Thermal hyperalgesia as a marker of oxaliplatin neurotoxicity: a prospective quantified sensory assessment study.
Neurotoxicity represents a major complication of oxaliplatin. This study aimed to identify early clinical markers of oxaliplatin neurotoxicity, in comparison with cisplatin, and detect predictors of chronic neuropathy. Forty-eight patients with mainly colorectal cancer were evaluated prospectively before oxaliplatin (n=28) or cisplatin (n=20) administration and then 2 weeks after the third (C3), sixth (C6) and ninth (C9) cycles. Eighteen oxaliplatin patients were re-assessed at 12+/-2 months. Evaluation included quantitative sensory testing, i.e., detection/pain thresholds for mechanical, vibration, cold and heat stimuli; pain induced by suprathreshold cold (5-25 degrees C) and heat (38-48 degrees C) stimuli and quantified assessment of symptoms (neuropathic pain symptom inventory). Symptoms of oxaliplatin neurotoxicity (cold-triggered dysesthesia of the hands; 96% of the cases) were reversible between cycles for up to C6. In contrast, thermal testing identified sustained (irreversible between cycles) neurotoxicity two weeks after C3 in the oxaliplatin group only, characterized by hyperalgesia to cold (5-25 degrees C) (F=11.4; p=0.0002 relative to cisplatin patient responses in the hand) and heat stimuli (38-48 degrees C) (F=4.1; p=0.049 for the hand). Cold-evoked symptoms lasting 4 days or more after C3 predicted chronic neuropathy (OR: 22; 95% CI: 1.54-314.74; p=0.02) whereas enhanced pain in response to cold (20 degrees C stimulus on the hand) predicted severe neuropathy (OR: 39; 95% CI: 1.8-817.8 p=0.02). Thermal hyperalgesia is a relevant clinical marker of early oxaliplatin neurotoxicity and may predict severe neuropathy.
Attal
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INSERM U-792, Centre de Traitement et d'Evaluation de la Douleur, CHU Ambroise Paré, APHP, 9, Avenue Charles de Gaulle, F-92100 Boulogne-Billancourt cedex, France Université Versailles-Saint-Quentin, Versailles F-78035, France Service de gastro-entérologie, CHU Ambroise Paré, APHP, Boulogne-Billancourt F-92100, France Equipe mobile de soins de support, soins palliatifs et traitement de la douleur, CHU Ambroise Paré, APHP, Boulogne-Billancourt F-92100, France.
Bouhassira
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D
Gautron
M
M
Vaillant
J N
JN
Mitry
E
E
Lepère
C
C
Rougier
P
P
Guirimand
F
F
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000633:toxicity*; D015415:Biomarkers / Q000032:analysis; D002277:Carcinoma / Q000188:drug therapy; D003080:Cold Temperature / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced* / Q000175:diagnosis* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000633:toxicity*; D000077150:Oxaliplatin; D010147:Pain Measurement / Q000379:methods; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000175:diagnosis* / Q000503:physiopathology; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D013697:Thermosensing / Q000187:drug effects / Q000502:physiology
D000970:Antineoplastic Agents; D015415:Biomarkers; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin