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Research paper
Early predictors of oxaliplatin-induced cumulative neuropathy in colorectal cancer patients
  1. Roser Velasco1,
  2. Jordi Bruna1,
  3. Chiara Briani2,
  4. Andreas A Argyriou3,
  5. Guido Cavaletti4,
  6. Paola Alberti4,
  7. Barbara Frigeni5,
  8. Mario Cacciavillani6,
  9. Sara Lonardi7,
  10. Diego Cortinovis8,
  11. Marina Cazzaniga8,
  12. Cristina Santos9,
  13. Haralabos P Kalofonos3
  1. 1Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain
  2. 2Department of Neurosciences, University of Padova, Padova, Italy
  3. 3Division of Clinical Oncology-Department of Medicine, University Hospital of Patras, Rion-Patras, Greece
  4. 4Department of Surgery and Translational Medicine, University of Milan-Bicocca, Monza, Italy
  5. 5Department of Neurology, S. Gerardo Hospital, Monza, Italy
  6. 6EMG Unit, CEMES, Gruppo Data Medica, Padova, Italy
  7. 7Oncology Unit 1, Veneto Oncology Institute–IRCCS, Padova, Italy
  8. 8Department of Oncology, S. Gerardo Hospital, Monza, Italy
  9. 9Unit of Colorectal Cancer, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain
  1. Correspondence to Dr Jordi Bruna, Neuro-Oncology Unit, Hospital Universitari de Bellvitge and ICO Duran i Reynals, C/Feixa Llarga s/n, L'Hospitalet de Llobregat, Barcelona 08907, Spain; 35078jbe{at}


Objectives Peripheral neuropathy ranks among the most common dose-limiting and disabling side-effect of oxaliplatin (OXA)-based chemotherapy. The aim of this prospective, multicentre study was to define early clinical and neurophysiological markers that may help to identify patients at risk of developing severe, treatment emergent, cumulative OXA-induced peripheral neuropathy (OXAIPN).

Methods 200 colorectal cancer patients, scheduled to receive OXA-based chemotherapy, were prospectively followed. Detailed neurological assessment employing the clinical Total Neuropathy Score (TNSc), oncological rating scales (National Common Institute-Common Toxicity Criteria V.3) and nerve conduction studies (NCS) were performed at baseline, mid-treatment and at the end of chemotherapy. Symptoms of OXA-induced acute neurotoxicity were systematically recorded.

Results According to TNSc, 36 (18%) patients developed grade 3 OXAIPN. These patients were predominantly men (p=0.005), presented a significant decrease in all NCS (p<0.001), reported more acute neuropathic symptoms (p<0.001) and received higher OXA cumulative dose (p=0.003). Multivariate analysis showed that three variables obtained at intermediate follow-up, namely, the number of acute symptoms (OR 1.9; CI 95% 1.2 to 3.2; p=0.012) and the >30% decrease in sensory nerve action potential amplitude from the baseline value in radial (OR 41.4; CI 95% 4.98 to 343.1; p=0.001) and dorsal sural nerves (OR 24.96; CI 95% 2.6 to 239.4; p=0.005) were independently associated with the risk of developing severe OXAIPN.

Conclusions High-grade OXA neurotoxicity can be predicted by clinical and neurophysiological information obtained at mid-treatment. Neurological assessment of acute neuropathy symptoms and radial and dorsal sural nerves NCS should be carefully monitored to predict and hopefully prevent the induction of severe OXAIPN.

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