• Users Online: 547
  • Print this page
  • Email this page


 
 
Table of Contents
PROFESSIONAL RESOURCE
Year : 2019  |  Volume : 2  |  Issue : 1  |  Page : 83-104

Radical Chemo-radiation (CRT) Protocols for Head and Neck Squamous Cell Carcinomas (HNSCC)


Department of Medical Oncology, Manipal Comprehensive Cancer Centre, Manipal Hospital, Bengaluru, Karnataka; Formerly at Tata Memorial Hospital, Mumbai, Maharashtra, India

Date of Web Publication9-Sep-2019

Correspondence Address:
Kushal Gupta
Flat No. 103, R.P. Serenity, 18th Cross, 22nd/B Main, Ayodhya Nagar, J. P. Nagar Phase-5, Bengaluru - 560 078, Karnataka
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_38_19

Get Permissions


How to cite this article:
Gupta K. Radical Chemo-radiation (CRT) Protocols for Head and Neck Squamous Cell Carcinomas (HNSCC). Cancer Res Stat Treat 2019;2:83-104

How to cite this URL:
Gupta K. Radical Chemo-radiation (CRT) Protocols for Head and Neck Squamous Cell Carcinomas (HNSCC). Cancer Res Stat Treat [serial online] 2019 [cited 2019 Sep 17];2:83-104. Available from: http://www.crstonline.com/text.asp?2019/2/1/83/266459




  1. Head and Neck Squamous Cell Carcinoma-Cisplatin-Therapy (3-Weekly) Protocol Top




Please enter exact total doses of each cycle in milligrams



Oral medications (once a day [OD]; twice a day [BD])

  1. Capsule Aprepitant PO 125 mg OD on Day (D) 1 (on D1 before chemotherapy) and 80 mg on D2 and D3
  2. Tablet Dexamethasone 4 mg BD (D2–D4) after food/feed
  3. Tablet Ranitidine 150 mg BD (D2–D4) 20 min before food
  4. Tablet Olanzapine 5 mg BD (D1–D5).


Toxicity incidence and adverse effects [1]



Dose-limiting toxicities

Hearing impairment (acute: 12.8%, delayed: 15.9%),[1] chemotherapy-induced nausea or vomiting, i.e. Chemotherapy-induced nausea and vomiting (6.7%), neurotoxicity (delayed), and nephrotoxicity (36%).[2]

Emetogenic potential

Cisplatin (any dose): Highly emetogenic.

Pharmacokinetics and metabolism [3]



Extravasation

Irritant.

Drug interactions: Cisplatin [2]



Dose modifications [2]



Renal dose modifications [2]



Special precautions [2]

Contraindications

  • Known hypersensitivity to platinum-containing compounds
  • Myelosuppressed (absolute neutrophil count (ANC) <1.5 × 109/mL, platelets <100 × 109/L)
  • Pre-existing renal impairment and hearing impairment, unless the possible benefits of treatment outweigh the risks.


Other drug properties

Carcinogenicity: Yes, Potential to cause infertility: Yes.

Pregnancy and lactation

Cisplatin is NOT recommended for use in pregnancy. Appropriate contraception should be used by both sexes during treatment, and for at least 6 months (females; general recommendation) and 2 years (males) after the last dose. Male patients should not donate semen while using cisplatin and up to 2 years after the last dose. Breastfeeding is NOT recommended.





  1. Noronha V, Joshi A, Patil VM, Agarwal J, Ghosh-Laskar S, Budrukkar A, et al. Once-a-week versus once-every-3-weeks cisplatin chemoradiation for locally advanced head and neck cancer: A phase III randomized noninferiority trial. J Clin Oncol 2018;36:1064-72.
  2. Drug Monograph-Cisplatin. Cancer Care Ontario Formulary-May 2018.
  3. Cisplatin. British Columbia Cancer Agency Drug Manual (Sept., 1994). Revised Ed. June, 2016;1-11.



  2. Head and Neck Squamous Cell Carcinoma-Cisplatin-Radiation Therapy 1-Weekly Protocol Top




Please enter exact total doses of each cycle in milligrams



Oral medications (once a day [OD]; twice a day [BD])

  1. Tablet Aprepitant 125 mg OD on D1 and 80 mg D2–D3
  2. Tablet Dexamethasone 4 mg BD (D2–D4) after food/feed
  3. Tablet Ranitidine 150 mg BD (D2–D4) 20 min before food.


Toxicity incidence (rare <5%) and adverse effects [1]



Emetogenic potential

Cisplatin (any dose) is highly emetogenic.

Note: For details on Pharmacokinetics, Metabolism, Extravasation, Emetogenicity, Drug interactions, Dose modifications, Renal dose modifications, Special Precautions, and Contraindications, please refer to the section at the end of the 3-weekly Cisplatin-CRT regimen.[2],[3]


  References Top


  1. Noronha V, Joshi A, Patil VM, Agarwal J, Ghosh-Laskar S, Budrukkar A, et al. Once-a-week versus once-every-3-weeks cisplatin chemoradiation for locally advanced head and neck cancer: A phase III randomized noninferiority trial. J Clin Oncol 2018;36:1064-72.
  2. Drug Monograph-Cisplatin. Cancer Care Ontario Formulary-May 2018.
  3. Cisplatin. British Columbia Cancer Agency Drug Manual (Sept., 1994). Revised Ed. June, 2016;1-11.



  3. Head and Neck Squamous Cell Carcinoma-Cetuximab-Radiation Therapy Weekly Protocol Top




Please enter exact total doses of each cycle in milligrams



Oral medications

None.

Toxicity incidence and adverse effects [1]



Dose-limiting toxicities [2]

Infusion reactions (Grade3 and Grade4 – immediate onset), pneumonitis and keratitis (early onset – discontinue after confirmation).

Pharmacokinetics [3]



Emetogenic potential of cetuximab

Minimal.

Extravasation

None.

Drug interactions

None.

Dose modifications [2]

Dosage modification for skin toxicity



  • No dosage adjustment required with hepatic or renal dysfunction [2]
  • No dosage adjustment required in the elderly or female sex.[2]


Special precautions [2]

Contraindications

Patients with known hypersensitivity to cetuximab, murine protein, or any components of this product.

Other warnings/precautions

Patients with a history of, or pre-existing keratitis, dry eyes or contact lens use due to higher risk of keratitis and patients with poor performance status, or cardiopulmonary disease, are at increased risk of severe hypersensitivity reactions.

Cetuximab plus radiation therapy for head and neck cancer should be used with caution in patients who are over age 65 years, have poor performance status, known history of coronary artery disease, arrhythmias, congestive heart failure or receiving cardiotoxic agents as fatal events such as sudden cardiac death have been reported. Close monitoring of serum electrolytes (magnesium, potassium, calcium), during and after cetuximab therapy is recommended.

Other drug properties

Carcinogenicity: Unknown; Potential to cause Infertility: Unknown.

Cetuximab has not been tested for carcinogenicity but is not mutagenic or clastogenic.

Pregnancy and lactation

  • Cetuximab is NOT recommended for use in pregnancy. Adequate contraception should be used by both sexes during treatment, and for at least 6 months after the last dose
  • Excretion into breast milk: Probable
  • Breastfeeding is NOT recommended during cetuximab therapy and for at least 60 days following the last dose.



  References Top


  1. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006;354:567-78.
  2. Drug Monologue-Cetuximab. Cancer care Ontario Formulary-February 2018.
  3. Cetuximab. British Columbia Cancer Agency Drug Manual (June., 2009). Revised Ed. May, 2013; 1-9.



  4. Head and Neck Squamous Cell Carcinoma-Nimotuzumab-Radiation Therapy 1-Weekly Protocol Top






Toxicity incidence and adverse effects:[1] Nimotuzumab*



Dose-limiting toxicities (Nimotuzumab)

  • Severe anaphylactic reaction (Grade 3)
  • Nimotuzumab should be used with caution in patients with known hypersensitivity to nimotuzumab or to any of the known components of the formulation.


Pharmacokinetics and metabolism: Nimotuzumab



Emetogenic potential

Nimotuzumab is not emetogenic.

Extravasation

Nimotuzumab has no reaction.

Drug interactions: Nimotuzumab

No reported drug interaction.

Interactions: Food and Nimotuzumab

  • No documented interactions
  • No special instruction for food.


Dose modifications: Nimotuzumab

Nil.

Special precautions

Contraindications (Nimotuzumab)

Not known. During dilution with normal saline, ensure that all precautions are taken to avoid accidental contamination. In case any turbidity is seen in the solution, this may due to accidental microbial contamination. Should be used with caution in patients with known hypersensitivity to nimotuzumab or to any of the known components of the formulation.

Other drug properties

No interactions.

