Head and Neck Cancer Treatment Protocols: Treatment Protocols

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Head and Neck Cancer Treatment Protocols

Sections Head and Neck Cancer Treatment Protocols
Treatment Protocols
References

Treatment Protocols

Treatment protocols for oral cavity, pharyngeal, and laryngeal cancers and for nasopharyngeal 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 oral cavity, pharyngeal, and laryngeal cancers

Surgery is preferred for most patients with early or localized disease, and may be considered for locally advanced disease. Selected patients with advanced or metastatic disease may receive surgical resection of their primary tumors, depending on their response to first-line therapy. However, surgery at the primary disease site has a very limited role, if any, in nasopharyngeal cancers, due to their anatomical location and radiosensitivity.

Treatment plans for all disease stages should be discussed at a multidisciplinary tumor conference involving ENT surgeons, radiation oncologists, and medical oncologists. In addition, the following subspecialities and supportive care services should be included in the management for all disease stages:

Dentistry
Diagnostic and interventional radiology
Plastic surgery
Lymphedema therapy
Speech/swallowing therapy
Social work
Nutrition
Finanacial counselors
Palliative care

Surgery or radiation therapy for early or localized disease (oral cavity, pharyngeal, and laryngeal cancers)

Stages I-II:

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-stage 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 66-72 Gy may be used with adequate results.

Chemotherapy with radiation therapy for locally advanced disease (oral cavity, pharyngeal, and laryngeal cancers)

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

Surgery should be considered for locally advanced disease; however, definitive radiation therapy, concurrent chemoradiation alone or after surgery, and induction therapy followed by concurrent chemoradation are alternative options for patients who are not candidates for surgery alone.
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 (2.0 Gy/fraction; daily Monday-Friday in 7wk).
Conventional fractionation for concurrent chemoradiation is up to 72 Gy (2.0 Gy/fraction).
Postoperative radiation dose is 60-66 Gy (2.0 Gy/fraction); preferred interval between resection and postoperative radiation therapy is ≤ 6wk.
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:

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 1wk before the start of radiation therapy, then 250 mg/m² weekly (premedicate with dexamethasone, diphenhydramine, and ranitidine)^{[6, 7, 8]} or
Cisplatin 20 mg/m² IV on day 2 weekly for up to 7wk plus paclitaxel 30 mg/m² IV on day 1 weekly for up to 7wk^[9] 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^{[10, 11, 12]} 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 q12h (11 doses per cycle); chemotherapy and radiation given every other week for a total of 13wk^[9] 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^[13] or
Carboplatin AUC 1.5 IV on day 1 weekly plus paclitaxel 45 mg/m² IV on day 1 weekly^[14](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 disease (oral cavity, pharyngeal, and laryngeal 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 subsequent surgery or radiation therapy.
The decision to treat 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, 15, 16]}

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 3wk for three cycles; then 3-8wk later, carboplatin AUC 1.5 IV weekly for up to 7wk during radiation therapy; then 6-12wk later; pursue surgery if applicable^{[17, 18]} 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^[19]
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 3wk for three cycles; then radiation with cisplatin 100 mg/m² IV on days 1, 22, and 43^[20]
Induction chemotherapy can be followed by concurrent chemoradiation with weekly carboplatin, weekly cisplatin, or weekly cetuximab ^[2]

First-line chemotherapy for metastatic or recurrent disease (oral cavity, pharyngeal, and laryngeal cancers)

Stage IVC:

Treatment recommendations include the use of single-agent or combination chemotherapy.
Platinum-based chemotherapy regimens are preferred if these agents can be tolerated by the patient; if they cannot be tolerated, 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 3wk 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
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 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 3wk^{[22, 23]} or
Cisplatin 75 mg/m² IV on day 1 plus paclitaxel 175 mg/m² IV on day 1 every 3wk^{[24, 25]} or
Carboplatin AUC 6 IV on day 1 plus docetaxel 65 mg/m² IV on day 1 every 3wk^[26] or
Carboplatin AUC 6 IV on day 1 plus paclitaxel 200 mg/m² IV on day 1 every 3wk^[27] or
Cisplatin 75-100 mg/m² IV on day 1 every 3-4wk plus cetuximab 400 mg/m² IV loading dose on day 1, then 250 mg/m² IV weekly^{[28, 29, 30]} 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^{[12, 25, 31, 32, 33]} or
Methotrexate 40 mg/m² IV weekly (3wk equals one cycle)^{[12, 31]} or
Paclitaxel 200 mg/m² IV every 3wk^{[34, 35]} or
Docetaxel 75 mg/m² IV every 3wk^{[36, 37, 38]} or
Cetuximab 400 mg/m² IV loading dose on day 1, then 250 mg/m² IV weekly until disease progression^[39] or
Platinum doublet therapy with docetaxel or paclitaxel can be combined with weekly cetuximab for a three-drug regimen option^{[40, 41]}
Pembrolizumab 200 mg IV every 3wk until disease progression, unacceptable toxicity, or up to 24 months as monotherapy for PD-L1–positive tumors^[42] or

Pembrolizumab 200 mg IV on Day 1 plus platinum (cisplatin 100 mg/m² or carboplatin AUC 5) on day 1 plus 5-FU 1000 mg/m²/day by continuous IV infusion on days 1-4 every 3wk^[42]

Second- and third-line chemotherapy for metastatic or recurrent disease (oral cavity, pharyngeal, and laryngeal 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 (unless otherwise stated, goal is to complete at least six cycles):

Cisplatin 100 mg/m² 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 cetuximab 400 mg/m² IV loading dose on day 1, then 250 mg/m² IV weekly until disease progression^[21] 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 six cycles plus cetuximab 400 mg/m² IV loading dose on day 1, then 250 mg/m² IV weekly until disease progression^[22] or
Cisplatin 75 mg/m² IV on day 1 plus docetaxel 75 mg/m² IV on day 1 every 3wk^[22] or
Cisplatin 75 mg/m² IV on day 1 plus paclitaxel 175 mg/m² IV on day 1 every 3wk^{[24, 25]} or
Carboplatin AUC 6 IV on day 1 plus docetaxel 65 mg/m² IV on day 1 every 3wk^[26] or
Carboplatin AUC 6 IV on day 1 plus paclitaxel 200 mg/m² IV on day 1 every 3wk^[27] or
Cisplatin 75-100 mg/m² IV on day 1 every 3-4wk plus cetuximab 400 mg/m² IV loading dose on day 1, then 250 mg/m² IV weekly^{[28, 29, 30]} 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^{[12, 25, 31, 32, 33]} or
Methotrexate 40 mg/m² IV weekly (3wk equals one cycle)^{[12, 31]} or
Paclitaxel 200 mg/m² IV every 3wk^{[2, 35]} or
Docetaxel 75 mg/m² IV every 3wk^{[36, 37, 38]} or
Cetuximab 400 mg/m² IV loading dose on day 1, then 250 mg/m² IV weekly until disease progression^[39] or
Platinum doublet therapy with docetaxel or paclitaxel can be combined with weekly cetuximab for a three drug regimen option^{[40, 41]} or
Capecitabine 1250 mg/m² PO BID days 1–14, then off 7 days (3-week period is one cycle)^[43] or
Afatinib 40 mg PO daily until disease progression^[44] or
Nivolumab 240 mg IV q2wk or 480 mg q4wk until disease progression^[2] or
Pembrolizumab 200 mg IV q3wk until disease progression^{[2, 45, 46]}

Radiation therapy for early or localized disease (nasopharyngeal cancers)

Stage I:

Patients with early or localized disease may be treated with definitive radiation therapy to the nasopharynx alone
Radiation doses of 66-72 Gy

Chemotherapy with radiation therapy for locally advanced nasopharyngeal cancers

Stages II-IVB:

Patients with stage II-IVB nasopharyngeal cancers are treated with concurrent chemotherapy and radiation +/- adjuvant chemotherapy or with induction chemotherapy followed by concurrent chemoradiation.

