Head and Neck Cancer Treatment Protocols 

Updated: Feb 29, 2016
  • 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 generalized first-line therapy based on stage; chemoradiation therapy and induction chemotherapy for locally advanced disease; and first-, second-, and third-line chemotherapy for metastatic or recurrent disease.

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

See the list below:

  • Treatment plans for all disease stages should be discussed at a multidisciplinary tumor conference involving 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 disease (oral cavity, pharyngeal, and laryngeal cancers)  [1, 2]

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 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 66-74 Gy (2.0 Gy/fraction; daily Monday-Friday in 7wk) 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, 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 66-74 Gy (2.0 Gy/fraction; daily Monday-Friday in 7wk)
  • Conventional fractionation for concurrent chemoradiation is up to  70 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/m 2 IV on days 1, 22, and 43 [1, 2, 3, 4] or  40-50 mg/m 2 IV weekly for 6-7wk [5] or
  • Cetuximab 400 mg/m 2 IV loading dose 1wk before the start of radiation therapy, then  250 mg/m 2 weekly (premedicate with dexamethasone, diphenhydramine, and ranitidine) [6, 7, 8] or
  • Cisplatin 20 mg/m 2 IV on day 2 weekly for up to 7wk plus  paclitaxel 30 mg/m 2 IV on day 1 weekly for up to 7wk [9] or
  • Cisplatin 20 mg/m 2/day IV on days 1-4 and 22-25 plus  5-FU 1000 mg/m 2/day by continuous IV infusion on days 1-4 and 22-25 [10, 11, 12] or
  • 5-FU 800 mg/m 2 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/m 2/day IV on days 1-4, 22-25, and 43-46 plus  5-FU 600 mg/m 2/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/m 2 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/m 2 IV on days 1, 22, and 43 [3, 4] or  40-50 mg/m 2 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 future surgery or radiation therapy
  • 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, 15, 16]

Acceptable chemotherapy regimens for induction chemotherapy:

  • Docetaxel 75 mg/m 2 IV on day 1 plus  cisplatin 100 mg/m 2 IV on day 1 plus  5-FU 100 mg/m 2/day by continuous IV infusion on days 1-4 every 3wk for 3 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/m 2 IV on day 1 plus  cisplatin 75 mg/m 2 IV on day 1 plus  5-FU 750 mg/m 2/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/m 2 IV on day 1 plus  cisplatin 100 mg/m 2 IV on day 2 plus  5-FU 500 mg/m 2/day by continuous IV infusion on days 2-6 every 3wk for 3 cycles; then  radiation with cisplatin 100 mg/m 2 IV on days 1, 22, and 43 [20]

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 (unless otherwise stated, goal is to complete at least 6 cycles):

  • Cisplatin 100 mg/m 2 IV on day 1 every 3wk for 6 cycles plus  5-FU 1000 mg/m 2/day by continuous IV infusion on days 1-4 every 3wk for 6 cycles plus  cetuximab 400 mg/m 2 IV loading dose on day 1, then  250 mg/m 2 IV weekly until disease progression (premedicate with dexamethasone, diphenhydramine, and ranitidine) [21] ; or
  • Carboplatin AUC 5 IV on day 1 every 3wk for 6 cycles plus  5-FU 1000 mg/m 2/day by continuous IV infusion on days 1-4 every 3wk for 6 cycles plus  cetuximab 400 mg/m 2 IV loading dose on day 1, then  250 mg/m 2 IV weekly until disease progression (premedicate with dexamethasone, diphenhydramine, and ranitidine) [21] ; or
  • Cisplatin 75 mg/m 2 IV on day 1 plus  docetaxel 75 mg/m 2 IV on day 1 every 3wk [22, 23] or
  • Cisplatin 75 mg/m 2 IV on day 1 plus  paclitaxel 175 mg/m 2 IV on day 1 every 3wk [24, 25] or
  • Carboplatin AUC 6 IV on day 1 plus  docetaxel 65 mg/m 2 IV on day 1 every 3wk [26] or
  • Carboplatin AUC 6 IV on day 1 plus  paclitaxel 200 mg/m 2 IV on day 1 every 3wk [27] or
  • Cisplatin 75-100 mg/m 2 IV on day 1 every 3-4wk plus  cetuximab 400 mg/m 2 IV loading dose on day 1, then  250 mg/m 2 IV weekly (premedicate with dexamethasone, diphenhydramine, and ranitidine) [28, 29, 30] ; or
  • Cisplatin 100 mg/m 2 IV on day 1 plus  5-FU 1000 mg/m 2/day by continuous IV infusion on days 1-4 every 3wk [12, 25, 31, 32, 33] or
  • Methotrexate 40 mg/m 2 IV weekly (3wk equals 1 cycle) [12, 31] or
  • Paclitaxel 200 mg/m 2 IV every 3wk [34, 35] or
  • Docetaxel 75 mg/m 2 IV every 3wk [36, 37, 38] or
  • Cetuximab 400 mg/m 2 IV loading dose on day 1, then  250 mg/m 2 IV weekly until disease progression (premedicate with dexamethasone, diphenhydramine, and ranitidine) [39]

