| Cycle length: 28 days. |
| Drug | Dose and route | Administration | Given on days |
| Bortezomib* | 1.3 mg/m2 SC | Given as a single SC injection. | Days 1, 8, 15, and 22[1,2] |
| Thalidomide¶ | 100 mg for first 14 days then 200 mg per day thereafter by mouth | Take with water on an empty stomach at least one hour after the evening meal. | Daily, days 1 through 21 |
| DexamethasoneΔ ("low dose") | 40 mg by mouth | Take with food (after meals or with food or milk) in the morning. | Days 1, 8, 15, and 22[1,2] |
| Pretreatment considerations: |
| Emesis risk | - MINIMAL TO LOW.
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Prophylaxis for infusion reactions | - Routine premedication is not indicated. If a hypersensitivity reaction (not including local reactions) occurs with bortezomib or thalidomide, then neither drug should be readministered.
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| Antithrombotic prophylaxis | - Routine antithrombotic prophylaxis is warranted. Thromboembolism (grade 3 and 4) was reported in 3% of patients in a clinical trial receiving VTd despite antithrombotic prophylaxis.[2] In addition, reported risk of thromboembolism (grade 3 and 4) was 5% in the Td arm of this study.[2]
- Refer to UpToDate topics on multiple myeloma, prevention of venous thromboembolism in patients receiving immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide).
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| Infection prophylaxis | - Bortezomib therapy may be associated with an increased risk of herpes zoster and infections not related to neutropenia. Antiviral prophylaxis (eg, acyclovir 400 mg orally twice a day) should be administered to all patients receiving VTd. Some clinicians also administer trimethoprim-sulfamethoxazole double strength once daily on Mondays, Wednesdays, and Fridays during treatment.[1,2] Primary prophylaxis with G-CSF is not indicated.
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| Vesicant/irritant properties | - Bortezomib is an irritant.
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
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| Dose adjustment for baseline liver or renal dysfunction | - Bortezomib: No dosage adjustment for bortezomib secondary to renal insufficiency is necessary. For patients undergoing hemodialysis, bortezomib should be administered after dialysis. Patients with moderate or severe hepatic impairment (serum bilirubin level >1.5 times the upper limit of normal) should be started on bortezomib at a reduced dose of 0.7 mg/m2 per injection during the first cycle, with further dose modifications based upon patient tolerance.[3]
- Refer to UpToDate topics on chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents and chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents.
- Thalidomide: Dosage adjustment of thalidomide is not required for either preexisting renal or hepatic dysfunction.[4]
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| Pregnancy warning | - Thalidomide can result in severe, life-threatening human birth defects. Pregnancy testing is required within 24 hours prior to initiation of thalidomide therapy.[4]
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| Monitoring parameters: |
- Assess CBC with differential, electrolytes, renal function, liver function, and M protein prior to starting each cycle. A CBC should also be performed prior to the dose of bortezomib on days 1, 8, 15, and 22.
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- Monitor for signs of neuropathy. Many clinicians provide a prophylactic bowel regimen for patients taking thalidomide.
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- Monitor for hypotension during therapy; adjustment of antihypertensives and/or administration of IV hydration may be needed.
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- Monitor for signs of rash, infection, or thrombotic event periodically.
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| Suggested dose modifications for toxicity: |
| Neuropathy | - Dose adjustment guidelines for bortezomib in patients who develop peripheral neuropathy or neuropathic pain are available.[3]
- Refer to UpToDate topics on overview of neurologic complications of conventional non-platinum cancer chemotherapy.
- Thalidomide should be discontinued or dose reduced if a patient develops paresthesias accompanied by pain, motor deficit, or interference with activities of daily living.
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| Rash | - Thalidomide has been associated with rashes including SJS and TEN. If a rash develops, thalidomide should be discontinued and the rash further evaluated. Thalidomide should not be administered again if the rash is exfoliative, purpuric, or bullous, or if SJS or TEN is suspected.[4]
- Refer to UpToDate topics on cutaneous side effects of conventional chemotherapy agents.
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| Thrombotic microangiopathy | - Rarely, bortezomib has been associated with TMA, which can present with Coombs-negative hemolysis, thrombocytopenia, renal failure, and/or neurologic findings.[3] If TMA is suspected, stop bortezomib and evaluate.
- Refer to UpToDate topics on drug-induced thrombotic microangiopathy.
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| Other nonhematologic toxicity | - For grade 3 or 4 nonhematologic toxicity other than neuropathy, bortezomib should be held. Once symptoms have resolved to grade 1 or baseline, 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).[2,3]
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