Acceptable chemotherapy regimens for advanced nasopharyngeal cancers (stages II-IVB):

Cisplatin 100 mg/m² IV on days 1, 22, and 43 with radiation +/- adjuvant chemotherapy with cisplatin 80 mg/m² IV on day 1 plus 5-FU 1000 mg/m²/day by continuous IV infusion on days 1-4 every 4wk for three cycles^{[47, 48, 49]}
Carboplatin AUC 6 IV every 3 weeks for three cycles with radiation +/- adjuvant chemotherapy with carboplatin AUC 5 IV on day 1 plus 5-FU 1000 mg/m²/day by continuous IV infusion on days 1-4 every 3 weeks for two cycles^[50]
Induction chemotherapy with docetaxel 70 mg/m² IV on day 1 plus cisplatin 75 mg/m² IV on day 1 plus 5-FU 1000 mg/m²/day by continuous IV infusion on days 1-4 for three cycles followed by concurrent chemoradiation with cisplatin 100 mg/m² IV on days 1, 22, and 43^[51]
Induction chemotherapy with docetaxel 75 mg/m² IV on day 1 plus cisplatin 75 mg/m² IV on day 1 every 3 weeks for two cycles followed by concurrent chemoradiation with weekly cisplatin 40 mg/m² IV^[52]
Radiation doses during concurrent chemoradiation are up to 70-72 Gy

First-line chemotherapy for metastatic or recurrent nasopharyngeal cancers

Stage IVC:

Patients with metastatic nasopharyngeal cancers or recurrent disease (after first-line therapy) are treated with standard platinum-based chemotherapies.
Single agents can be used if patients cannot tolerate platinum doublets.^{[1, 2]}

Acceptable chemotherapy regimens in patients with progressing or recurrent nasopharyngeal cancers (unless otherwise stated, goal is to complete four to six cycles):

Cisplatin 50-70 mg/m² IV on day 1 plus gemcitabine 1000 mg/m² IV on days 1, 8, and 15 every 4wk^{[53, 54]} or
Cisplatin 75 mg/m² IV on day 1 plus docetaxel 75 mg/m² IV on day 1 every 3wk^{[22, 55, 56]} or
Cisplatin 75 mg/m² IV on day 1 plus paclitaxel 175 mg/m² IV on day 1 every 3wk^{[24, 25]} or
Carboplatin AUC 6 IV on day 1 plus docetaxel 65 mg/m² IV on day 1 every 3wk^[26] or
Carboplatin AUC 6 IV on day 1 plus paclitaxel 200 mg/m² IV on day 1 every 3wk^{[57, 58, 59]} 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^{[12, 25, 31, 32, 33]} or
Gemcitabine 1000 mg/m² IV on days 1, 8, and 15 every 4wk^{[53, 60]} or
Gemcitabine 1250 mg/m² IV on days 1 and 8 every 3wk^[61] or
Carboplatin AUC 5 IV on day 1 every 3 weeks plus cetuximab 400 mg/m² IV loading dose on day 1, then 250 mg/m² IV weekly^[62] or
Methotrexate 40 mg/m² IV weekly (3wk equals one cycle)^{[2, 12]} or
Paclitaxel 200 mg/m² IV every 3wk^[63] or
Docetaxel 75 mg/m² IV every 3wk^{[36, 37, 38, 64, 65]}

Second- and third-line chemotherapy for metastatic or recurrent nasopharyngeal 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- 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 chemotherapies if they have not previously received a platinum-based drug.
Some regimens are typically used in head and neck cancers in general, and others have been specifically studied in nasopharyngeal cancer.^{[1, 2]}

Acceptable chemotherapy regimens in patients with progressing or recurrent nasopharyngeal cancers after completion of first-line therapy (unless otherwise stated, goal is to complete four to six cycles):

