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Feasibility study of intraarterial vs intravenous cisplatin, BCNU, and teniposide combined with systemic cisplatin, teniposide, cytosine arabinoside, glycerol and mannitol in the treatment of primary and metastatic brain tumors

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Abstract

Sixteen patients with intracerebral tumors received intraarterial cisplatin, teniposide, and BCNU combined with intravenous cisplatin, teniposide, and cytosine arabinoside. Oral glycerol and intravenous mannitol were given along with the intravenous chemotherapy in an attempt to increase drug delivery to tumor by augmenting tumor blood flow. Thirteen additional patients were treated with the same regimen, but received all the chemotherapy intravenously. Of the 16 patients receiving intraarterial chemotherapy (median survival, 14 weeks), none responded, 5 (31%) were stable for > 8 weeks, 8 (50%) failed, and 3 (19%) were unevaluable due to early death. Of the 13 patients receiving all their treatment intravenously (median survival, 13 weeks), 3 (23%) responded, 1 (8%) was stable, 7 (54%) failed, and 2 (15%) were unevaluable due to early death. In the patients receiving intraarterial chemotherapy, toxicity included ipsilateral retinal toxicity (2 patients), ocular pain or headache (10), periorbital swelling and flushing (6), increased brain edema with focal neurological deficits and drowsiness (5), and catheter-related carotid artery thrombosis followed by fatal herniation (1). Myelosuppression was worse in patients who received all their treatment intravenously than in those receiving intraarterial chemotherapy (p < 0.05). Neutropenic sepsis developed in 4 patients on the intraarterial arm (1 fatal) and in 5 patients on the intravenous arm (2 fatal). Other toxic effects were similar whether or not patients received intraarterial treatment or only intravenous treatment. Overall, toxicity of this regimen was excessive, and response rates were lower than would have been expected with single agent therapy.

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References

  1. Stewart DJ: The role of chemotherapy in the treatment of gliomas in adults. Cancer Treat Rev 16: 129–160, 1989

    Google Scholar 

  2. Stewart DJ: Pros and cons of intra-arterial chemotherapy. Oncology 3: 20–26, 1989

    PubMed  Google Scholar 

  3. Stewart DJ: Intraarterial chemotherapy of primary and metastatic brain tumors. In: Rottenberg DA (ed) The Neurological Complications of Cancer Treatment. Butterworth-Heinemann, Boston 143–170, 1991

    Google Scholar 

  4. Shapiro WR, Green SB, Burger PC, Selker RG, VanGilder JD, Robertson JT, Mealey J, Ransohoff J, Mahaley MS: A randomized comparison of intraarterial vs intravenous BCNU for patients with malignant glioma: Interim analysis demonstrating lack of efficacy for IA BCNU. Proc Am Soc Clin Oncol 6: 69, 1987

    Google Scholar 

  5. Stewart D J, Grahovac Z, Benoit B, Addison D, Richard MT, Dennery J, Hugenholtz H, Russell N, Peterson E, Maroun JA, Vandenberg T, Hopkins HS: Intracarotid chemotherapy with a combination of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU), cis-diamminedichloroplatinum (Cisplatin), and 4′-O-demethyl-1-O-(4,6-O-2-thenylidene-β-D-glucopyranosyl) epipodophyllotoxin (VM-26) in the treatment of primary and metastatic brain tumors. Neurosurgery 15: 828–833, 1984

    PubMed  Google Scholar 

  6. Stewart DJ, Grahovac Z, Hugenholtz H, Russell N, Richard M, Benoit B: Combined intraarterial and systemic chemotherapy for intracerebral tumors. Neurosurgery 21: 207–214, 1987

    PubMed  Google Scholar 

  7. Coldman AJ, Goldie JH: Impact of dose-intense chemotherapy on the development of permanent drug resistance. Sem Oncol 14 (Suppl 4): 29–33, 1987

    Google Scholar 

  8. Bergerat JP, Drewinko B, Corry P, Barlogie B, Ho DH: Synergistic lethal effect of cis-dichlrodiammineplatinum and 1-B-D-arabinofuranosylcytosine. Cancer Res 41: 25–30, 1981

    PubMed  Google Scholar 

  9. Canetta R, Hilgard P, Florentine S, Bedogni P, Lenaz L: Current development of podophyllotoxins. Cancer Chemother Pharmacol 7: 93–98, 1982

    PubMed  Google Scholar 

  10. Boghdan U: Chemosensitivity of malignant brain tumors: preliminary results. J Neuro-Oncol 1: 149–166, 1983

    Google Scholar 

  11. Stewart DJ, Richard M, Hugenholtz HN, Benoit B, Russell N, Dennery J, Peterson E, Maroun J: Cisplatin plus cytosine arabinoside in adults with malignant gliomas. J Neuro-Oncol 2: 29–34, 1984

    Google Scholar 

  12. Meyer JS, Itoh Y, Okamoto S, Welch KM, Matthew R, Ott EO, Sakaki S, Miyakawa Y, Chabi E, Ericsson AD: Circulatory and metabolic effects of glycerol infusion in patients with recent cerebral infarction. Circulation 51: 701–712, 1975

