Oxaliplatin- and docetaxel-induced polyneuropathy: clinical and neurophysiological characteristics

Abstract

The aim of this study was to evaluate the presence and characterization of chemotherapy-induced neuropathy (CIPN) and neuropathic pain 5 years after adjuvant chemotherapy with docetaxel or oxaliplatin. Patients from an ongoing prospective study, who had received adjuvant chemotherapy with docetaxel or oxaliplatin in 2011 to 2012 were invited to participate. The patients underwent a thorough examination with interview, neurological examination, questionnaires, assessment tools, nerve conduction studies (NCS), quantitative sensory testing, MScan motor unit number estimation (MUNE), and corneal confocal microscopy (CCM). Patients were divided into no, possible, probable, and confirmed CIPN. Out of the 132 eligible patients, 63 agreed to participate: 28 had received docetaxel and 35 had received oxaliplatin. Forty-one percent had confirmed CIPN, 34% possible or probable CIPN, and 22% did not have CIPN. The CIPN was characterized mainly by sensory nerve fiber loss, with a more pronounced large fiber than small fiber loss but also some motor fiber loss identified on NCS and MUNE. In general, patients had mild neuropathy with relatively low scores on assessment tools and no association with mood and quality of life. CCM was not useful as a diagnostic tool. Of the patients with probable or confirmed CIPN, 30% experienced pain, which was most often mild, but still interfered moderately with daily life in 20% to 25% and was associated with lower quality of life. In conclusion CIPN was confirmed in 41% 5 years after chemotherapy. The neuropathy was generally mild, but in patients with neuropathic pain it was associated with lower quality of life.

Keywords: assessment tools; chemotherapy; corneal confocal microscopy; large fiber neuropathy; motor unit number estimation; nerve conduction study; neuropathic pain; neuropathy; pain; small fiber neuropathy.

FIGURE 1

Total scores of the questionnaire Michigan Neuropathy Screening Instrument questionnaire (MNSIq), the Toronto Clinical Scoring System (TCSS), and the total neuropathy score (TNS)Filled line median score, dashes lines cut‐point between no CIPN and mild CIPN.Red dots: docetaxel; black dots: oxaliplatin r_s, Spearman's Rho

FIGURE 2

Quantitative sensory testing showing loss or gain of function (z‐scores outside the 95% confidence interval of the DFNS reference database) on the 12 parameters. The comparisons were done between the groups with A, no CIPN, possible/probable CIPN, and confirmed CIPN and B, confirmed CIPN with and without neuropathic pain. Patients with subclinical neuropathy were excluded. * P < .05. CDT, cold detection threshold; CIPN, chemotherapy‐induced peripheral neuropathy; CPT, cold pain threshold; DMA, dynamic mechanical allodynia; HPT, heat pain threshold; MDT, mechanical detection threshold; MPS, mechanical pain sensitivity; MPT, mechanical pain threshold; PHS, paradoxical heat sensation; PPT, pain pressure threshold; TSL, thermal sensory limen; VDT, vibration detection threshold; WDT, warm detection threshold

FIGURE 3

Quantitative sensory testing showing z‐scores indicating loss or gain in function on the 10 parameters. The comparisons were done between the groups with A, no CIPN, possible/probable CIPN, and confirmed CIPN and B, Confirmed CIPN with and without neuropathic pain. Patients with subclinical neuropathy are excluded (n = 2). CDT, cold detection threshold; CIPN, chemotherapy‐induced peripheral neuropathy; CPT, cold pain threshold; DMA, dynamic mechanical allodynia; HPT, heat pain threshold; MDT, mechanical detection threshold; MPS, mechanical pain sensitivity; MPT, mechanical pain threshold; PHS, paradoxical heat sensation; PPT, pain pressure threshold; TSL, thermal sensory limen; VDT, vibration detection threshold; WDT, warm detection threshold. * P value < .05

FIGURE 4

Mscan parameters A‐C, and corneal confocal microscopy (CCM) parameters D‐F. MScan parameters were compared between patients with large fiber polyneuropathy (LPNP+), patients without large fiber polyneuropathy (LPNP‐), and local age‐matched healthy controls. A, The compound muscle action potential (CMAP) amplitude, B, Motor unit number estimations (MScan MUNE), C, The Largest unit (%). CCM parameters were compared between patients with no small fiber loss (SPNP‐), with small fiber loss (SPNP+), and local age‐matched controls in D, Cornea nerve fiber length (CNFL), E, Cornea nerve branch density (CNBD), and F, Cornea nerve fiber density (CNFD. Patients were excluded from the MScan evaluation if they had carpal tunnel syndrome (n = 7) or did not wish to participate (n = 9). CCM was performed on 53 of the participants; 10 did not wish to participate, and two patients had a subclinical CIPN and were not included here. Horizontal lines indicate means, and dashed lines SDs. * P = .018 between healthy controls and LPNP+, ** P = .006 between healthy controls and LPNP+