Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1995 Jan;71(1):83–91. doi: 10.1038/bjc.1995.17

An overview of randomised controlled trials of adjuvant chemotherapy in head and neck cancer.

A J Munro 1
PMCID: PMC2033467  PMID: 7819055

Abstract

Meta-analysis of the published results from 54 randomised controlled trials of adjuvant chemotherapy in head and neck cancer suggests that chemotherapy might increase absolute survival by 6.5% (95% confidence interval 3.1-9.9%). The odds ratio in favour of chemotherapy is 1.37 (95% confidence interval 1.24-1.5). Single-agent chemotherapy given synchronously with radiotherapy increased survival by 12.1% (95% confidence interval 5-19%). The benefit from neoadjuvant chemotherapy was less: a rate difference of 3.7% (95% confidence interval 0.9-6.5%). The results suggest that the investigation of optimal agents and scheduling for synchronous radiotherapy and chemotherapy might still be important in clinical trials in head and neck cancer.

Full text

PDF
83

Selected References

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

  1. Antman E. M., Lau J., Kupelnick B., Mosteller F., Chalmers T. C. A comparison of results of meta-analyses of randomized control trials and recommendations of clinical experts. Treatments for myocardial infarction. JAMA. 1992 Jul 8;268(2):240–248. [PubMed] [Google Scholar]
  2. 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]
  3. Bachaud J. M., David J. M., Boussin G., Daly N. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. Int J Radiat Oncol Biol Phys. 1991 Feb;20(2):243–246. doi: 10.1016/0360-3016(91)90098-o. [DOI] [PubMed] [Google Scholar]
  4. Bezwoda W. R., de Moor N. G., Derman D. P. Treatment of advanced head and neck cancer by means of radiation therapy plus chemotherapy--a randomised trial. Med Pediatr Oncol. 1979;6(4):353–358. doi: 10.1002/mpo.2950060412. [DOI] [PubMed] [Google Scholar]
  5. Brunin F., Rodriguez J., Jaulerry C., Jouve M., Pontvert D., Point D., Mosseri V., Pouillart P., Asselain B., Brugere J. Induction chemotherapy in advanced head and neck cancer. Preliminary results of a randomized study. Acta Oncol. 1989;28(1):61–65. doi: 10.3109/02841868909111183. [DOI] [PubMed] [Google Scholar]
  6. DerSimonian R., Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986 Sep;7(3):177–188. doi: 10.1016/0197-2456(86)90046-2. [DOI] [PubMed] [Google Scholar]
  7. Detsky A. S., Sackett D. L. When was a "negative" clinical trial big enough? How many patients you needed depends on what you found. Arch Intern Med. 1985 Apr;145(4):709–712. [PubMed] [Google Scholar]
  8. Dimery I. W., Hong W. K. Overview of combined modality therapies for head and neck cancer. J Natl Cancer Inst. 1993 Jan 20;85(2):95–111. doi: 10.1093/jnci/85.2.95. [DOI] [PubMed] [Google Scholar]
  9. Ervin T. J., Clark J. R., Weichselbaum R. R., Fallon B. G., Miller D., Fabian R. L., Posner M. R., Norris C. M., Jr, Tuttle S. A., Schoenfeld D. A. An analysis of induction and adjuvant chemotherapy in the multidisciplinary treatment of squamous-cell carcinoma of the head and neck. J Clin Oncol. 1987 Jan;5(1):10–20. doi: 10.1200/JCO.1987.5.1.10. [DOI] [PubMed] [Google Scholar]
  10. Eschwege F., Sancho-Garnier H., Gerard J. P., Madelain M., DeSaulty A., Jortay A., Cachin Y. Ten-year results of randomized trial comparing radiotherapy and concomitant bleomycin to radiotherapy alone in epidermoid carcinomas of the oropharynx: experience of the European Organization for Research and Treatment of Cancer. NCI Monogr. 1988;(6):275–278. [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. 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]
  14. 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]
  15. 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]
  16. 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]
  17. 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]
  18. Jaulerry C., Rodriguez J., Brunin F., Jouve M., Mosseri V., Point D., Pontvert D., Validire P., Zafrani B., Blaszka B. Induction chemotherapy in advanced head and neck tumors: results of two randomized trials. Int J Radiat Oncol Biol Phys. 1992;23(3):483–489. doi: 10.1016/0360-3016(92)90002-y. [DOI] [PubMed] [Google Scholar]
  19. Jortay A., Demard F., Dalesio O., Blanchet C., Desaulty A., Gehanno C., Lefebvre J. L., Molinari R., Traissac L., Dehesdin M. A randomized EORTC study on the effect of preoperative polychemotherapy in pyriform sinus carcinoma treated by pharyngolaryngectomy and irradiation. Results from 5 to 10 years. Acta Chir Belg. 1990 May-Jun;90(3):115–122. [PubMed] [Google Scholar]
  20. 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]
  21. Keane T. J., Cummings B. J., O'Sullivan B., Payne D., Rawlinson E., MacKenzie R., Danjoux C., Hodson I. A randomized trial of radiation therapy compared to split course radiation therapy combined with mitomycin C and 5 fluorouracil as initial treatment for advanced laryngeal and hypopharyngeal squamous carcinoma. Int J Radiat Oncol Biol Phys. 1993 Mar 15;25(4):613–618. doi: 10.1016/0360-3016(93)90006-h. [DOI] [PubMed] [Google Scholar]
  22. Kligerman M. M., Hellman S., Bertino J. R., Von Essen C. F. Sequential chemotherapy and radiotherapy. Preliminary results of clinical trial with methotrexate in head and neck cancer. Radiology. 1966 Feb;86(2):247–250. doi: 10.1148/86.2.247. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Laramore G. E., Scott C. B., al-Sarraf M., Haselow R. E., Ervin T. J., Wheeler R., Jacobs J. R., Schuller D. E., Gahbauer R. A., Schwade J. G. Adjuvant chemotherapy for resectable squamous cell carcinomas of the head and neck: report on Intergroup Study 0034. Int J Radiat Oncol Biol Phys. 1992;23(4):705–713. doi: 10.1016/0360-3016(92)90642-u. [DOI] [PubMed] [Google Scholar]
  25. Lau J., Antman E. M., Jimenez-Silva J., Kupelnick B., Mosteller F., Chalmers T. C. Cumulative meta-analysis of therapeutic trials for myocardial infarction. N Engl J Med. 1992 Jul 23;327(4):248–254. doi: 10.1056/NEJM199207233270406. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Lustig R. A., DeMare P. A., Kramer S. Adjuvant methotrexate in the radiotherapeutic management of advanced tumors of the head and neck. Cancer. 1976 Jun;37(6):2703–2708. doi: 10.1002/1097-0142(197606)37:6<2703::aid-cncr2820370620>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  28. Martin M., Hazan A., Vergnes L., Peytral C., Mazeron J. J., Sénéchaut J. P., Lelièvre G., Peynègre R. Randomized study of 5 fluorouracil and cis platin as neoadjuvant therapy in head and neck cancer: a preliminary report. Int J Radiat Oncol Biol Phys. 1990 Oct;19(4):973–975. doi: 10.1016/0360-3016(90)90021-b. [DOI] [PubMed] [Google Scholar]
  29. Merlano M., Vitale V., Rosso R., Benasso M., Corvò R., Cavallari M., Sanguineti G., Bacigalupo A., Badellino F., Margarino G. Treatment of advanced squamous-cell carcinoma of the head and neck with alternating chemotherapy and radiotherapy. N Engl J Med. 1992 Oct 15;327(16):1115–1121. doi: 10.1056/NEJM199210153271602. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. 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]
  32. Peto J., Easton D. Cancer treatment trials--past failures, current progress and future prospects. Cancer Surv. 1989;8(3):511–533. [PubMed] [Google Scholar]
  33. 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]
  34. 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]
  35. Richard J. M., Sancho H., Lepintre Y., Rodary J., Pierquin B. Intra-arterial methotrexate chemotherapy and telecobalt therapy in cancer of the oral cavity and oropharynx. Cancer. 1974 Sep;34(3):491–496. doi: 10.1002/1097-0142(197409)34:3<491::aid-cncr2820340303>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Sanchíz F., Millá A., Torner J., Bonet F., Artola N., Carreño L., Moya L. M., Riera D., Ripol S., Cirera L. Single fraction per day versus two fractions per day versus radiochemotherapy in the treatment of head and neck cancer. Int J Radiat Oncol Biol Phys. 1990 Dec;19(6):1347–1350. doi: 10.1016/0360-3016(90)90342-h. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. 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]
  40. Siodlak M. Z., Dalby J. E., Bradley P. J., Campbell J. B., Strickland P., Fraser J. G., Willatt D. J., Flood L. M., Stell P. M. Induction VBM plus radiotherapy, versus radiotherapy alone for advanced head and neck cancer: long-term results. Clin Otolaryngol Allied Sci. 1989 Feb;14(1):17–22. doi: 10.1111/j.1365-2273.1989.tb00331.x. [DOI] [PubMed] [Google Scholar]
  41. Stell P. M., Rawson N. S. Adjuvant chemotherapy in head and neck cancer. Br J Cancer. 1990 May;61(5):779–787. doi: 10.1038/bjc.1990.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Stell PM. Adjuvant Chemotherapy in Head and Neck Cancer. Semin Radiat Oncol. 1992 Jul;2(3):195–205. doi: 10.1053/SRAO00200195. [DOI] [PubMed] [Google Scholar]
  43. Stewart L. A., Parmar M. K. Meta-analysis of the literature or of individual patient data: is there a difference? Lancet. 1993 Feb 13;341(8842):418–422. doi: 10.1016/0140-6736(93)93004-k. [DOI] [PubMed] [Google Scholar]
  44. 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]
  45. Szpirglas H., Chastang C., Bertrand J. C. Adjvant treatment of tongue and floor of the mouth cancers. Recent Results Cancer Res. 1978;68:309–317. doi: 10.1007/978-3-642-81332-0_47. [DOI] [PubMed] [Google Scholar]
  46. 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]
  47. 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]
  48. 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]
  49. 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]
  50. Von Essen C. F., Joseph L. B., Simon G. T., Singh A. D., Singh S. P. Sequential chemotherapy and radiation therapy of buccal mucosa carcinoma in South India. Methods and preliminary results. Am J Roentgenol Radium Ther Nucl Med. 1968 Mar;102(3):530–540. doi: 10.2214/ajr.102.3.530. [DOI] [PubMed] [Google Scholar]
  51. Withers H. R., Taylor J. M., Maciejewski B. The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol. 1988;27(2):131–146. doi: 10.3109/02841868809090333. [DOI] [PubMed] [Google Scholar]

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

RESOURCES