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:
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Treatment plans for all disease stages should be discussed at a multidisciplinary tumor conference involving ENT surgeons, radiation oncologists, and medical oncologists
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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:
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Primary treatment for oropharyngeal cancers is surgical resection or definitive radiation therapy
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Surgery is the preferred approach except for some patients who may have early lip, retromolar trigone, and soft palate cancers
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Radiation therapy is preferred for patients who may not be able to tolerate surgery
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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)
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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
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Concurrent chemoradiation therapy is the current standard of care for patients with locally advanced squamous cell carcinoma of the head and neck
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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)
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Conventional fractionation for concurrent chemoradiation is up to 70 Gy (2.0 Gy/fraction)
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Postoperative radiation dose is 60-66 Gy (2.0 Gy/fraction); preferred interval between resection and postoperative radiation therapy is ≤ 6wk
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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:
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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
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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
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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
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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
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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:
Induction chemotherapy for locally advanced disease (oral cavity, pharyngeal, and laryngeal cancers)
Stages III-IVB:
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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
Acceptable chemotherapy regimens for induction chemotherapy:
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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
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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]
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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]
First-line chemotherapy for metastatic or recurrent disease (oral cavity, pharyngeal, and laryngeal cancers)
Stage IVC:
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Treatment recommendations include the use of single-agent or combination chemotherapy
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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):
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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
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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
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Carboplatin AUC 6 IV on day 1 plus docetaxel 65 mg/m2 IV on day 1 every 3wk [26] or
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Carboplatin AUC 6 IV on day 1 plus paclitaxel 200 mg/m2 IV on day 1 every 3wk [27] or
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Methotrexate 40 mg/m2 IV weekly (3wk equals 1 cycle) [12, 31] or
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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) [39]
Second- and third-line chemotherapy for metastatic or recurrent disease (oral cavity, pharyngeal, and laryngeal cancers)
Stage IVC:
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Second-line chemotherapy is given after disease progression or recurrence following completion of first-line therapy
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Third-line therapies are given after disease progression or recurrence following completion of first-line and second-line therapies
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Second- and third-line regimens are similar to regimens used as first-line therapy but usually offer lower response rates and survival benefits
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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):
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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
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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) [22] ; or
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Cisplatin 75 mg/m2 IV on day 1 plus docetaxel 75 mg/m2 IV on day 1 every 3wk [22] or
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Carboplatin AUC 6 IV on day 1 plus docetaxel 65 mg/m2 IV on day 1 every 3wk [26] or
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Carboplatin AUC 6 IV on day 1 plus paclitaxel 200 mg/m2 IV on day 1 every 3wk [27] or
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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) [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
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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:
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Patients with early or localized disease may be treated with definitive radiation therapy to the nasopharynx alone
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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:
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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):
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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 [43]
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Radiation doses during concurrent chemoradiation are 70 Gy (2.0 Gy/fraction)
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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 [44]
First-line chemotherapy for metastatic or recurrent nasopharyngeal cancers
Stage IVC:
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Patients with metastatic nasopharyngeal cancers or recurrent disease (after first-line therapy) are treated with standard platinum-based chemotherapies
Acceptable chemotherapy regimens in patients with progressing or recurrent nasopharyngeal cancers (unless otherwise stated, goal is to complete 4-6 cycles):
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Carboplatin AUC 6 IV on day 1 plus docetaxel 65 mg/m2 IV on day 1 every 3wk [26] or
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Cisplatin 50-70 mg/m2 IV on day 1 plus gemcitabine 1000 mg/m2 IV on days 1, 8, and 15 every 4wk [50, 51] or
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Paclitaxel 200 mg/m2 IV every 3wk [54] or
Second- and third-line chemotherapy for metastatic or recurrent nasopharyngeal cancers
Stage IVC:
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Second-line chemotherapy is given after disease progression or recurrence following completion of first-line therapy
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Third-line therapies are given after disease progression or recurrence following completion of first- and second-line therapies
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Second- and third-line regimens are similar to regimens used as first-line therapy but usually offer lower response rates and survival benefits
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Patients should be treated with platinum-based chemotherapies if they have not previously received a platinum-based drug
Acceptable chemotherapy regimens in patients with progressing or recurrent nasopharyngeal cancers after completion of first-line therapy: