Approved
Dosing Regimen - Lung Cancer
Cyramza
in combination with erlotinib for the treatment of NSCLC with
activating EGFR mutations
The
recommended dose of ramucirumab in combination with erlotinib is 10
mg/kg every two weeks.1
EGFR
mutation status should be determined prior to initiation of treatment
with ramucirumab and erlotinib using a validated test method. See
erlotinib prescribing information for the posology and method of
administration of erlotinib.1
Cyramza
in combination with docetaxel for the treatment of NSCLC after
platinum-based chemotherapy
The
recommended dose of ramucirumab is 10 mg/kg on day 1 of a 21 day
cycle, prior to docetaxel infusion. The recommended dose of docetaxel
is 75 mg/m2
administered by intravenous infusion over approximately 60 minutes on
day 1 of a 21 day cycle. For East Asian patients, a reduced docetaxel
starting dose of 60 mg/m2
on day 1 of a 21 day cycle should be considered. See docetaxel
prescribing information for specific dosing advice.1
Premedication
Premedication
is recommended with a histamine H1
antagonist (for example diphenhydramine) prior to infusion of
ramucirumab. 1
If a
patient experiences a Grade 1 or 2 infusion-related reaction
premedication must be given for all subsequent infusions. If a
patient experiences a second Grade 1 or 2 infusion-related reaction
(IRR) administer dexamethasone (or equivalent); then, for subsequent
infusions, premedicate with the following or equivalent medicinal
products: an intravenous histamine H1
antagonist (for example diphenhydramine hydrochloride), paracetamol
and dexamethasone.1
Dose
Adjustments
Infusion-related
reactions
The
infusion rate of ramucirumab should be reduced by 50% for the
duration of the infusion and all subsequent infusions if the patient
experiences a grade 1 or 2 IRR. Ramucirumab should be immediately and
permanently discontinued in the event of a grade 3 or 4 IRR.1
Hypertension
The
blood pressure of patients should be monitored prior to each
ramucirumab administration and treated as clinically indicated.
Ramucirumab therapy should be temporarily discontinued in the event
of severe hypertension, until controlled with medical management. If
there is medically significant hypertension that cannot be controlled
safely with antihypertensive therapy, ramucirumab therapy should be
permanently discontinued.1
Proteinuria
Patients
should be monitored for the development or worsening of proteinuria
during ramucirumab therapy. If the urine protein is ≥2+ on a
dipstick, a 24 hour urine collection should be performed. Ramucirumab
therapy should be temporarily discontinued if the urine protein level
is ≥2 g/24 hours. Once the urine protein level returns to <2
g/24 hours, treatment should be resumed at a reduced dose level (see
Table 1). A second dose
reduction (see Table 1)
is recommended if a urine protein level ≥2 g/24 hours reoccurs.1
Ramucirumab
therapy should be permanently discontinued if the urine protein level
is >3 g/24 hours or in the event of nephrotic syndrome.1
Table
1. Ramucirumab dose reductions for proteinuria1
Initial
ramucirumab dose:
|
First
dose reduction to:
|
Second
dose reduction to:
|
10
mg/kg
|
8
mg/kg
|
6
mg/kg
|
Elective
surgery or impaired wound healing
Ramucirumab
therapy should be temporarily discontinued for at least 4 weeks prior
to elective surgery. Ramucirumab therapy should be temporarily
discontinued if there are wound healing complications, until the
wound is fully healed.1
Severe
arterial thromboembolic events, gastrointestinal perforations, severe
bleeding, spontaneous development of fistula, hepatic encephalopathy
or hepatorenal syndrome
Ramucirumab
therapy should be permanently discontinued in the event of:
Severe
arterial thromboembolic events
Gastrointestinal
perforations
Severe
bleeding: NCI CTCAE Grade 3 or 4 bleeding
Spontaneous
development of fistula
Hepatic
encephalopathy or hepatorenal syndrome1
References
1.
Cyramza [summary of product characteristics]. Eli Lilly Nederland
B.V., The Netherlands.
Glossary
CTCAE
= Common Terminology Criteria for Adverse Events
EGFR
= epidermal growth factor receptor
IRR
= infusion-related reaction
IV
= intravenous
NCI
= National Cancer Institute
NSCLC
= non-small cell lung cancer