Adam Vilmar1, Jens Benn Sørensen. 1. Department of Oncology 5073, Finsen Centre, National University Hospital, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark. adamvilmar@hotmail.com
Abstract
BACKGROUND: Patients diagnosed with advanced non-small cell lung cancer have a dismal prognosis and are often relative resistant to chemotherapy. A need for markers has emerged based on tumour biology in order to predict which patients will respond to treatment. Excision repair cross-complementation group 1 (ERCC1) has shown potential as a predictive marker in patients with NSCLC treated with cisplatin-based chemotherapy. Carboplatin has gained widespread use in the treatment of advanced NSCLC and its mechanisms of action are likely similar to that of cisplatin. MATERIALS AND METHODS: A literature review on ERCC1 was conducted as predictor in NSCLC patients receiving platinum-based treatment with emphasis on carboplatin. English language publications from January 1996 to February 2008 were eligible and data on methodology and outcome were recorded. RESULTS: Eight preclinical articles, 25 clinical articles and 1 clinical abstract were identified. Laboratory methods were mainly RT-PCR (reverse transcriptase polymerase chain reaction) or immunohistochemistry (IHC) for expression of ERCC1. Preclinical studies pointed towards similar mechanisms of chemotherapy-resistance among platinum compounds. A statistically significant benefit in outcome was found among NSCLC patients, who received adjuvant treatment, and had low-ERCC1 expression. Advanced NSCLC patients treated with cisplatin showed improved response rates (RR) but no difference in other endpoints. Studies on advanced NSCLC patients treated with carboplatin were sparse, heterogeneous and small thus reporting varying results. CONCLUSION: The literature on advanced NSCLC patients treated with carboplatin or cisplatin are dominated by small and heterogeneous patient populations and yielded different results. No firm conclusions can be drawn on carboplatin based on the current literature. Research on the development of a reliable methodology is warranted followed by validation in large, prospective, randomized trials as ERCC1 may possibly play an important role as tumour marker in tailored chemotherapy for NSCLC.
BACKGROUND:Patients diagnosed with advanced non-small cell lung cancer have a dismal prognosis and are often relative resistant to chemotherapy. A need for markers has emerged based on tumour biology in order to predict which patients will respond to treatment. Excision repair cross-complementation group 1 (ERCC1) has shown potential as a predictive marker in patients with NSCLC treated with cisplatin-based chemotherapy. Carboplatin has gained widespread use in the treatment of advanced NSCLC and its mechanisms of action are likely similar to that of cisplatin. MATERIALS AND METHODS: A literature review on ERCC1 was conducted as predictor in NSCLCpatients receiving platinum-based treatment with emphasis on carboplatin. English language publications from January 1996 to February 2008 were eligible and data on methodology and outcome were recorded. RESULTS: Eight preclinical articles, 25 clinical articles and 1 clinical abstract were identified. Laboratory methods were mainly RT-PCR (reverse transcriptase polymerase chain reaction) or immunohistochemistry (IHC) for expression of ERCC1. Preclinical studies pointed towards similar mechanisms of chemotherapy-resistance among platinum compounds. A statistically significant benefit in outcome was found among NSCLCpatients, who received adjuvant treatment, and had low-ERCC1 expression. Advanced NSCLCpatients treated with cisplatin showed improved response rates (RR) but no difference in other endpoints. Studies on advanced NSCLCpatients treated with carboplatin were sparse, heterogeneous and small thus reporting varying results. CONCLUSION: The literature on advanced NSCLCpatients treated with carboplatin or cisplatin are dominated by small and heterogeneous patient populations and yielded different results. No firm conclusions can be drawn on carboplatin based on the current literature. Research on the development of a reliable methodology is warranted followed by validation in large, prospective, randomized trials as ERCC1 may possibly play an important role as tumour marker in tailored chemotherapy for NSCLC.
Authors: Ming Yin; Jingrong Yan; Alexandra Voutsina; Carmelo Tibaldi; David C Christiani; Rebecca S Heist; Rafael Rosell; Richard Booton; Qingyi Wei Journal: Lung Cancer Date: 2010-11-13 Impact factor: 5.705