Head and Neck Cancer Treatment Protocols 

Updated: Aug 20, 2019
  • Author: Marvaretta M Stevenson, MD; Chief Editor: Guy J Petruzzelli, MD, PhD, MBA, FACS  more...
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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]