Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1990 May;61(5):779–787. doi: 10.1038/bjc.1990.175

Adjuvant chemotherapy in head and neck cancer.

P M Stell 1, N S Rawson 1
PMCID: PMC1971597  PMID: 2140045

Abstract

An overview is presented of 23 trials of adjuvant chemotherapy in squamous cell carcinoma of the head and neck. These were reviewed from the point of view of design of the trial, analysis of survival, response rates, meta-analysis, site of failure, toxicity and cost. The minimal increase in survival that could be detected ranged from 11 to 51%, with a median of 25%. No trial was big enough to detect the likely increase of survival, which is 5%. Many trials excluded some eligible patients before randomisation, the proportion being 21% in those series with details. A further 9% of treated patients were excluded from analysis. A response rate in four induction studies of 47% equated with a 6% increase in cancer mortality. Meta-analysis showed an insignificant overall improvement in cancer mortality of 0.5%. Induction chemotherapy, synchronous chemotherapy and induction/maintenance chemotherapy did not affect cancer mortality whereas synchronous/maintenance therapy did. Cisplatinum, methotrexate, bleomycin, 5-FU and a variety of other regimens did not affect the death rate from cancer, but the combination of VBM significantly increased it. Neither single agent nor combination chemotherapy produced a significant reduction of cancer deaths. The rate of locoregional failure was significantly lower in the treated arms, whereas the metastatic rate was similar in both arms. Only three papers gave full details of toxicity with grading: these showed a high toxicity rate. The mortality rate from chemotherapy in nine series averaged 6.5%.

Full text

PDF
781

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arcangeli G., Nervi C., Righini R., Creton G., Mirri M. A., Guerra A. Combined radiation and drugs: the effect of intra-arterial chemotherapy followed by radiotherapy in head and neck cancer. Radiother Oncol. 1983 Nov;1(2):101–107. doi: 10.1016/s0167-8140(83)80013-9. [DOI] [PubMed] [Google Scholar]
  2. Bakowski M. T., Macdonald E., Mould R. F., Cawte P., Sloggem J., Barrett A., Dalley V., Newton K. A., Westbury G., James S. E. Double blind controlled clinical trial of radiation plus razoxane (ICRF 159) versus radiation plus placebo in the treatment of head and neck cancer. Int J Radiat Oncol Biol Phys. 1978 Jan-Feb;4(1-2):115–119. doi: 10.1016/0360-3016(78)90125-6. [DOI] [PubMed] [Google Scholar]
  3. Bulpitt C. J. Subgroup analysis. Lancet. 1988 Jul 2;2(8601):31–34. doi: 10.1016/s0140-6736(88)92956-x. [DOI] [PubMed] [Google Scholar]
  4. Cachin Y. Adjuvant chemotherapy in head and neck carcinoma. Clin Otolaryngol Allied Sci. 1982 Apr;7(2):121–132. doi: 10.1111/j.1365-2273.1982.tb01571.x. [DOI] [PubMed] [Google Scholar]
  5. Cachin Y., Jortay A., Sancho H., Eschwege F., Madelain M., Desaulty A., Gerard P. Preliminary results of a randomized E.O.R.T.C. study comparing radiotherapy and concomitant bleomycin to radiotherapy alone in epidermoid carcinomas of the oropharynx. Eur J Cancer. 1977 Dec;13(12):1389–1395. doi: 10.1016/0014-2964(77)90151-7. [DOI] [PubMed] [Google Scholar]
  6. Chang T. M. Induction chemotherapy for advanced head and neck cancers: a literature review. Head Neck Surg. 1988 Jan-Feb;10(3):150–159. doi: 10.1002/hed.2890100303. [DOI] [PubMed] [Google Scholar]
  7. FLETCHER G. H., SUIT H. D., HOWE C. D., SAMUELS M., JESSE R. H., Jr, VILLAREAL R. U. Clinical method of testing radiation-sensitizing agents in squamous cell carcinoma. Cancer. 1963 Mar;16:355–363. doi: 10.1002/1097-0142(196303)16:3<355::aid-cncr2820160310>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  8. Fazekas J. T., Sommer C., Kramer S. Adjuvant intravenous methotrexate or definitive radiotherapy alone for advanced squamous cancers of the oral cavity, oropharynx, supraglottic larynx or hypopharynx. Int J Radiat Oncol Biol Phys. 1980 May;6(5):533–541. doi: 10.1016/0360-3016(80)90379-x. [DOI] [PubMed] [Google Scholar]
  9. Fu K. K., Phillips T. L., Silverberg I. J., Jacobs C., Goffinet D. R., Chun C., Friedman M. A., Kohler M., McWhirter K., Carter S. K. Combined radiotherapy and chemotherapy with bleomycin and methotrexate for advanced inoperable head and neck cancer: update of a Northern California Oncology Group randomized trial. J Clin Oncol. 1987 Sep;5(9):1410–1418. doi: 10.1200/JCO.1987.5.9.1410. [DOI] [PubMed] [Google Scholar]
  10. Glick J. H., Taylor S. G., 4th Integration of chemotherapy into a combined modality treatment plan for head and neck cancer: a review. Int J Radiat Oncol Biol Phys. 1981 Feb;7(2):229–242. doi: 10.1016/0360-3016(81)90442-9. [DOI] [PubMed] [Google Scholar]
  11. Gollin F. F., Ansfield F. J., Brandenburg J. H., Ramirez G., Vermund H. Combined therapy in advanced head and neck cancer: a randomized study. Am J Roentgenol Radium Ther Nucl Med. 1972 Jan;114(1):83–88. [PubMed] [Google Scholar]
  12. Gupta N. K., Pointon R. C., Wilkinson P. M. A randomised clinical trial to contrast radiotherapy with radiotherapy and methotrexate given synchronously in head and neck cancer. Clin Radiol. 1987 Nov;38(6):575–581. doi: 10.1016/s0009-9260(87)80327-6. [DOI] [PubMed] [Google Scholar]
