The Role of Chemotherapy in the Management of Patients with Head and Neck Cancer

ABSTRACT

Recent advances in the management of patients with head and neck cancer point to an expanding role of chemotherapy, resulting in an increased involvement of the medical oncologist in the multidisciplinary care of these patients. This review focuses on patients with squamous cell carcinoma of the oral cavity, pharynx, and larynx. A comprehensive review of the clinical trial data that have defined new standards of care and a detailed presentation of widely used chemotherapeutic regimens, including both cytotoxic and molecularly targeted agents, are presented. Information on human papilloma virus–associated squamous cell cancer of the head and neck is presented, and implications in the clinical management of this subgroup of patients based on the epidemiologic and pathologic characteristics are discussed.

KEYWORDS

Cancer of the head and neck - chemotherapy - squamous cell carcinoma

REFERENCES

• 1 Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun M J. Cancer statistics, 2009.  CA Cancer J Clin. 2009;  59 225-249
• 2 Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006.  Ann Oncol. 2007;  18 581-592
• 3 Edwards B K, Brown M L, Wingo P A et al.. Annual report to the nation on the status of cancer, 1975-2002, featuring population-based trends in cancer treatment.  J Natl Cancer Inst. 2005;  97 1407-1427
• 4 Kamangar F, Dores G M, Anderson W F. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world.  J Clin Oncol. 2006;  24 2137-2150
• 5 Spector J G, Sessions D G, Chao K S, Hanson J M, Simpson J R, Perez C A. Management of stage II (T2N0M0) glottic carcinoma by radiotherapy and conservation surgery.  Head Neck. 1999;  21 116-123
• 6 Spector J G, Sessions D G, Chao K S et al.. Stage I (T1 N0 M0) squamous cell carcinoma of the laryngeal glottis: therapeutic results and voice preservation.  Head Neck. 1999;  21 707-717
• 7 Sessions D G, Lenox J, Spector G J. Supraglottic laryngeal cancer: analysis of treatment results.  Laryngoscope. 2005;  115 1402-1410
• 8 Forastiere A A, Goepfert H, Maor M et al.. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer.  N Engl J Med. 2003;  349 2091-2098
• 9 Ang K K, Trotti A, Brown B W et al.. Randomized trial addressing risk features and time factors of surgery plus radiotherapy in advanced head-and-neck cancer.  Int J Radiat Oncol Biol Phys. 2001;  51 571-578
• 10 Bernier J, Domenge C, Ozsahin M European Organization for Research and Treatment of Cancer Trial 22931 et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer.  N Engl J Med. 2004;  350 1945-1952
• 11 Cooper J S, Pajak T F, Forastiere A A Radiation Therapy Oncology Group 9501/Intergroup et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck.  N Engl J Med. 2004;  350 1937-1944
• 12 Bernier J, Cooper J S, Pajak T F et al.. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501).  Head Neck. 2005;  27 843-850
• 13 Cooper J S, Pajak T F, Forastiere A A et al.. Precisely defining high-risk operable head and neck tumors based on RTOG #85-03 and #88-24: targets for postoperative radiochemotherapy?.  Head Neck. 1998;  20 588-594
• 14 Ang K K, Trotti A, Brown B W et al.. Randomized trial addressing risk features and time factors of surgery plus radiotherapy in advanced head-and-neck cancer.  Int J Radiat Oncol Biol Phys. 2001;  51 571-578
• 15 Rosenthal D I, Liu L, Lee J H et al.. Importance of the treatment package time in surgery and postoperative radiation therapy for squamous carcinoma of the head and neck.  Head Neck. 2002;  24 115-126
• 16 Vokes E E, Weichselbaum R R, Lippman S N, Itong W K. Head and neck cancer.  NEJM. 1993;  328 184-194
