BC Cancer Protocol Summary for Second-Line Treatment of ALK-

Positive Advanced Non-Small Cell Lung Cancer (NSCLC) with

Crizotinib
Protocol Code: LUAVCRIZ

Tumour Group: Lung

Contact Physician: Dr. Christopher Lee

ELIGIBILITY:
 Advanced non-small cell lung cancer
 Laboratory confirmed anaplastic lymphoma kinase (ALK)-positive tumour
defined as either IHC 3+ or FISH positive
 ECOG 0-2
 Second-line monotherapy for disease progression after prior platinum-based
chemotherapy
 NOTE: Patients must have progressive disease on or after first-line therapy
 NOTE:
o Sequential ALK targeted therapies (e.g., crizotinib, ceritinib) is not
funded after first-line alectinib or brigatinib

EXCLUSIONS:
 Congenital long QT syndrome or a persistent corrected electrocardiogram
interval (QTc) of ≥ 500 msec

TESTS:
 Baseline: CBC & Diff, creatinine, alkaline phosphatase, ALT,
total bilirubin, LDH, calcium, magnesium, sodium, potassium, ECG
 Baseline, if clinically indicated: C-reactive protein and albumin
 Cycles 1 and 2, every 2 weeks: CBC & Diff, alkaline phosphatase, ALT, total
bilirubin and LDH
 Cycles 3 onwards, prior to each visit: CBC & Diff, alkaline phosphatase, ALT,
total bilirubin and LDH
 If clinically indicated: ECG, calcium, magnesium, sodium, potassium,
creatinine, heart rate, blood pressure, chest X-ray, CT chest

BC Cancer Protocol Summary LUAVCRIZ Page 1 of 4

Activated: 1 March 2014 Revised: 1 Oct 2024 (Tests updated)
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
PREMEDICATIONS:
 no premedications needed

TREATMENT:

Drug Dose BC Cancer Administration

Guideline

crizotinib 250 mg twice daily PO

Dose reduction:
Dose level -1: 200 mg twice daily
Dose level -2: 250 mg once daily

 Careful re-evaluation after initiation of therapy is essential as crizotinib should

be continued only if tumour regression continues or the disease is stable and
cancer-related symptoms have improved. Continued crizotinib for
“psychological” palliation in the face of progressive disease is inappropriate.

DOSE MODICATIONS:
1. Hematological:

ANC (x109/L) Platelets (x109/L) Dose

greater than or greater than or

and 250 mg twice daily
equal to 1.0 equal to 50

Withhold until recovery, then

0.5 to less than 1.0 or 25 to less than 50
resume at same dose schedule

Withhold until recovery, then

less than 0.5 or less than 25
resume at 200 mg twice dailya
a In
case of recurrence, withhold until recovery, then resume at 250 mg once daily. Permanently discontinue in
case of Grade 4 recurrence (ANC< 0.5 or Platelets <25).

BC Cancer Protocol Summary LUAVCRIZ Page 2 of 4

Activated: 1 March 2014 Revised: 1 Oct 2024 (Tests updated)
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. Hepatic Dysfunction:

Baseline bilirubin > 1.5 x ULN and ≤ 3

Reduce starting dose to dose level -1
x ULN (with any ALT or AST)
(200 mg twice daily)

Baseline bilirubin > 3 x ULN (with any Reduce starting dose to dose level -2
ALT or AST) (250 mg once daily)

Withhold until recovery of ALT to ≤ 3.0

ALT elevation to > 5.0 x ULN with x ULN or baseline, then resume at the
bilirubin ≤1.5 x ULN next lower dosea

ALT elevation to > 3.0 x ULN and

concurrent bilirubin elevation to > 1.5 x Permanently discontinue
ULN
aIn case of recurrence, withhold until recovery to Grade <1 or baseline, then resume at 250 mg once daily.
Permanently discontinue in case of further Grade 3 or 4 recurrence. For patients treated with 250 mg once
daily or whose dose was reduced to 250 mg once daily, discontinue during evaluation.

3. Pneumonitis: permanently discontinue crizotinib for development of any grade

of treatment-related pneumonitis
4. Renal dysfunction: for severe impairment (CrCl < 30mL/min), not requiring
dialysis, reduce dose to 50% (250mg once daily)
5. QTc Prolongation: treatment interruption and subsequent dose reduction is
required for QTc ≥ 500 msec. Refer to the BC Cancer Drug Manual.
6. Bradycardia: for symptomatic, non-life threatening bradycardia, withhold
treatment until asymptomatic or heart rate increases to > 60 bpm. Consider
dose reduction when treatment resumes. Refer to the BC Cancer Drug
Manual.
7. Severe visual loss: discontinue crizotinib for new onset of severe visual loss.

PRECAUTIONS:
1. Cardiotoxicity: QT interval prolongation and symptomatic bradycardia have
been observed in patients treated with crizotinib. Crizotinib should be
administered with caution in patients with pre-existing or those predisposed to
QTc prolongation, or those who are taking medications that are known to
prolong the QT interval. Caution should be exercised in patients with a low
heart rate at baseline (<60 beats per minute), a history of syncope or
arrhythmia, sick sinus syndrome, sinoatrial block, atrioventricular block,
ischemic heart disease, or congestive heart failure. Concomitant medications
that result in a decrease in heart rate should be avoided if possible during

BC Cancer Protocol Summary LUAVCRIZ Page 3 of 4

Activated: 1 March 2014 Revised: 1 Oct 2024 (Tests updated)
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 with crizotinib. Heart rate and blood pressure should be monitored
regularly.
2. Respiratory: Crizotinib has been associated with severe, life-threatening or
fatal treatment-related pneumonitis. These cases occurred within 2 months
after the initiation of treatment. Patients should be regularly monitored for
pulmonary symptoms indicative of pneumonitis.
3. Vision disorders: diplopia, photopsia, blurred vision, and vitreous floaters were
frequently reported by patients treated with crizotinib. Ophthalmological
evaluation should be considered if vision disorder persists or worsens in
severity. Patient’s ability to drive or operate machinery may be compromised.
4. Drug interactions: Crizotinib is a substrate and inhibitor of CYP3A. The
concurrent use of strong CYP3A inhibitors may increase crizotinib plasma
concentration and should be avoided. The concurrent use of strong CYP3A
inducers may decrease crizotinib plasma concentration and should be avoided.
5. Hepatic Impairment: Crizotinib is extensively metabolized in the liver and
hepatic impairment may result in higher plasma concentrations. Treatment with
crizotinib should be used with caution in patients with hepatic impairment.
6. Crizotinib-Induced hepatotoxicity: Drug-induced hepatotoxicity, including
hepatic failure, with fatal outcome has occurred in <1% of patients treatment
with crizotinib.

Call Dr. Christopher Lee or tumour group delegate at (604) 877-6000 or 1-800-
663-3333 with any problems or questions regarding this treatment program.

References:
1. Pfizer Canada Inc. Crizotinib (XALKORI®) product monograph. Kirkland, Quebec: Pfizer
Canada Inc; 23 November 2012.
2. Shaw T, Kim DW, Nakagawa K. Crizotinib versus chemotherapy in advanced ALK-positive
lung cancer. N Engl J Med 2013; 368:2385-94.
3. Lexi-Drugs® (database on the Internet). Crizotinib. Lexi-Comp Inc., 17 December 2013.
Available at http://online.lexi.com. Accessed 13 February, 2014.

BC Cancer Protocol Summary LUAVCRIZ Page 4 of 4

Activated: 1 March 2014 Revised: 1 Oct 2024 (Tests updated)
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