Randomized phase II trial of All-trans-retinoic acid with chemotherapy based on paclitaxel and cisplatin as first-line treatment in patients with advanced non-small-cell lung cancer

J Clin Oncol. 2010 Jul 20;28(21):3463-71.
Arrieta O, González-De la Rosa CH, Aréchaga-Ocampo E, Villanueva-Rodríguez G, Cerón- Lizárraga TL, Martínez-Barrera L, Vázquez-Manríquez ME, Ríos-Trejo MA, Alvarez-Avitia MA, Hernández-Pedro N, Rojas-Marín C, De la Garza J.
J Clin Oncol. 2010 Jul 20;28(21):3463-71.
Azione: l'aggiunta di acido all-trans retinoico (ATRA) alla chemioterapia potrebbe aumentare la percentuale di risposta (RR) e la sopravvivenza Libera da progressione (PFS) in pazienti con cancro del polmone non a piccole cellule (NSCLC) in stadio avanzato, con un profilo di tossicità accettabile.
ATRA/cancro del polmone.

This randomized phase II trial evaluated whether the combination of cisplatin and paclitaxel (PC) plus all-trans retinoic acid (ATRA) increases response rate (RR) and progression-free survival (PFS) in patients with advanced non-small-cell lung cancer (NSCLC) with an acceptable toxicity profile and its association with the expression of retinoic acid receptor beta 2 (RAR-beta2) as a response biomarker.
Patients with stages IIIB with pleural effusion and IV NSCLC were included to receive PC, and randomly assigned to receive ATRA 20 mg/m(2)/d (RA/PC) or placebo (P/PC) 1 week before treatment until two cycles were completed. RAR-beta2 expression was analyzed in tumor and adjacent lung tissue.11
One hundred seven patients were included, 55 in the P/PC group and 52 in the RA/PC group. RR for RA/PC was 55.8% (95% CI, 46.6% to 64.9%) and for P/PC, 25.4% (95% CI, 21.3 to 29.5%; P = .001). The RA/PC group had a longer median PFS (8.9 v 6.0 months; P = .008). Multivariate analysis of PFS showed significant differences for the RA/PC group (hazard ratio, 0.62; 95% CI, 0.4 to 0.95). No significant differences in toxicity grade 3/4 were found between groups, except for hypertriglyceridemia (10% v 0%) in RA/PC (P = .05). Immunohistochemistry and reverse-transcriptase polymerase chain reaction assays showed expression of RAR-beta2 in normal tissues of all tumor samples, but only 10% of samples in the tumor tissue.
Adding ATRA to chemotherapy could increase RR and PFS in patients with advanced NSCLC with an acceptable toxicity profile. A phase III clinical trial is warranted to confirm these findings.