Abstract
A phase I study of the intracarotid administration of PCNU was conducted in patients with intracerebral tumors recurring after cranial radiation. Seventeen patients were treated including 16 with recurrent gliomas or glioblastomas and 1 with recurrent brain metastases from adenocarcinoma of the lung. An additional patient received a vertebral artery infusion of PCNU for a recurrent glioblastoma. Seven of 17 patients receiving intracarotid PCNU responded for a response rate of 41%. If only evaluable patients with gliomas are considered, the response rate was 44010. Tumor grade at time of initial diagnosis, exposure to prior chemotherapy, and dose of PCNU did not appear to have a major impact on response rate. Zubrod performance status 3 patients had a lower response rate (2501o) than did patients with performance status 1 or 2 (response rate 63%). Thrombocytopenia and reversible central nervous system toxicity were dose limiting at a PCNU dose of 110 mg/m2. Two patients had possible permanent central nervous system toxicity. Three patients had permanent ipsilateral visual impairment, including one at the lowest dose used into the carotid artery (60 mg/m2). Orbital pain appeared to be substantially less than that seen with intracarotid BCNU but headaches may have been somewhat more common. The single patient receiving a vertebral artery infusion developed marked headaches and restlessness after receiving 25 mg/m2 of a planned 75 mg/m2 treatment into the vertebral artery and the treatment had to be discontinued. Symptoms were rapidly reversible upon stopping the medication. Our overall impression is that intracarotid PCNU causes less ocular pain but more transient central nervous system toxicity than does intracarotid BCNU. There does not seem to be any response advantage compared to intracarotid BCNU or IV PCNU.
Similar content being viewed by others
References
Stewart DJ, Benjamin RS, Leavens M, Valdivieso M, Burgess MA, Bodey GP: Phase I study of intravenous 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosurea (PCNU, NSC 95466) in adults with solid tumors. Cancer Research 40:3750–3754, 1980
Feun LG, Stewart DJ, Leavens ME, Burgess MA, Savaraj N, Benjamin RS, Bodey GP: A phase II trial of 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitroourea (PCNU, NSC 95466) in recurrent malignant brain tumors. J Neuro-Oncology 1:45–48, 1983
Levin VA, Resser KJ, McGrath L, Vestnys P, Nutik S, Wilson CB: PCNU treatment for recurrent malignant gliomas. Cancer Treat Rep 68:969–970, 1984
Hancock C, Allen J, Tan CTC: Phase II trial of PCNU in children with recurrent brain tumors and Hodgkin's disease. Cancer Treat Rep 68:441–442, 1984
Woolley PV III, Luc PVT, Rahman A, Korsmeger SJ, Smith FP, Schein PS: Phase I trial and clinical pharmacology of 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosurea. Cancer Res 41:3896–3900, 1981
Poster DA, Penta JS, Bruno S: PCNU: a new nitrosurea in clinical oncology. Am J Clin Oncol 5:9–12, 1982
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. 1984, pp 32–50
Fenstermacher JD, Cowles AK: Theoretic limitations of intracarotid infusions in brain tumor chemotherapy. Cancer Treat Rep 61:519–526, 1977
Collins J: Pharmacologic rationale for regional drug delivery. J Clin Oncol 2:498–504, 1984
Stewart DJ, Benjamin RS, Luna M, Seifert WE, Loo TL: Human tissue distribution of platinum after cisdiamminedichloroplatinum. Cancer Chemother & Pharm 10:51–54, 1982
Carlson Jr J, Litterst C, Greenberg R, Day Jr T, Masterson B: Platinum tissue concentrations following intraarterial and intravenous cis-diamminedichloroplatinum II in New Zealand white rabbits. Am J Obstet Gynecol 148:313, 1984
Loeffler T, Schulte-Mattler K, Huck L, Bertram H, Weber F, Hausaman 'I'. Levels of cisplatin (DD), in tumor tissues after intraarterial (A) and systemic chemotherapy (B). Proc. of the Intraarterial and Intracavitary Chemotherapy 1984 Conference, San Diego, California. Feb 24–25, 1984, p 234
Levin VA, Kabra PM, Freeman-Dove MA: Pharmacokinetics of intracarotid artery 14C-BCNU in the squirrel monkey. Neurosurgery 48:587–593, 1978.
Yamada K, Bremer AM, West CR, Ghoorah J, Park HY, Takita H: Intraarterial BCNU therapy in the treatment of metastatic brain tumor from lung carcinoma. Cancer 44:2000–2007, 1979
Hochberg FH, Pruitt AA, Beck DO, DeBrun G, Davis K: The rationale and methodology for intraarterial chemotherapy with BCNU as treatment for glioblastoma. J Neurosurg 63:876–880, 1985
Greenberg HS, Ensminger WD, Seeger JF, Kindt GW Chandler WF, Doan K, Dakhil SR: Intraarterial BCNU chemotherapy for the treatment of malignant gliomas of the central nervous system: a preliminary report. Cancer Treat Rep 65:803–810, 1981
Stewart DJ, 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-nitrosurea (BCNU), cis-diamminedichloroplatinum (cisplatin) and 4′-0-demethyl-1–0-(4,6–0–2-thenylidene-B-D-glucopyranosyl)epipodophyllotoxin (VM-26) in the treatment of primary and metastatic brain tumors. Neurosurgery 15:828–833, 1984
Kanter PM, Schwartz HS, West CR: Functional and chemical markers of PCNU activity. Cancer Drug Delivery 1:11–20, 1983
Stewart DJ, Grahovac Z, Maroun J, Hugenholtz H, Benoit B, Richard M, Russell N, Dennery J, Peterson E, Luke B, Hopkins H: Intraarterial (IA) chemotherapy (CT) for brain tumors (BT). Proc Amer Soc Clin Oncol 4:132, 1985
Kapp JP, Ross RL, Tucker EM: Supraopthalmic carotid infusion for brain-tumor chemotherapy. Technical note. J Neurosurg 58:616–618, 1983
Stewart DJ, Benjamin RS, Zimmerman S, Caprioli RM, Wallace S, Chuang V, Calvo III D, Samuels M, Bonura J, Loo TL: Clinical pharmacology of intraarterial cis-diamminedichloroplatinum (II). Cancer Research 43:917–920, 1983
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stewart, D.J., Grahovac, Z., Russel, N.A. et al. Phase I study of intracarotid PCNU. J Neuro-Oncol 5, 245–250 (1987). https://doi.org/10.1007/BF00151229
Issue Date:
DOI: https://doi.org/10.1007/BF00151229