Cisplatin 50-70 mg/m² IV on day 1 plus gemcitabine 1000 mg/m² IV on days 1, 8, and 15 every 4wk^{[53, 54]} or
Cisplatin 75 mg/m² IV on day 1 plus docetaxel 75 mg/m² IV on day 1 every 3wk^[22] or
Cisplatin 75 mg/m² IV on day 1 plus paclitaxel 175 mg/m² IV on day 1 every 3wk^{[24, 25]} or
Carboplatin AUC 6 IV on day 1 plus docetaxel 65 mg/m² IV on day 1 every 3wk^[26] or
Carboplatin AUC 6 IV on day 1 plus paclitaxel 200 mg/m² IV on day 1 every 3wk^{[57, 59]} 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^{[12, 25, 31, 32, 33]} or
Gemcitabine 1000 mg/m² IV on days 1, 8, and 15 every 4wk or gemcitabine 1250 mg/m² IV on days 1 and 8 every 3wk^{[53, 60]} or
Carboplatin AUC 5 IV on day 1 every 3 weeks plus cetuximab 400 mg/m² IV loading dose on day 1, then 250 mg/m² IV weekly^[62] or
Capecitabine 1250 mg/m² PO BID days 1-14, then off 7 days (3-week period is one cycle)^[43] or
Afatinib 40 mg po daily until disease progression or unacceptable toxicity^[44] or
Methotrexate 40 mg/m² IV weekly (3wk equals one cycle) or
Paclitaxel 200 mg/m² IV every 3wk^[63] or
Docetaxel 75 mg/m² IV every 3wk^{[36, 37, 38, 64, 65]} or
Pembrolizumab 200 mg IV q3wk^{[2, 45, 66]} or
Nivolumab 240 mg IV q2wk or 480 mg q4wk until disease progression ^[67]

