What are the symptoms and timeline of Chemotherapy-Induced Peripheral Neuropathy (CIPN) associated with different chemotherapy agents, including platinum-based drugs (e.g. cisplatin, oxaliplatin), taxanes (e.g. paclitaxel), and vinca alkaloids?

Symptoms and Timeline of Chemotherapy-Induced Peripheral Neuropathy (CIPN) by Agent Type

Different chemotherapy agents cause distinct peripheral neuropathy patterns with varying symptom profiles and timelines, with platinum compounds and taxanes being the most commonly associated with CIPN. 1

Platinum-Based Agents (Cisplatin, Oxaliplatin)

Oxaliplatin

• Acute neuropathy symptoms:
  • Cold sensitivity (hallmark feature)
  • Throat discomfort
  • Difficulty swallowing cold liquids
  • Muscle cramps 1
• Timing pattern:
  • Symptoms can begin during infusion
  • Peak severity occurs 2-3 days after each dose
  • Symptom severity doubles with subsequent treatment cycles
  • Does not return to baseline between cycles when administered every 2 weeks 1
• Chronic/cumulative neuropathy:
  • More severe in upper limbs than lower limbs 2
  • Exhibits "coasting phenomenon" - worsens for 2-3 months after therapy completion before beginning to improve 2
  • Partially reversible in ~80% of patients
  • Complete resolution in ~40% of patients at 6-8 months post-treatment 1

Cisplatin

• Symptoms:
  • Peripheral neuropathies affecting sensory nerves
  • Characterized by numbness, tingling, and pain in "glove and stocking" distribution 3
• Timing pattern:
  • Usually occurs after prolonged therapy (4-7 months)
  • Neurologic symptoms can appear after a single dose
  • Symptoms may begin 3-8 weeks after the last dose
  • May progress further even after stopping treatment
  • May be irreversible in some patients 3
  • Elderly patients may be more susceptible 3

Taxanes (Paclitaxel)

• Acute neuropathy symptoms:
  • Pain syndrome occurring days after each dose
  • Previously mislabeled as arthralgias/myalgias
  • Primarily pain in truncal/hip distribution 1
• Timing pattern:
  • Peaks approximately 2-3 days after each dose
  • More prominent in lower limbs during treatment 2
  • Tends to improve in months following treatment completion 2

Vinca Alkaloids

• Symptoms:
  • Sensory symptoms predominate (numbness, tingling)
  • Motor symptoms more common than with other agents
  • Symmetric, distal, length-dependent distribution 1, 4
• Timing pattern:
  • Dose-dependent
  • Less neurotoxic than platinum compounds or taxanes 2, 4
  • Can persist after treatment discontinuation 4

Bortezomib and Thalidomide

• Symptoms:
  • Predominantly sensory neuropathy
  • Painful paresthesias
  • Sensory loss in stocking-and-glove distribution 4, 5
• Timing pattern:
  • Can develop early in treatment course
  • May improve after dose reduction
  • Variable recovery after treatment cessation 4

General CIPN Characteristics Across Agents

• Distribution pattern:
  • Symmetric, distal, length-dependent "glove and stocking" distribution 1
• Symptom predominance:
  • Primarily sensory symptoms rather than motor symptoms
  • Sensory axonal damage with reduced amplitude of sensory nerve action potentials 1
• Dose relationship:
  • Dose-dependent occurrence
  • Higher incidence with increased cumulative dose 4
• Risk factors:
  • Dose per cycle
  • Cumulative dose
  • Treatment schedule
  • Duration of infusion
  • Combination with other neurotoxic agents
  • Pre-existing peripheral neuropathy
  • Age (elderly more susceptible) 3, 6

Management Considerations

• No agents are recommended for CIPN prevention 1
• Duloxetine is the only agent with evidence supporting its use for established painful CIPN, though benefit is limited 1, 2
• Consider dose delay, reduction, substitution, or discontinuation in patients with intolerable neuropathy and/or functional impairment 1

Monitoring and Assessment

• Diagnosis primarily through clinical history and symptom assessment 2
• Regular monitoring during treatment is essential to detect early signs of CIPN 1
• Assessment of both sensory and motor function is important for comprehensive evaluation 7

CIPN significantly impacts quality of life and may necessitate chemotherapy dose modifications, potentially affecting survival outcomes 4.