What is the best approach to treating a patient with painful burning in hands and feet, likely due to bortezomib (Velcade) induced neuropathic pain, who has been receiving bortezomib for multiple myeloma?

Management of Bortezomib-Induced Peripheral Neuropathy

Start pregabalin 150-600 mg/day as first-line treatment for this patient's painful burning neuropathy, while simultaneously reducing the bortezomib dose to 1.0 mg/m² or switching to weekly administration. 1, 2

Immediate Bortezomib Dose Modification (Priority Action)

The most critical intervention is modifying the bortezomib regimen itself, as this addresses the root cause and prevents progression to irreversible neuropathy. 1

Dose reduction algorithm:

• Reduce bortezomib to 1.0 mg/m² immediately for this patient experiencing painful Grade 1-2 neuropathy 1, 2
• If symptoms worsen or interfere with daily activities, suspend bortezomib until resolution, then restart at 0.7 mg/m² once weekly 1, 2
• Switch to subcutaneous administration if currently using IV route, as this reduces peripheral neuropathy rates from 53% to 38% for all grades and from 16% to 6% for Grade 3-4 2
• Consider weekly instead of twice-weekly dosing, which reduces Grade 3-4 neuropathy from 18% to 9% without compromising efficacy 2

This dose modification is critical because 45% of patients who discontinue due to Grade ≥2 neuropathy do so within the first three cycles, emphasizing the urgency of early intervention. 1, 2

First-Line Pharmacologic Pain Management: Pregabalin

Pregabalin is the recommended first-line agent among the options presented, based on European Myeloma Network guidelines and expert consensus. 1, 3

Dosing regimen:

• Start at 150 mg/day (75 mg twice daily or 50 mg three times daily) 1, 3
• Titrate to 300 mg/day (150 mg twice daily) if tolerated and pain persists 3
• Maximum dose: 600 mg/day (300 mg twice daily) if needed 1, 3
• Continue for at least 3 months before declaring treatment failure 1, 3

Why pregabalin over the other options:

• Pregabalin has the strongest guideline support as first-line therapy for bortezomib-induced neuropathic pain specifically 1
• Gabapentin (not listed as an option) and pregabalin are calcium channel blockers that are "very effective, especially in painful PN" 1
• Hydrocodone (an opioid) should be reserved as adjunctive therapy for breakthrough pain, not first-line monotherapy 1
• Amitriptyline is not mentioned in any of the myeloma-specific guidelines provided

Second-Line Option: Duloxetine

If pregabalin fails after 3 months at optimized doses or causes intolerable side effects, switch to duloxetine 30-60 mg/day. 1, 3

Duloxetine, a serotonin-norepinephrine reuptake inhibitor, is explicitly recommended as a "valid second-line choice" and can be "very effective, especially in painful PN." 1

Role of Opioids (Hydrocodone)

Hydrocodone and other opioids should be used as adjunctive therapy combined with pregabalin or duloxetine, not as monotherapy. 1

• Opioids "can be effective" for neuropathic pain that is "poorly responsive to standard analgesic treatment" 1
• Tramadol is specifically recommended "to fight against chronic pain" as an adjunct 1
• Use opioids for breakthrough pain while optimizing the primary neuropathic pain medication 3

Critical Pitfalls to Avoid

Do not use high-dose vitamin C as it may interfere with bortezomib metabolism and reduce its anticancer efficacy. 1, 2

Avoid high-dose pyridoxine (vitamin B6), especially if the patient has renal insufficiency, as it can induce sensory neuron lesions. 1, 2

Do not delay dose modification of bortezomib—early intervention is essential as neuropathy can progress rapidly in some patients. 1, 2

Assess renal function before starting pregabalin and adjust doses accordingly, particularly in elderly patients. 3

Do not abruptly discontinue pregabalin or duloxetine—taper gradually to avoid withdrawal symptoms. 3

Supportive Non-Pharmacologic Measures

Advise the patient to: 1, 2

• Wear loose-fitting shoes, roomy cotton socks, and padded slippers 1, 2
• Keep hands and feet uncovered at night (bedding pressure worsens symptoms) 1, 2
• Soak hands and feet in icy water and massage for temporary pain relief 1, 2
• Walk to help circulation, but avoid excessive walking or standing 1, 2

Expected Prognosis

Bortezomib-induced neuropathy is largely reversible with appropriate management. 1, 2, 4

• Improvement or resolution occurs in 71% of patients with Grade ≥3 neuropathy after dose reduction or discontinuation 2, 4
• Median time to improvement is 47 days (range 1-529 days), typically within 3 months 2
• However, some patients may take up to 1.7 years for complete recovery 5

Monitoring Parameters

• Reassess neuropathy severity at 2-4 weeks after initiating treatment, then monthly 3
• Monitor for pregabalin side effects: peripheral edema, weight gain, dizziness, somnolence 3
• Use validated tools like the Total Neuropathy Score for objective assessment 1, 3