Introduction
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect of certain chemotherapies which frequently necessitates dose modification (DM) of treatment. This large-scale study investigates the impact of CIPN on chemotherapy dosing and identifies potential predictors of treatment DM.
Methods
Patients who received neurotoxic chemotherapies (taxanes, platinums, vinca-alkaloids, bortezomib and thalidomide) were recruited between August 2015-February 2024 from six Australian cancer centres. Demographic information (age, body mass index, cancer type and stage, medical history) and treatment dosing information (cumulative dose, reasons for DM) were collected from medical records. Patients were categorised into DM-CIPN if they experienced dose reduction (DR) or early cessation due to CIPN. Results presented as mean±SEM or median(IQR).
Results
1174 patients were included in the study (age=59 (49-67) years, 66% female, 26% stage IV disease). Patients predominantly received paclitaxel (43%), oxaliplatin (23%) or docetaxel (12%). DM information was available for 1134 patients. CIPN was the most common reason for DM (DM-CIPN=30%, DM-other reasons=23%). 40% of oxaliplatin-treated patients experienced DM-CIPN, compared to 36% of paclitaxel- and 16% of docetaxel-treated patients. Of patients with DM-CIPN, 28% had DR only, 44% had early cessation only, and 29% had both.
Cumulative paclitaxel and oxaliplatin doses were higher in patients who received DR only (Paclitaxel:885.19±38.50mg/m2, Oxaliplatin:905±105.72mg/m2) compared to early cessation only (Paclitaxel:712.13±23.77mg/m2, Oxaliplatin:760.47±19.80mg/m2) or both (Paclitaxel:702.96±26.62mg/m2, Oxaliplatin:694.32±31.09mg/m2) (P<0.001).
Older (OR=1.02, CI:1.01-1.03, P<0.001) and female patients (OR=1.67, CI 1.25-2.23, P=0.001) were more likely to have DM-CIPN, even after controlling for chemotherapy type, whereas there was no association between metastatic disease, diabetes and BMI.
Discussion
CIPN is dose-limiting in a significant proportion of neurotoxic chemotherapy treated patients. Early cessation of neurotoxic treatment was a more common DM strategy than dose reduction, resulting in lower cumulative dose exposure. Closer monitoring of CIPN symptoms may assist to maximise chemotherapy exposure, particularly in higher risk cohorts such as older age groups.