Usual Adult Dose for Lymphoma

DOSAGE IN PREVIOUSLY UNTREATED MANTLE CELL LYMPHOMA:
1.3 mg/m2 as a bolus IV injection twice weekly in combination with IV rituximab, cyclophosphamide, doxorubicin, and oral prednisone for two weeks (days 1, 4, 8, and 11) followed by a ten day rest period (days 12 through 21)

Comments:

• The three week period is considered a treatment cycle.
• A minimum of 72 hours should elapse between consecutive doses of bortezomib.
• For patients with a response first documented at cycle 6, two additional cycles (for a total of 8 cycles) are recommended.

FOR USE IN THE TREATMENT OF RELAPSED MANTLE CELL LYMPHOMA:

• Usual dose: 1.3 mg/m2 as a bolus IV injection or subcutaneously twice weekly for two weeks (days 1, 4, 8, and 11) followed by a ten day rest period (days 12 through 21). Therapy extending beyond 8 cycles may be administered by the standard schedule or may be given once weekly for 4 weeks (days 1, 8, 15, and 22), followed by a 13-day rest (days 23 through 35).

Uses: For the treatment of mantle cell lymphoma

Usual Adult Dose for Multiple Myeloma

FOR USE IN THE TREATMENT OF PREVIOUSLY UNTREATED MULTIPLE MYELOMA:

• Usual dose: 1.3 mg/m2 administered as a 3 to 5 second bolus IV injection or subcutaneously in combination with oral melphalan and oral prednisone for nine 6-week treatment cycles:
• In cycles 1 through 4, bortezomib is administered twice weekly (days 1, 4, 8, 11, 22, 25, 29, and 32). In cycles 5 through 9, bortezomib is administered once weekly (days 1, 8, 22, and 29).

Comments:

• At least 72 hours should elapse between consecutive doses of bortezomib.

FOR USE IN THE TREATMENT OF RELAPSED MULTIPLE MYELOMA:

• Usual dose: 1.3 mg/m2 as a bolus intravenous injection or subcutaneously twice weekly for two weeks (days 1, 4, 8, and 11) followed by a ten day rest period (days 12 through 21). Therapy extending beyond 8 cycles may be administered by the standard schedule or may be given once weekly for 4 weeks (days 1, 8, 15, and 22), followed by a 13-day rest (days 23 through 35).

Comments:

• Bortezomib may be administered alone or in combination with dexamethasone.
• The three week period is considered a treatment cycle.
• A minimum of 72 hours should elapse between consecutive doses of bortezomib.
• Patients with multiple myeloma who have previously responded to treatment with bortezomib (either alone or in combination) and who have relapsed at least 6 months after their prior therapy may be started on the last tolerated dose.

Use: For the treatment of multiple myeloma (who had previously responded to treatment with this drug and who have relapsed at least 6 months after completing treatment)

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

Moderate to severe hepatic impairment (bilirubin levels greater than 1.5 times the upper limit of normal range [ULN]): Starting doses should be reduced to 0.7 mg/m2 in the first cycle. Dose escalation to 1 mg/m2 or further dose reduction to 0.5 mg/m2 may be considered in subsequent cycles based on patient tolerability.

Dose Adjustments

DOSE MODIFICATION GUIDELINES FOR COMBINATION THERAPY WITH BORTEZOMIB, MELPHALAN AND PREDNISONE:

Prior to initiating any cycle of therapy with bortezomib in combination with melphalan and prednisone:

• Platelet count should be greater than or equal to 70 x 10^9/L and the ANC should be greater than or equal to 1.0 x 10^9/L.
• Non-hematological toxicities should have resolved to grade 1 or baseline.

Hematological toxicity during a cycle:

• If prolonged grade 4 neutropenia, thrombocytopenia, or thrombocytopenia with bleeding is observed in the previous cycle, then reduction of the melphalan dose by 25% in the next cycle should be considered.
• If the platelet count is less than or equal to 30 x 10^9/L or ANC less than or equal to 0.75 x 10^9/L on a bortezomib dosing day (other than day 1), then the bortezomib dose should be withheld.
• If several bortezomib doses in consecutive cycles are withheld due to toxicity, the bortezomib 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)
• Nonhematological toxicities greater than or equal to grade 3: Bortezomib therapy should be withheld until symptoms of the toxicity have resolved to grade 1 or baseline. Then, bortezomib may be reinitiated with one dose level reduction (from 1.3 mg/m2 to 1 mg/m2, or from 1 mg/m2 to 0.7 mg/m2).

DOSE MODIFICATION GUIDELINES FOR BORTEZOMIB WHEN GIVEN IN COMBINATION WITH RITUXIMAB, CYCLOPHOSPHAMIDE, DOXORUBICIN, AND PREDNISONE:

Prior to the first day of each cycle (other than Cycle 1) of therapy with bortezomib in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone:

• Platelet count should be at least 100 x 10^9/L and absolute neutrophil count (ANC) should be at least 1.5 x 10^9/L
• Hemoglobin should be at least 8 g/dL (at least 4.96 mmol/L)
• Non-hematologic toxicity should have recovered to Grade 1 or baseline

Bortezomib therapy should be interrupted at the onset of any Grade 3 hematologic or non-hematological toxicities, excluding neuropathy.

Hematological toxicity during a cycle:

• Grade 3 or higher neutropenia, or a platelet count not at or above 25 x 10^9/L:

Withhold bortezomib therapy for up to 2 weeks until the patient has an ANC at or above 0.75 x 10^9/L and a platelet count at or above 25 x 10^9/L. If, after bortezomib has been withheld, the toxicity does not resolve, discontinue bortezomib. If toxicity resolves such that the patient has an ANC at or above 0.75 x 10^9/L and a platelet count at or above 25 x 10^9/L, the bortezomib 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)

• Grade 3 or higher non-hematological toxicities: Withhold bortezomib therapy until symptoms of the toxicity have resolved to Grade 2 or better. Then, bortezomib may be reinitiated with one dose level reduction (from 1.3 mg/m2 to 1 mg/m2, or from 1 mg/m2 to 0.7 mg/m2).

DOSE MODIFICATION GUIDELINES FOR RELAPSED MULTIPLE MYELOMA AND MANTLE CELL LYMPHOMA:

• Bortezomib should be withheld at the onset of any grade 3 nonhematologic or grade 4 toxicities excluding neuropathy. Once the symptoms of the toxicity have been resolved, bortezomib therapy may be reinitiated at a 25% reduced dose (1.3 mg/m2 is reduced to 1 mg/m2, 1 mg/m2 is reduced to 0.7 mg/m2).
• Patients with preexisting severe neuropathy should be treated with bortezomib only after a careful risk/benefit assessment.

DOSE MODIFICATION GUIDELINES FOR ALL PATIENTS ON BORTEZOMIB:
For patients who experience bortezomib related neuropathic pain and/or peripheral sensory neuropathy the following modifications in the dose or regimen is recommended:

• Grade 1 (paresthesias and/or loss of reflexes) without pain or loss of function - no action is required.
• Grade 1 with pain or Grade 2 (interfering with function but not with activities of daily living) - reduce the dose of bortezomib to 1 mg/m2.
• Grade 2 with pain or Grade 3 (interfering with activities of daily living) - withhold bortezomib therapy until toxicity resolves. Once the toxicity resolves, reinitiate therapy with a reduced dose of bortezomib at 0.7 mg/m2 and change the frequency to once a week.
• Grade 4 (permanent sensory loss that interferes with function) - discontinue bortezomib.

Precautions

Safety and effectiveness have not been established in pediatric patients (less than 18 years of age).

Consult WARNINGS section for additional precautions.

Dialysis

Because dialysis may reduce bortezomib concentrations, the drug should be administered after the dialysis procedure.

Other Comments

The manufacturer product information should be consulted for current reconstitution, dilution and administration recommendations.

Frequently asked questions

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