Phase I study of eniluracil, a dihydropyrimidine dehydrogenase inactivator, and oral 5-fluorouracil with radiation therapy in patients with recurrent or advanced head and neck cancer

Clinical Cancer Research

Volumn 5, Issue 2, 1999, Pages 291-298

  Humerickhouse, Rod A ^b   Dolan, M Eileen ^b   Haraf, Daniel J ^b   Brockstein, Bruce ^b   Stenson, Kerstin ^b   Kies, Merrill ^c   Sulzen, Laura ^b   Ratain, Mark J ^b   Vokes, Everett E ^a,b  

^a UNIVERSITY OF CHICAGO MEDICAL CENTER   (United States)

^b UNIVERSITY OF CHICAGO   (United States)

^c NORTHWESTERN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 ETHYNYLURACIL; DIHYDROPYRIMIDINE DEHYDROGENASE; ENZYME INHIBITOR; FLUOROURACIL;

ADULT; ADVANCED CANCER; AGED; ARTICLE; BONE MARROW SUPPRESSION; CANCER COMBINATION CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER SURVIVAL; CLINICAL ARTICLE; CLINICAL TRIAL; DIARRHEA; FATIGUE; FEMALE; HEAD AND NECK CANCER; HUMAN; MALE; MUCOSA INFLAMMATION; NEUTROPENIA; PRIORITY JOURNAL; RADIATION DOSE FRACTIONATION; RECURRENT CANCER; THROMBOCYTOPENIA;

ADULT; AGED; ANTIMETABOLITES, ANTINEOPLASTIC; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; COMBINED MODALITY THERAPY; DIHYDROURACIL DEHYDROGENASE (NADP); ENZYME INHIBITORS; FEASIBILITY STUDIES; FEMALE; FLUOROURACIL; HEAD AND NECK NEOPLASMS; HUMANS; MALE; MIDDLE AGED; NEOPLASM RECURRENCE, LOCAL; OXIDOREDUCTASES; TREATMENT OUTCOME; URACIL;

EID: 0033049035     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (24)