• 17 Ensley J F, Jacobs J R, Weaver A et al.. 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. 1984;  54 811-814
• 18 Rosenthal D I, Pistenmaa D A, Glatstein E. A review of neoadjuvant chemotherapy for head and neck cancer: partially shrunken tumors may be both leaner and meaner.  Int J Radiat Oncol Biol Phys. 1994;  28 315-320
• 19 The Department of Veterans Affairs Laryngeal Cancer Study Group . Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer.  N Engl J Med. 1991;  324 1685-1690
• 20 Pignon J P, Bourhis J, Domenge C, Designé L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer.  Lancet. 2000;  355 949-955
• 21 Vermorken J B, Remenar E, van Herpen C EORTC 24971/TAX 323 Study Group et al. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer.  N Engl J Med. 2007;  357 1695-1704
• 22 Schrijvers D, Van Herpen C, Kerger J et al.. Docetaxel, cisplatin and 5-fluorouracil in patients with locally advanced unresectable head and neck cancer: a phase I-II feasibility study.  Ann Oncol. 2004;  15 638-645
• 23 Dunphy F R, Dunleavy T L, Harrison B R et al.. Induction paclitaxel and carboplatin for patients with head and neck carcinoma. Analysis of 62 patients treated between 1994 an 1999.  Cancer. 2001;  91 940-948
• 24 Dietz A, Rudat V, Dreyhaupt J et al.. Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial).  Eur Arch Otorhinolaryngol. 2009;  266 1291-1300
• 25 Urba S, Wolf G, Eisbruch A et al.. Single-cycle induction chemotherapy selects patients with advanced laryngeal cancer for combined chemoradiation: a new treatment paradigm.  J Clin Oncol. 2006;  24 593-598
• 26 Worden F P, Kumar B, Lee J S et al.. Chemoselection as a strategy for organ preservation in advanced oropharynx cancer: response and survival positively associated with HPV16 copy number.  J Clin Oncol. 2008;  26 3138-3146
• 27 Urba S, Worden F, Carey T et al.. One cycle of induction chemotherapy (IC) to select for organ preservation for patients (PTS) with advanced squamous carcinoma of the oral cavity (SCCOC) [abstract].  J Clin Oncol. 2005;  23 513s
• 28 Adelstein D J. Redefining the role of induction chemotherapy in head and neck cancer.  J Clin Oncol. 2008;  26 3117-3119
• 29 Forastiere A A, Goepfert H, Maor M et al.. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer.  N Engl J Med. 2003;  349 2091-2098
• 30 Forastiere A A, Maor M, Weber R S et al.. Long-term results of Intergroup RTOG 91–11: a phase III trial to preserve the larynx-induction cisplatin/5-FU and radiation therapy versus concurrent cisplatin and radiation therapy versus radiation therapy [abstract].  J Clin Oncol. 2006;  24 284s
• 31 Pignon J P, le Maître A, Maillard E, Bourhis J P. MACH-NC Collaborative Group . Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients.  Radiother Oncol. 2009;  92 4-14
• 32 Bonner J A, Harari P M, Giralt J et al.. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck.  N Engl J Med. 2006;  354 567-578
• 33 Posner M R, Hershock D M, Blajman C R TAX 324 Study Group et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer.  N Engl J Med. 2007;  357 1705-1715
• 34 Hitt R, López-Pousa A, Martínez-Trufero J et al.. Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer.  J Clin Oncol. 2005;  23 8636-8645
• 35 Paccagnella A, Buffoli A, Koussis H et al.. Concomitant chemoradiotherapy versus neoadjuvant chemotherapy with docetaxel, cisplatin, 5-fluorouracil (TPF) followed by chemoradiotherapy in locally advanced head and neck cancer [abstract].  J Clin Oncol. 2008;  26 6000
