Preliminary indication of survival benefit from ERCC1 and RRM1-tailored chemotherapy in patients with advanced nonsmall cell lung cancer: evidence from an individual patient analysis.
Cancer
; 118(9): 2525-31, 2012 May 01.
Article
em En
| MEDLINE
| ID: mdl-22028294
ABSTRACT
BACKGROUND:
Excision repair cross complementing 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) are molecular determinants that predict sensitivity or resistance to platinum agents and gemcitabine, respectively. Tailored therapy using these molecular determinants suggested patient benefit in a previously reported phase 2 trial. Here, we report an individual patient analysis of prospectively accrued patients who were treated with the "personalized therapy" approach versus other "standard," noncustomized approaches.METHODS:
Patients who had nonsmall cell lung cancer (NSCLC) with extranodal metastatic disease and an Eastern Cooperative Oncology Group performance status of 0/1 were accrued to 4 phase 2 clinical trials conducted at the H. Lee Moffitt Cancer Center Trial A (first-line carboplatin/gemcitabine followed by docetaxel), Trial B (docetaxel and gefitinib in patients aged ≥70 years), Trial C (combination therapy with carboplatin/paclitaxel/atrasentan), and Trial D (personalized therapy based on ERCC1 and RRM1 expression). Patients with low RRM1/low ERCC1 expression received gemcitabine/carboplatin, patients with low RRM1/high ERCC1 expression received gemcitabine/docetaxel, patients with high RRM1/low ERCC1 expression received docetaxel/carboplatin, and patients with high RRM1/high ERCC1 expression received vinorelbine/docetaxel. Patients who were treated on Trials A, B, and C were pooled together and analyzed as the "standard therapy" group. Patients accrued to Trial D were called the "personalized therapy" group. Individual patient data were updated as of February 8, 2011. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method.RESULTS:
There were statistically significant improvements between the personalized therapy group versus the standard therapy group in response (44% vs 22%; P = .002), OS (median 13.3 months vs 8.9 months; P = .016), and PFS (median 7.0 months vs 4.3 months; P = .03).CONCLUSIONS:
The results from individual patient analyses suggest that ERCC1 and RRM1/tailored selection of first-line therapy improved survival over standard treatment-selection approaches.
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Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
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Carcinoma Pulmonar de Células não Pequenas
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Proteínas Supressoras de Tumor
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Proteínas de Ligação a DNA
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Endonucleases
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Neoplasias Pulmonares
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos