BC Cancer Protocol Summary for Treatment of Locally Advanced

Squamous Cell Carcinoma of the Head and Neck with DOCEtaxel,

CISplatin and Infusional Fluorouracil
Protocol Code: HNLADCF

Tumour Group: Head and Neck

Contact Physician: Cheryl Ho

ELIGIBILITY:
 Locally advanced (unresectable) squamous cell carcinoma of the oral cavity, larynx,
oropharynx or hypopharynx, including primary unknown with cervical lymphadenopathy
 ECOG 0-1
 Adequate hepatic, renal, marrow and cardiac function
 Age 65 years or younger recommended. Caution should be used for patients over 65 years
of age
 Caution: This regimen has been associated with a high rate (25%) of febrile neutropenia and
should only be administered in settings with appropriate support
 To be followed by HNLAPRT

EXCLUSIONS:
 Uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure,
myocardial infarction within the preceding 6 months, serious uncontrolled cardiac
dysrhythmia

TESTS:
• Baseline: CBC & diff, platelets, serum Creatinine, Bilirubin, ALT, Alkaline Phosphatase,
DPYD test
• Before each treatment: CBC & diff, platelets, serum Creatinine, ALT, Alkaline Phosphatase

PREMEDICATIONS:
 dexamethasone 8 mg PO bid for 3 days starting one day prior to each administration of
DOCEtaxel
 A minimum of 3 doses of dexamethasone pre-treatment are required
 Antiemetic protocol for highly emetogenic chemotherapy (see SCNAUSEA protocol)
 DOCEtaxel-induced onycholysis and cutaneous toxicity of the hands may be prevented by
wearing frozen gloves starting 15 minutes before DOCEtaxel infusion until 15 minutes after end
of DOCEtaxel infusion; gloves should be changed after 45 minutes of wearing to ensure they
remain cold during the entire DOCEtaxel infusion.

BC Cancer Protocol Summary HNLADCF 1/5

Activated: 1 Jul 2010 Revised: 1 Aug 2023 (DPYD test and Fluorouracil Dosing added)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to
apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is at
your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use
TREATMENT:

Drug Dose BC Cancer Administration Guideline

DOCEtaxel 75 mg/m2 IV in NS 250 to 500 mL* over 1 hour (use

non-DEHP equipment)

CISplatin 75 mg/m2 Prehydrate with NS 1000 mL over 1 hour,

then give CISplatin IV in NS 500 mL with
potassium chloride 20 mEq, magnesium
sulfate 1 g, mannitol 30 g over 1 hour

fluorouracil 750 mg/m2/day for 5 days IV in D5W to a total volume of 240 mL by

continuous infusion at 2 mL/h via
(total dose = 3750 mg/m2 over
appropriate infusor device*
120 h)
*Inpatients: 750 mg/m2/day in D5W 1000 mL by continuous infusion daily over 24 h for 5 days

Patients with PICC lines should have a weekly assessment of the PICC site for evidence of
infection or thrombosis.

 Repeat every 21 days x 3 cycles

DOSE MODIFICATIONS:

Fluorouracil Dosing Based on DPYD Activity Score (DPYD-AS)

Refer to “Fluorouracil and Capecitabine Dosing Based on DPYD Activity Score (DPYD-AS) on
www.bccancer.bc.ca/health-professionals/clinical-resources/cancer-drug-manual.

1. Hematology For DOCEtaxel and fluorouracil

ANC (x 109/L) Platelets (x 109/L) Dose*

greater than or equal to 1.5 and greater than or equal to 100 100%

1.0 to less than 1.5 or 75 to less than 100 75%

less than 1.0 or less than 75 Delay

*Consider decreasing to 75% if an episode of febrile neutropenia occurs with the prior cycle of
treatment

BC Cancer Protocol Summary HNLADCF 2/5

Activated: 1 Jul 2010 Revised: 1 Aug 2023 (DPYD test and Fluorouracil Dosing added)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to
apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is at
your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use
2. Gastrointestinal toxicity: For fluorouracil

Grade Stomatitis Diarrhea Dose Fluorouracil

Grade 1 Painless ulcers, Increase of 2 to 3 stools/day or 100%

erythema or mild nocturnal stools; or moderate
soreness increase in loose watery
colostomy output

Grade 2 Painful erythema, Increase of 4 to 6 stools/day, or 75%

edema, or ulcers but nocturnal stools or moderate
can eat increase in loose watery
colostomy output

Grade 3 or 4 As above, but Increase of greater than 7 Discontinue or delay until

cannot eat, mucosal stools/day or grossly bloody toxicity resolved then
necrosis, requires diarrhea, or incontinence, resume at 50%
parenteral support. malabsorption; or severe increase
in loose watery colostomy output
requiring parenteral support

3. Hand-Foot Syndrome for fluorouracil

Grade Hand-Foot Syndrome Dose

Grade 1 Skin changes or dermatitis without 100%

pain e.g. erythema, peeling

Grade 2 Skin changes with pain not 75% until resolved then consider
interfering with function increasing dose by 10%

Grade 3 Skin changes with pain, interfering Delay until resolved then resume at
with function 75%

4. Hepatic dysfunction: for DOCEtaxel

Alkaline phosphatase AST and/or ALT Dose

less than 2.5 x ULN and less than 1.5 x ULN 100%

2.5 to 5 x ULN and 1.5 to 5 x ULN 75%

greater than 5 x ULN or greater than 5 x ULN Delay

BC Cancer Protocol Summary HNLADCF 3/5

Activated: 1 Jul 2010 Revised: 1 Aug 2023 (DPYD test and Fluorouracil Dosing added)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to
apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is at
your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use
5. Renal dysfunction: for CISplatin

Calculated Cr Clearance (mL/min) CISplatin dose

by Cockcroft/Gault formula

greater than or equal to 60 100%

45 to less than 60 80%

less than 45 Hold CISplatin or delay with additional IV fluids

Cockcroft/Gault formula:
N (140-age) x weight (kg)
CrCl =
serum creatinine (micromol/L)
Where N = 1.04 for females, and 1.23 for males

PRECAUTIONS:
1. Fluid retention: Dexamethasone premedication must be given to reduce incidence and
severity of fluid retention.
2. Hypersensitivity reactions to DOCEtaxel are common but it is not necessary to routinely
initiate the infusion slowly. If slow initiation of infusion is needed, start infusion at 30 mL/h x
5 minutes, then 60 mL/h x 5 minutes, then 120 mL/h x 5 minutes, then complete infusion at
250 mL/h (for 500 mL bag, continue 250 mL/h for 5 minutes and then complete infusion at
500 mL/h). Refer to BC Cancer Hypersensitivity Guidelines.
3. Extravasation: DOCEtaxel causes pain and tissue necrosis if extravasated. Refer to BC
Cancer Extravasation Guidelines.
4. Neutropenia: Fever or other evidence of infection must be assessed promptly and treated
aggressively.
5. Hepatic Dysfunction: DOCEtaxel undergoes hepatic metabolism. Hepatic dysfunction
(particularly elevated AST) may lead to increased toxicity and usually requires a dose
reduction.
6. Renal Toxicity: Nephrotoxicity is common with CISplatin. Encourage oral hydration. Avoid
nephrotoxic drugs such as aminoglycoside antibiotics.
7. Myocardial ischemia and angina occurs rarely in patients receiving fluorouracil or
capecitabine. Development of cardiac symptoms including signs suggestive of ischemia or
of cardiac arrhythmia is an indication to discontinue treatment. If there is development of
cardiac symptoms patients should have urgent cardiac assessment. Generally re-challenge
with either fluorouracil or capecitabine is not recommended as symptoms potentially have a
high likelihood of recurrence which can be severe or even fatal. Seeking opinion from
cardiologists and oncologists with expert knowledge about fluorouracil or capecitabine
toxicity is strongly advised under these circumstances. The toxicity should also be noted in
the patient’s allergy profile.
8. Dihydropyrimidine dehydrogenase (DPD) deficiency may result in severe and
unexpected toxicity – stomatitis, diarrhea, neutropenia, neurotoxicity – secondary to reduced
drug metabolism. This deficiency is thought to be present in about 3% of the population.
9. Ototoxicity and sensory neural damage should be assessed by history prior to each
cycle.
10. Possible drug interactions with fluorouracil and warfarin, phenytoin and fosphenytoin
have been reported and may occur at any time. Close monitoring is recommended (eg, for
BC Cancer Protocol Summary HNLADCF 4/5
Activated: 1 Jul 2010 Revised: 1 Aug 2023 (DPYD test and Fluorouracil Dosing added)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to
apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is at
your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use
 warfarin, monitor INR weekly during fluorouracil therapy and for 1 month after stopping
fluorouracil).

Call Cheryl Ho or tumour group delegate at (604) 877-6000 with any problems or
questions regarding this treatment program.

Reference:
1. Posner M, et al. Phase III trial of cisplatin and fluorouracil alone or with docetaxel in head and neck
cancer. N Engl J Med 2007;357:1705-15.
2. Vermorken M, et al. Phase II study of cisplatin, fluorouracil, and docetaxel in unresectable head and
neck cancer. N Engl J Med 2007;357:1695-704.
3. Lorch JH, et al. Induction chemotherapy with cisplatin and fluorouracil alone or in combination with
docetaxel in locally advanced squamous-cell cancer of the head and neck: long-term results of the TAX
324 randomised phase 3 trial. Lancet Oncol 2011;12(2):153-9.

BC Cancer Protocol Summary HNLADCF 5/5

Activated: 1 Jul 2010 Revised: 1 Aug 2023 (DPYD test and Fluorouracil Dosing added)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to
apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is at
your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use