This is 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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
88
Gemcitabine I.V at the dose of 1000mg/m2 on Day 1 and Day 8
Cisplatin I.V at the dose of 75mg/m2 on Day 1
Docetaxel I.V at the dose of 75mg/m2 on Day 1
University General Hospital of Alexandroupolis, Dept. of Medical Oncology
Alexandroupoli, Greece
"Laikon" General Hospital, Medical Oncology Unit, Propedeutic Dep of Internal Medicine
Athens, Greece
401 Military Hospital, Medical Oncology Unit
Athens, Greece
Objective Response Rate (ORR) based on the pharmacogenomic profile of the ERCC1, RRM1 and BRCA1 expression
Time frame: Objective responses confirmed by CT or MRI
Determine the incidence of the different pharmacogenomic profiles as defined by the combined expression of ERCC1, RRM1 and BCRA1
Time frame: Comparison of molecular determinants for response in the primary tumor and peripheral blood (ERCC1 polymorphism ,TXR1 and TSP1 mRNA expression by Q-RT-PCR, Molecular markers related to responsiveness to Alimta )
Time to Tumor Progression
Time frame: 1 year
Overall Survival
Time frame: 1 year
Toxicity
Time frame: Toxicity assessment on each chemotherapy cycles
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Cisplatin I.V at the dose of 80mg/m2 on Day 1
Vinorelbine per os 50mg every Monday, Wednesday and Friday
Pemetrexate I.V 500mg/m2 on Day 1
Air Forces Military Hospital, Dep of Medical Oncology
Athens, Greece
IASO" General Hospital of Athens, 1st Dep of Medical Oncology
Athens, Greece
Sismanogleio General Hospital, 1st, 2nd Dep of Pulmonary Diseases
Athens, Greece
Sotiria" General Hospital, 1st, 3rd, 8th Dep of Pulmonary Diseases
Athens, Greece
"Metaxa's" Anticancer Hospital of Piraeus,1st Dep of Medical Oncology
Piraeus, Greece
"Theagenion" Anticancer Hospital of Thessaloniki
Thessaloniki, Greece