All-Trans-Retinoic Acid - (Atra is een vorm van vitamine A) gegeven naast chemo bij niet-klein-cellige longkanker zorgt voor significant langere levensduur en minder bijwerkingen. Aldus gerandomiseerde fase II studie. Artikel update 30 september 2011

26 juli 2010: Journal of Clinical Oncology, Vol 28, No 21 (July 20), 2010: pp. 3463-3471

Atra - All-trans-retinoic Acid (een vorm van vitamine A) wordt gegeven naast chemo aan longkankerpatienten met pleurale niet-kleincelliige longkanker (stadium IIIB en IV) dan geeft dat een significant langere ziektevrije tijd en levensduur. Dit blijkt uit een gerandomiseerde fase II studie bij 104 longkankerpatienten waarbij elke groep wel chemo kreeg maar 1 groep een placebo als toevoeging en de andere groep dus de Atra - All-trans-Retinoic Acid.  Het verschil in progressievrije tijd bleek significant beter voor de Atra groep: (hazard ratio, 0.62; 95% CI, 0.4 to 0.95). Ook de responserate, het aanslaan van de behandeling verdubbelde in de Atra groep t.o.v. de alleen chemogroep. Overigens wordt Atra - All-trans-retinoic Acid ook veel en succesvol gebruikt voor kinderen met leukemie.

Journal of Clinical Oncology, Vol 28, No 21 (July 20), 2010: pp. 3463-3471
© 2010 American Society of Clinical Oncology.

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

Oscar Arrieta, Claudia H. González-De la Rosa, Elena Aréchaga-Ocampo, Geraldine Villanueva-Rodríguez, Tania L. Cerón-Lizárraga, Luis Martínez-Barrera, María E. Vázquez-Manríquez, Miguel Ángel Ríos-Trejo, Miguel Á. Álvarez-Avitia, Norma Hernández-Pedro, Carlos Rojas-Marín, Jaime De la Garza

From the Instituto Nacional de Cancerología; Universidad Autónoma Metropolitana; and the Clinic of Thoracic Oncology, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.

Corresponding author: Oscar Arrieta, MD, Department of Medical Oncology, Instituto Nacional de Cancerología, San Fernando #22, Col Sección XVI, Tlalpan, 14080 México, DF, México; e-mail: ogar@servidor.unam.mx .

Purpose 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-β2) as a response biomarker.

Patients and Methods Patients with stages IIIB with pleural effusion and IV NSCLC were included to receive PC, and randomly assigned to receive ATRA 20 mg/m2/d (RA/PC) or placebo (P/PC) 1 week before treatment until two cycles were completed. RAR-β2 expression was analyzed in tumor and adjacent lung tissue.

Results 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-β2 in normal tissues of all tumor samples, but only 10% of samples in the tumor tissue.

Conclusion 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.

Supported in part by the National Council of Science and Technology of Mexico (CONACyT-México 44395 and 71276). Roche Laboratories (Mexico City) provided all-trans retinoic acid as a donation, with no interference in the trial design and results analysis.

Presented in part at the Annual Meeting on Molecular Markers in Cancer of the American Society of Clinical Oncology-National Cancer Institute-European Organisation for the Research and Treatment of Cancer, October 30-November 1, 2008, Hollywood, FL; at the 13th World Conference on Lung Cancer, International Association for the Study of Lung Cancer, July 31-August 4, 2009, San Francisco, CA; and at the ECCO 15 34th ESMO Multidisciplinary Congress, September 20-24, 2009, Berlin, Germany.