Paclitaxel and cisplatin versus paclitaxel and cisplatin plus all-trans retinoic acid for the prevention of chemotherapy-induced neuropathy: A randomized phase II trial

Abstract

e14506 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event, similar to that of diabetes where there is reduction of the expression and transport of Neural Growth Factor (NGF). Retinoic acid regulates genes related to cellular proliferation and NGF expression. We conducted this clinical trial to determine the effect of all-trans retinoic acid (ATRA) on the development of CIPN with paclitaxel and cisplatin in patients with advanced non-small cell lung cancer (NSCLC). Methods: Ninety five patients with advanced NSCLC were included to receive chemotherapy based on paclitaxel 175 mg/m2 and cisplatin 80 mg/m2 every 3 weeks for a maximum of 6 cycles. The patients were randomized to receive ATRA 20 mg/day or placebo 1 week before treatment until after completing 2 cycles. Prior to chemotherapy and after 2 cycles of treatment neurophysiology tests, clinical exam and serum NGF levels (34 patients) were performed. Results: There were no differences in general characteristics of the patients between groups. NGF serum levels were lower in the placebo group 4.89 pg/ml baseline and 4.6 pg/ml 2C (p = 0.007) versus ATRA 4.8 pg/ml and 4.7 pg/ml (p=0.107). The electrophysiological studies showed a greater degree of motor axonal damage in the right (p=0.003) and left (p=0.013) tibial nerves in the placebo group after 2C. In the ATRA group there were no significant differences baseline and after chemotherapy. Conclusions: ATRA might have a neuroprotective effect in patients with NSCLC treated with paclitaxel and cisplatin. A phase III trial is needed to confirm these findings. No significant financial relationships to disclose.