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 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 66-72 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 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 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 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 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/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 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/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 3 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 carboplatin or cisplatin as listed above or by concurrent chemoradiation with 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 6 cycles):

Cisplatin 100 mg/m² IV on day 1 every 3wk for 6 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 (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/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 (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 1 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 include (unless otherwise stated, goal is to complete at least 6 cycles):

Cisplatin 100 mg/m² IV on day 1 every 3wk for 6 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 6 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^[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 1 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 Day 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]63 or
Pembrolizumab 200 mg IV q3wk until disease progression^{[2, 45, 46]}

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 due to its anatomical location and radiosensitivity

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) include:

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 fluorouracil (5-FU) 1000 mg/m²/day by continuous IV infusion on days 1-4 every 4wk for 3 cycles^{[47, 48, 49]}
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/m²/day by continuous IV infusion on days 1-4 every 3 weeks for 2 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]
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 include (unless otherwise stated, goal is to complete 4-6 cycles):

Cisplatin 75 mg/m² IV on day 1 plus docetaxel 75 mg/m² IV on day 1 every 3wk^{[22, 52, 53]}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^{[54, 55, 56]}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
Cisplatin 50-70 mg/m² IV on day 1 plus gemcitabine 1000 mg/m² IV on days 1, 8, and 15 every 4wk^{[57, 58]}or
Gemcitabine 1000 mg/m² IV on days 1, 8, and 15 every 4wk^{[57, 59]}or gemcitabine 1250 mg/m² IV on days 1 and 8 every 3wk^[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^[61] or
Methotrexate 40 mg/m² IV weekly (3wk equals 1 cycle)^{[2, 12]}or
Paclitaxel 200 mg/m² IV every 3wk^[62]or
Docetaxel 75 mg/m² IV every 3wk^{[36, 37, 38, 63, 64]}

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 include (unless otherwise stated, goal is to complete 4-6 cycles):

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^{[54, 56]}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
Cisplatin 50-70 mg/m² IV on day 1 plus gemcitabine 1000 mg/m² IV on days 1, 8, and 15 every 4wk^{[57, 58]}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^{[57, 59]}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^[61] or
Capecitabine 1250 mg/m² po bid Day 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 1 cycle) or
Paclitaxel 200 mg/m² IV every 3wk^[62]or
Docetaxel 75 mg/m² IV every 3wk^{[36, 37, 38, 63, 64]}
Pembrolizumab 200 mg IV q3wk ^{[2, 45]}

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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)

Generalized treatment recommendations for nasopharyngeal 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

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Head and Neck Cancer Treatment Protocols

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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)

Generalized treatment recommendations for nasopharyngeal 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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