Treatment Protocols

Treatment protocols for pharyngeal cancers are provided below, including the following:

Generalized first-line therapy based on stage
Chemoradiation therapy and induction chemotherapy for locally advanced disease
First-, second-, and third-line chemotherapy for metastatic or recurrent disease

Generalized treatment recommendations for pharyngeal cancers

See the list below:

Treatment plans for all disease stages should be discussed at a multidisciplinary tumor conference involving ear, nose, throat (ENT) surgeons; radiation oncologists; and medical oncologists
Selected patients with advanced or metastatic disease may receive surgical resection of their primary tumors, depending on their response to first-line therapy

Surgery or radiation therapy for early or localized pharyngeal cancers

Stages I-II^{[1, 2]}:

Primary treatment for oropharyngeal cancers is surgical resection or definitive radiation therapy
Surgery is the preferred approach, except for some patients who may have early lip, retromolar trigone, and soft palate cancers
Radiation therapy is preferred for patients who may not be able to tolerate surgery
The radiation dose depends on tumor size; however, for early stage disease, doses of 66-72Gy may be used with adequate results

Chemotherapy with radiation therapy for locally advanced pharyngeal cancers

Stages III-IVB^{[1, 2]}:

Surgery should be considered for locally advanced disease; however, definitive radiation therapy, concurrent chemoradiation, and induction therapy are alternative options for patients who are not candidates for surgery
Concurrent chemoradiation therapy is the current standard of care for patients with locally advanced squamous cell carcinoma of the head and neck
Chemotherapy is given for the duration of radiation therapy unless otherwise stated; definitive radiation doses used are 66-72 Gy
Conventional fractionation for concurrent chemoradiation up to 72 Gy
Postoperative radiation dose is 60-66 Gy (2.0 Gy/fraction); preferred interval between resection and postoperative radiation therapy is 6 wk
The decision to treat the patient with concurrent chemoradiation therapy rather than surgery, radiation, or chemotherapy individually should be made by a multidisciplinary tumor board (including a medical oncologist, a radiation therapist, and an ENT surgeon)

Acceptable chemotherapy regimens for primary systemic therapy with concurrent radiation include:

Cisplatin 100 mg/m² IV on days 1, 22, and 43^{[1, 2, 3, 4]}or 40 mg/m² IV weekly for 6-7wk^[5]or
Cetuximab 400 mg/m² IV loading dose 1 wk before the start of radiation therapy, then 250 mg/m² weekly^{[6, 7]}; or
Cisplatin 20 mg/m² IV on day 2 weekly for up to 7 wk plus paclitaxel 30 mg/m² IV on day 1 weekly for up to 7 wk^[8]or
Cisplatin 20 mg/m²/day IV on days 1-4 and 22-25 plus fluorouracil (5-FU) 1000 mg/m²/day by continuous IV infusion on days 1-4 and 22-25^{[9, 10, 11]}or
5-FU 800 mg/m² by continuous IV infusion on days 1-5 given on the days of radiation plus hydroxyurea 1 g PO q12 h (11 doses per cycle); chemotherapy and radiation given every other week for a total of 13 wk^[8]or
Carboplatin 70 mg/m²/day IV on days 1-4, 22-25, and 43-46 plus 5-FU 600 mg/m²/day by continuous IV infusion on days 1-4, 22-25, and 43-46^[12]or
Carboplatin area under the curve (AUC) 1.5 IV on day 1 weekly plus paclitaxel 45 mg/m² IV on day 1 weekly^[13](see also the Carboplatin AUC Dose Calculation [Calvert formula] calculator)

Acceptable chemotherapy regimens for patients receiving postoperative concurrent chemoradiation:

Cisplatin 100 mg/m² IV on days 1, 22, and 43^{[3, 4]}or 40 mg/m² IV weekly for 6-7wk^[5]

Induction chemotherapy for locally advanced pharyngeal cancers

Stages III-IVB:

Induction chemotherapy is typically given to patients with stage III-IVB disease in order to shrink a primary tumor to reduce its bulkiness in preparation for future surgery or radiation therapy
The decision to treat the patient with induction chemotherapy rather than concurrent chemoradiation or surgery, radiation, or chemotherapy alone should be made by a multidisciplinary tumor board (including a medical oncologist, a radiation therapist, and an ENT surgeon)^{[1, 2]}

Acceptable chemotherapy regimens for induction chemotherapy:

Docetaxel 75 mg/m² IV on day 1 plus cisplatin 100 mg/m² IV on day 1 plus 5-FU 100 mg/m²/day by continuous IV infusion on days 1-4 every 3 wk for 3 cycles; then 3-8 wk later, carboplatin AUC 1.5 IV weekly for up to 7wk during radiation therapy; then 6-12 wk later, pursue surgery, if applicable^{[14, 15]}; or
Docetaxel 75 mg/m² IV on day 1 plus cisplatin 75 mg/m² IV on day 1 plus 5-FU 750 mg/m²/day by continuous IV infusion on days 1-4 every 3wk for 4 cycles; then 4-7wk later, radiation; surgical resection can be pursued before or after chemotherapy^[16]
Paclitaxel 175 mg/m² IV on day 1 plus cisplatin 100 mg/m² IV on day 2 plus 5-FU 500 mg/m²/day by continuous IV infusion on days 2-6 every 3 wk for 3 cycles; then radiation with cisplatin 100 mg/m² IV on days 1, 22, and 43^[17]
Induction chemotherapy can be followed by concurrent chemoradiation with carboplatin or cisplatin as listed above or by concurrent chemoradiation with weekly cetuximab ^[2]

First-line chemotherapy for metastatic or recurrent pharyngeal cancers

Stage IVC:

Treatment recommendations include the use of single-agent or combination chemotherapy
Platinum-based chemotherapy regimens are preferred if the patient can tolerate these agents; if not, single agents have been used in this setting^{[1, 2]}
Below are first-line chemotherapy options for metastatic disease or recurrent squamous head and neck cancers (after surgery and/or radiation)

Acceptable chemotherapy regimens in patients with metastatic (incurable) head and neck cancers include (unless otherwise stated, goal is to complete at least six cycles):

Cisplatin 100 mg/m² IV on day 1 every 3 wk for six cycles plus 5-FU 1000 mg/m²/day by continuous IV infusion on days 1-4 every 3 wk for six cycles plus cetuximab 400 mg/m² IV loading dose on day 1, then 250 mg/m² IV weekly until disease progression (premedicate with dexamethasone, diphenhydramine, and ranitidine)^[18]; or
Carboplatin AUC 5 IV on day 1 every 3 wk for six cycles plus 5-FU 1000 mg/m²/day by continuous IV infusion on days 1-4 every 3 wk for six cycles plus cetuximab 400 mg/m² IV loading dose on day 1, then 250 mg/m² IV weekly until disease progression (premedicate with dexamethasone, diphenhydramine, and ranitidine)^[18] or
Cisplatin 100 mg/m² IV or carboplatin AUC 5 IV on day 1 every 3wk for six cycles plus 5-FU 1000 mg/m²/day by continuous IV infusion on days 1-4 every 3wk for 6 cycles plus pembrolizumab 200 mg IV over 30 min every 3wk until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression^{[19, 20]}
Pembrolizumab 200 mg IV over 30 min every 3wk until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression, in patients whose tumors express PD‑L1 (Combined Positive Score [CPS] ≥1), as determined by an FDA‑approved test^{[19, 20]} or
Cisplatin 75 mg/m² IV on day 1 plus docetaxel 75 mg/m² IV on day 1 every 3 wk^{[21, 22]}or
Cisplatin 75 mg/m² IV on day 1 plus paclitaxel 175 mg/m² IV on day 1 every 3 wk^{[23, 24]}or
Carboplatin AUC 6 IV on day 1 plus docetaxel 65 mg/m² IV on day 1 every 3 wk^[25]or
Carboplatin AUC 6 IV on day 1 plus paclitaxel 200 mg/m² IV on day 1 every 3 wk^[26]or
Cisplatin 75-100 mg/m² IV on day 1 every 3-4 wk plus cetuximab 400 mg/m² IV loading dose on day 1, then 250 mg/m² IV weekly^{[27, 28, 29]}; or
Cisplatin 100 mg/m² IV on day 1 plus 5-FU 1000 mg/m²/day by continuous IV infusion on days 1-4 every 3 wk^{[11, 24, 30, 31, 32]}or
Methotrexate 40 mg/m² IV weekly (3 wk equals one cycle)^{[11, 30]}or
Paclitaxel 200 mg/m² IV every 3 wk^{[33, 34]}or
Docetaxel 75 mg/m² IV every 3 wk^{[35, 36, 37]}or
Cetuximab 400 mg/m² IV loading dose on day 1, then 250 mg/m² IV weekly until disease progression (premedicate with dexamethasone, diphenhydramine, and ranitidine)^[38] or
Platinum doublet therapy with docetaxel or paclitaxel can be combined with weekly cetuximab for a three drug regimen option ^{[39, 40]}