Pazdur R, Wagman L, Camphausen K, et al, eds. 12th ed. Cancer Management: A Multidisciplinary Approach. Norwalk, Connecticut: CMP Healthcare Media LLC; 2009.
National Comprehensive Cancer Network Head and Neck Cancers v1.2019. www.nccn.org. Available at https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf. 2019 Mar 06; Accessed: June 12, 2019.
Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27. 349(22):2091-8. [Medline].
Adelstein DJ, Li Y, Adams GL, 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. [Medline].
Bachaud JM, Cohen-Jonathan E, Alzieu C, et al. 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. [Medline].
Bonner JA, Harari PM, Giralt J, Cohen RB, 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. [Medline].
Bonner JA, Harari PM, Giralt J, 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. [Medline].
Li J, Srivastava RM, Ettyreddy A, Ferris RL. Cetuximab ameliorates suppressive phenotypes of myeloid antigen presenting cells in head and neck cancer patients. J Immunother Cancer. 2015. 3:54. [Medline].
Garden AS, Harris J, Vokes EE, 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. [Medline].
Soo KC, Tan EH, Wee J, 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. [Medline]. [Full Text].
Adelstein DJ, Lavertu P, Saxton JP, 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. [Medline].
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. [Medline].
Calais G, Alfonsi M, Bardet E, 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. [Medline].
Haddad R, Sonis S, Posner M, 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. [Medline].
Hitt R, Grau JJ, López-Pousa A, Berrocal A, García-Girón C, Irigoyen A, et al. A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer. Ann Oncol. 2014 Jan. 25 (1):216-25. [Medline].
Budach W, Bölke E, Kammers K, Gerber PA, Orth K, Gripp S, et al. Induction chemotherapy followed by concurrent radio-chemotherapy versus concurrent radio-chemotherapy alone as treatment of locally advanced squamous cell carcinoma of the head and neck (HNSCC): A meta-analysis of randomized trials. Radiother Oncol. 2015 Nov 14. [Medline].
Posner MR, Hershock DM, Blajman CR, 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. [Medline].
Lorch JH, Goloubeva O, Haddad RI, 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. [Medline].
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. [Medline].
Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11. 359(11):1116-27. [Medline].
Glisson BS, Murphy BA, Frenette G, et al. 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. [Medline].
Baur M, Kienzer HR, Schweiger 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. [Medline].
Forastiere AA, 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 Feb 15. 19(4):1088-95. [Medline].
Gibson MK, Li Y, Murphy B, 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. [Medline].
Samlowski WE, Moon J, Kuebler JP, 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. [Medline].
Clark JI, Hofmeister C, Choudhury A, 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. [Medline].
Burtness B, Goldwasser MA, Flood W, et al. 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. [Medline].
Baselga J, Trigo JM, Bourhis J, 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. [Medline].
Herbst RS, Arquette M, Shin DM, 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. [Medline].
Forastiere AA, Metch B, Schuller DE, 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. [Medline].
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 Feb. 10(2):257-63. [Medline].
Clavel M, Vermorken JB, 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 Jul. 5(6):521-6. [Medline].
Lee AW, Sze WM, Au JS, 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. [Medline].
Forastiere AA, Shank D, Neuberg D, et al. 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. [Medline].
Catimel G, Verweij J, Mattijssen V, 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. [Medline].
Dreyfuss AI, Clark JR, Norris CM, et al. Docetaxel: an active drug for squamous cell carcinoma of the head and neck. J Clin Oncol. 1996 May. 14(5):1672-8. [Medline].
Couteau C, Chouaki N, Leyvraz S, 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. [Medline].
Vermorken JB, 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 Jun 1. 25(16):2171-7. [Medline].
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. [Medline].
Price KA, Cohen EE. Current treatment options for metastatic head and neck cancer. Curr Treat Options Oncol. 2012 Mar. 13 (1):35-46. [Medline].
Rischin D, Harrington KJ, Greil R, et al. Protocol-specified final analysis of the phase 3 KEYNOTE-048 trial of pembrolizumab (pembro) as first-line therapy for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) (abstract 6000). Presented at the American Society of Clinical Oncology (ASCO). Chicago, IL. May 31, 2019. [Full Text].
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. [Medline].
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. [Medline].
Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol. 2016 Jul. 17 (7):956-965. [Medline]. [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. [Medline].
Al-Sarraf M, LeBlanc M, Giri PG, et al. Superiority of five year survival with chemo-radiotherapy (CT-RT) vs radiotherapy in patients (Pts) with locally advanced nasopharyngeal cancer (NPC). Intergroup (0099) (SWOG 8892, RTOG 8817, ECOG 2388) Phase III Study: Final Report. 2001.
Al-Sarraf M, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998 Apr. 16(4):1310-7. [Medline].
Lee AW, Lau WH, Tung SY, 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 Oct 1. 23(28):6966-75. [Medline].
Dechaphunkul T, Pruegsanusak K, Sangthawan D, Sunpaweravong P. Concurrent chemoradiotherapy with carboplatin followed by carboplatin and 5-fluorouracil in locally advanced nasopharyngeal carcinoma. Head Neck Oncol. 2011 Jun 5. 3:30. [Medline].
Bae WK, Hwang JE, Shim HJ, Cho SH, Lee JK, Lim SC, et al. Phase II study of docetaxel, cisplatin, and 5-FU induction chemotherapy followed by chemoradiotherapy in locoregionally advanced nasopharyngeal cancer. Cancer Chemother Pharmacol. 2010 Feb. 65 (3):589-95. [Medline].
Hui EP, Ma BB, Leung SF, King AD, Mo F, Kam MK, et al. Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma. J Clin Oncol. 2009 Jan 10. 27 (2):242-9. [Medline].
Ma BB, Tannock IF, Pond GR, et al. Chemotherapy with gemcitabine-containing regimens for locally recurrent or metastatic nasopharyngeal carcinoma. Cancer. 2002 Dec 15. 95(12):2516-23. [Medline].
Ngan RK, Yiu HH, Lau WH, et al. Combination gemcitabine and cisplatin chemotherapy for metastatic or recurrent nasopharyngeal carcinoma: report of a phase II study. Ann Oncol. 2002 Aug. 13(8):1252-8. [Medline].
McCarthy JS, Tannock IF, Degendorfer P, et al. A Phase II trial of docetaxel and cisplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. Oral Oncol. 2002 Oct. 38(7):686-90. [Medline].
Chua DT, Sham JS, Au GK. A phase II study of docetaxel and cisplatin as first-line chemotherapy in patients with metastatic nasopharyngeal carcinoma. Oral Oncol. 2005 Jul. 41(6):589-95. [Medline].
Airoldi M, Pedani F, Marchionatti S, et al. Carboplatin plus taxol is an effective third-line regimen in recurrent undifferentiated nasopharyngeal carcinoma. Tumori. 2002 Jul-Aug. 88(4):273-6. [Medline].
Tan EH, Khoo KS, Wee J, et al. Phase II trial of a paclitaxel and carboplatin combination in Asian patients with metastatic nasopharyngeal carcinoma. Ann Oncol. 1999 Feb. 10(2):235-7. [Medline].
Ciuleanu TE, Fountzilas G, Ciuleanu E, et al. Paclitaxel and carboplatin in relapsed or metastatic nasopharyngeal carcinoma: a multicenter phase II study. J BUON. 2004 Apr-Jun. 9(2):161-5. [Medline].
Zhang L, Zhang Y, Huang PY, et al. Phase II clinical study of gemcitabine in the treatment of patients with advanced nasopharyngeal carcinoma after the failure of platinum-based chemotherapy. Cancer Chemother Pharmacol. 2008 Jan. 61(1):33-8. [Medline].
Foo KF, Tan EH, Leong SS, et al. Gemcitabine in metastatic nasopharyngeal carcinoma of the undifferentiated type. Ann Oncol. 2002 Jan. 13(1):150-6. [Medline].
Chan AT, Hsu MM, Goh BC, Hui EP, Liu TW, Millward MJ, et al. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. J Clin Oncol. 2005 May 20. 23 (15):3568-76. [Medline].
Au E, Tan EH, Ang PT. Activity of paclitaxel by three-hour infusion in Asian patients with metastatic undifferentiated nasopharyngeal cancer. Ann Oncol. 1998 Mar. 9(3):327-9. [Medline].
Guardiola E, Peyrade F, Chaigneau L, et al. Results of a randomised phase II study comparing docetaxel with methotrexate in patients with recurrent head and neck cancer. Eur J Cancer. 2004 Sep. 40(14):2071-6. [Medline].
Zenda S, Onozawa Y, Boku N, et al. Single-agent docetaxel in patients with platinum-refractory metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). Jpn J Clin Oncol. 2007 Jul. 37(7):477-81. [Medline].
Hsu C, Lee SH, Ejadi S, Even C, Cohen RB, Le Tourneau C, et al. Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 20. 35 (36):4050-4056. [Medline].
Ma BBY, Lim WT, Goh BC, Hui EP, Lo KW, Pettinger A, et al. Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742). J Clin Oncol. 2018 May 10. 36 (14):1412-1418. [Medline].
Cancer Protocols. College of American Pathologists. Available at http://www.cap.org. Accessed: 2011.
Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin. 2010 Sep-Oct. 60(5):277-300. [Medline].
O'Neil BH, Allen R, Spigel DR, et al. High incidence of cetuximab-related infusion reactions in Tennessee and North Carolina and the association with atopic history. J Clin Oncol. 2007 Aug 20. 25(24):3644-8. [Medline].
Practice Guidelines and Appropriateness Criteria. American College of Radiology. Available at http://www.acr.org. Accessed: 2011.
SEER Cancer Statistics Review. National Cancer Institute. Available at http://seer.cancer.gov/csr/1975_2007/. Accessed: 2011.
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. [Medline]. [Full Text].
Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016 Nov 10. 375 (19):1856-1867. [Medline]. [Full Text].