    PubMed  Google Scholar 

  13. Burke AM, Quest DO, Chien S, Cerri C: The effects of mannitol on blood viscosity. J Neurosurg 55: 550–553, 1981

    PubMed  Google Scholar 

  14. Bischoff KB: Some fundamental considerations of the applications of pharmacokinetics to cancer chemotherapy. Cancer Chemother Rep 59: 777–793, 1975

    PubMed  Google Scholar 

  15. Stewart DJ, Richard MT, Hugenholtz H, Dennery J, Nundy D, Prior J, Montpetit V, Hopkins HS: Penetration of teniposide (VM-26) into human intracerebral tumors: preliminary observations on the effect of tumor type, rate of drug infusion, and prior treatment with amphotericin-B or oral glycerol. J Neuro-Oncol 2: 315–324, 1984

    Google Scholar 

  16. Villemure JG: Personal communication

  17. Stewart DJ, Grahovac Z, Russell NA, Hugenholtz H, Gupta S, Benoit BC, Richard MT, Maroun JA, Hopkins HS, Locke L: Phase I study of intracarotid PCNU. J Neuro-Oncol 5: 245–250, 1987

    Google Scholar 

  18. Stewart DJ, Grahovac Z, Hugenholtz H, Russell NA, Richard MT, Benoit B, Riding MD, Danjoux C, Maroun JA: Intraarterial mitomycin-C for recurrent brain metastases. Am J Clin Oncol 10: 432–436, 1987

    PubMed  Google Scholar 

  19. Stewart DJ, Belanger JMEG, Grahovac Z, Curuvija S, Gionet LR, Aitken SE, Hugenholtz H, Benoit B, DaSilva V: Phase I study of intracarotid administration of carboplatin. Neurosurg. 30: 512–517, 1992

    Google Scholar 

  20. Fenstermacher JD, Cowles AK: Theoretic limitations of intracarotid infusions in brain tumor chemotherapy. Cancer Treat Rep 61: 519–526, 1977

    PubMed  Google Scholar 

  21. Teicher B, Holden S, Kelley M, Shea T, Cucchi Q, Rosowsky A, Henner W, Frei E III: Characterization of a human squamous carcinoma cell line resistant to cis-diamminedichloroplatinum (II). Cancer Res 47: 388–393, 1987

    PubMed  Google Scholar 

  22. Andrews P, Murphy MP, Howell SB,et al.: Metallothioneinmediated cisplatin resistance in human ovarian carcinoma cells. Cancer Chemotherapy Pharmacol 19: 149–154, 1987

    Google Scholar 

  23. Kelley S, Lazo J: Metallothionein (MT) content and antineoplastic drug resistance. (Abstr) Proc Am Assoc Cancer Res 28: 281, 1987

    Google Scholar 

  24. Spigelman MK, Zappulla RA, Strauchen JA, Feuer EJ, Johnson J, Goldsmith SJ, Malis LI, Holland JF: Etoposide induced blood-brain barrier disruption in rats: duration of opening and histological sequelae. Cancer Res 46: 1453–1457, 1986

    PubMed  Google Scholar 

  25. Neuwelt EA, Glasberg M, Frenkel E,et al.: Neurotoxicity of chemotherapeutic agents after blood-brain barrier modification: neuropathological studies. Ann Neurol 14: 316–324, 1983

    PubMed  Google Scholar 

  26. Phillips PC, Reinhard CS: Antipyrimidine neurotoxicity: cytosine arabinoside and 5-fluorouracil. In: Rottenberg DA (ed) Neurological Complications of Cancer Treatment. Butterworth-Heinemann, Boston 97–114, 1991

    Google Scholar 

  27. Jafar JJ, Johns LM, Mullan SF: The effect of mannitol on cerebral blood flow. J Neurosurg 64: 754–759, 1986

    PubMed  Google Scholar 

  28. Mendelow AD, Teasdale GM, Russell T, Flood J, Patterson J, Murray GD: Effect of mannitol on cerebral blood flow and cerebral perfusion pressure in human head injury. J Neurosurg 63: 43–48, 1985

    PubMed  Google Scholar 

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Authors and Affiliations

  1. The Ontario Cancer Treatment and Research Foundation, Ottawa Regional Cancer Centre, and the University of Ottawa Faculty of Medicine, Canada

    David J. Stewart, Zvonimir Grahovac, Herman Hugenholtz, Vasco DaSilva, Michael T. Richard, Brien Benoit, Gary Belanger & Neville Russell

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  1. David J. Stewart
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  2. Zvonimir Grahovac
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  3. Herman Hugenholtz
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  4. Vasco DaSilva
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  5. Michael T. Richard
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  6. Brien Benoit
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  7. Gary Belanger
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  8. Neville Russell
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Stewart, D.J., Grahovac, Z., Hugenholtz, H. et al. Feasibility study of intraarterial vs intravenous cisplatin, BCNU, and teniposide combined with systemic cisplatin, teniposide, cytosine arabinoside, glycerol and mannitol in the treatment of primary and metastatic brain tumors. J Neuro-Oncol 17, 71–79 (1993). https://doi.org/10.1007/BF01054276

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