• 36 Hitt R, Grau J J, Lopez-Pousa A et al.. Randomized phase II/III clinical trial of induction chemotherapy (ICT) with either cisplatin/5-fluorouracil (PF) or docetaxel/cisplatin/5-fluorouracil (TPF) followed by chemoradiotherapy (CRT) vs. CRT alone for patients (pts) with unresectable locally advanced head and neck cancer (LAHNC) [abstract].  J Clin Oncol. 2006;  24 5515
• 37 Grandis J R, Tweardy D J. Elevated levels of transforming growth factor alpha and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer.  Cancer Res. 1993;  53 3579-3584
• 38 Dassonville O, Formento J L, Francoual M et al.. Expression of epidermal growth factor receptor and survival in upper aerodigestive tract cancer.  J Clin Oncol. 1993;  11 1873-1878
• 39 Woodburn J R. The epidermal growth factor receptor and its inhibition in cancer therapy.  Pharmacol Ther. 1999;  82 241-250
• 40 Villaflor V M, Cohen E E, Haraf D et al.. Phase II trial pemetrexed-based induction chemotherapy followed by concomitant chemoradiotherapy in previously irradiated head and neck cancer patients [abstract].  J Clin Oncol. 2008;  26(Suppl) 323s
• 41 Spencer S A, Harris J, Wheeler R H et al.. Final report of RTOG 9610, a multi-institutional trial of reirradiation and chemotherapy for unresectable recurrent squamous cell carcinoma of the head and neck.  Head Neck. 2008;  30 281-288
• 42 Langer C J, Harris J, Horwitz E M et al.. Phase II study of low-dose paclitaxel and cisplatin in combination with split-course concomitant twice-daily reirradiation in recurrent squamous cell carcinoma of the head and neck: results of Radiation Therapy Oncology Group Protocol 9911.  J Clin Oncol. 2007;  25 4800-4805
• 43 Constenla D O, Hill M E, A'Hern R P et al.. Chemotherapy for symptom control in recurrent squamous cell carcinoma of the head and neck.  Ann Oncol. 1997;  8 445-449
• 44 Vermorken J B, Mesia R, Rivera F et al.. Platinum-based chemotherapy plus cetuximab in head and neck cancer.  N Engl J Med. 2008;  359 1116-1127
• 45 Specenier P M, Vermorken J B. Current concepts for the management of head and neck cancer: chemotherapy.  Oral Oncol. 2009;  45 409-415
• 46 Go R S, Adjei A A. Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin.  J Clin Oncol. 1999;  17 409-422
• 47 Jacobs C, Lyman G, Velez-García E et al.. A phase III 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. 1992;  10 257-263
• 48 Catimel G, Verweij J, Mattijssen V EORTC Early Clinical Trials Group et al. Docetaxel (Taxotere): an active drug for the treatment of patients with advanced squamous cell carcinoma of the head and neck.  Ann Oncol. 1994;  5 533-537
• 49 Dreyfuss A I, Clark J R, Norris C M et al.. Docetaxel: an active drug for squamous cell carcinoma of the head and neck.  J Clin Oncol. 1996;  14 1672-1678
• 50 Jacobs C, Lyman G, Velez-García E et al.. A phase III 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. 1992;  10 257-263
• 51 Tapazoglou E, Kish J, Ensley J, Al-Sarraf M. The activity of a single-agent 5-fluorouracil infusion in advanced and recurrent head and neck cancer.  Cancer. 1986;  57 1105-1109
• 52 Raguse J D, Gath H J, Bier J, Riess H, Oettle H. Gemcitabine in the treatment of advanced head and neck cancer.  Clin Oncol (R Coll Radiol). 2005;  17 425-429
• 53 Catimel G, Vermorken J B, Clavel M EORTC Early Clinical Trials Group et al. A phase II study of gemcitabine (LY 188011) in patients with advanced squamous cell carcinoma of the head and neck.  Ann Oncol. 1994;  5 543-547
• 54 Pivot X, Raymond E, Laguerre B et al.. Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck.  Br J Cancer. 2001;  85 649-655
• 55 Gedlicka C, Kornfehl J, Turhani D, Burian M, Formanek M. Salvage therapy with oral etoposide in recurrent and/or metastatic squamous cell carcinoma of the head and neck.  Cancer Invest. 2006;  24 242-245
