Bortezomib, Cyclophosphamide and
Dexamethasone
Regimen
Indication
Multiple myeloma
Therapeutic Intent
Disease modification
Day
1, 4, 8 and
11
1, 4, 8 and
11
1, 8, 15
Medication
Dose
Route
Bortezomib
1.3mg/m2
SC or IV
Dexamethasone
20mg
PO
Usually given as a single dose in the morning.
Cyclophosphamide
500mg
PO
Once a week
“Weekly” Regime
Day
Medication
Dose
Route
1 and 8 only
Bortezomib
1.6mg/m2
SC or IV
1, 8, 15
1, 8, 15
Dexamethasone
Cyclophosphamide
20mg
500mg
PO
PO
Cycle Frequency
Tests required prior to
initiation of course
Tests required prior to
individual cycle
Concurrent Medication
Administration Details
Note different dilution for SC administration.
Ensure at least 72 hours between consecutive
doses of bortezomib.
Administration Details
Note different dilution for SC administration.
Ensure at least 72 hours between consecutive
doses of bortezomib.
Note differing dose schedule.
Usually given as a single dose in the morning
Once a week
Repeat every 21 days for 4 cycles then assess response. If less than 50%
response, stop treatment, otherwise continue for two cycles after a complete
remission to a maximum of 8 cycles
FBC, LFT, U+E, bone profile, glucose
Serum Igs/ electrophoresis/ serum free light chains
Neurological assessment for neuropathy
FBC, LFT, U+E
Serum Igs/ electrophoresis/ serum free light chains (if indicated)
Neurological assessment for neuropathy
Allopurinol (during 1st cycle)
PPI
Anti-emetics as per local policy
GCSF support as per local policy
Antimicrobial prophylaxis as per local policy – include PCP and antiviral
prophylaxis
Bisphosphonate monthly
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Dose Modifications
Hepatic
Renal
Patients with mild hepatic impairment do not require a dose adjustment and should
be treated per the recommended dose.
Patients with moderate or severe hepatic impairment should be started on
bortezomib at a reduced dose of 0.7 mg/m2 per injection during the first treatment
cycle, and a subsequent dose escalation to 1.0 mg/m2 or further dose reduction to
0.5 mg/m2 may be considered based on patient tolerability. (See SPC for further
details).
Serum Creatinine (micromol/L)
Modification
>300
Omit cyclophosphamide
The pharmacokinetics of bortezomib is not influenced in patients with mild to
moderate renal impairment therefore, dose adjustments are not necessary for these
patients.
It is unknown if the pharmacokinetics of bortezomib are influenced in patients with
severe renal impairment not undergoing dialysis.
Since dialysis may reduce bortezomib concentrations, bortezomib should be
administered after the dialysis procedure.
Haematological
Platelets (x 109/L)
Neutrophils (x
109/L)
≥ 1 x 109/L
Modification
and
≥ 50 x 109/L
100% dose.
0.75 - 1 x 109/L
or
30 - 50 x 109/L
Delay cyclophosphamide 1 week
(continue dexamethasone). Restart
at same dose when neutrophils and
platelets recovered as above. If
recurrent,
i.e.
if
neutrophils
9
<1.0x10 /L and platelets < 50x109/L
on day 1 of subsequent cycles (when
previously > than these levels), delay
cyclophosphamide and consider
dose
reduction
of
cyclophosphamide. If the patient
was receiving 500 mg weekly, reduce
to 400 mg, if 400 mg reduce to 300
mg, if 300 mg reduce to 200 mg.
Consider adding G-CSF for 2 to 3
days per cycle or week (usually only
requires low doses).
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≤ 0.75 x 109/L
Peripheral
neuropathy
or
≤ 30 x 109/L
Severity of neuropathy
Grade 1 (paraesthesia, weakness and/or loss
of reflexes) with no pain or loss of function
Bortezomib should be withheld with
these blood counts on a bortezomib
dosing day (other than day 1). If
several bortezomib doses in a cycle
are withheld ( ≥ 3 doses during twice
weekly administration) the dose
should be reduced by 1 dose level
from 1.3 mg/m2 to 1 mg/m2, or from
1 mg/m2 to 0.7 mg/m2).
Withhold cyclophosphamide dose
until count recovers and consider
starting at a reduced dose.
Modification
None.
Grade 1 with pain or Grade 2 (interfering
with function but not with activities of daily
living)
Reduce bortezomib to 1.0 mg/m2
Grade 2 with pain or Grade 3 (interfering
with activities of daily living)
Withhold bortezomib treatment
until symptoms of toxicity have
resolved. When toxicity resolves reinitiate bortezomib treatment and
reduce dose to 0.7 mg/m2 and
change treatment schedule to once
per week.
Grade 4 (sensory neuropathy which is
disabling or motor neuropathy that is life
threatening or leads to paralysis) and/or
severe autonomic neuropathy
Discontinue bortezomib.
Additional Information
The current NICE recommendation is to give 4 cycles initially, then review
and proceed as follows:
 If responding (defined as 50% of greater reduction in paraprotein i.e.
CR or PR) continue until 2 cycles after CR to a maximum of 8 cycles.
 For non-responders after 4 cycles, discontinue treatment. The
manufacturer will be required to reimburse the full cost of bortezomib
under the Velcade® Response Scheme.
References
http://emc.medicines.org.uk
NICE technology appraisal guidance 228 July 2011.
Author
Pharmacy CNG
Approved & Checked by
Haematology CNG (Review Date = Sept 2017)
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