  13. Holoye P. Y., Grossman T. W., Toohill R. J., Kun L. E., Byhardt R. W., Duncavage J. A., Teplin R. W., Ritch P. S., Hoffman R. G., Malin T. C. Randomized study of adjuvant chemotherapy for head and neck cancer. Otolaryngol Head Neck Surg. 1985 Dec;93(6):712–717. doi: 10.1177/019459988509300604. [DOI] [PubMed] [Google Scholar]
  14. Hong W. K. Induction chemotherapy for advanced head and neck cancer. Head Neck Surg. 1988 Jan-Feb;10(3):147–149. doi: 10.1002/hed.2890100302. [DOI] [PubMed] [Google Scholar]
  15. Hussey D. H., Abrams J. P. Combined therapy in advanced head and neck cancer: hydroxyurea and radiotherapy. Prog Clin Cancer. 1975;6:79–86. [PubMed] [Google Scholar]
  16. Johnson J. T., Myers E. N., Srodes C. H., Mayernik D. G., Sigler B. A., Schramm V. L., Jr, Nolan T. A., Wagner R. L. Maintenance chemotherapy for high-risk patients. A preliminary report. Arch Otolaryngol. 1985 Nov;111(11):727–729. doi: 10.1001/archotol.1985.00800130059005. [DOI] [PubMed] [Google Scholar]
  17. Kapstad B., Bang G., Rennaes S., Dahler A. Combined preoperative treatment with cobalt and bleomycin in patients with head and neck carcinoma--a controlled clinical study. Int J Radiat Oncol Biol Phys. 1978 Jan-Feb;4(1-2):85–89. doi: 10.1016/0360-3016(78)90120-7. [DOI] [PubMed] [Google Scholar]
  18. Knowlton A. H., Percarpio B., Bobrow S., Fischer J. J. Methotrexate and radiation therapy in the treatment of advanced head and neck tumors. Radiology. 1975 Sep;116(3):709–712. doi: 10.1148/116.3.709. [DOI] [PubMed] [Google Scholar]
  19. Lo T. C., Wiley A. L., Jr, Ansfield F. J., Brandenburg J. H., Davis H. L., Jr, Gollin F. F., Johnson R. O., Ramirez G., Vermund H. Combined radiation therapy and 5-fluorouracil for advanced squamous cell carcinoma of the oral cavity and oropharynx: a randomized study. AJR Am J Roentgenol. 1976 Feb;126(2):229–235. doi: 10.2214/ajr.126.2.229. [DOI] [PubMed] [Google Scholar]
  20. Mead G. M., Jacobs C. Changing role of chemotherapy in treatment of head and neck cancer. Am J Med. 1982 Oct;73(4):582–595. doi: 10.1016/0002-9343(82)90339-4. [DOI] [PubMed] [Google Scholar]
  21. Miller A. B., Hoogstraten B., Staquet M., Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207–214. doi: 10.1002/1097-0142(19810101)47:1<207::aid-cncr2820470134>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  22. Morton R. P., Rugman F., Dorman E. B., Stoney P. J., Wilson J. A., McCormick M., Veevers A., Stell P. M. Cisplatinum and bleomycin for advanced or recurrent squamous cell carcinoma of the head and neck: a randomised factorial phase III controlled trial. Cancer Chemother Pharmacol. 1985;15(3):283–289. doi: 10.1007/BF00263902. [DOI] [PubMed] [Google Scholar]
  23. Nissenbaum M., Browde S., Bezwoda W. R., de Moor N. G., Derman D. P. Treatment of advanced head and neck cancer: multiple daily dose fractionated radiation therapy and sequential multimodal treatment approach. Med Pediatr Oncol. 1984;12(3):204–208. doi: 10.1002/mpo.2950120312. [DOI] [PubMed] [Google Scholar]
  24. Pearlman N. W., Johnson F. B., Braun T. J., Kennaugh R. C., Spofford B. F., Borlase B. C., Meyer T. J., Stiegmann G. V., Meyers A. D. A prospective study of preoperative chemotherapy and split-course irradiation for locally advanced or recurrent oral/pharyngeal squamous carcinoma. Am J Clin Oncol. 1985 Dec;8(6):490–496. doi: 10.1097/00000421-198512000-00008. [DOI] [PubMed] [Google Scholar]
  25. Peto R. Why do we need systematic overviews of randomized trials? Stat Med. 1987 Apr-May;6(3):233–244. doi: 10.1002/sim.4780060306. [DOI] [PubMed] [Google Scholar]
  26. Petrovich Z., Block J., Kuisk H., Mackintosh R., Casciato D., Jose L., Barton R. A randomized comparison of radiotherapy with a radiotherapy--chemotherapy combination in stage IV carcinoma of the head and neck. Cancer. 1981 May 1;47(9):2259–2264. doi: 10.1002/1097-0142(19810501)47:9<2259::aid-cncr2820470926>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  27. Rentschler R. E., Wilbur D. W., Petti G. H., Chonkich G. D., Hilliard D. A., Camacho E. S., Thorpe R. B. Adjuvant methotrexate escalated to toxicity for resectable stage III and IV squamous head and neck carcinomas--a prospective, randomized study. J Clin Oncol. 1987 Feb;5(2):278–285. doi: 10.1200/JCO.1987.5.2.278. [DOI] [PubMed] [Google Scholar]
  28. Richards G. J., Jr, Chambers R. G. Hydroxyurea: a radiosensitizer in the treatment of neoplasms of the head and neck. Am J Roentgenol Radium Ther Nucl Med. 1969 Mar;105(3):555–565. doi: 10.2214/ajr.105.3.555. [DOI] [PubMed] [Google Scholar]
  29. Schuller D. E., Metch B., Stein D. W., Mattox D., McCracken J. D. Preoperative chemotherapy in advanced resectable head and neck cancer: final report of the Southwest Oncology Group. Laryngoscope. 1988 Nov;98(11):1205–1211. doi: 10.1288/00005537-198811000-00011. [DOI] [PubMed] [Google Scholar]
  30. Schuller D. E., Stein D. W., Metch B. Analysis of treatment failure patterns. A Southwest Oncology Group Study. Arch Otolaryngol Head Neck Surg. 1989 Jul;115(7):834–836. doi: 10.1001/archotol.1989.01860310072026. [DOI] [PubMed] [Google Scholar]
  31. Shanta V., Krishnamurthi S. Combined bleomycin and radiotherapy in oral cancer. Clin Radiol. 1980 Sep;31(5):617–620. doi: 10.1016/s0009-9260(80)80069-9. [DOI] [PubMed] [Google Scholar]
  32. Stefani S., Eells R. W., Abbate J. Hydroxyurea and radiotherapy in head and neck cancer. Results of a prospective controlled study in 126 patients. Radiology. 1971 Nov;101(2):391–396. doi: 10.1148/101.2.391. [DOI] [PubMed] [Google Scholar]
  33. Stell P. M. Can we afford to treat head and neck cancer? Clin Otolaryngol Allied Sci. 1987 Oct;12(5):321–325. doi: 10.1111/j.1365-2273.1987.tb00210.x. [DOI] [PubMed] [Google Scholar]
  34. Stell P. M., Dalby J. E., Strickland P., Fraser J. G., Bradley P. J., Flood L. M. Sequential chemotherapy and radiotherapy in advanced head and neck cancer. Clin Radiol. 1983 Jul;34(4):463–467. doi: 10.1016/s0009-9260(83)80247-5. [DOI] [PubMed] [Google Scholar]
  35. Stolwijk C., Wagener D. J., Van den Broek P., Levendag P. C., Kazem I., Bruaset I., De Mulder P. H. Randomized neo-adjuvant chemotherapy trial for advanced head and neck cancer. Neth J Med. 1985;28(9):347–351. [PubMed] [Google Scholar]
  36. Tannock I. F., Browman G. Lack of evidence for a role of chemotherapy in the routine management of locally advanced head and neck cancer. J Clin Oncol. 1986 Jul;4(7):1121–1126. doi: 10.1200/JCO.1986.4.7.1121. [DOI] [PubMed] [Google Scholar]
  37. Taylor S. G., 4th, Applebaum E., Showel J. L., Norusis M., Holinger L. D., Hutchinson J. C., Jr, Murthy A. K., Caldarelli D. D. A randomized trial of adjuvant chemotherapy in head and neck cancer. J Clin Oncol. 1985 May;3(5):672–679. doi: 10.1200/JCO.1985.3.5.672. [DOI] [PubMed] [Google Scholar]
  38. Toohill R. J., Anderson T., Byhardt R. W., Cox J. D., Duncavage J. A., Grossman T. W., Haas C. D., Haas J. S., Hartz A. J., Libnoch J. A. Cisplatin and fluorouracil as neoadjuvant therapy in head and neck cancer. A preliminary report. Arch Otolaryngol Head Neck Surg. 1987 Jul;113(7):758–761. doi: 10.1001/archotol.1987.01860070072019. [DOI] [PubMed] [Google Scholar]
  39. Vermund H., Kaalhus O., Winther F., Trausjø J., Thorud E., Harang R. Bleomycin and radiation therapy in squamous cell carcinoma of the upper aero-digestive tract: a phase III clinical trial. Int J Radiat Oncol Biol Phys. 1985 Nov;11(11):1877–1886. doi: 10.1016/0360-3016(85)90267-6. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES