What are the criteria guiding bortezomib (Velcade) dosage in multiple myeloma?

From the Guidelines

Bortezomib dosing in multiple myeloma is guided by a standard dosage of 1.3 mg/m², administered subcutaneously on days 1,8,15, and 22, as part of various regimens such as VMP, VCD, or VTD, with adjustments based on patient's clinical status, renal and hepatic function, and adverse effects like peripheral neuropathy 1. The criteria guiding bortezomib dosage in multiple myeloma include:

• Patient's clinical status and treatment phase
• Presence of adverse effects, particularly peripheral neuropathy
• Renal and hepatic function, with necessary dose adjustments for impairment
• Treatment regimen, with bortezomib being part of combinations like VMP, VCD, VTD, or VRd Some key regimens and their dosing schedules are:
• VMP: Bortezomib 1.3 mg/m² subcutaneously days 1,8,15,22; melphalan 9 mg/m² orally days 1–4; prednisone 60 mg/m² orally days 1–4; repeated every 35 days
• VCD: Cyclophosphamide 300 mg/m² orally days 1,8,15 and 22; bortezomib 1.3 mg/m² i.v. on days 1,8,15,22; dexamethasone 40 mg orally on days 1,8,15,22; repeated every 4 weeks
• VTD: Bortezomib 1.3 mg/m² subcutaneously days 1,8,15,22; thalidomide 100–200 mg orally days 1–21; dexamethasone 20 mg on day of and day after bortezomib (or 40 mg days 1,8,15,22); repeated every 4 weeks Dose adjustments for adverse effects, such as peripheral neuropathy, are crucial to balance efficacy and toxicity, with recommendations including dose reduction or temporary discontinuation based on the severity of neuropathy 1.

From the FDA Drug Label

The recommended starting dose of bortezomib is 1.3 mg/m2 administered as a 3 to 5 second bolus intravenous injection Retreatment for Multiple Myeloma: May retreat starting at the last tolerated dose. Hepatic Impairment: Use a lower starting dose for patients with moderate or severe hepatic impairment. Dose must be individualized to prevent overdose

The criteria guiding bortezomib (Velcade) dosage in multiple myeloma include:

• Starting dose: 1.3 mg/m2
• Retreatment: starting at the last tolerated dose
• Hepatic impairment: using a lower starting dose for patients with moderate or severe hepatic impairment
• Individualization: of the dose to prevent overdose 2 2

From the Research

Bortezomib Dosage Criteria in Multiple Myeloma

The criteria guiding bortezomib dosage in multiple myeloma are based on several factors, including the patient's overall health, kidney function, and the specific treatment regimen being used.

• Dosage Recommendations: The recommended dosage of bortezomib is 1.3 mg/m² per dose, administered as an intravenous bolus injection twice weekly on days 1,4,8, and 11 of a 21-day cycle 3.
• Administration: Bortezomib can be administered subcutaneously or intravenously, with a minimum of 72 hours between doses to allow for recovery of normal proteasome function 4.
• Dose Modification: The dose of bortezomib should be reduced or held immediately upon development of painful neuropathy, as described in the product monograph; dose modification may also be required for peripheral sensory neuropathy without pain or for other toxicities 4.
• Treatment Regimens: Bortezomib is often used in combination with other medications, such as lenalidomide and dexamethasone, to treat multiple myeloma. The specific treatment regimen and dosage may vary depending on the patient's individual needs and the clinical trial or study being conducted 5, 6, 7.

Key Considerations

When determining the appropriate dosage of bortezomib for a patient with multiple myeloma, several key considerations must be taken into account, including:

• Patient's Overall Health: The patient's overall health, including their kidney function and any underlying medical conditions, should be carefully evaluated to determine the appropriate dosage of bortezomib.
• Treatment Goals: The treatment goals, such as achieving a complete remission or managing symptoms, should be considered when determining the dosage of bortezomib.
• Potential Side Effects: The potential side effects of bortezomib, such as peripheral neuropathy and fatigue, should be carefully monitored and managed to ensure the patient's safety and well-being.

Clinical Trials and Studies

Several clinical trials and studies have investigated the use of bortezomib in multiple myeloma, including:

• SWOG S0777: A randomized, open-label, phase 3 trial that compared the efficacy of bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant 6.
• SWOG-1211: A randomized phase 2 trial that compared the efficacy of bortezomib, lenalidomide, and dexamethasone with or without elotuzumab in patients with untreated, high-risk multiple myeloma 7.
• ENDURANCE: A multicentre, open-label, phase 3, randomised, controlled trial that compared the efficacy of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma without intention for immediate autologous stem-cell transplantation 5.