Second- and third-line chemotherapy for metastatic or recurrent pharyngeal cancers

Stage IVC:

Second-line chemotherapy is given after disease progression or recurrence following completion of first-line therapy
Third-line therapies are given after disease progression or recurrence following completion of first-line and second-line therapies
Second- and third-line regimens are similar to regimens used as first-line therapy but usually offer lower response rates and survival benefits
Patients should be treated with platinum-based chemotherapy regimens if they have not previously received a platinum-based drug

Acceptable chemotherapy regimens in patients with recurrent head and neck cancers include (unless otherwise stated, goal is to complete at least six cycles):

Cisplatin 100 mg/m² IV on day 1 every 3 wk for six cycles plus 5-FU 1000 mg/m²/day by continuous IV infusion on days 1-4 every 3 wk for six cycles plus cetuximab 400 mg/m² IV loading dose on day 1, then 250 mg/m² IV weekly until disease progression (premedicate with dexamethasone, diphenhydramine, and ranitidine)^[18] or
Carboplatin AUC 5 IV on day 1 every 3 wk for six cycles plus 5-FU 1000 mg/m²/day by continuous IV infusion on days 1-4 every 3wk for six cycles plus cetuximab 400 mg/m² IV loading dose on day 1, then 250 mg/m² IV weekly until disease progression (premedicate with dexamethasone, diphenhydramine, and ranitidine)^[21] or
Cisplatin 75 mg/m² IV on day 1 plus docetaxel 75 mg/m² IV on day 1 every 3 wk^[21] or
Cisplatin 75 mg/m² IV on day 1 plus paclitaxel 175 mg/m² IV on day 1 every 3 wk^{[23, 24]} or
Carboplatin AUC 6 IV on day 1 plus docetaxel 65 mg/m² IV on day 1 every 3 wk^[25] or
Carboplatin AUC 6 IV on day 1 plus paclitaxel 200 mg/m² IV on day 1 every 3 wk^[26] or
Cisplatin 75-100 mg/m² IV on day 1 every 3-4 wk plus cetuximab 400 mg/m² IV loading dose on day 1, then 250 mg/m² IV weekly (premedicate with dexamethasone, diphenhydramine, and ranitidine)^{[27, 28, 29]} or
Cisplatin 100 mg/m² IV on day 1 plus 5-FU 1000 mg/m²/day by continuous IV infusion on days 1-4 every 3wk^{[11, 24, 30, 31, 32]}or
Methotrexate 40 mg/m² IV weekly (3 wk equals one cycle)^{[11, 30]}or
Paclitaxel 200 mg/m² IV every 3 wk^{[2, 34]}or
Docetaxel 75 mg/m² IV every 3 wk^{[35, 36, 37]} or
Cetuximab 400 mg/m² IV loading dose on day 1, then 250 mg/m² IV weekly until disease progression (premedicate with dexamethasone, diphenhydramine, and ranitidine)^[38] or
Platinum doublet therapy with docetaxel or paclitaxel can be combined with weekly cetuximab for a three drug regimen option ^{[39, 40]} or
Capecitabine 1250 mg/m²PO BID on days 1-14, then off 7 days (3-week period is one cycle)^[41]or
Afatinib 40 mg PO daily until disease progression^[42]or
Nivolumab 240 mg IV q2wk or 480 mg IV q4 wk until disease progression^[43]or
Pembrolizumab 200 mg IV q 3 weeks until disease progression^{[44, 45, 19]}

