Bortezomib, Doxorubicin and Dexamethasone
Regimen
Indication
Multiple myeloma
Therapeutic Intent
Disease modification
Day
Medication
Dose
Route
1 to 4
Doxorubicin
9mg/m2/day
IV
1, 4, 8 and 11
Bortezomib
1.3mg/m2
SC or IV
Dexamethasone
40mg
PO
Administration Details
Continuous infusion in sodium chloride 0.9%
over four days (total dose is 36mg/m2).
Can also be given as a single bolus or
infusion of 9mg/m2 on days 1 to 4 (four daily
doses).
Note different dilution for SC administration.
Ensure at least 72 hours between
consecutive doses of bortezomib.
1 to 4
(all cycles)
8 to 11 and
15 to 18
(cycle 1 only)
Cycle Frequency
Tests required prior to
initiation of course
Tests required prior to
individual cycle
Concurrent Medication
Usually given as a single dose in the
morning.
Repeat every 21 days for 4 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
Haematological
Bortezomib
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).
Doxorubicin
Bilirubin (micromol/L)
Modification
21 to 50
50% dose doxorubicin
51 to 85
25% dose doxorubicin
>85
Omit
Bortezomib
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.
The following parameters must be met on the first day of a new cycle (other than cycle
one, when the inclusion for registration parameters must be met):
 Platelet count >75x109/L, Haemoglobin >8g/dl, (prior red blood cell transfusion
or recombinant Human Erythropoietin usage is allowed), and neutrophil count
>1x109/L.
On any day of bortezomib administration during a cycle (other than day one of each
cycle), the haematological results must be:
 Platelet count >30x109/L, Haemoglobin >8g/dl (prior red blood cell transfusion
or recombinant Human Erythropoietin usage is allowed), and neutrophil count
>0.75x109/L.
In the event of a patient experiencing haematological toxicity >Grade 3 (neutrophil <1
x109/L and platelets <75 x109/L ) on day 1 of a cycle, the following dose reductions
should be applied to all further cycles:
 Bortezomib: 1mg/m2, doxorubicin: 6mg/m2/day (ie 24mg/m2 total),
dexamethasone: no reduction.
If further haematological toxicity >Grade 3 (neutrophil <1 x109/L and platelets <50
x109/L) occurs on day 1, then the following dose reduction should be applied to all
further cycles:
 Bortezomib: 0.7mg/m2, doxorubicin: 4.5mg/m2/day (ie 18mg/m2 total),,
dexamethasone: no reduction.
Dose interruption or discontinuation of treatment is not required for lymphopenia of
any grade.
The use of G-CSF and/or platelet support is permitted, at the discretion of the treating
physician.
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Peripheral
neuropathy
Severity of neuropathy
Grade 1 (paraesthesia, weakness and/or loss of
reflexes) with no pain or loss of function
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
Consider modifying steroid doses for patients at risk of significant steroidrelated side-effects.
References
http://emc.medicines.org.uk
Myeloma X clinical trial protocol version 7
Author
Pharmacy CNG
Approved & Checked by
Haematology CNG (Review Date = Sept 2017)
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