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Head and Neck Cancer Treatment Protocols

Treatment Protocols

Generalized treatment recommendations for oral cavity, pharyngeal, and laryngeal cancers

Chemotherapy with radiation therapy for locally advanced disease (oral cavity, pharyngeal, and laryngeal cancers)

Induction chemotherapy for locally advanced disease (oral cavity, pharyngeal, and laryngeal cancers)

First-line chemotherapy for metastatic or recurrent disease (oral cavity, pharyngeal, and laryngeal cancers)

Second- and third-line chemotherapy for metastatic or recurrent disease (oral cavity, pharyngeal, and laryngeal cancers)

Radiation therapy for early or localized disease (nasopharyngeal cancers)

Chemotherapy with radiation therapy for locally advanced nasopharyngeal cancers

First-line chemotherapy for metastatic or recurrent nasopharyngeal cancers

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

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Head and Neck Cancer Treatment Protocols

Treatment Protocols

Generalized treatment recommendations for oral cavity, pharyngeal, and laryngeal cancers

Chemotherapy with radiation therapy for locally advanced disease (oral cavity, pharyngeal, and laryngeal cancers)

Induction chemotherapy for locally advanced disease (oral cavity, pharyngeal, and laryngeal cancers)

First-line chemotherapy for metastatic or recurrent disease (oral cavity, pharyngeal, and laryngeal cancers)

Second- and third-line chemotherapy for metastatic or recurrent disease (oral cavity, pharyngeal, and laryngeal cancers)

Radiation therapy for early or localized disease (nasopharyngeal cancers)

Chemotherapy with radiation therapy for locally advanced nasopharyngeal cancers

First-line chemotherapy for metastatic or recurrent nasopharyngeal cancers

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

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