Pazdur R, Wagman L, Camphausen K, et al, eds. 12th ed. Cancer Management: A Multidisciplinary Approach. Norwalk, Conn: CMP Healthcare Media LLC; 2009:
[Guideline] National Comprehensive Cancer Network: Head and Neck Cancers. NCCN. Available at https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf. Version 3.2019 — September 16, 2019; Accessed: November 26, 2019.
Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27. 349(22):2091-8. [QxMD MEDLINE Link].
Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, et al. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol. 2003 Jan 1. 21(1):92-8. [QxMD MEDLINE Link].
Bachaud JM, Cohen-Jonathan E, Alzieu C, David JM, Serrano E, Daly-Schveitzer N. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial. Int J Radiat Oncol Biol Phys. 1996 Dec 1. 36(5):999-1004. [QxMD MEDLINE Link].
Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010 Jan. 11(1):21-8. [QxMD MEDLINE Link].
Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9. 354(6):567-78. [QxMD MEDLINE Link].
Garden AS, Harris J, Vokes EE, Forastiere AA, Ridge JA, Jones C, et al. Preliminary results of Radiation Therapy Oncology Group 97-03: a randomized phase ii trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. J Clin Oncol. 2004 Jul 15. 22(14):2856-64. [QxMD MEDLINE Link].
Soo KC, Tan EH, Wee J, Lim D, Tai BC, Khoo ML, et al. Surgery and adjuvant radiotherapy vs concurrent chemoradiotherapy in stage III/IV nonmetastatic squamous cell head and neck cancer: a randomised comparison. Br J Cancer. 2005 Aug 8. 93(3):279-86. [QxMD MEDLINE Link]. [Full Text].
Adelstein DJ, Lavertu P, Saxton JP, Secic M, Wood BG, Wanamaker JR, et al. Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck. Cancer. 2000 Feb 15. 88(4):876-83. [QxMD MEDLINE Link].
A phase III randomised trial of cisplatinum, methotrextate, cisplatinum + methotrexate and cisplatinum + 5-FU in end stage squamous carcinoma of the head and neck. Liverpool Head and Neck Oncology Group. Br J Cancer. 1990 Feb. 61(2):311-5. [QxMD MEDLINE Link]. [Full Text].
Calais G, Alfonsi M, Bardet E, Sire C, Germain T, Bergerot P, et al. Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst. 1999 Dec 15. 91(24):2081-6. [QxMD MEDLINE Link].
Haddad R, Sonis S, Posner M, Wirth L, Costello R, Braschayko P, et al. Randomized phase 2 study of concomitant chemoradiotherapy using weekly carboplatin/paclitaxel with or without daily subcutaneous amifostine in patients with locally advanced head and neck cancer. Cancer. 2009 Oct 1. 115(19):4514-23. [QxMD MEDLINE Link].
Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007 Oct 25. 357(17):1705-15. [QxMD MEDLINE Link].
Lorch JH, Goloubeva O, Haddad RI, Cullen K, Sarlis N, Tishler R, et al. Induction chemotherapy with cisplatin and fluorouracil alone or in combination with docetaxel in locally advanced squamous-cell cancer of the head and neck: long-term results of the TAX 324 randomised phase 3 trial. Lancet Oncol. 2011 Feb. 12(2):153-9. [QxMD MEDLINE Link].
Vermorken JB, Remenar E, van Herpen C, et al. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007;357:1695-704:
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 Dec 1. 23(34):8636-45. [QxMD MEDLINE Link].
Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11. 359(11):1116-27. [QxMD MEDLINE Link].
Burtness B, et al; KEYNOTE-048 Investigators. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019 Oct 31. [QxMD MEDLINE Link].
FDA approves pembrolizumab for first-line treatment of head and neck squamous cell carcinoma. U.S. Food & Drug Administration. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-first-line-treatment-head-and-neck-squamous-cell-carcinoma. June 11, 2019; Accessed: November 26, 2019.
Glisson BS, Murphy BA, Frenette G, Khuri FR, Forastiere AA. Phase II Trial of docetaxel and cisplatin combination chemotherapy in patients with squamous cell carcinoma of the head and neck. J Clin Oncol. 2002 Mar 15. 20(6):1593-9. [QxMD MEDLINE Link].
Baur M, Kienzer HR, Schweiger J, DeSantis M, Gerber E, Pont J, et al. Docetaxel/cisplatin as first-line chemotherapy in patients with head and neck carcinoma: a phase II trial. Cancer. 2002 Jun 1. 94(11):2953-8. [QxMD MEDLINE Link].
Forastiere AA, Leong T, Rowinsky E, Murphy BA, Vlock DR, DeConti RC, 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 Feb 15. 19(4):1088-95. [QxMD MEDLINE Link].
