Clinical pattern and associations of oxaliplatin acute neurotoxicity: a prospective study in 170 patients with colorectal cancer.
BACKGROUND
The objective of the current prospective, multicenter, international study was to trace the incidence and severity of acute oxaliplatin-induced peripheral neuropathy (OXLIPN) and to determine its clinical pattern. The authors also specifically tested whether patients who had more symptoms of acute OXLIPN eventually would develop a more severe chronic, cumulative form of OXLIPN.


METHODS
One hundred seventy patients (mean ± standard deviation age, 63.7 ± 8.7 years) who were scheduled to receive either combined leucovorin, 5-fluoruracil, and oxaliplatin (FOLFOX) or combined capecitabine and oxaliplatin (XELOX) for metastatic colorectal cancer were monitored prospectively at baseline and were followed in 4 European sites. The incidence of hyperexcitability symptoms secondary to acute OXLIPN was assessed by using a descriptive questionnaire (yes/no question) at each clinical evaluation. Motor and neurosensory criteria according to version 3 of the National Cancer Institute's Common Toxicity Criteria were applied to clinically grade the severity of OXLIPN.


RESULTS
Acute OXLIPN was present in 146 of 170 patients (85.9%). The vast majority of these patients manifested cold-induced perioral (95.2%) or pharyngolaryngeal (91.8%) dysesthesias. Severe acute OXLIPN that required prolongation of oxaliplatin infusion from 2 hours to 4 to 6 hours occurred in 32 of 146 patients (21.9%). The increased number of acute OXLIPN symptoms was correlated significantly (Spearman rho correlation coefficient [r]) with both the development (r = 0.602; P < .001) and the degree of the chronic, cumulative form (r = 0.702; P < .001).


CONCLUSIONS
The current results indicated that the vast majority of patients with colorectal cancer who receive oxaliplatin-based chemotherapy will manifest symptoms of a transient acute syndrome soon after oxaliplatin administration. Patients who have a more complex combination of acute phenomena related to axonal hyperexcitability are those who eventually develop more severe OXLIPN. Therefore, it may be advisable to test agents against acute OXLIPN to verify their effects on the chronic form.
Department of Neurology, St. Andrew's State General Hospital of Patras, Patras, Greece.
Andreas A
AA
Argyriou
Guido
G
Cavaletti
Chiara
C
Briani
Roser
R
Velasco
Jordi
J
Bruna
Marta
M
Campagnolo
Paola
P
Alberti
Francesca
F
Bergamo
Diego
D
Cortinovis
Marina
M
Cazzaniga
Cristina
C
Santos
Konstantinos
K
Papadimitriou
Haralabos P
HP
Kalofonos
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000077150:Oxaliplatin; D010292:Paresthesia / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D011446:Prospective Studies; D018709:Statistics, Nonparametric
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin