It was reported that among 169,400 new cases of lung cancer diagnosed in 2002 in USA, approximately 154,900 deaths were recorded [
20]. Unfortunately, only 14% of all lung cancer patients (all stages) will be alive for five or more years after diagnosis [
21]. Over 70% of lung cancer patients, when diagnosed, have locally advanced or metastatic disease. This situation implies an obvious need for systemic chemotherapy since the majority of NSCLC tumors are inoperable at diagnosis [
21].
Our study showed that vinorelbine/cisplatinum combination is an active combination with an overall RR of 54%. The RR achieved in the current study was higher than those reported in other clinical trials which investigated platinum based combination chemotherapy for NSCLC & ranged from 20 to 41% [22-25]. This higher RR may be explained by the higher percentage of stage IIIB patients include in this study in comparison to other trials. Yet the role of biological factors that can modulate the response to certain therapies should not be neglected.
The median TTP for the whole group was 5.5 months higher than that reported in the ECOG and SWOG trials which was 4 months for both [22,23]. The median OS was 12 months and the one year survival was 50%, also longer than that reported by most of the trials which included a third generation chemotherapy (gemcitabine, taxanes and vinorelbine) in combination with cisplatinum which resulted in a survival rate of 33% at one year [20,22-24].
The adverse events associated with the dosing schedule of vinorelbine/cisplatinum combination used were predictable and controllable, with no toxic deaths. The most frequently reported were leukopenia (43.5%) and anemia (25.6%) which were comparable to that reported in the ECOG and SWOG trials and less than that reported by Sandler et al. [22-24]. Non-hematological adverse events included GIT toxicity and neurotoxicity, which were mostly grade I and II toxicities and were comparable to other trials.
EGFR overexpression was encountered in 59% of patients enrolled in the trial, a finding that is consistent with other reports in similar settings [3-5].
In our study, overexpression of EGFR was not found to be associated with advanced stage of disease, pathological subtype, pathological grade or poor performance.
In 1998, Volm et al. [12] reported that patients with squamous cell carcinoma of the lung overexpress EGFR protein more frequently than other subtypes (p=0.01) and such patients suffer a more advanced disease with a poor performance status. This was confirmed a couple of years later by Ohsaki et al. [11]. However, our trial failed to further strengthen this finding. It was also found that patients with normal serum levels of EGFR showed higher RR than patients with over-expressed EGFR, the difference was however statistically insignificant unlike that reported by Salomon et al. [3], and Ohsaki et al. [11]. It might be related to the small number of patients enrolled in our trial.
The median TTP was significantly longer in patients with Arm 1 versus Arm 2 while the median survival time was not significantly prolonged. The long-term survival (21 months) was significantly longer in Arm 1 compared to Arm 2. These results point to the role of EGFR overexpression as a potential prognostic factor in NSCLC patients and confirm the data previously reported by Ohsaki et al. [11] and Volm et al. [12] correlating EGFR expression and survival.
The overexpression of EGFR has been linked with signaling pathways and has many effects including increased proliferation, angiogenesis, and decreased apoptosis explaining the poor treatment outcome in these patients[6].
Since EGFR is often found in NSCLC cells, it has been the focus of efforts to develop new agents that target the EGFR pathway. Erlotinib and gefitinib inhibit the tyrosine kinase activity of EGFR and have been studied extensively.
In a phase III, multicenter, randomized controlled trial, erlotinib as monotherapy was used for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. Survival of erlotinib-treated patients was superior to that of placebotreated patients. The median survival duration of erlotinibtreated patients was 6.67 months, compared with 4.70 months for placebo-treated patients (p < 0.001). Erlotinib was also superior to placebo for progression-free survival and a RR of 8.9% versus 0.9% [26].
Both erlotinib and gefitinib received registration approval by the U.S. Food and Drug Administration (FDA) for the second- and third-line treatment of non-small cell lung cancer (NSCLC), but the failure of gefitinib to show a survival advantage over placebo has resulted in a discussion about the registration of gefitinib [27].
;){kind=link}
;){kind=link}
;){kind=link}
;){kind=link}
;){kind=link}
;){kind=link}