Gibson MK, Li Y, Murphy B, Hussain MH, DeConti RC, Ensley J, 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 May 20. 23(15):3562-7. [QxMD MEDLINE Link].
Samlowski WE, Moon J, Kuebler JP, Nichols CR, Gandara DR, Ozer H, 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 Apr-May. 25(3):182-8. [QxMD MEDLINE Link].
Clark JI, Hofmeister C, Choudhury A, Matz G, Collins S, Bastian R, et al. Phase II evaluation of paclitaxel in combination with carboplatin in advanced head and neck carcinoma. Cancer. 2001 Nov 1. 92(9):2334-40. [QxMD MEDLINE Link].
Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA. 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 Dec 1. 23(34):8646-54. [QxMD MEDLINE Link].
Baselga J, Trigo JM, Bourhis J, Tortochaux J, Cortés-Funes H, Hitt R, et al. Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol. 2005 Aug 20. 23(24):5568-77. [QxMD MEDLINE Link].
Herbst RS, Arquette M, Shin DM, Dicke K, Vokes EE, Azarnia N, et al. Phase II multicenter study of the epidermal growth factor receptor antibody cetuximab and cisplatin for recurrent and refractory squamous cell carcinoma of the head and neck. J Clin Oncol. 2005 Aug 20. 23(24):5578-87. [QxMD MEDLINE Link].
Forastiere AA, Metch B, Schuller DE, Ensley JF, Hutchins LF, Triozzi P, 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 Aug. 10(8):1245-51. [QxMD MEDLINE Link].
Jacobs C, Lyman G, Velez-García E, Sridhar KS, Knight W, Hochster H, 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 Feb. 10(2):257-63. [QxMD MEDLINE Link].
Clavel M, Vermorken JB, Cognetti F, Cappelaere P, de Mulder PH, Schornagel JH, 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 Jul. 5(6):521-6. [QxMD MEDLINE Link].
Lee AW, Sze WM, Au JS, Leung SF, Leung TW, Chua DT, et al. Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience. Int J Radiat Oncol Biol Phys. 2005 Mar 15. 61(4):1107-16. [QxMD MEDLINE Link].
Forastiere AA, Shank D, Neuberg D, Taylor SG 4th, DeConti RC, Adams G. Final report of a phase II evaluation of paclitaxel in patients with advanced squamous cell carcinoma of the head and neck: an Eastern Cooperative Oncology Group trial (PA390). Cancer. 1998 Jun 1. 82(11):2270-4. [QxMD MEDLINE Link].
Catimel G, Verweij J, Mattijssen V, Hanauske A, Piccart M, Wanders J, et al. Docetaxel (Taxotere): an active drug for the treatment of patients with advanced squamous cell carcinoma of the head and neck. EORTC Early Clinical Trials Group. Ann Oncol. 1994 Jul. 5(6):533-7. [QxMD MEDLINE Link].
Dreyfuss AI, Clark JR, Norris CM, Rossi RM, Lucarini JW, Busse PM, et al. Docetaxel: an active drug for squamous cell carcinoma of the head and neck. J Clin Oncol. 1996 May. 14(5):1672-8. [QxMD MEDLINE Link].
Couteau C, Chouaki N, Leyvraz S, Oulid-Aissa D, Lebecq A, Domenge C, et al. A phase II study of docetaxel in patients with metastatic squamous cell carcinoma of the head and neck. Br J Cancer. 1999 Oct. 81(3):457-62. [QxMD MEDLINE Link]. [Full Text].
Vermorken JB, Trigo J, Hitt R, Koralewski P, Diaz-Rubio E, Rolland F, 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 Jun 1. 25(16):2171-7. [QxMD MEDLINE Link].
Guigay J, Fayette J, Dillies AF, Sire C, Kerger JN, Tennevet I, et al. Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study. Ann Oncol. 2015 Sep. 26 (9):1941-7. [QxMD MEDLINE Link].
Price KA, Cohen EE. Current treatment options for metastatic head and neck cancer. Curr Treat Options Oncol. 2012 Mar. 13 (1):35-46. [QxMD MEDLINE Link].
Martinez-Trufero J, Isla D, Adansa JC, Irigoyen A, Hitt R, Gil-Arnaiz I, et al. Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment. Br J Cancer. 2010 Jun 8. 102 (12):1687-91. [QxMD MEDLINE Link].
Machiels JP, Haddad RI, Fayette J, et al. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. Lancet Oncol. 2015 May. 16 (5):583-94. [QxMD MEDLINE Link].
Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016 Oct 8. [QxMD MEDLINE Link]. [Full Text].
Mehra R, Seiwert TY, Gupta S, Weiss J, Gluck I, Eder JP, et al. Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012. Br J Cancer. 2018 Jul. 119 (2):153-159. [QxMD MEDLINE Link].
Larkins E, Blumenthal GM, Yuan W, He K, Sridhara R, Subramaniam S, et al. FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Oncologist. 2017 Jul. 22 (7):873-878. [QxMD MEDLINE Link].