• 56 Murphy B A, Cmelak A, Burkey B et al.. Topoisomerase I inhibitors in the treatment of head and neck cancer.  Oncology (Williston Park). 2001;  15(7, Suppl 8) 47-52
• 57 Murphy B A. Topoisomerases in the treatment of metastatic or recurrent squamous carcinoma of the head and neck.  Expert Opin Pharmacother. 2005;  6 85-92
• 58 Williams S D, Velez-Garcia E, Essessee I, Ratkin G, Birch R, Einhorn L H. Chemotherapy for head and neck cancer. Comparison of cisplatin + vinblastine + bleomycin versus methotrexate.  Cancer. 1986;  57 18-23
• 59 Eisenberger M, Krasnow S, Ellenberg S et al.. A comparison of carboplatin plus methotrexate versus methotrexate alone in patients with recurrent and metastatic head and neck cancer.  J Clin Oncol. 1989;  7 1341-1345
• 60 Vermorken J B, Trigo J, Hitt R et al.. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy.  J Clin Oncol. 2007;  25 2171-2177
• 61 Soulieres D, Senzer N N, Vokes E E, Hidalgo M, Agarwala S S, Siu L L. Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck.  J Clin Oncol. 2004;  22 77-85
• 62 Cohen E E, Kane M A, List M A et al.. Phase II trial of gefitinib 250 mg daily in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.  Clin Cancer Res. 2005;  11 8418-8424
• 63 Kirby A M, A'Hern R P, D'Ambrosio C et al.. Gefitinib (ZD1839, Iressa) as palliative treatment in recurrent or metastatic head and neck cancer.  Br J Cancer. 2006;  94 631-636
• 64 Stewart J S, Cohen E E, Licitra L et al.. Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck [corrected].  J Clin Oncol. 2009;  27 1864-1871
• 65 Lorch J H, Posner M R, Wirth L J, Haddad R I. Seeking alternative biological therapies: the future of targeted molecular treatment.  Oral Oncol. 2009;  45 447-453
• 66 Le Tourneau C, Chen E X. Molecularly targeted agents in the treatment of recurrent or metastatic squamous cell carcinomas of the head and neck.  Hematol Oncol Clin North Am. 2008;  22 1209-1220 ix
• 67 Forastiere A A, Metch B, Schuller D E et al.. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study.  J Clin Oncol. 1992;  10 1245-1251
• 68 Clavel M, Vermorken J B, Cognetti F et al.. Randomized comparison of cisplatin, methotrexate, bleomycin and vincristine (CABO) versus cisplatin and 5-fluorouracil (CF) versus cisplatin (C) in recurrent or metastatic squamous cell carcinoma of the head and neck. A phase III study of the EORTC Head and Neck Cancer Cooperative Group.  Ann Oncol. 1994;  5 521-526
• 69 Forastiere A A, Leong T, Rowinsky E et al.. Phase III comparison of high-dose paclitaxel + cisplatin + granulocyte colony-stimulating factor versus low-dose paclitaxel + cisplatin in advanced head and neck cancer: Eastern Cooperative Oncology Group Study E1393.  J Clin Oncol. 2001;  19 1088-1095
• 70 Gibson M K, Li Y, Murphy B Eastern Cooperative Oncology Group et al. Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): an intergroup trial of the Eastern Cooperative Oncology Group.  J Clin Oncol. 2005;  23 3562-3567
• 71 Glisson B S, Murphy B A, Frenette G, Khuri F R, Forastiere A A. Phase II trial of docetaxel and cisplatin combination chemotherapy in patients with squamous cell carcinoma of the head and neck.  J Clin Oncol. 2002;  20 1593-1599
• 72 Specht L, Larsen S K, Hansen H S. Phase II study of docetaxel and cisplatin in patients with recurrent or disseminated squamous-cell carcinoma of the head and neck.  Ann Oncol. 2000;  11 845-849
• 73 Baur M, Kienzer H R, Schweiger J et al.. Docetaxel/cisplatin as first-line chemotherapy in patients with head and neck carcinoma: a phase II trial.  Cancer. 2002;  94 2953-2958
