Neurotoxicity in Ovarian Cancer Patients on GOG 218

abstract

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.

OBJECTIVES:

To 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.

METHODS:

The 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.

RESULTS:

Of 1,864 evaluable patients, 1,329 (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), 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%).

CONCLUSIONS:

Age and worse QoL at baseline are associated with NT. Substitution of docetaxel did not improve NT symptoms.