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

• Published in: Journal of clinical oncology Vol. 28; no. 21; pp. 3463 - 3471
• Main Authors: Arrieta, Oscar, González-De la Rosa, Claudia H, Aréchaga-Ocampo, Elena, Villanueva-Rodríguez, Geraldine, Cerón-Lizárraga, Tania L, Martínez-Barrera, Luis, Vázquez-Manríquez, María E, Ríos-Trejo, Miguel Angel, Alvarez-Avitia, Miguel A, Hernández-Pedro, Norma, Rojas-Marín, Carlos, De la Garza, Jaime
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 20.07.2010
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Cisplatin - administration & dosage; Double-Blind Method; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Male; Middle Aged; Paclitaxel - administration & dosage; Receptors, Retinoic Acid - analysis; Tretinoin - administration & dosage
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2009.26.6452

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. 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.