• 74 Guntinas-Lichius O, Appenrodt S, Veelken F, Krug B. Phase II study of weekly docetaxel and cisplatin in patients with advanced recurrent and metastatic head and neck cancer.  Laryngoscope. 2006;  116 613-618
• 75 Stathopoulos G P, Rigatos S, Papakostas P, Fountzilas G. Effectiveness of paclitaxel and carboplatin combination in heavily pretreated patients with head and neck cancers.  Eur J Cancer. 1997;  33 1780-1783
• 76 Clark J I, Hofmeister C, Choudhury A et al.. Phase II evaluation of paclitaxel in combination with carboplatin in advanced head and neck carcinoma.  Cancer. 2001;  92 2334-2340
• 77 Samlowski W E, Moon J, Kuebler J P et al.. Evaluation of the combination of docetaxel/carboplatin in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN): a Southwest Oncology Group Phase II study.  Cancer Invest. 2007;  25 182-188
• 78 Burtness B, Goldwasser M A, Flood W, Mattar B, Forastiere A A. Eastern Cooperative Oncology Group . Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study.  J Clin Oncol. 2005;  23 8646-8654
• 79 Gillison M L, Koch W M, Capone R B et al.. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers.  J Natl Cancer Inst. 2000;  92 709-720
• 80 D'Souza G, Kreimer A R, Viscidi R et al.. Case-control study of human papillomavirus and oropharyngeal cancer.  N Engl J Med. 2007;  356 1944-1956
• 81 Gillison M L, Lowy D R. A causal role for human papillomavirus in head and neck cancer.  Lancet. 2004;  363 1488-1489
• 82 Kreimer A R, Clifford G M, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review.  Cancer Epidemiol Biomarkers Prev. 2005;  14 467-475
• 83 Ryerson A B, Peters E S, Coughlin S S et al.. Burden of potentially human papillomavirus-associated cancers of the oropharynx and oral cavity in the US, 1998-2003.  Cancer. 2008;  113(10, Suppl) 2901-2909
• 84 Dahlstrand H, Näsman A, Romanitan M, Lindquist D, Ramqvist T, Dalianis T. Human papillomavirus accounts both for increased incidence and better prognosis in tonsillar cancer.  Anticancer Res. 2008;  28 1133-1138
• 85 Näsman A, Attner P, Hammarstedt L et al.. Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma?.  Int J Cancer. 2009;  125 362-366
• 86 Gillison M L, D'Souza G, Westra W et al.. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers.  J Natl Cancer Inst. 2008;  100 407-420
• 87 Al-Sarraf M, LeBlanc M, Giri P G et al.. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099.  J Clin Oncol. 1998;  16 1310-1317
• 88 Chan A T, Leung S F, Ngan R K et al.. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma.  J Natl Cancer Inst. 2005;  97 536-539
• 89 Wee J, Tan E H, Tai B C et al.. Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety.  J Clin Oncol. 2005;  23 6730-6738
• 90 Lin J C, Jan J S, Hsu C Y, Liang W M, Jiang R S, Wang W Y. Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival.  J Clin Oncol. 2003;  21 631-637
• 91 Chan A TC, Teo P ML, Ngan R K et al.. Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial.  J Clin Oncol. 2002;  20 2038-2044
• 92 Lee A W, Lau W H, Tung S Y Hong Kong Nasopharyngeal Cancer Study Group et al. Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group.  J Clin Oncol. 2005;  23 6966-6975
• 93 Kwong D L, Sham J S, Au G K et al.. Concurrent and adjuvant chemotherapy for nasopharyngeal carcinoma: a factorial study.  J Clin Oncol. 2004;  22 2643-2653
• 94 Baujat B, Audry H, Bourhis J MAC-NPC Collaborative Group et al. Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients.  Int J Radiat Oncol Biol Phys. 2006;  64 47-56
• 95 Langendijk J A, Leemans C R, Buter J, Berkhof J, Slotman B J. The additional value of chemotherapy to radiotherapy in locally advanced nasopharyngeal carcinoma: a meta-analysis of the published literature.  J Clin Oncol. 2004;  22 4604-4612