Neurotoxicity in ovarian cancer patients on Gynecologic Oncology Group (GOG) protocol 218: Characteristics associated with toxicity and the effect of substitution with docetaxel: An NRG Oncology/Gynecologic Oncology Group study

•Age and worse QoL at baseline are associated with chemotherapy-induced NT.•Substitution of docetaxel does not improve NT symptoms, as examined in GOG 218.•The use of non-taxane based doublets in upfront ovarian cancer therapy may be considered in certain patients.

ObjectivesTo describe characteristics associated with neurotoxicity (NT) in advanced ovarian cancer patients treated on Gynecologic Oncology Group 218 and examine effect of substituting docetaxel for paclitaxel in these patients.MethodsThe development of NT was defined as Common Toxicity Criteria grade (G) ≥ 1. The association between substitution with docetaxel and NT improvement was explored with generalized estimating equations adjusting for treatment cycle and NT grading at previous cycle.ResultsOf 1864 evaluable patients, 1329 (71%) developed G ≥ 1 NT during the study. Nearly half appeared within the first two cycles of chemotherapy, with 31% experiencing G ≥ 2. Older patients or those with worse quality of life (QoL) scores at baseline (p < 0.05) were more likely to experience NT. One-hundred-six patients received docetaxel as substitute for paclitaxel. Of them, 47 patients started with docetaxel at cycle one due to reaction to paclitaxel (n = 32), fear of NT (n = 4), and other reasons (n = 11), whereas 59 patients switched to docetaxel during cycle 2-6 due to NT (n = 32), reaction to paclitaxel (n = 19), and other reasons (n = 8). Although the protocol instructed otherwise, the majority continued paclitaxel despite G ≥ 2 NT symptoms. There was no evidence that substitution with docetaxel improved NT (Odds Ratio: 1.57; 95% CI 0.98-2.54; p > 0.05). Of 59 patients who switched to docetaxel, only seven (12%) discontinued taxane prior to chemotherapy completion. A roughly equal chance of worsening NT was reported on paclitaxel (6%) as on docetaxel (5%).ConclusionsAge and worse QoL at baseline are associated with NT. Substitution of docetaxel did not improve NT symptoms.