Phase III randomized study of postradiotherapy chemotherapy with combination α-difluoromethylornithine-PCV versus PCV for anaplastic gliomas

Clinical Cancer Research

Volumn 9, Issue 3, 2003, Pages 981-990

  Levin, Victor A ^a   Hess, Kenneth R ^a   Choucair, Ali ^b   Flynn, Patrick J ^c   Jaeckle, Kurt A ^a   Kyritsis, Athanassios P ^a   Yung, W K Alfred ^a   Prados, Michael D ^d   Bruner, Janet M ^a   Ictech, Sandra ^a   Gleason, Mary Jo ^a   Kim, Hyung Woo ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b MARSHFIELD CLINIC   (United States)

^c Metro Minnesota CCOP   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EFLORNITHINE; GADOLINIUM; LOMUSTINE; ORNITHINE DECARBOXYLASE; PROCARBAZINE; VINCRISTINE;

ADULT; AGED; ANAPLASTIC CARCINOMA; ANEMIA; ARTICLE; BIOSAFETY; CANCER RADIOTHERAPY; CANCER REGISTRY; CANCER SURVIVAL; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; FEMALE; FOLLOW UP; GLIOBLASTOMA; GRANULOCYTOPENIA; HEMATOLOGY; HISTOPATHOLOGY; HUMAN; HUMAN TISSUE; LABORATORY TEST; LEUKOPENIA; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NAUSEA; NUCLEAR MAGNETIC RESONANCE IMAGING; OLIGODENDROGLIOMA; OTOTOXICITY; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; PROGNOSIS; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SKIN TOXICITY; STATISTICAL SIGNIFICANCE; SURGICAL TECHNIQUE; THROMBOCYTOPENIA; VOMITING;

ADOLESCENT; ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; ASTROCYTOMA; BRAIN NEOPLASMS; DISEASE-FREE SURVIVAL; EFLORNITHINE; FEMALE; GLIOMA; HUMANS; MALE; MIDDLE AGED; OLIGODENDROGLIOMA; TIME FACTORS; VINCRISTINE;

EID: 0037342691     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (56)

1. Levin, V. A., Uhm, J. H., Jaeckle, K. A., Choucair, A., Flynn, P. J., Yung, W. K. A., Prados, M. D., Bruner, J. M., Chang, S. M., Kyritsis, A. P., Gleason, M. J., and Hess, K. R. Phase III randomized study of postradiotherapy chemotherapy with alpha-difluoromethylornithineprocarbazine, N-(2-chloroethyl)-N′-cyclohexyl-N-nitrosourea, vincristine (DFMO-PCV) versus PCV for glioblastoma multiforme. Clin. Cancer Res., 6: 3878-3884, 2000.
2. Bloomfield, V. A., Wilson, R. W., and Rau, D. C. Polyelectrolyte effects in DNA condensation by polyamines. Biophysical Chemistry, 11: 339-343, 1980.
3. O'Shaughnessy, J. A., Demers, L. M., Jones, S. E., Arseneau, J., Khandelwal, P., George, T., Gersh, R., Mauger, D., and Manni, A. Alpha-difluoromethylornithine as treatment for metastatic breast cancer patients. Clin. Cancer Res., 5: 3438-3444, 1999.
4. Love, R. R., Jacoby, R., Newton, M. A., Tutsch, K. D., Simon, K., Pomplun, M., and Verma, A. K. A randomized, placebo-controlled trial of low-dose alpha-difluoromethylornithine in individuals at risk for colorectal cancer. Cancer Epidemiol. Biomark. Prev., 7: 989-992, 1998.
5. Oredsson, S. M., Deen, D. F., and Marton, L. J. Influence of polyamine depletion caused by alpha-difluoromethylornithine, an enzyme-activated irreversible inhibitor of ornithine decarboxylase, on alkylation- and carbamoylation-induced cytotoxicity in 9L rat brain tumor cells in vitro. Cancer Res., 43: 4606-4609, 1983.
6. Oredsson, S. M., Tofilon, P. J., Feuerstein, B. G., Deen, D. F., Rosenblum, M. L., and Marton, L. J. Differential potentiation of 1, 3-bis(2-chloroethyl)-1-nitrosourea by alpha-difluoromethylornithine in chloroethylnitrosourea-sensitive and -resistant 9L rat brain tumor cells in vitro. Cancer Res., 43: 3576-3578, 1983.
7. Oredsson, S. M., Pegg, A. E., Alhonen-Hongisto, L., Deen, D. F., and Marton, L. J. Possible factors in the potentiation of 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl-l-nitrosourea cytotoxicity by alpha-difluoromethylornithine in 9L rat brain tumor cells. Eur. J. Cancer Clin. Oncol., 20: 535-542, 1984.
8. Seidenfeld, J., and Komar, K. A. Chemosensitization of cultured human carcinoma cells to 1, 3-bis(2- chloroethyl)-1-nitrosourea by difluoromethylornithine-induced polyamine depletion. Cancer Res., 45: 2132-2138, 1985.
9. Seidenfeld, J., Komar, K. A., Naujokas, M. F., and Block, A. L. Effects of DFMO-induced polyamine depletion on human tumor cell sensitivity to antineoplastic DNA-crosslinking drugs. Cancer Chemother. Pharmacol., 17: 16-20, 1986.
10. Hunter, K. J., Deen, D. F., Pellarin, M., and Marton, L. J. Effect of alpha-difluoromethylornithine on 1, 3-bis(2-chloroethyl)-1-nitrosourea and cis-diamminedichloroplatinum(ii) cytotoxicity. DNA interstrand cross-linking, and growth in human brain tumor cell lines in vitro. Cancer Res., 50: 2769-2772, 1990.
11. Sarkar, A., Dolan, M. E., Marton, L. J., Pegg, A. E., and Deen, D. F. Combined alpha-difluoromethylornithine and O6-benzylguanine potentiate 1, 3-bis(2-chloroethyl)-1-nitrosourea cytotoxicity in nitrosourea-resistant human brain tumor cells (Meeting abstract). Proc. Annu. Meet Am. Assoc. Cancer Res., 34: A1764, 1993.
12. Marton, L. J., Levin, V. A., Hervatin, S. J., Koch-Weser, J., McCann, P. P., and Sjoerdsma, A. Potentiation of the antitumor therapeutic effects of 1, 3-bis(2-chloroethyl)-1-nitrosourea by alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor. Cancer Res., 41: 4426-4431, 1981.
13. Cohen, A. R., Pietronigro, D. D., Cravioto, H., and Flamm, E. S. Effect of difluoromethylornithine on the antiglioma therapeutic efficacy of intra-arterial BCNU. J. Neurosurg., 65: 671-678, 1986.
14. Hunter, K. J., Deen, D. F., and Marton, L. J. Differential response to 1, 3-bis (2-chloroethyl)-1-nitrosourea in drug-resistant and -sensitive 91 rat brain tumor cells pretreated with alpha-difluoromethylornithine and 6-thioguanine. Int. J. Cancer, 44: 658-660, 1989.
15. Terzis, A. A., Pedersen, P. H., Feuerstein, B. G., Arnold, H., Bjerkvig, R., and Deen, D. E. Effects of DFMO on glioma cell proliferation, migration and invasion in vitro. J. Neuro-Oncol., 36: 113-121, 1998.
16. Hung, D. T., Deen, D. F., Seidenfeld, J., and Marton, L. J. Sensitization of 9L rat brain gliosarcoma cells to 1, 3-bis(2-chloroethyl)-1-nitrosourea by alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor. Cancer Res., 41: 2783-2785, 1981.
17. Hung, D. T., Marton, L. J., Deen, D. F., and Shafer, R. H. Depletion of intracellular polyamines may alter DNA conformation in 9L rat brain tumor cells. Science, 221: 368-370, 1983.
18. Hung, D. T., Oredsson, S. M., Pegg, A. E., Deen, D. F., and Marton, L. J. Potentiation of 1, 3-bis(2-chloroethyl)-1-nitrosourea cytotoxicity in 9L rat brain tumor cells by methylglyoxal-bis(guanylhydrazone), an inhibitor of S-adenosyl-L-methionine decarboxylase. Eur. J. Cancer Clin. Oncol., 20: 417-420, 1984.
19. Alhonen-Hongisto, L., Deen, D. F., and Marton, L. J. Time dependence of the potentiation of 1, 3-bis(2-chloroethyl)-1-nitorosurea cytotoxicity caused by alpha-difluoromethylornithine-induced polyamine depletionin 9L rat brain tumor cells. Cancer Res., 44: 1819-1822, 1984.
20. Levin, V. A., Prados, M. D., Yung, W. K., Gleason, M. J., Ictech, S., and Malec, M. Treatment of recurrent gliomas with eflornithine. J. Natl. Cancer Inst. (Bethesda), 84: 1432-1437, 1992.
21. Levin, V. A., Chamberlain, M. C., Prados, M. D., Choucair, A. K., Berger, M. S., Silver, P., Seager, M., Gutin, P. H., Davis, R. L., and Wilson, C. B. Phase I-II study of eflornithine and mitoguazone combined in the treatment of recurrent primary brain tumors. Cancer Treat. Rep., 71: 459-464, 1987.
22. Prados, M., Rodriguez, L., Chamberlain, M., Silver, P., and Levin, V. Treatment of recurrent gliomas with 1, 3-bis(2-chloroethyl)-1-nitrosourea and alpha-difluoromethylornithine. Neurosurgery, 24: 806-809, 1989.
23. Levin, V. A., Silver, P., Hannigan, J., Wara, W. M., Gutin, P. H., Davis, R. L., and Wilson, C. B. Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. Int. J. Radiat. Oncol. Biol. Phys., 18: 321-324, 1990.
24. Burger, P. C., Scheithauer, B. W., and Vogel, F. S. (eds.). Surgical Pathology of the Nervous System and its Coverings, Ed. 3, pp. 214-234. New York: Churchill Livingstone, 1991.
25. Berger, M. S., Leibel, S. A., Bruner, J. M., Finlay, J. L., and Levin, V. A. Primary cerebral tumors. In: V. A. Levin (ed.), Cancer in the Nervous System, Ed. 2, pp. 75-148. New York: Oxford University Press, 2002.
26. Levin, V. A., Edwards, M. S., Wright, D. C., Seager, M. L., Schimberg, T. P., Townsend, J. J., and Wilson, C. B. Modified procarbazine, CCNU, and vincristine (PCV 3) combination chemothjerapy in the treatment of malignant brain tumors. Cancer Treat. Rep., 64: 237-244, 1980.
27. MacDonald, D. R., Gaspar, L. E., and Cairncross, J. G. Successful chemotherapy for newly diagnosed aggressive oligodendroglioma. Ann. Neurol., 27: 573-574, 1990.
28. Norman, D., Enzmann, D. R., Levin, V. A., Wilson, C. B., and Newton, T. H. Computed tomography in the evaluation of malignant glioma before and after therapy. Radiology, 121: 85-88, 1976.
29. Levin, V. A., Crafts, D. C., Norman, D. M., Hoffer, P. B., Spire, J. P., and Wilson, C. B. Criteria for evaluating patients undergoing chemotherapy for malignant brain tumors. J. Neurosurg., 47: 329-335, 1977.
30. Cox, D. R. Regression models and life tables. J. Royal Stat. Soc., 34: 187-220, 1972.
31. Hess, K. R., Serachitopol, D. M., and Brown, B. W. Hazard function estimators: a simulation study. Stat. Med., 18: 3075-3088, 1999.
32. Hess, K. R. Graphical methods for assessing violations of the proportional hazards assumption in Cox regression. Stat. Med., 14: 1707-1723, 1995.
33. George, S. L., and Desu, M. M. Planning the size and duration of a clinical trial studying the time to some critical event. J. Chronic Dis., 27: 15-24, 1974.
34. O'Brien, P. C., and Fleming, T. R. A multiple testing procedure for clinical trials. Biometrics, 35: 549-556, 1979.
35. Lee, J. J., Hess, K. R., and Dubin, J. A. Extensions and applications of event charts. American Statistician, 54: 63-70, 2000.
36. Scalabrino, G., Modena, D., Ferioli, M. E., Puerari, M., and Luccarelli, G. Degrees of malignancy in human primary central nervous system tumors: ornithine decarboxylase levels as better indicators than adenosylmethionine decarboxylase levels. J. Natl. Cancer Inst. (Bethesda), 68: 751-754, 1982.
37. Scalabrino, G., and Ferioli, M. E. Degree of enhancement of polyamine biosynthetic decarboxylase activities in human tumors: a useful new index of degree of malignancy. Cancer Detect. Prev., 8: 11-16, 1985.
38. Ernestus, R. I., Rohn, G., Schroder, R., Klug, N., Hossmann, K. A., and Paschen, W. Activity of ornithine decarboxylase (ODC) and polyamine levels as biochemical markers of malignancy in human brain tumors. Acta Histochem. Suppl., 42: 159-164, 1992.
39. Ernestus, R. I., Rohn, G., Schroder, R., Els, T., Lee, J. Y., Klug, N., and Paschen, W. Polyamine metabolism in gliomas. J. Neurooncol., 29: 167-174, 1996.
40. Ernestus, R. I., Rohn, G., Schroder, R., Els, T., Klekner, A., Paschen, W., and Klug, N. Polyamine metabolism in brain tumours: diagnostic relevance of quantitative biochemistry. J. Neurol. Neurosurg. Psychiat., 71: 88-92, 2001.
41. Glikman, P., Vegh, I., Pollina, M. A., Mosto, A. H., and Levy, C. M. Ornithine decarboxylase activity, prolactin blood levels, and estradiol and progesterone receptors in human breast cancer. Cancer, 60: 2237-2243, 1987.
42. Thomas, T., Kiang, D. T., Janne, O. A., and Thomas, T. J. Variations in amplification and expression of the ornithine decarboxylase gene in human breast cancer cells. Breast Cancer Res. Treat., 19: 257-267, 1991.
43. Manni, A., Wechter, R., Wei, L., Heitjan, D., and Demers, L. Phenotypic features of breast cancer cells overexpressing ornithinedecarboxylase. J. Cell. Physiol., 163: 129-136, 1995.
44. Manni, A., Wechter, R., Grove, R., Wei, L., Martel, J., and Demers, L. Polyamine profiles and growth properties of ornithine decarboxylase overexpressing MCF-7 breast cancer cells in culture. Breast Cancer Res. Treat., 34: 45-53, 1995.
45. Manni, A., Mauger, D., Gimotty, P., and Badger, B. Prognostic influence on survival of increased ornithine decarboxylase activity in human breast cancer. Clin. Cancer Res., 2: 1901-1906, 1996.
46. Mimori, K., Mori, M., Shiraishi, T., Tanaka, S., Haraguchi, M., Ueo, H., Shirasaka, C., and Akiyoshi, T. Expression of ornithine decarboxylase mRNA and c-myc mRNA in breast tumours. Int. J. Oncol., 12: 597-601, 1998.
47. Canizares, F., Salinas, J., de las Heras, M., Diaz, J., Tovar, I., Martinez, P., and Penafiel, R. Prognostic value of ornithine decarboxylase and polyamines in human breast cancer: correlation with clinicopathologic parameters. Clin. Cancer Res., 5: 2035-2041, 1999.
48. Mohan, R. R., Challa, A., Gupta, S., Bostwick, D. G., Ahmad, N., Agarwal, R., Marengo, S. R., Amini, S. B., Paras, F., MacLennan, G. T., Resnick, M. I., and Mukhtar, H. Overexpression of ornithine decarboxylase in prostate cancer and prostatic fluid in humans. Clin. Cancer Res., 5: 143-147, 1999.
49. LaMuraglia, G. M., Lacaine, F., and Malt, R. A. High ornithine decarboxylase activity and polyamine levels in human colorectal neoplasia. Ann. Surg., 204: 89-93, 1986.
50. Berdinskikh, N. K., Ignatenko, N. A., Zaletok, S. P., Ganina, K. P., and Chorniy, V. A. Ornithine decarboxylase activity and polyamine content in adenocarcinomas of human stomach and large intestine. Int. J. Cancer, 47: 496-498, 1991.
51. Levin, V. A., Leibel, S. A., and Gutin, P. H. Neoplasms of the central nervous system. In: S. A. Rosenberg (ed.), Cancer: Principles and Practice of Oncology, Ed. 6, pp. 2100-2160. Philadelphia: Lippincott-Raven, 2001.
52. Leibel, S. A., Sheline, G. E., Wara, W. M., Boldrey, E. B., and Nielsen, S. L. The role of radiation therapy in the treatment of astrocytomas. Cancer (Phila.), 35: 1551-1557, 1975.
53. Jeremic, B., Jovanovic, D., Djuric, L. J., Jevremovic, S., and Mijatovic, L. J. Advantage of post-radiotherapy chemotherapy with CCNU, procarbazine, and vincristine (mPCV) over chemotherapy with VM-26 and CCNU for malignant gliomas. J. Chemotherapy, 4: 123-126, 1992.
54. Levin, V. A., Prados, M. R., Wara, W. M., Davis, R. L., Gutin, P. H., Phillips, T. L., Lamborn, K., and Wilson, C. B. Radiation therapy and bromodeoxyuridine chemotherapy followed by procarbazine, lomustine, and vincristine for the treatment of anaplastic gliomas. Int. J. Radiat. Oncol. Biol. Phys., 32: 75-83, 1995.
55. Prados, M. D., Scott, C., Sandler, H., Buckner, J. C., Phillips, T., Schultz, C., Urtasun, R., Davis, R., Gutin, P., Cascino, T. L., Greenberg, H. S., and Curran, W. J. A phase 3 randomized study of radiotherapy plus procarbazine, CCNU, and vincristine (PCV) with or without BUdR for the treatment of anaplastic astrocytoma: a preliminary report of RTOG 9404. Int. J. Radiat. Oncol. Biol. Phys., 45: 1109-1115, 1999.
56. Prados, M. D., Scott, C., Curran, W. J. J., Nelson, D. F., Leibel, S., and Kramer, S. Procarbazine, lomustine, and vincristine (PCV) chemotherapy for anaplastic astrocytoma: a retrospective review of Radiation Therapy Oncology Group protocols comparing survival with carmustine or PCV adjuvant chemotherapy. J. Clin. Oncol., 17: 3389-3395, 1999.