubMedCrossRefGoogle Scholar
  10. 10.
    Crooke S, Bradner W: Mitomycin-C: A Review. Cancer Treat Rev 3: 121–139, 1976PubMedCrossRefGoogle Scholar
  11. 11.
    Anderson T, Andreasson L, Biorklund A, Brismar J, Elver A, Eneroth C, Hellekant C, Landberg T, Mattisson W: Intra-arterial Chemotherapy of Malignant Head and Neck Tumors with Superselective Angiographic Technique. Acta Otolaryngol 360 (Suppl): 167–170, 1979Google Scholar
  12. 12.
    Misra NC, Jaiswal M, Singh R, Das B: Intrahepatic Arterial Infusion of Combination of Mitomycin-C and 5-Fluorouracil in the Treatment of Primary and Metastatic Liver Carcinoma. Cancer 39: 1425–1429, 1977PubMedCrossRefGoogle Scholar
  13. 13.
    Den Hartigh J, McVie J, Van Oort J, Pinedo H: Pharmacokinetics of Mitomycin-C in Humans. Cancer Res 43: 5017–5021, 1983Google Scholar
  14. 14.
    Takakura K: Chemotherapy of Metastatic Brain Tumors, with Particular Reference to Continuous Intracranial Infusion of Mitomycin-C and a Radiosensitizing Agent, BUDR. Jpn J Cancer Clin 17: 263–268, 1971Google Scholar
  15. 15.
    Stewart DJ, Grahovac Z, Benoit B, Addison D, Richard MT, Dennery J, Hugenholtz H, Russel N, Peterson E, Maroun JA, Vandenberg T, Hopkins HS: Intracarotid Chemotherapy with a Combination of BCNU, Cisplatin and VM-26 in the Treatment of Primary and Metastatic Brain Tumors. Neurosurgery 15: 828–833, 1984PubMedCrossRefGoogle Scholar
  16. 16.
    Lehane D, Ehni G, Moiel R, Bryon R, Horowitz B, DeSantos L, Aldama-Luebert A, Zublir M, Rudolph L, Lane M: Adjuvant Therapy for Malignant Gliomas (MG) Using Intra-Arterial (IA) Cisplatinum (CP), Radiation Therapy (RT) and CCNU. Proc Am Soc Clin Oncol 2: 236, 1983 (abstr)Google Scholar

Copyright information

© Martinas Nijhoff Publishers, Boston 1986

Authors and Affiliations

  • David J. Stewart
    • 1
  • Zvonimir Grahovac
    • 1
  • Michael T. Richard
    • 1
  • Brien Benoit
    • 1
  • Jean A. Maroun
    • 1
  • Herman Hugenholtz
    • 1
  • Neville Russell
    • 1
  • Jean Dennery
    • 1
  • Eric Peterson
    • 1
  • Brian Luke
    • 1
  • Enrique G. Ventureyra
    • 1
  • André Girard
    • 1
  • Harry S. Hopkins
    • 1
  1. 1.The Ontario Cancer Treatment and Research Foundation Ottawa ClinicsThe University of Ottawa, the Ottawa General Hospital, the Ottawa Civic Hospital, and the Children’s Hospital of Eastern OntarioOttawaCanada

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