Intercalated Dosing Schedule of Erlotinib and Docetaxel as a Therapeutic Strategy to Avoid Antagonism and Optimize Its Benefits in Advanced Non-Small-Cell Lung Cancer. A Randomized Phase II Clinical Trial

Autores de IIS La Fe

• Óscar José Juan Vidal

  Autor

• Francisco Aparisi Rodriguez

  Autor

• José Muñoz Langa

  Autor

• Jose Garcia Sanchez

  Autor

• Javier Garde Noguera

  Autor

Participantes ajenos a IIS La Fe

• Sánchez-Hernández A
• Esquerdo G
• López A
• Giner V

Grupos

• Investigación Clínica y Traslacional en Cáncer

Abstract

Docetaxel and erlotinib are used as second-line treatment of advanced non-small-cell lung cancer. With the aim of assessing whether sequential administration of both could avoid possible negative interactions and optimize the benefit obtained, a clinical trial was designed. Outcomes showed improved progression-free survival and disease control rates compared with erlotinib alone, proving the absence of antagonism between them on this basis. Introduction: The purpose of this study was to assess whether an intercalated dosing schedule of erlotinib and docetaxel could avoid possible negative interactions and optimize the benefit obtained as second-line therapy in non-small-cell lung cancer (NSCLC) patients. Patients and Methods: A phase II randomized clinical trial was designed for advanced NSCLC patients in whom previous chemotherapy treatment had failed. The experimental arm with 33 patients consisted of erlotinib 150 mg/d orally, intermittent administration on days 2 to 16 every 21 days, combined with docetaxel 75 mg/m(2) every 21 days; the control arm with 35 patients consisted of erlotinib 150 mg/d orally, administered continuously. The study's primary end point was the proportion of patients who remained progression-free at 6 months in the 2 arms. Results: The proportion of patients who remained progression-free at 6 months was of 5 patients (15%) in the intercalated arm and 3 patients (9%) in the erlotinib monotherapy arm respectively. Median progression-free survival (PFS) was 3.0 versus 2.1 months (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.39-1.06; P = .086). Median overall survival (OS) was 7.5 and 5.2 months (HR, 0.70; 95% CI, 0.41-1.19; P = .19). Disease control rates were 51.7% and 36.4%, respectively. No new safety signals were observed. Conclusion: Erlotinib and docetaxel with intermittent administration of erlotinib improved PFS, OS, and disease control rates compared with erlotinib alone. All of our results indicated that an intercalated dosing schedule of erlotinib and docetaxel could be more efficient than erlotinib treatment alone. Therefore, further studies should be developed in a larger number of patients. This study has shown the absence of antagonism between docetaxel and erlotinib when given in an intercalated fashion.

Keywords

• Adverse effects; Antineoplastic Combined Chemotherapy; Carcinoma; Docetaxel; Erlotinib