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Clinical Therapy Trials—Drug |
Brain Tumor Center and the Departments of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 (V.A.L.); Brain Tumor Research Center, Department Neurological Surgery, University of California, San Francisco, CA 94143 (K.L., M.E., J.R., M.M., M.D.P.); Department of Radiation Oncology, University of California, San Francisco, CA 94143 (W.W.); and Department of Pathology, University of California, San Francisco, CA 94143 (R.D.)
2 Address correspondence and reprint requests to Victor A. Levin, M.D., Department of Neuro-Oncology - 100, U.T. M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.
Abstract
We conducted a single-arm phase II study to evaluate the efficacy and safety of radiotherapy combined with 6-thioguanine, procarbazine, dibromodulcitol, lomustine, and vincristine (TPDCV) chemotherapy for treating malignant astrocytoma in children and anaplastic ependymoma in patients of all ages. Between 1984 and 1992, 42 patients who had malignant astrocytomas (glioblastomas multiforme, anaplastic astrocytomas, or mixed anaplastic oligoastrocytomas) were treated with TPDCV chemotherapy and radiation therapy. Of these patients, 40 were younger than 18 years, but 2 were older (22 and 23 years) when treated. Cranial radiation averaged 58 Gy. TPDCV chemotherapy was given for 1 year or until progression. Between 1989 and 1991, 17 patients with malignant ependymoma were treated with TPDCV chemotherapy and craniospinal radiation. Radiation was given at an average dose of 54 Gy to the tumor, 28 Gy to the whole brain, and 31 Gy to the spinal axis. TPDCV chemotherapy was given for 1 year or until tumor progressed. Of the patients with glioblastoma multiforme, 13 of 17 died; the median time to progression was 49 weeks, and median survival was 85 weeks. The four patients surviving at this writing were followed a median 537 weeks (range 364-635 weeks). Of the patients with nonglioblastoma malignant astrocytoma, 14 of 25 died; the median time to progression was 224 weeks. Median survival was not reached in this group. The median follow-up for those surviving was 494 weeks. For the patients with ependymoma, 11 of 17 died with a median time to progression of 141 weeks. The median follow-up for the eight who survive was 469 weeks. Nine patients died with a median survival of 183 weeks. The combination of TPDCV and radiotherapy has activity against childhood anaplastic astrocytoma, glioblastoma multiforme, and anaplastic ependymoma. The results of this study for children with glioblastoma were comparable to results in the literature, while the results for children with anaplastic astrocytoma appeared better than most reports. The combination of TPDCV chemotherapy and radiation therapy for anaplastic ependymomas appears to be active and at least as good as published reports using radiation therapy alone.
References
Berger, M.S., Leibel, S.A., Bruner, J.M., Finlay, J.L., and Levin, V.A. (1996) Primary central nervous system tumors of the supratentorial compartment. In: Levin, V.A. (Ed.), Cancer in the Nervous System. New York: Churchill Livingstone. pp.57 -125.
Bodell, W.J., Morgan, W.F., Rasmussen, J., Williams, M.E., and Deen, D.F. (1985) Potentiation of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-induced cytotoxicity in 9L cells by pretreatment with 6-thioguanine. Biochem. Pharmacol. 34,515 -520.[CrossRef][Web of Science][Medline]
Burger, P.C., Scheithauer, B.W., and Vogel, F.S. (1991) Surgical Pathology of the Nervous System and its Coverings. Third edition. New York: Churchill Livingstone. pp. 214-23.
Finlay, J.L., Boyett, J.M., Yates, A.J., Wisoff, J.H., Milstein,
J.M., Geyer, J.R., Bertolone, S.J., McGuire, P., Cherlow, J.M., and Tefft, M.
(1995) Randomized phase III trial in childhood high-grade
astrocytoma comparing vincristine, lomustine, and prednisone with the
eight-drugs-in-1-day regimen. Children's Cancer Group. J. Clin.
Oncol. 13,112
-123.
Florell, R.C., Macdonald, D.R., Irish W.D., Bernstein, M., Leibel, S.A., Gutin, P.H., and Cairncross, J.G. (1992) Selection bias, survival, and brachytherapy for glioma. J. Neurosurg. 76,179 -183.[Web of Science][Medline]
Fujimoto, S., Ogawa, M., and Sakurai, Y. (1982)
Hypothetical mechanism of therapeutic synergism induced by the combination of
6-thioguanine and
3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea
hydrochloride. Cancer Res.
42,4079
-4085.