1. Brockstein, B., and Vokes, E. E. Chemoradiotherapy for head and neck cancer. PPO Updates, 10: 1-19, 1996.
2. Munro, A. An overview of randomized controlled trials of adjuvant chemotherapy in head and neck cancer. Br. J. Cancer, 71: 83-91, 1995.
3. El-Sayed, S., and Nelson, N. Adjuvant and adjunctive chemotherapy in the management of squamous cell carcinoma of the head and neck region: a meta-analysis of prospective and randomized trials. J. Clin. Oncol., 14: 838-847, 1996.
4. Vokes, E. E., Panje, W. R., Schilsky, R. L., Mick, R., Awan, A. M., Moran, W. J., Goldman, M. D., Tybor, A. G., and Weichselbaum, R. R. Hydroxyurea, fluorouracil, and concomitant radiotherapy in poor-prognosis head and neck cancer: a Phase I-II study. J. Clin. Oncol., 7: 761-768, 1989.
5. Haraf, D. J., Vokes, E. E., Panje, W. R., and Weichselbaum, R. R. Survival and analysis failure following hydroxyurea, 5-fluorouracil and concomitant radiation therapy in poor-prognosis head and neck cancer. Am. J. Clin. Oncol., 14: 419-426, 1991.
6. Vokes, E. E., Haraf, D. J., McEvilly, J. M., Mick, R., Kozloff, M. F., Goldman, M. D., Moran, W. J., Clendeninn, N. J., Collier, M. A., Weichselbaum, R. R., and Panje, W. R. Neoadjuvant PFL augmented by methotrexate and piritrexim followed by concomitant chemoradio-therapy for advanced head and neck cancer: a feasible and active approach. Ann. Oncol., 3: 79-81, 1992.
7. Kies, M. S., Haraf, D. J., Mitta, L. B., Athanasiadis, L., Kozloff, M., McEvilly, J., Mick, R., Moran, W., Panje, W., Pelzer, H., Sheehan, T. K., Weichselbaum, R., Wenig, B., and Vokes, E. E. A Phase II trial of induction cisplatin, 5FU, leucovorin and interferon α-2B (PFL-α) followed by concurrent hydrea-5FU and radiation for stage IV squamous cell cancers of the head and neck (HNC). In: P. Banzet, J. G. Holland, D. Khayat, and M. Weil (eds.), Cancer Treatment: An Update, pp. 207-210. Paris: Springer-Verlag, 1994.
8. Arekapudi, A., Haraf, D., Mittal, B., Kies, M., Stenson, K., Pelzer, H., Witt, M., Weichselbaum, R., and Vokes, E. Concomitant radiotherapy (XRT) and chemotherapy (FHX) with 5-fluorouracil (5-FU) and hydroxyurea (HU) for organ preservation in stage II and III squamous cell head and neck cancer (SCHNC): preliminary results of an ongoing trial. In: Fourth International Conference on Head and Neck Cancer, Toronto, Canada, p. 118. 1996.
9. Vokes, E. E., Panje, W. R., Mick, R., Kozloff, M. F., Moran, W. J., Sutton, H. G., Goldman, M. D., Tybor, A. G., and Weichselbaum, R. R. A randomized study comparing 2 regimens of neoadjuvant and adjuvant chemotherapy in multimodal treatment for locally advanced head and neck cancer. Cancer (Phila.), 66: 206-213, 1990.
10. Vokes, E. E., Haraf, D. J., Mick, R., McEvilly, J. M., and Weichselbaum, R. R. Intensified concomitant chemoradiotherapy with and without filgrastim for poor prognosis head and neck cancer. J. Clin. Oncol., 12: 2351-2359, 1994.
11. Kies, M. S., Haraf, D. J., Mittal, B., Stenson, K., Athanasiadis, I., Kozloff, M., Miller, M., Pelzer, H., Wenig, B., Weichselbaum, R., and Vokes, E. E. Intense combined therapy with C-DDP, 5-FU, hydroxyurea, and BID radiotherapy (C-FHX) for stage IV squamous cell cancer (SCC) of the head and neck. Proc. Am. Soc. Clin. Oncol., 15: 314, 1996.
12. Brockstein, B., Haraf, D. J., Stenson, K., Fasanmade, A., Stupp, R., glisson, B., Lippman, S. M., Ratain, M. J., Sulzen, L., Klepsch, A., Weichselbaum, R. R., and Vokes, E. E. A Phase I study of concomitant chemoradiotherapy with paclitaxel, 5-FU, and hydroxyurea with granulocyte stimulating factor support for patients with poor prognosis cancer of the head and neck. J. Clin. Oncol., 16: 735-744, 1998.
13. Haraf, D. J., Weichselbaum, R. R., and Vokes, E. E. Reirradiation with concomitant chemotherapy of unresectable recurrent head and neck cancer: a potentially curable disease. Ann. Oncol., 7: 913-918, 1996.
14. Heggie, D., Sommadossi, J. P., Cross, D. S., Huster, W. J., and Diasio, R. B. Clinical pharmacokinetics of 5-fluorouracil and its metabolites in plasma, urine and bile. Cancer Res., 47: 2203-2206, 1987.
15. Diasio, R. B., and Harris, B. E. Clinical pharmacology of 5-fluourouracil. Clin. Pharmacokinet., 16: 215-237, 1989.
16. Porter, D. J. T, Chestnut, W. G., Merrill, B. M., and Spector, T. Mechanism-based inactivation of dihydropyrimidine dehydrogenase by 5-ethynyluracil. J. Biol. Chem., 267: 5236-5242, 1992.
17. Baker, S. D., Khor, S. P., Adjei, A. A., Doucette, M., Spector, T., Donehower, R. C., Grochow, L. B., Sartorius, S. E., Noe, D. A., Hohneker, J. A., and Rowinsky, E. K. Pharmacokinetic, oral bioavailability, and safety study of fluorouracil in patients treated with 776C85. and inactivator of dihydropyrimidine dehydrogenase. J. Clin. Oncol., 14: 3085-3096, 1996.
18. Diasio, R. B., Beavers, T. L., and Carpenter, J. T. Familial deficiency in dihydropyrimidine dehydrogenase: biochemical basis for familial pyridinemia and severe 5-fluorouracil-induced toxicity. J. Clin. Invest., 81: 47-51, 1988.
19. Spector, T., Harrington, J. A., and Porter, D. J. 5-Ethynyluracil (776C85): inactivation of dihydropyrimidine dehydrogenase in vivo. Biochem. Pharmacol., 46: 2243-2248, 1993.
20. Beck, Q., Etienne, M. C., Cheradame, S., Fischel, J. L., Formento, P., Renee, N., and Milano, G. A role for dihydropyrimidine dehydrogenase and thymidylate synthase in tumour sensitivity to fluorouracil. Eur. J. Cancer, 30A: 1517-1522, 1994.
21. Etienne, M. C., Cheradame, S., Fischel, J. L., Formento, P., Dassonville, O., Renee, N., Schneider, M., Thyss, A., Demard, F., and Milano, G. Response to fluorouracil therapy in cancer patients; the role of tumoral dihydropyrimidine dehydrogenase activity. J. Clin. Oncol., 13: 1663-1670, 1995.
22. Fleming, G. F., Vokes, E. E., Buse, J, B., Mick, R., Dushay, J., Levitan, D., and Dolan, M. E. Peripheral blood mononuclear cell dihydropyrimidine dehydrogenase activity in volunteers with and without diabetes mellitus. Cancer Chemother. Pharmacol., 37: 569-573, 1996.
23. Schilsky, R., Bokowski, R., Burris, H., Crawford, J., Hochster, H., O'Rourke, M., Steinfeldt, H., Doucette, M., Levin, J., and Hohneker, J. A Phase II study of a five day regimen of oral 5-fluorouracil (5-FU) plus GW776 (776C85) with or without leucovorin in patients with metastatic colorectal cancer. Proc. Am. Soc. Clin. Oncol., 16: 271a, 1997.
24. Vokes, E. E., Mick, R., Kies, M. S., Dolan, M. E., Malone, D., Athanasiadis, I., Haraf, D. J., Kozloff, M., Weichselbaum, R. R., and Ratain, M. J. Pharmacodynamics of fluorouracil-based induction chemotherapy in advanced head and neck cancer. J. Clin. Oncol., 14: 1663-1671, 1996.