Dosage Schedule for Velcade-MP
Velcade might be given in combination with melphalan and prednisone (Velcade-MP).
| Cycles 1 to 4 (twice-weekly Velcade) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Week | 1 | 2 | 3 | 4 | 5 | 6 | ||||||
| Velcade | Day 1 | -- | -- | Day 4 | Day 8 | Day 11 | Rest | Day 22 | Day 25 | Day 29 | Day 32 | Rest |
| MP | Day 1 | Day 2 | Day 3 | Day 4 | -- | -- | Rest | -- | -- | -- | -- | Rest |
| Cycles 5 to 9 (once-weekly Velcade) | ||||||||||||
| Week | 1 | 2 | 3 | 4 | 5 | 6 | ||||||
| Velcade | Day 1 | -- | -- | -- | Day 8 | -- | Rest | Day 22 | -- | Day 29 | -- | Rest |
| MP | Day 1 | Day 2 | Day 3 | Day 4 | -- | -- | Rest | -- | -- | -- | -- | Rest |
Dose Modifications To Be Made During Treatment Cycles of Combination Velcade, Melphalan, and Prednisone Therapy
| Toxicity | Dose Modification or Delay |
| If prolonged very serious Grade 4neutropenia or thrombocytopenia is experienced during a cycle, or thrombocytopenia with bleeding is observed in the previous cycle | Consider reduction of the melphalan dose by 25% in the next cycle |
| If platelet count is =30 x 109/L or absolute neutrophil count (ANC) is =0.75 x 109/L on a Velcade dosing day (other than day 1) | Velcade dose should be withheld |
| If several Velcade doses in consecutive cycles are withheld due to toxicity | Velcade dose should be reduced by one dose level (from 1.3 mg/m2 to 1 mg/m2, or from 1 mg/m2 to 0.7 mg/m2) |
| Serious (Grade 3) or higher non-hematological toxicities | Velcade therapy should be withheld until symptoms of the toxicity have resolved to Grade 1 or baseline. Then, Velcade may be restarted with one dose level reduction (from 1.3 mg/m2 to 1 mg/m2, or from 1 mg/m2 to 0.7 mg/m2). For Velcade-related neuropathic pain and/or peripheral neuropathy, hold or modify Velcade as outlined here. |
Recommended Dose Modifications for Velcade-related Neuropathic Pain and/or Peripheral Sensory or Motor Neuropathy
| Severity of Peripheral Neuropathy Signs and Symptoms | Modification of Dose and Regimen |
| Grade 1* (asymptomatic; loss of deep tendon reflexes or paresthesia [sensations of numbness, tingling, or prickling]) without pain or loss of function | No action |
| Grade 1 with pain or Grade 2 (moderate symptoms; symptoms that limit instrumental activities of daily living [eg, meal preparation, shopping, using the telephone, etc.]) | Reduce Velcade dose to 1.0 mg/m2 |
| Grade 2 with pain or Grade 3 (severe symptoms; symptoms that limit self-care activities of daily living [eg, bathing, dressing, feeding self, toileting, etc.]) | Withhold Velcade therapy until toxicity resolves. When toxicity resolves, reinitiate with a reduced dose of Velcade at 0.7 mg/m2 once per week. |
| Grade 4 (life-threatening consequences; urgent intervention indicated) | Discontinue Velcade |
Recommended Starting Dose Modification for Velcade in Patients with Hepatic Impairment
This chart shows how the starting dose of Velcade should be modified in patients with liver (hepatic) impairment.
| Level of impairment* | Bilirubin level | SGOT (AST) level | Modification of Velcade starting dose |
| Mild | ≤ 1.0 x ULN | > ULN | None Needed |
| > 1.0 x – 1.5 x ULN | Any | None Needed | |
| Moderate | > 1.5 x – 3.0 x ULN | Any | First cycle: Reduce Velcade to 0.7 mg/m2 Subsequent cycles: Consider raising dose to 1.0 mg/m2 if tolerated well, or reducing dose further if necessary |
| Severe | > 3.0 x ULN | Any |
Abbreviations: AST = aspartate aminotransferase; SGOT = serum glutamic oxaloacetic transaminase; ULN = upper limit of the normal range.
*Liver impairment is noted by increased levels of certain substances that can be measured in the blood. These include bilirubin, a breakdown product of red blood cells that is normally removed by the liver, and the liver enzyme SGOT, which is also called AST.
Most common side effects seen in relapsed or refractory studies
| APEX Trial - Most Common Side Effects (all grades) | ||
|---|---|---|
| Side Effect | Velcade Percentage of Patients (N=331) |
Dexamethasone Percentage of Patients (N=332) |
| Asthenic conditions (fatigue, malaise, weakness) |
61% | 45% |
| Diarrhea | 57% | 21% |
| Nausea | 57% | 14% |
| Constipation | 42% | 15% |
| Peripheral neuropathy* | 36% | 9% |
| Vomiting | 35% | 6% |
| Fever | 35% | 16% |
| Thrombocytopenia | 35% | 11% |
| Psychiatric disorders | 35% | 49% |
| Decreased appetite or weight loss |
34% | 9% |
| Tingling sensation and impairment of sensitivity |
27% | 11% |
| Anemia | 26% | 22% |
| Headache | 26% | 13% |
| Cough | 21% | 11% |
*Represents treatment emergent neuropathy
