Treatment Protocols
Treatment protocols for pharyngeal cancers are provided below, including the following:
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Generalized first-line therapy based on stage
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Chemoradiation therapy and induction chemotherapy for locally advanced disease
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First-, second-, and third-line chemotherapy for metastatic or recurrent disease
Generalized treatment recommendations for pharyngeal cancers
See the list below:
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Treatment plans for all disease stages should be discussed at a multidisciplinary tumor conference involving ear, nose, throat (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 pharyngeal cancers
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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 66-72Gy may be used with adequate results
Chemotherapy with radiation therapy for locally advanced pharyngeal 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 66-72 Gy
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Conventional fractionation for concurrent chemoradiation up to 72 Gy
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Postoperative radiation dose is 60-66 Gy (2.0 Gy/fraction); preferred interval between resection and postoperative radiation therapy is 6 wk
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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 include:
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Cisplatin 20 mg/m2 IV on day 2 weekly for up to 7 wk plus paclitaxel 30 mg/m2 IV on day 1 weekly for up to 7 wk [8] or
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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 [9, 10, 11] 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 q12 h (11 doses per cycle); chemotherapy and radiation given every other week for a total of 13 wk [8] 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 [12] or
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Carboplatin area under the curve (AUC) 1.5 IV on day 1 weekly plus paclitaxel 45 mg/m2 IV on day 1 weekly [13] (see also the Carboplatin AUC Dose Calculation [Calvert formula] calculator)
Acceptable chemotherapy regimens for patients receiving postoperative concurrent chemoradiation:
Induction chemotherapy for locally advanced pharyngeal 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 3 wk for 3 cycles; then 3-8 wk later, carboplatin AUC 1.5 IV weekly for up to 7wk during radiation therapy; then 6-12 wk later, pursue surgery, if applicable [14, 15] ; 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 [16]
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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 3 wk for 3 cycles; then radiation with cisplatin 100 mg/m2 IV on days 1, 22, and 43 [17]
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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 pharyngeal 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 include (unless otherwise stated, goal is to complete at least six cycles):
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Cisplatin 100 mg/m2 IV on day 1 every 3 wk for six cycles plus 5-FU 1000 mg/m2/day by continuous IV infusion on days 1-4 every 3 wk 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) [18] ; or
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Carboplatin AUC 5 IV on day 1 every 3 wk for six cycles plus 5-FU 1000 mg/m2/day by continuous IV infusion on days 1-4 every 3 wk 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) [18] or
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Cisplatin 100 mg/m2 IV 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 6 cycles plus pembrolizumab 200 mg IV over 30 min every 3wk until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression [19, 20]
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Carboplatin AUC 6 IV on day 1 plus docetaxel 65 mg/m2 IV on day 1 every 3 wk [25] or
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Carboplatin AUC 6 IV on day 1 plus paclitaxel 200 mg/m2 IV on day 1 every 3 wk [26] or
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Methotrexate 40 mg/m2 IV weekly (3 wk equals one cycle) [11, 30] 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) [38] or
Second- and third-line chemotherapy for metastatic or recurrent pharyngeal 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 include (unless otherwise stated, goal is to complete at least six cycles):
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Cisplatin 100 mg/m2 IV on day 1 every 3 wk for six cycles plus 5-FU 1000 mg/m2/day by continuous IV infusion on days 1-4 every 3 wk 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) [18] or
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Carboplatin AUC 5 IV on day 1 every 3 wk 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
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Cisplatin 75 mg/m2 IV on day 1 plus docetaxel 75 mg/m2 IV on day 1 every 3 wk [21] or
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Carboplatin AUC 6 IV on day 1 plus docetaxel 65 mg/m2 IV on day 1 every 3 wk [25] or
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Carboplatin AUC 6 IV on day 1 plus paclitaxel 200 mg/m2 IV on day 1 every 3 wk [26] 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) [38] or
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Capecitabine 1250 mg/m2 PO BID on days 1-14, then off 7 days (3-week period is one cycle) [41] or
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Pembrolizumab 200 mg IV q 3 weeks until disease progression [44, 45, 19]