Pregnancy and lactation

It has potential hazard to the fetus and/or the potential risk for loss of the pregnancy. Human IgG1 is known to cross the placental barrier; therefore, the antibody has the potential to be transmitted from the mother to the developing fetus.

It is not known whether the antibody is secreted in human milk. No recommendation is made in the potential benefit versus risk of administering nimotuzumab to nursing mothers.


  References Top


  1. Drug insert-Biomab (Nimotuzumab); Biocon Bio-pharmaceuticals.



  5. Head and Neck Squamous Cell Carcinoma-Nimotuzumab-Cisplatin-Radiation Therapy 1-Weekly Protocol Top




Please enter exact total doses of each cycle in milligrams



Oral medications

  • Tablet Aprepitant 125 mg PO D1 and 80 mg PO D2–D3
  • Tablet Dexamethasone 4mg BD (D2–D4) after food/feed
  • Tablet Ranitidine 150 mg twice a day (D2–D4) 20 min before food.


Toxicity incidence and adverse effects [1]



Note: For Pharmacokinetics, Metabolism, Extravasation, Emetogenicity, Drug interactions, Instructions on food, Renal dose modifications, Special Precautions with use of Cisplatin and Nimotuzumab combination, please refer to the separate section at the end of 1-weekly Cisplatin-CRT and 1-weekly Nimotuzumab-CRT protocols.[2],[3],[4]


  References Top


  1. Patil VM, Noronha V, Joshi A, Agarwal J, Ghosh-Laskar S, Budrukkar A, et al. A Randomised Phase 3 Trial comparing Nimotuzumab plus Cisplatin Chemoradiotherapy versus Ciplatin Chemoradiotherapy alone in Locally Advanced Head and NeckCancer. Cancer. 2019;0:1-14.
  2. Cisplatin. British Columbia Cancer Agency Drug Manual (Sept., 1994). Revised Ed. June, 2016;1-11.
  3. Drug Monograph-Cisplatin. Cancer Care Ontario Formulary-May 2018.
  4. Drug insert-Biomab (Nimotuzumab); Biocon Bio-Pharmaceticals.



  6. Head and Neck Squamous Cell Carcinoma-Docetaxel-Radiation Therapy 1-Weekly Protocol Top




Please enter exact total doses of each cycle in milligrams



Oral medications

  • Tablet Dexamethasone 4 mg BD (D0–D2) after food/feed
  • Tablet Ranitidine 150 mg BD (D2–D3) 20 min before food.


Toxicity incidence and adverse effects [1]





Dose-limiting toxicities [2]

Myelosuppression (ANC <1.0 × 109/mL, platelets <100 × 109/L).

Pharmacokinetics and metabolism [3]



Emetogenic potential [2]

Low.

Extravasation potential [2]

Irritant.

Drug interactions: Docetaxel [2]



Dose modifications [2]

Febrile neutropenia and other toxicities (in previous cycle)



Hypersensitivity



Hepatic



Renal

No modification required.

Special precautions [2]

Contraindications

  • Patients who have a history of severe hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80
  • Patients with neutrophil count <1.5 × 109/L or with severe liver impairment
  • Patients with hepatic impairment.


Other warnings/precautions

  • Use with caution in patients with pre-existing effusions or ascites
  • Use with caution in patients who are hypersensitive to paclitaxel.


Other drug properties

Carcinogenicity: Yes, Potential to cause infertility: Yes.

Pregnancy and lactation

  • Embryotoxicity: Yes
  • Fetotoxicity: Yes
  • Mutagenicity: Yes
  • Genotoxicity: Yes
  • Docetaxel is contraindicated in pregnancy. Adequate contraception must be used by both sexes, during docetaxel treatment and for at least 6 months after the last dose
  • Breastfeeding: Contraindicated
  • Fertility effects: Probable.



  References Top


  1. Jomon Raphael C, Rajesh I, Rajesh B, Selvamani B. Feasibility and response of concurrent weekly docetaxel with radical radiotherapy in locally advanced head and neck squamous cell carcinoma. J Clin Diagn Res 2015;9:XC01-4.
  2. Drug Monograph-Docetaxel. Cancer Care Ontario Formulary-September 2018.
  3. Docetaxel. British Columbia Cancer Agency Drug Manual (May,2012). Revised Ed. Jan, 2015;1-12.



  7. Head and Neck Squamous Cell Carcinoma-Carboplatin-5-Fluorouracil-Radiation Therapy 3-Weekly Protocol Top





  Please Enter Exact Total Doses of Each Cycle in Milligrams [1],[2] Top




Oral medications (once a day [OD]; twice a day [BD])

  • Tablet Dexamethasone 4mg orally twice a day (D5–D7) after food/feed
  • Tablet Ranitidine 150 mg orally daily at night (D1–D4) and BD (D5–D7) 20 min before food.


Toxicity incidence and adverse effects [1]



Emetogenic potential of carboplatin-5-fluorouracil combination

Moderately emetogenic.

Pharmacokinetics and metabolism:[3] Carboplatin



Pharmacokinetics and metabolism:[4] 5-Fluorouracil



Extravasation

  • Carboplatin: Irritant
  • 5-Fluorouracil: Inflammitant.


Drug interactions:[3] Carboplatin



Drug interactions:[4] 5-Fluorouracil



Dose modifications-Carboplatin [3]


Renal failure: No dose modification at 70 mg/m 2.

Liver failure: No dose modification required.

Dose modification-5-Fluorouracil [4]

Renal failure

No adjustment required.

Hepatic failure

Standard doses have been used in some patients with elevated bilirubin; may consider 50% dose reduction for starting doses or omit dose for bilirubin >5 mg/dl or AST >180 units/L.

Special precautions:[3] Carboplatin

  • Contraindication: Contraindicated in patients with known hypersensitivity to carboplatin, other platinum agents (e.g. cisplatin) or mannitol. However, with appropriate precautions, re-challenging with carboplatin or switching to cisplatin has been tolerated by some patients with hypersensitivity reactions to carboplatin.
  • Geriatrics: Incidence of peripheral neuropathy is increased, and myelosuppression may be more severe in patients older than 65 years of age. In addition, elderly patients are more likely to have age-related renal function impairment, which may require dosage reduction and careful monitoring of blood counts.
  • Prior exposure to cisplatin: Increases the risk and severity of toxicities (e.g., myelosuppression, nausea, vomiting, peripheral neuropathy, ototoxicity).
  • Carcinogenicity: Has not been fully studied, but drugs with similar mechanisms of action and mutagenicity have been reported to be carcinogenic.
  • Mutagenicity: Mutagenic in both in vitro and in vivo studies.
  • Fertility: May cause gonadal suppression (amenorrhea, azoospermia) which is generally related to dose and length of therapy and may be irreversible.
  • Pregnancy: FDA Pregnancy Category D. Positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g. if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
  • Breastfeeding is not recommended due to the potential secretion into breast milk.


Special precautions:[4] 5-Fluorouracil

  • Contraindications


    • History of hypersensitivity reaction to fluorouracil
    • Relatively contraindicated in patients who have a known hypersensitivity to capecitabine.


  • Caution


    • Dihydropyrimidine dehydrogenase deficiency may result in life-threatening or fatal toxicity in patients receiving fluorouracil via parenteral or topical administration
    • Non-linear pharmacokinetics may result in unpredictable plasma concentrations and toxicity at high doses.


  • Special populations


    • Elderly patients are at increased risk for developing toxicities, likely due to decreased bone marrow reserve.


  • Carcinogenicity: Not yet studied
  • Mutagenicity: Fluorouracil has been shown to be mutagenic in some bacterial strains. It is clastogenic in mammalian in vitro and in vivo chromosome tests.
  • Fertility: The effects of fluorouracil on fertility have not been established.
  • Pregnancy: Food and Drug Administration (FDA) Pregnancy Category D. There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g. if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
  • Breastfeeding is not recommended due to the potential secretion into breast milk.



  References Top


  1. Barkati M, Fortin B, Soulières D, Clavel S, Després P, Charpentier D, et al. Concurrent chemoradiation with carboplatin-5-fluorouracil versus cisplatin in locally advanced oropharyngeal cancers: Is more always better? Int J Radiat Oncol Biol Phys 2010;76:410-6.
  2. Krengli M, Masini L, Gambaro G, Turri L, Loi G, Aluffi P, et al. Concurrent chemotherapy with carboplatin + 5-fluorouracil and radiotherapy in advanced squamous cell head and neck carcinoma: A retrospective single institution's study. Tumori 2001;87:312-6.
  3. Carboplatin. British Columbia Cancer Agency Drug Manual (Sept., 1994). Revised Ed. Jan, 2014;1-9.
  4. Fluorouracil. British Columbia Cancer Agency Drug Manual (Sept., 1994). Revised Ed. Jan, 2019;1-12.



  8. Head and Neck Squamous Cell Carcinoma-Hydroxyurea-5-Fluorouracil-Radiation Therapy 2-Weekly Protocol: the Fhx Regimen Top




Please enter exact total doses of each cycle in milligrams [1],[2]



Oral chemotherapy (twice a day [BD])[1],[2]

Capsule hydroxyurea 1000 mg (2 × 500 mg capsules) after food × BD 12-hourly starting on the evening of Day zero, continued until the evening of Day 5 (every alternate week for total 7 cycles)



Schedule overview: [1] FHX Regimen (F-5-fluorouracil, H-hydroxyurea, X-radiation)



Oral med]ications (twice a day [BD], at night [HS]): Every alternate week

  • Tablet Dexamethasone 4 mg BD (D1–D5) after food/feed
  • Tablet Ranitidine 150 mg HS (D1–D5) 20 min before food.


Toxicity incidence and adverse effects [3]



Dose-limiting toxicities [2]

Myelosuppression (ANC <1.0 × 109/mL, Platelets <100 × 109/L).

Emetogenic potential: Hydroxyurea-5FU combination

Low emetogenic.

Pharmacokinetics and metabolism:[3] Hydroxyurea



Pharmacokinetics and metabolism:[4] 5-Fluorouracil



Extravasation

  • Hydroxyurea: Not applicable (oral medicine)
  • 5-Fluorouracil: Inflammitant.


Drug interactions:[3] Hydroxyurea



Drug interactions:[4] 5-Fluorouracil

Please refer to previous protocol of 5-fluorouracil (5FU) + carboplatin.

Dose modifications: Hydroxyurea [3]

Dosage in renal failure

Initial dose adjustment may be required; use with caution and monitor hematological parameters;[3] suggested initial dose modification.





*For males N = 1; for females, N = 0.85.

Dosage in hepatic failure

Monitor hematological parameters.

Dose modifications:[4] 5-Fluorouracil

Please refer to previous protocol of 5FU-carboplatin.

Special precautions:[3] Hydroxyurea

  • Contraindicated in patients who have a history of hypersensitivity reaction to hydroxyurea, any components of the formulation, or marked bone marrow depression
  • Caution: Use of hydroxyurea in combination with antiretroviral agents, particularly didanosine and/or stavudine, is not recommended due to risk of serious toxicities, namely pancreatitis, hepatotoxicity, and peripheral neuropathy; if the combination is used, monitor for toxicities
  • Previous or current chemotherapy: Increased risk of bone marrow suppression; dose adjustment may be required
  • Carcinogenicity: Hydroxyurea is carcinogenic
  • Mutagenicity: Mutagenic in Ames test and mammalian in vitro mutation test. Hydroxyurea is clastogenic in mammalian in vitro and in vivo chromosome tests
  • Fertility: Hydroxyurea should not be used in men contemplating fatherhood. No information found for women
  • Pregnancy: FDA Pregnancy Category D.[2],[4] There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective)
  • Breastfeeding is not recommended due to the secretion of hydroxyurea into breast milk.


Special precautions:[4] 5-Fluorouracil

Please refer to previous protocol of 5FU-carboplatin.


  References Top


  1. Argiris A, Haraf DJ, Kies MS, Vokes EE. Intensive concurrent chemoradiotherapy for head and neck cancer with 5-fluorouracil- and hydroxyurea-based regimens: Reversing a pattern of failure. Oncologist 2003;8:350-60.
  2. Spencer SA, Harris J, Wheeler RH, Machtay M, Schultz C, Spanos W, et al. RTOG 96-10: Reirradiation with concurrent hydroxyurea and 5-fluorouracil in patients with squamous cell cancer of the head and neck. Int J Radiat Oncol Biol Phys 2001;51:1299-304.
  3. Hydroxyurea. British Columbia Cancer Agency Drug Manual (Sept., 1994). Revised Ed. Oct., 2013;1-7.
  4. Fluorouracil. British Columbia Cancer Agency Drug Manual (Sept., 1994). Revised Ed. Jan, 2019;1-12.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.






 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
1. Head and Neck...
References
2. Head and Neck...
References
3. Head and Neck...
References
4. Head and Neck...
References
5. Head and Neck...
References
6. Head and Neck...
References
7. Head and Neck...
Please Enter Exa...
References
8. Head and Neck...
References

 Article Access Statistics
    Viewed20    
    Printed0    
    Emailed0    
    PDF Downloaded3    
    Comments [Add]    

Recommend this journal