Goldwein, J.W., Glauser, T.A., Packer, R.J., Finlay, J.L., Sutton, L.N., Curran, W.J., Laehy, J.M., Rorke, L.B., Schut, L., and D'Angio, G.J. (1990) Recurrent intracranial ependymomas in children: Survival, patterns of failure, and prognostic factors. Cancer 66,557 -563.[CrossRef][Web of Science][Medline]
Hunter, K.J., Deen, D.F., and Marton, L.J. (1989) Differential response to 1,3-bis (2-chloroethyl)-1-nitrosourea in drug-resistant and -sensitive 9L rat brain tumor cells pretreated with a-difluoromethylornithine and 6-thioguanine. Int. J. Cancer 44,658 -660.[Web of Science][Medline]
Kaplan, E.L., and Meier, P. (1958) Nonparametric estimates from incomplete observations. J. Am. Stat. Assoc. 53,457 -481.[CrossRef][Web of Science]
Kovalic, J.J., Flaris, N., Grigsby, P.W., Pirkowski, M., Simpson, J.R., and Roth, K.A. (1993) Intracranial ependymoma long term outcome, patterns of failure. J. Neurooncol. 15,125 -131.[CrossRef][Medline]
Levin, V.A., and Wheeler, K.T. (1982) Chemotherapeutic approaches to brain tumors: Experimental observations with dianhydrogalactitol and dibromodulcitol. Cancer Chemother. Pharmacol. 8, 125-131.[CrossRef][Web of Science][Medline]
Levin, V.A., and Wilson, C.B. (1978) Correlations between experimental chemotherapy in the murine glioma and effectiveness of clinical therapy regimens. Cancer Chemother. Pharmacol. 1,41 -48.[Web of Science][Medline]
Levin, V.A., Crafts, D.C., Norman, D.M., Hoffer, P.B., Spire, J.P., and Wilson, C.B. (1977) Criteria for evaluating patients undergoing chemotherapy for malignant brain tumors. J. Neurosurg. 47,329 -335.[Web of Science][Medline]
Levin, V.A., Leibel, S.A., and Gutin, P.H. (1997) Neoplasms of the central nervous system. In DeVita, V.T., Jr., Hellman, S., and Rosenberg, S.A. (Eds.), Cancer: Principles and Practice of Oncology, Vol. 2. Fifth edition. Philadelphia: Lippincott-Raven. pp.2022 -2082.
Loeffler, J.S., Alexander, E., III, Shea, W.M., Wen, P.Y., Fine,
H.A., Kooy, H.M., and Black P.M. (1992) Radiosurgery as part of
the initial management of patients with malignant gliomas. J. Clin.
Oncol. 10,1379
-1385.
Lyons, M.K., and Kelly, P.J. (1991) Posterior foss ependymomas: Report of 30 cases and review of the literature. Neurosurgery 28,659 -664.[CrossRef][Web of Science][Medline]
Meer, L., Schold, S.C., and Kleihues, P. (1989) Inhibition of the hepatic O6-alkylguanine-DNA alkyltransferase in vivo by pretreatment with anitineoplastic agents. Biochem. Pharmacol. 38,929 -934.[CrossRef][Web of Science][Medline]
Prados, M.D., Edwards, M.S.B., Rabbitt, J., Lamborn, K., Davis, R.L., and Levin, V.A. (1997) Treatment of pediatric low-grade gliomas with a nitrosourea-based multiagent chemotherapy regimen. J. Neurooncol. 32,235 -241.[CrossRef][Medline]
Prados, M.D., Larson, D.A., Lamborn, K., McDermott, M.W., Sneed, P.K., Wara, W.M., Chang, S.M., Mack, E.E., Krouwer, H.G.J., Chandler, K.L., Warnick, R.E., Davis, R.L., Rabbitt, J.E., Malec, M., Levin, V.A., Gutin, P.H., Phillips, T.L., and Wilson, C.B. (1998) Radiation therapy and hydroxyurea followed by the combination of 6-thioguanine and BCNU for the treatment of primary malignant brain tumors. Int. J. Radiat. Oncol. Biol. Phys. 40,57 -63.[CrossRef][Web of Science][Medline]
Pulst, S.M., Levin, V.A., and Deen, D.F.(1986) In vitro cytotoxic effects of dibromodulcitol in 9L rat brain tumor cells. Pharm. Res. 3,302 -306.[CrossRef]
Ringertz, N. (1950) "Grading" of gliomas. Acta. Pathol. Microbiol. Scand. 27, 51-64.[Web of Science][Medline]
Robertson, P.L., Zeltzer, P.M., Boyett, J.M., Rorke, L.B., Allen, J.C., Geyer, J.R., Stanley, P., Li, H., Albright, A.L., McGuire-Cullen, P., Finlay, J.L., Stevens, K.R., Jr., Milstein, J.M., Packer, R.J., and Wisoff, J. (1998) Survival and prognostic factors following radiation therapy and chemotherapy for ependymomas in children: A report of the Children's Cancer Group. J. Neurosurg. 88,695 -703.[Web of Science][Medline]
Schiffer, D., Chio, A., Cravioto, H., Giordana, M.T., Migheli, A., Soffietti, R., and Vigliani, M.C. (1991) Ependymoma: Internal correlations among pathological signs: The anaplastic variant. Neurosurg. 29,206 -210.
Schold, S.C., Jr., Brent, T.P., von Hofe, E., Friedman, H.S., Mitra, S., Bigner, D.D., Swenberg, J.A., and Kleihues, P. (1989) O6-alkylguanine-DNA alkyltransferase and sensitivity to procarbazine in human brain-tumor xenografts. J. Neurosurg. 70,573 -577.[Web of Science][Medline]
Shaw, E.G., Evans, R.G., Scheithauer, B.W., Ilstrup, D.M., and Earle, J.D. (1987) Postoperative radiotherapy of intracranial ependymoma in pediatric and adult patients. Int. J. Radiat. Oncol. Biol. Phys. 13,1457 -1462.[Web of Science][Medline]
Valavanis, C., Souliotis, V.L., and Kyrtopoulos, S.A.
(1994) Differential effects of procarbazine and methylnitrosourea
on the accumulation of O6-methylguanine and the depletion and
recovery of O6-alkylguanine-DNA alkyltransferase in rat
tissues. Carcinogenesis
15,1681
-1688.
Weinkam, R.J., and Shiba, D.A. (1978) Metabolic activation of procarbazine. Life Sci. 22,937 -945.[CrossRef][Web of Science][Medline]
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