Feasibility and Efficacy of Molecular Analysis-Directed Individualized Therapy Based of Tumoral mRNA Levels of ERCC1, RRM1 and BRCA1 in Advanced Non-Small-Cell Lung Cancer
Advanced stage NSCLC is essentially a fatal disease and treatment is mainly palliative.
Systemic cisplatin-based chemotherapy remains the mainstream for the treatment of advanced
non-small cell lung cancer (NSCLC) since it improves survival, symptom control and quality
of life compared to best supportive care.
The selection of appropriate treatment for individual patients remains a challenge in
clinical oncology, particularly in the advanced disease. Several lines of evidence indicate
that polymorphisms, gene transcripts and gene mutations can play a predictive role and can
be used to tailor chemotherapy in different subgroups of cancer patients. There are evidence
lead us to use the expression levels of ERCC1 by the tumor as a molecular marker for
customized chemotherapy. Another gene, the BRCA1 has a crucial role in DNA repair, since it
is implicated in transcription-coupled nucleotide excision repair (TC-NER), leading to
radio- and chemo-resistance. RRM1,localized in 11p15.5,also acts as a putative tumor
suppressor gene. RRM1 overexpression was related to gemcitabine resistance in human
oropharyngeal epidermoid carcinoma KB cells as well as in patients with NSCLC. For those
reason we decided to conduct a prospective pilot phase II trial, in patients with wet stage
IIIb and IV NSCLC using chemotherapy regimens which will be defined according to the
pharmacogenomic profile (tumoral expression of ERCC1, BRCA1 and RRM1) of the tumor cells.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective Response Rate (ORR) based on the pharmacogenomic profile of the ERCC1, RRM1 and BRCA1 expression
Objective responses confirmed by CT or MRI
John Souglakos, MD
University Hospital of Crete, Dep of Medical Oncology
Greece: National Organization of Medicines