5-Fluorouracil/Folinic Acid/Cisplatin-Combination and Simultaneous Accelerated Split-Course Radiotherapy in Advanced Head and Neck Cancer
In advanced inoperable head and neck cancer radiotherapy alone is unsatisfying. Better results can be obtained by simultaneous 5-Fluorouracil/Cisplatin-chemotherapy and irradiation. The cytotoxicity of 5-Fluorouracil can be enhanced synergistically by adding Folinic Acid in excess.
In a clinical phase II trial 62 previously untreated patients suffering from unresectable AJCC-stage III (4 pts.) and IV (58 pts.) squamous cell carcinoma of the head and neck were treated with a simultaneous chemoradiotherapy consisting of high-dose Folinic Acid in addition to a 5-Fluorouracil/Cisplatin combination and of accelerated split-course radiotherapy.
As results, three pts. died from tumor arrosion bleeding during the treatment. Median follow up time of the surviving pts. is 27 + months (range 18–44 months). 48/62 pts. (77 %) achieved complete remission, 11/62 pts. (18 %) partial remission. Presently, 32 pts. (52 %) are without evidence of disease. Actuarial three years overall survival rate (Kaplan-Meier method) out of 62 pts. is 53 %. Actuarial disease free survival and local tumor control rates at three years are 58 % and 72 %.
Mucositis was severe but tolerable, bone marrow depression was moderate to marked. In conclusion, this combined simultaneous modality approach is highly effective in locally advanced head and neck cancer. It seems to provide superior survival and local control rates as compared to conventional radiotherapy or sequential chemo-radiotherapy or as compared to simultaneous 5-Fluorouracil/Cisplatin and non-fractionated radiotherapy. A comparative phase III study is required.
KeywordsFolinic Acid Local Control Rate Squamous Cell Cancer Advanced Head Bone Marrow Depression
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- 1.J. Tannock, B. Cummings, V. Sorrenti, and the ENT group: Combination chemotherapy used prior to radiation therapy for locally advanced squamous cell carcinoma of the head and neck. Cancer Treat. Rep. 66: 1421–1424 (1982).Google Scholar
- 4.J.R. Bertino, D. Cooper, J. Chang, and L. Smaldone: Overview of chemotherapeutic agents with activity in cancer of the head and neck region, in “Head and neck cancer: Scientific perspectives in management ând strategies for cure”, J.R. Jacobs, J.D. Crissman, F.A. Valeriote, and M. Al-Sarraf, ed., Elsevier Amsterdam, pp. 159–174 (1987).Google Scholar
- 6.M. Al-Sarraf, J. Kish, J. Ensley, J. Jacobs, J. Kinzie, J. Crissman, and A. Weaver: Induction Cis-platinum and 5-Fluorouracil infusion before surgery and/or radiotherapy in patients with advanced head and neck cancer. Proc. Am. Ass. Cancer Res. 25: 196 (1984).Google Scholar
- 9.S. Waxman, H. Bruckner, and A. Wagles: Increased FUra cytotoxicity with LCV in-vitro. Proc. Am. Ass. Cancer Res. 19: 149 (1978).Google Scholar
- 11.D. Machover, L. Schwarzenberg, E. Goldschmidt, J.M. Towani, B. Michalski, M. Hayat, T. Dorval, J.L. Misset, C. Jasmin R. Moral, and G. Mathé: Treatment of advanced colorectal and gastric Adenocarcinomas with 5-FU combined with high-dose Folinic Acid: a piolt study. Cancer Treat. Rep. 66: 1803–1807 (1982).Google Scholar
- 12.G. Marini, P. Marpicati, A. Zaniboni, G.C. Cervi, F. Gorni, and E. Simoncini: Treatment of advanced breast cancer with 5-Fluorouracil and high-dose Folinic Acid: Preliminary results. Chemioterapie 6: 135–138 (1985).Google Scholar
- 14.T.C.M. Lo, A.L. Wily, F.J. Ansfield, J.H. Brandenburg, H.L. Davis, F.E. Gollin, R.O. Johson, G. Ramirez, and H. Vermund: Combined radiation therapy and 5-Fluorouracil for advanced squamous cell carcinoma of the oral cavity and oropharynx: a randomized study. Radiology 126: 229–235 (1976).Google Scholar
- 16.K.R. Trott, and J. Kummermehr: What is known about tumor proliferation rates to choose between accelerated fractionation or hyperfractionation? Radiother. Oncol. 3: 1–9 (1985).Google Scholar
- 17.E. Van der Schueren, W. Van den Bogaert, and K.K. Ang: Radiotherapy with multiple fractions per day:in “The biological basis of radiotherapy”, G.G. Steel, G.E. Adams, and M.J. Peckham, ed., Elsevier Amsterdam, pp. 195–210 (1983).Google Scholar
- 18.R.C. Hartenstein, T.G. Wendt, T.P.U. Wustrow, and K.R. Trott: Simultaneous twice-daily radiotherapy (RT) and Cisplatin (DDP)5-FU-chemotherapy with Folinic Acid (FA) enhancement in advanced squamous cell cancer (SCC) of the head and neck. Proc. Am. Soc. Clinc. Oncol. 5: 126 (1986).Google Scholar
- 19.T.G. Wendt, R.C. Hartenstein, T.P.U. Wustrow: Improved two years survival and local control rate in locally advanced squamous cell carcinoma (SCC) of the head and neck by simultaneous Chemo (CT)-Radiotherapy (RT): Progress report. Proc. Am. Soc. Clin. Oncol. 6: 125 (1987).Google Scholar
- 21.WHO Handbook for reporting results of cancer treatment. WHO Offset Publication N° 48, Geneva (1979).Google Scholar
- 22.T.G. Wendt, T.P.U. Wustrow, R.C. Hartenstein, R. Rohloff, and K.R. Trott: Accelerated split-course radiotherapy and simultaneous cis-dichlorodiammine-platinum and 5-fluorouracil chemotherapy with folinic acid enhancement for unresectable carcinoma of the head and neck. Radiother. Oncol. 10: 277–284 (1987).PubMedCrossRefGoogle Scholar
- 24.D.J. Adelstein, V.M. Sharan, A.S. Earle, A.C. Shah, C. Vlastou, D.D. Haria, C. Damm, S.G. Carter, and J.D. Hines: Combined modality therapy (CMT) with simultaneous 5-fluorouracil (5-FU), cis-platinum (DDP)and radiation therapy (RT) in the treatment of squamous cell cancer of the head and neck. Proc.Am.Soc.Clin. Oncol. 5: 128 (1986).Google Scholar