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 4) neutropenia 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* (paresthesias [sensations of numbness, tingling, or prickling], weakness, and/or loss of reflexes) without pain or loss of function

No action

Grade 1 with pain or Grade 2 (interfering with function but not with activities of daily living)

Reduce Velcade dose to 1.0 mg/m2

Grade 2 with pain or Grade 3 (interfering with activities of daily living)

Withhold Velcade therapy until toxicity resolves. When toxicity resolves, reinitiate with a reduced dose of Velcade at 0.7 mg/m2 and change treatment schedule to once per week.

Grade 4 (permanent sensory loss that interferes with function, sensory neuropathy which is disabling, or motor neuropathy that is life threatening or leads to paralysis)

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