Fluorouracil Modulation in Head and Neck Cancer

  • Everett E. Vokes
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 339)

Abstract

The majority of patients with head and neck cancer present with locoregionally advanced disease (1–3). For most of these patients, standard therapy consists of surgery followed by radiotherapy, unless the patient has unresectable disease due to the specific anatomic location (e.g. nasopharynx) or widespread involvement of neighboring structures, or is medically inoperable. In these cases, standard therapy consists of radiotherapy alone. However, less than 30% of patients are cured and locoregional disease persistence/ recurrence is the most common pattern of failure. Distant metastases, second malignancies, and medical problems related to smoking and alcohol consumption are significant additional causes of treatment failure and death (4,5). Chemotherapy has traditionally been investigated in patients with recurrent or metastatic disease (1–3). In that setting, response rates of 30% with a median response duration of 3 months are usually achieved. Commonly used regimens include single agent methotrexate or cisplatin, and the combination of cisplatin and a 4 to 5 day continuous infusion of fluorouracil. The latter combination, in particular, has been frequently investigated with response rates ranging from 20% to 74% (6).

Keywords

Toxicity Oncol Methotrexate Folate Straw 

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References

  1. 1).
    Vokes, E.E., 1992, Head and neck cancer, In: Perry MC, ed. Chemotherapy Source Book. Baltimore: Williams and Wilkins, 918.Google Scholar
  2. 2).
    Hong, W.K. and Bromer, R., 1983, Current Concepts: Chemotherapy in head and neck cancer, N Engl J Med 308: 75.PubMedCrossRefGoogle Scholar
  3. 3).
    Clark, J.R. and Frei, E. III, 1989, Chemotherapy for head and neck cancer: Progress and controversy in the management of patients with M0 disease, Sem Oncol 16 (Suppl 6): 44.Google Scholar
  4. 4).
    Cooper, J.S., Pajak, T.F., Rubin, P., et al, 1989, Second malignancies in patients who have head and neck cancer: Incidence, effect on survival and implications based on the RTOG experience, Int J Radiat Oncol Biol Phys 17: 449.PubMedCrossRefGoogle Scholar
  5. 5).
    Hong, W.K., Lippman, S.M., Itri, L.M., et al, 1990, Prevention of second primary tumors with isotretinoin in squamous cell carcinoma of the head and neck, N Engl J Med 323: 795.PubMedCrossRefGoogle Scholar
  6. 6).
    Urba, S.G. and Forastiere, A.A, 1989, Systemic therapy of head and neck cancer: Most effective agents, areas of promise, Oncology 3: 79.PubMedGoogle Scholar
  7. 7).
    Vokes, E.E., Awan, A.M., and Weichselbaum, R.R., 1991, Radiotherapy with concomitant chemotherapy for head and neck cancer, Hematol/Oncol Clin North Am 5: 753.Google Scholar
  8. 8).
    Jacobs, C. and Makuch, R., 1990, Efficacy of adjuvant chemotherapy for patients with resectable head and neck cancer: A subset analysis of the head and neck contracts program, J Clin Oncol 8: 838.PubMedGoogle Scholar
  9. 9).
    Schuller, D.E., Metch, B., Mattox, D., et al, 1988, Preoperative chemotherapy in advanced resectable head and neck cancer: Final report of the Southwest Oncology Group, Laryngoscope 98: 1205.PubMedCrossRefGoogle Scholar
  10. 10).
    The Department of Veterans Affairs Laryngeal Cancer Study Group, 1991, Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer, N Engl J Med 324: 1685.CrossRefGoogle Scholar
  11. 11).
    Laramore, G.E., Scott, C.B., Al-Sarraf, M., et al, 1992, Adjuvant chemotherapy for resectable squamous cell carcinomas of the head and neck: Report on Intergroup Study 0034, Ira J Radiat Oncol Biol Phys 23: 705.CrossRefGoogle Scholar
  12. 12).
    Rooney, M., Kish, J., Jacobs, J., et al, 1985, Improved complete response rate and survival in advanced head and neck cancer after three-course induction therapy with 120-hour 5-FU infusion and cisplatin, Cancer 55: 1123.PubMedCrossRefGoogle Scholar
  13. 13).
