Evaluation of c-erb2 in locally advanced and/or metastatic non-small cell lung cancer(nsclc) and response to gemcitabine cisplatin protocol

Lung cancer is the leading cause of cancer death all over the world, and based on histological study is classified into NSCLC (75%), SCLC (20%) and others (5%).C-erb-B2 (also known as HER2), is one of oncogene that studied in lung cancer and showed overexpression in up to 25% ofNSCLC only.Overexpression of c-erbB2 has been shown to be associated with an adverse prognosis in adenocarcinoma of the lung. Patients with HER2 neu overexpression had a significantly higher incidence of early tumor recurrence. Survival was also significantly better in-patients without HER2 neu overexpression than in those with HER2 neu overexpression.This study had been carried out in Medical Oncology and Hematology Unite, Internal Medicine Department, Zagazig University Hospitals between Oct. 2000 to Feb. 2002 on 50 chemotherapy-naive patients with histologically or cytologically confIrmed NSCLC stage HIB or IV measurable disease.Each patient was subjected to complete history, complete physical examination with assessment of performance status, routine laboratory investigation with evaluation of creatinine clearance to identify the tolerability of patient to receive cisplatin, radiological work up to diagnose stage of disease and metastasis lesion and evaluation of cerbB2 (HER2) neu status by immohistochemisty.Patients were treated with gemcitaline-cisplatin protocol and evaluated after three cycles for response and responding patients continued for 6 cycles and stage UIB shift to local radiotherapy modality on primary site of disease.Our results showed that:+ cerbB2 expression in 24% of cases.• cerbB2 expression was a good predictor for poor prognosis.• Gemcitabine- cisplatin protocol induced CR in 8 % of patients, PR in 24% (OR was 32%), SD in 28% and PD in 40% .• Toxicity was tolerated and did not lead to stoppage of therapy or therapy related death.• There was significant association between cerbB2 overexpresslOn (24%) and response to chemotherapy (P=0.037); i.e. CR (8%) observed totally in cerbB2 negative and PR (24%) observed in 91.6% of cerbB2 negative, while PD in 45% of cerbB2 positive patients.• Also there was significant association between c-erbB2 and survival (P=0.Ol2); i.e., in living patients 91.7% were HER2 negative and 8.3% were HER2 positive. Gemcitabine-cisplatine protocol provides effective short-term therapy in locally advanced and metastatic NSCLC but new agents will be necessary for long term survival. Assessment of cerbBz(HERz)neu expressIOn as well as other genes that more selectively expressed or absent in NSCLC such as( P53, c.sis and c.fes). These genes may be of important in study of the tumor biology. Further studies on large scale of patient and different methods for assessment HERz status to evaluate the best cost-benefit approach to evaluate HER2 status. Development of a new prognostic index based on actual measures of drug resistance including clinical variables, biological and molecular markers, then patients adverse prognostic features should be subjected to new strategies of therapy to improve the results obtained.