Laryngeal Cancer Treatment Protocols
Updated: Nov 26, 2019
Author: Marvaretta M Stevenson, MD; Chief Editor: Guy J Petruzzelli, MD, PhD, MBA, FACS
Treatment protocols for laryngeal cancers are provided below, including the following:
See the list below:
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
Selected patients with advanced or metastatic disease may receive surgical resection of their primary tumors, depending on their response to first-line therapy
Stages I-II[1, 2] :
Primary treatment for laryngeal cancers is surgical resection or definitive radiation therapy
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
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[3]
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/m2 IV on days 1, 22, and 43[1, 2, 4, 5, 6] or 40-50 mg/m2 IV weekly for 6-7wk[7] 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)[8, 9, 6] ; or
Cisplatin 20 mg/m2 IV on day 2 weekly for up to 7wk pluspaclitaxel 30 mg/m2 IV on day 1 weekly for up to 7wk[10] or
Cisplatin 20 mg/m2/day IV on days 1-4 and 22-25 plusfluorouracil (5-FU) 1000 mg/m2/day by continuous IV infusion on days 1-4 and 22-25[11, 12, 13] or
5-FU 800 mg/m2 by continuous IV infusion on days 1-5 given on the days of radiation plushydroxyurea 1 g PO q12h (11 doses per cycle); chemotherapy and radiation given every other week for a total of 13wk[10] 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[14] or
Carboplatin area under the curve (AUC) 1.5 IV on day 1 weekly plus paclitaxel 45 mg/m2 IV on day 1 weekly[15] (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[4, 5] or 40-50 mg/m2 IV weekly for 6-7wk[7]
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
The 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]
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[16, 17] ; 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[18]
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[19]
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]
Pembrolizumab is approved for use in combination with platinum and 5-FU for all patients with metastatic or unresectable recurrent head and neck squamous cell carcinoma, and as a single agent for patients whose tumors express PD‑L1 (Combined Positive Score [CPS] ≥1) as determined by an FDA‑approved test.[20, 21]
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/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)[22] ; 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)[22] ; or
Cisplatin 100 mg/m2 IV 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 pembrolizumab 200 mg IV over 30 min every 3wk until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression
Pembrolizumab 200 mg IV over 30 min every 3wk until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression, in patients whose tumors express PD‑L1 or
Cisplatin 75 mg/m2 IV on day 1 plus docetaxel 75 mg/m2 IV on day 1 every 3wk[23, 24] or
Cisplatin 75 mg/m2 IV on day 1 plus paclitaxel 175 mg/m2 IV on day 1 every 3wk[25, 26] or
Carboplatin AUC 6 IV on day 1 plus docetaxel 65 mg/m2 IV on day 1 every 3wk[27] or
Carboplatin AUC 6 IV on day 1 plus paclitaxel 200 mg/m2 IV on day 1 every 3wk[28] 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 (premedicate with dexamethasone, diphenhydramine, and ranitidine)[29, 30, 31] 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[13, 26, 32, 33, 34] or
Cisplatin 75 mg/m2 IV on day 1 plus docetaxel 75 mg/m2 IV on day 1 plus cetuximab (400 mg/m2 IV on day 1, then 250 mg/m2 IV weekly) every 21 days for 4 cycles followed by cetuximab maintenance (500 mg/m2 IV every 2 weeks) until disease progression or unacceptable toxicity[35] or
Methotrexate 40 mg/m2 IV weekly (3wk equals 1 cycle)[13, 32] or
Paclitaxel 200 mg/m2 IV every 3wk[36, 37] or
Docetaxel 75 mg/m2 IV every 3wk[38, 39, 40] or
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)[41]
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.
Immunotherapy (nivolumab or pembrolizumab) can be used in patients who experience disease progression on or after platinum therapy.[2]
Acceptable chemotherapy regimens in patients with recurrent head and neck cancers (unless otherwise stated, goal is to complete at least 6 cycles):
Nivolumab 240 mg IV every 2wk or 480 mg IV every 4wk until disease progression or unacceptable toxicity[42]
Pembrolizumab 200 mg IV every 3wk until disease progression, unacceptable toxicity, or up to 24 months without disease progression[20]
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)[22] ; 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)[23] ; or
Cisplatin 75 mg/m2 IV on day 1 plus docetaxel 75 mg/m2 IV on day 1 every 3wk[23] or
Cisplatin 75 mg/m2 IV on day 1 plus paclitaxel 175 mg/m2 IV on day 1 every 3wk[25, 26] or
Carboplatin AUC 6 IV on day 1 plus docetaxel 65 mg/m2 IV on day 1 every 3wk[27] or
Carboplatin AUC 6 IV on day 1 plus paclitaxel 200 mg/m2 IV on day 1 every 3wk[28] 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 (premedicate with dexamethasone, diphenhydramine, and ranitidine)[29, 30, 31] ; 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[13, 26, 32, 33, 34] or
Cisplatin 75 mg/m2 IV on day 1 plus docetaxel 75 mg/m2 IV on day 1 plus cetuximab (400 mg/m2 IV on day 1, then 250 mg/m2 IV weekly) every 21 days for 4 cycles followed by cetuximab maintenance (500 mg/m2 IV every 2 weeks) until disease progression or unacceptable toxicity[35] or
Methotrexate 40 mg/m2 IV weekly (3wk equals 1 cycle)[13, 32] or
Paclitaxel 200 mg/m2 IV every 3wk[2, 37] or
Docetaxel 75 mg/m2 IV every 3wk[38, 39, 40] or
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)[41]