    Ervin, T.J., Clark, J.R., Weichselbaum, R.R., et al, 1987, An analysis of induction and adjuvant chemotherapy in the multidisciplinary treatment of squamous-cell carcinoma of the head and neck, J Clin Oncol 5: 10.PubMedGoogle Scholar
  14. 14).
    Spaulding, M.B., Lore, J.M., Sundquist, N., 1989, Long-term follow-up of chemotherapy in advanced head and neck cancer, Arch Otolaryngol Head Neck Surg, 115: 68.PubMedCrossRefGoogle Scholar
  15. 15).
    Vokes, E.E., Mick, R., Lester, E.P., et al, 1991, Cisplatin and fluorouracil chemotherapy does not yield long-term benefit in locally advanced head and neck cancer: results from a single institution, J Clin Oncol 9: 1376.PubMedGoogle Scholar
  16. 16).
    Ensley, J., Jacobs, J., Weaver, A., et al, 1984, Correlation between response to cisplatinum-combination chemotherapy and subsequent radiotherapy in previously untreated patients with advanced squamous cell cancers of the head and neck, Cancer, 54: 811.PubMedCrossRefGoogle Scholar
  17. 17).
    Vokes, E.E. and Weichselbaum, R.R., 1990, Concomitant chemoradiotherapy: Rationale and clinical experience in patients with solid tumors, J Clin Oncol 8: 911.PubMedGoogle Scholar
  18. 18).
    Lo, T.C., Wiley, A.L. Jr., Ansfield, F.J., et al, 1976, Combined radiation therapy and 5-fluorouracil for advanced squamous cell carcinoma of the oral cavity and oropharynx: A randomized study, Am J Roentgenol 126: 229.Google Scholar
  19. 19).
    Browman, G.P., Archibald, S.D., Young, J.E.M., et al, 1983, Prospective randomized trial of one-hour sequential versus simultaneous methotrexate plus 5-fluorouracil in advanced and recurrent squamous cell head and neck cancer, J Clin Oncol 12: 787.Google Scholar
  20. 20).
    Browman, G.P., Levine, M.N., Goodyear, M.D., et al, 1988, Methotrexate/fluorouracü scheduling influences normal tissue toxicity but not antitumor effects in patients with squamous cell head and neck cancer: Results from a randomized trial, J Clin Oncol 6: 963.PubMedGoogle Scholar
  21. 21).
    Lindelov, B., Hansen, H.S., 1989, The effect of sequential methotrexate and 5-fluorouracil in patients with recurrent head and neck cancer, Acta Oncol 28 (2): 227.PubMedCrossRefGoogle Scholar
  22. 22).
    Browman, G.P., Goodyear, M.D.E., Levine, M.N., et al, 1990, Modulation of the antitumor effect of methotrexate by low-dose leucovorin in squamous cell head and neck cancer: A randomized placebo-controlled clinical trial, J Clin Oncol 8: 203.PubMedGoogle Scholar
  23. 23).
    Ackland, S.P. and Schilsky, R.L., 1987, High-dose methotrexate: A critical reappraisal, J Clin Oncol 5: 2017.PubMedGoogle Scholar
  24. 24).
    Sironak, F.M., DeGraw, J.I., Schmid, F.A., et al, 1984, New folate analogs of the 10-Deaza-Aminopterin series. Further evidence for markedly increased antitumor efficacy compared with methotrexate in ascitic and solid murine models, Cancer Chemother Pharmacol 12: 26.Google Scholar
  25. 25).
    Moccio, D.M., Sironak, F.M., Samuels, L.L., et al, 1984, Similar specificity of membrane transport for folate analogues and their metabolites by murine and human tumor cells. A clinically directed laboratory study, Cancer Res 44: 352.PubMedGoogle Scholar
  26. 26).
    Braakhuis, B.J., van Dongen, G.A., Bagnay, M., et al, 1989, Preclinical chemotherapy on human head and neck cancer xenografts grown in athymic nude mice, Head-Neck 11 (6): 511.PubMedCrossRefGoogle Scholar
  27. 27).
    Brown, D.H., Braakhuis, B.J., van Dongen, G.A., et al, 1989, Activity of the folate analog 10-ethyl, 10-deaza-aminopterin (10-EdAM) against human head and neck cancer xenografts, Anticancer Res 9 (6): 1549.PubMedGoogle Scholar
  28. 28).
    Schomagel, J.H., Verweij, J., Cognetti, F., et al, for the EORTC Head and Neck Cancer Cooperative Group, 1991, A randomized phase HI trial of methotrexate vs 10-ethyl-10-deaza-aminopterin in patients with advanced and/or metastatic squamous cell carcinoma of the head and neck, Eur J Cancer 27 (2): 138 (Abstract #825).Google Scholar
  29. 29).
    Schornagel, J.H., Verweij, J,., de Mulder, P.H.M. et al, 1992, A phase II trial of 10-ethyl-10-deaza-aminopterin, a novel antifolate, in patients with advanced or/or recurrent squamous cell carcinoma of the head and neck, Ann Oncol 3: 223.PubMedCrossRefGoogle Scholar
  30. 30).
    Robert, F., 1988, Trimetrexate as a single agent in patients with advanced head and neck cancer, Semin Oncol 15 (2): 22.PubMedGoogle Scholar
  31. 31).
    Duch, D.S., Edelstein, M.P., Bowers, S.W., Nichol, C.A., 1982, Biochemical and chemotherapeutic studies on 2,4-diamino-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d] pyrimidine (BW 301U), a novel lipid-soluble inhibitor of dihydrofolate reductase, Cancer Res 42: 3987.PubMedGoogle Scholar
  32. 32).
    Sedwick, W.D., Hamrell, M., Brown, O.E., Laszlo, J., 1982, Metabolic inhibition by a new antifolate, 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methyl-pyrido[2,3-d] pyrimidine (BW301U), an effective inhibitor of human lymphoid and dihydrofolate reductase-overproducing mouse cell lines. Mol Pharmacol 22: 766.PubMedGoogle Scholar
  33. 33).
    Taylor, I.W., Slowiaczek, P., Friedlander, M.L., et al, 1985, Selective toxicity of a new lipophilic antifolate, BW301U, for methotrexate-resistant cells with reduced drug uptake, Cancer Res 45: 978.PubMedGoogle Scholar
  34. 34).
    Uen, W.-C., Huang, A.T., Mennel, R., et al, 1992, A phase H study of piritrexim in patients with advanced squamous head and neck cancer, Cancer 69: 1008.PubMedCrossRefGoogle Scholar
  35. 35).
    Vokes, E.E., Dimery, I.W., Jacobs, C.D., et al, 1991, A phase II study of piritrexim in combination with methotrexate in recurrent and metastatic head and neck cancer, Cancer 67: 2253.PubMedCrossRefGoogle Scholar
  36. 36).
    Vokes, E.E., Moran, W.J., Mick, R., et al, 1989, Neoadjuvant and adjuvant methotrexate, cisplatin, and fluorouracil in multimodal therapy of head and neck cancer, J Clin Oncol 7: 838.PubMedGoogle Scholar
  37. 37).
    Vokes, E.E., Panje, W.R., Mick, R., et al, 1990, A randomized study comparing two regimens of neoadjuvant and adjuvant chemotherapy in multimodal therapy for locally advanced head and neck cancer, Cancer 66: 206.PubMedCrossRefGoogle Scholar
  38. 38).
    Vokes, E.E., Haraf, D.J., Panje, W.R., et al, 1992, Hydroxyurea with concomitant radiotherapy for locally advanced head and neck cancer, Semin Oncol 19 (9): 53.PubMedGoogle Scholar
  39. 39).
    Kinsella, T.J., 1992, Radiosensitization and cell kinetics: Clinical implications for S-phase-specific radiosensitizers, Semin Oncol 19 (9): 41.PubMedGoogle Scholar
  40. 39).
    Kinsella, T.J., 1992, Radiosensitization and cell kinetics: Clinical implications for S-phase-specific radiosensitizers, Semin Oncol 19 (9): 41.PubMedGoogle Scholar
  41. 41).
    Moran, R.G., Danenberg, P.V., Heidelberger, C., 1982, Therapeutic response of leukemic mice treated with fluorinated pyrimidines and inhibitors of deoxyuridylate synthesis. Biochem Pharmacol 31: 2929.PubMedCrossRefGoogle Scholar
  42. 42).
    Schilsky, R.L., Ratain, M.J., Vokes, E.E., et al, 1992, Laboratory and clinical studies of biochemical modulation by hydroxyurea, Semin Oncol 19 (9): 84.PubMedGoogle Scholar
  43. 43).
    Byfield, J.E., Sharp, T.R., Frankel, S.S., et al, 1984, Phase I and II trial of five-day infused 5-fluorouracil and radiation in advanced cancer of the head and neck, J Clin Oncol 2: 406.PubMedGoogle Scholar
  44. 44).
    Vokes, E.E., Panje, W.R., Schilsky, R.L., et al, 1989, Hydroxyurea, fluorouracil, and concomitant radiotherapy in poor-prognosis head and neck cancer: A phase I-II study, J Clin Oncol 7: 761.PubMedGoogle Scholar
  45. 45).
    Haraf, D.J., Vokes, E.E., Panje, W.R., et al, 1991, Survival and analysis of failure following hydroxyurea, 5-fluorouracil and concomitant radiation therapy in poor prognosis head and neck cancer, Am J Clin Oncol 14 (5): 419.PubMedCrossRefGoogle Scholar
  46. 45).
    Haraf, D.J., Vokes, E.E., Panje, W.R., et al, 1991, Survival and analysis of failure following hydroxyurea, 5-fluorouracil and concomitant radiation therapy in poor prognosis head and neck cancer, Am J Clin Oncol 14 (5): 419.PubMedCrossRefGoogle Scholar