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 6 cycles):

  • Cisplatin 100 mg/m 2 IV on day 1 every 3wk for 6 cycles plus  5-FU 1000 mg/m 2/day by continuous IV infusion on days 1-4 every 3wk for 6 cycles plus  cetuximab 400 mg/m 2 IV loading dose on day 1, then  250 mg/m 2 IV weekly until disease progression (premedicate with dexamethasone, diphenhydramine, and ranitidine) [21] ; or
  • Carboplatin AUC 5 IV on day 1 every 3wk for 6 cycles plus  5-FU 1000 mg/m 2/day by continuous IV infusion on days 1-4 every 3wk for 6 cycles plus  cetuximab 400 mg/m 2 IV loading dose on day 1, then  250 mg/m 2 IV weekly until disease progression (premedicate with dexamethasone, diphenhydramine, and ranitidine) [22] ; or
  • Cisplatin 75 mg/m 2 IV on day 1 plus  docetaxel 75 mg/m 2 IV on day 1 every 3wk [22] or
  • Cisplatin 75 mg/m 2 IV on day 1 plus  paclitaxel 175 mg/m 2 IV on day 1 every 3wk [24, 25] or
  • Carboplatin AUC 6 IV on day 1 plus  docetaxel 65 mg/m 2 IV on day 1 every 3wk [26] or
  • Carboplatin AUC 6 IV on day 1 plus  paclitaxel 200 mg/m 2 IV on day 1 every 3wk [27] or
  • Cisplatin 75-100 mg/m 2 IV on day 1 every 3-4wk plus  cetuximab 400 mg/m 2 IV loading dose on day 1, then  250 mg/m 2 IV weekly (premedicate with dexamethasone, diphenhydramine, and ranitidine) [28, 29, 30] ; or
  • Cisplatin 100 mg/m 2 IV on day 1 plus  5-FU 1000 mg/m 2/day by continuous IV infusion on days 1-4 every 3wk [12, 25, 31, 32, 33] or
  • Methotrexate 40 mg/m 2 IV weekly (3wk equals 1 cycle) [12, 31] or
  • Paclitaxel 200 mg/m 2 IV every 3wk [2, 35] or
  • Docetaxel 75 mg/m 2 IV every 3wk [36, 37, 38] or
  • Cetuximab 400 mg/m 2 IV loading dose on day 1, then  250 mg/m 2 IV weekly until disease progression (premedicate with dexamethasone, diphenhydramine, and ranitidine) [39]

Generalized treatment recommendations for nasopharyngeal cancers

See the list below:

  • Treatment plans for all disease stages should be discussed at a multidisciplinary tumor conference involving ENT surgeons, radiation oncologists, and medical oncologists
  • Selected patients with advanced or metastatic disease may receive additional therapy (radiation or neck dissection) depending on their response to first-line therapy
  • Surgery at the primary disease site has a very limited role, if any, in nasopharyngeal cancers

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 66-70 Gy (2.0 Gy/fraction; daily Monday-Friday in 7wk)

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 regimen for advanced nasopharyngeal cancers (stages II-IVB):

  • Cisplatin 100 mg/m 2 IV on days 1, 22, and 43 with radiation +/- adjuvant chemotherapy with cisplatin 80 mg/m 2 IV on day 1 plus  fluorouracil (5-FU) 1000 mg/m 2/day by continuous IV infusion on days 1-4 every 4wk for 3 cycles [40, 41, 42]
  • Carboplatin AUC 6 IV every 3 weeks for 3 cycles with radiation +/- adjuvant chemotherapy with carboplatin AUC 5 IV on day 1 plus  fluorouracil (5-FU) 1000 mg/m 2/day by continuous IV infusion on days 1-4 every 3 weeks for 2 cycles [43]
  • Radiation doses during concurrent chemoradiation are 70 Gy (2.0 Gy/fraction)
  • Induction chemotherapy with docetaxel 70 mg/m 2 IV on day 1 plus  cisplatin 75 mg/m 2 IV on day 1 plus  5-FU 1000 mg/m 2/day by continuous IV infusion on days 1-4 for three cycles followed by concurrent chemoradiation with cisplatin 100 mg/m 2 IV on days 1, 22, and 43 [44]

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-based agents [1, 2]

Acceptable chemotherapy regimens in patients with progressing or recurrent nasopharyngeal cancers (unless otherwise stated, goal is to complete 4-6 cycles):

  • Cisplatin 75 mg/m 2 IV on day 1 plus  docetaxel 75 mg/m 2 IV on day 1 every 3wk [22, 45, 46] or
  • Cisplatin 75 mg/m 2 IV on day 1 plus  paclitaxel 175 mg/m 2 IV on day 1 every 3wk [24, 25] or
  • Carboplatin AUC 6 IV on day 1 plus  docetaxel 65 mg/m 2 IV on day 1 every 3wk [26] or
  • Carboplatin AUC 6 IV on day 1 plus  paclitaxel 200 mg/m 2 IV on day 1 every 3wk [47, 48, 49] or
  • Cisplatin 100 mg/m 2 IV on day 1 plus  5-FU 1000 mg/m 2/day by continuous IV infusion on days 1-4 every 3wk [12, 25, 31, 32, 33] or
  • Cisplatin 50-70 mg/m 2 IV on day 1 plus  gemcitabine 1000 mg/m 2 IV on days 1, 8, and 15 every 4wk [50, 51] or
  • Gemcitabine 1000 mg/m 2 IV on days 1, 8, and 15 every 4wk [50, 52] or  gemcitabine 1250 mg/m 2 IV on days 1 and 8 every 3wk [53] or
  • Methotrexate 40 mg/m 2 IV weekly (3wk equals 1 cycle) [2, 12] or
  • Paclitaxel 200 mg/m 2 IV every 3wk [54] or
  • Docetaxel 75 mg/m 2 IV every 3wk [36, 37, 38, 55, 56]

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:

  • Cisplatin 75 mg/m 2 IV on day 1 plus  docetaxel 75 mg/m 2 IV on day 1 every 3wk [22] or
  • Cisplatin 75 mg/m 2 IV on day 1 plus  paclitaxel 175 mg/m 2 IV on day 1 every 3wk [24, 25] or
  • Carboplatin AUC 6 IV on day 1 plus  docetaxel 65 mg/m 2 IV on day 1 every 3wk [26] or
  • Carboplatin AUC 6 IV on day 1 plus  paclitaxel 200 mg/m 2 IV on day 1 every 3wk [47, 49] or
  • Cisplatin 100 mg/m 2 IV on day 1 plus  5-FU 1000 mg/m 2/day by continuous IV infusion on days 1-4 every 3wk [12, 25, 31, 32, 33] or
  • Cisplatin 50-70 mg/m 2 IV on day 1 plus  gemcitabine 1000 mg/m 2 IV on days 1, 8, and 15 every 4wk [50, 51] or
  • Gemcitabine 1000 mg/m 2 IV on days 1, 8, and 15 every 4wk or  gemcitabine 1250 mg/m 2 IV on days 1 and 8 every 3wk [50, 52] or
  • Methotrexate 40 mg/m 2 IV weekly (3wk equals 1 cycle) or
  • Paclitaxel 200 mg/m 2 IV every 3wk [54] or
  • Docetaxel 75 mg/m 2 IV every 3wk [36, 37, 38, 55, 56]