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
Por:
Juan, O, Aparisi, F, Sanchez-Hernandez, A, Munoz-Langa, J, Esquerdo, G, Garcia-Sanchez, J, Lopez, A, Garde, J and Giner, V
Publicada:
1 may 2015
Resumen:
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.
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