  47. 47).
    Weppelman, B., Wheeler, R.H., Peters, G.E., et al, 1992, Treatment of recurrent head and neck cancer with 5-fluorouracil, hydroxyurea, and reirradiation, Int J Radiat Oncol Biol Phys 22: 1051.CrossRefGoogle Scholar
  48. 48).
    Greenberg, B., Ahmann, F., Garewal, H., et al, 1987, Neoadjuvant therapy for advanced head and neck cancer with allopurinol-mpdulated high dose 5-fluorouracil and cisplatin: A phase I-II study, Cancer 59: 1860.PubMedCrossRefGoogle Scholar
  49. 49).
    Loprinzi, C.L., Cianflone, S.G., Dose, A.M., et al, 1990, A controlled evaluation of an allopurinol mouthwash as prophylaxis against 5-fluorouracil-induced stomatitis, Cancer 65 (8): 1879.PubMedCrossRefGoogle Scholar
  50. 50).
    Vokes, E.E., Choi, K.E., Schilsky, R.L., et al, 1988, Cisplatin, fluorouracil, and high-dose leucovorin for recurrent or metastatic head and neck cancer, J Clin Oncol 6: 618.PubMedGoogle Scholar
  51. 51).
    Straw, J.A., Szapary, D., Wynn, W.T., 1984, Pharmacokinetics of the diastereoisomers of leucovorin after intravenous and oral administration to normal subjects, Cancer Res 44: 3114.PubMedGoogle Scholar
  52. 52).
    Vokes, E.E., Schilsky, R.L., Weichselbaum, R.R., et al, 1990, Induction chemotherapy with cisplatin, fluorouracil, and high-dose leucovorin for locally advanced head and neck cancer: A clinical and pharmacologic analysis, J Clin Oncol 8: 241.PubMedGoogle Scholar
  53. 53).
    Vokes, E.E., Weichselbaum, R.R., Mick, R., et al, 1992, Favorable long-term survival following induction chemotherapy with cisplatin, fluorouracil, and leucovorin and concomitant chemoradiotherapy for locally advanced head and neck cancer, J Natl Cancer Inst 84: 877.PubMedCrossRefGoogle Scholar
  54. 54).
    Dreyfuss, A.I., Clark, J.R., Wright, J.E., et al, 1990 Continuous infusion high-dose leucovorin with 5-fluorouracil and cisplatin for untreated stage IV carcinoma of the head and neck, Ann Int Med 112: 167.PubMedGoogle Scholar
  55. 55).
    Loeffler, T.M., Lindemann, J., Luckhaupt, H., et al, 1988, Chemotherapy of advanced and relapsed squamous cell cancer of the head and neck with splitdose cisplatinum, 5-fluorouracil and leucovorin, Adv Exp Med Biol 244: 267.PubMedCrossRefGoogle Scholar
  56. 56).
    Merlano, M., Bacigalupo, A., Benasso, M., et al, 1990, 5-fluorouracil and high-dose folinic acid as second-line chemotherapy in head and neck cancer, Am J Clin Oncol 13 (1): 1.Google Scholar
  57. 57).
    Jacobs, C., Lyman G., Velez-Garcia, E., et al, 1992, A phase HI randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck, J Clin Oncol 10: 257.PubMedGoogle Scholar
  58. 58).
    Wendt, T.G., Hartenstein, R.C., Wustrow, T.P.U., and Lissner, J., 1989, Cisplatin, fluorouracil with leucovorin calcium enhancement, and synchronous accelerated radiotherapy in the management of locally advanced head and neck cancer: A phase II study, J Clin Oncol 7: 471.PubMedGoogle Scholar
  59. 59).
    Vokes, E.E., Haraf, D.J., McEvilly, J.-M., et, 1992, Neoadjuvant PFL augmented by methotrexate and piritrexim followed by concomitant chemoradiotherapy for advanced head and neck cancer: A feasible and active approach, Ann Oncol 3: 79.Google Scholar
  60. 60).
    Vokes, E.E., Ratain, M.J., Mick, R., et al, 1992, A clinical and pharmacologic phase I-II study of PFL with interferon alfa-2B for head and neck cancer, Proc Am Soc Clin Oncol 11: 243 (Abstract #782).Google Scholar
  61. 61).
    Bensmaine, A., Azli, N., Soulie, P., et al, 1992, CDDP-5FU Modulation by alpha IFN2B in metastatic and or recurrent head and neck squamous cell carcinoma, Proc AACR 33: 223 (Abstract #1338).Google Scholar
  62. 62).
    Santini, J., Milano, G., Thyss, A., et al, 1989, 5-FU therapeutic monitoring with dose adjustment leads to an improved therapeutic index in head and neck cancer, Br J Cancer 59: 287.Google Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Everett E. Vokes
    • 1
  1. 1.Department of Medicine and Radiation OncologyUniversity of Chicago Medical CenterChicagoUSA

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