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


 

VISTA Frontline Trial - Most Common Side Effects (all grades)
Side Effect Velcade-MP
Percentage of patients
(N=340)
MP
Percentage of patients
(N=337)
Thrombocytopenia 52% 47%
Neutropenia 49% 46%
Nausea 48% 28%
Peripheral neuropathy 47% 5%
Diarrhea 46% 17%
Anemia 43% 55%
Constipation 37% 16%
Neuralgia (nerve pain) 36% 1%
Low white blood cell count 33% 30%
Vomiting 33% 16%
Fever 29% 19%
Fatigue 29% 26%
Low lymphocyte count 24% 17%
Decreased appetite or weight loss 23% 10%
Weakness, malaise 21% 18%
Cough 21% 13%
Difficulty in sleeping 20% 13%
Swelling in the hands or feet 20% 10%

 

 

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