PATIENTS AND METHODS: Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0-2 were randomized 1:1 to receive erlotinib (oral; 150 mg once daily until progression/unacceptable toxicity) or GP [G 1250 mg/m(2) i.v. days 1 and 8 (3-weekly cycle); P 75 mg/m(2) i.v. day 1, (3-weekly cycle) for up to four cycles]. Primary end point: investigator-assessed progression-free survival (PFS). Other end points include objective response rate (ORR), overall survival (OS), and safety.
RESULTS: A total of 217 patients were randomized: 110 to erlotinib and 107 to GP. Investigator-assessed median PFS was 11.0 months versus 5.5 months, erlotinib versus GP, respectively [hazard ratio (HR), 0.34, 95% confidence interval (CI) 0.22-0.51; log-rank P < 0.0001]. Independent Review Committee-assessed median PFS was consistent (HR, 0.42). Median OS was 26.3 versus 25.5 months, erlotinib versus GP, respectively (HR, 0.91, 95% CI 0.63-1.31; log-rank P = .607). ORR was 62.7% for erlotinib and 33.6% for GP. Treatment-related serious adverse events (AEs) occurred in 2.7% versus 10.6% of erlotinib and GP patients, respectively. The most common grade ≥3 AEs were rash (6.4%) with erlotinib, and neutropenia (25.0%), leukopenia (14.4%), and anemia (12.5%) with GP.
CONCLUSION: These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC (NCT01342965).
MATERIALS AND METHODS: Cell viability assay using MTT, DNA fragmentation assay and real-time PCR were used to evaluate the cytotoxic effects of latex whole C-serum and its subfractions on the cell lines.
RESULTS: MTT assay revealed very low LC(50) values, 2.0 and 280 ng/ml, for DCS and DCP treatments, respectively. DCS was proven to be more potent compared to DCP, in conferring specific anti-proliferative effects on the cancer cell lines. The study also indicated that anti-proliferative activity of pre-heated C-serum fractions diminished significantly.
CONCLUSION: Although noteworthy cell death was reported, DNA fragmentation assay and real-time PCR confirmed that that induced by latex C-serum subfractions was not promoted via the classical apoptotic signalling pathway.
METHODS: We investigated the anti-proliferative efficacy of polar leaf extracts (LP), non-polar leaf extracts (LN), polar stem extract (SP) and non-polar stem extracts (SN) in human breast, colorectal, lung, endometrial, nasopharyngeal, and pancreatic cancer cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT assay. The most potent extracts was tested along with gemcitabine using our established drug combination analysis. The effect of the combinatory treatment in apoptosis were quantified using enzyme-linked immunosorbent assay (ELISA), Annexin V assay, antibody array and immunoblotting. Statistical significance was analysed using one-way analysis of variance (ANOVA) and post hoc Dunnett's test. A p-value of less than 0.05 (p
AIM OF THE STUDY: To investigate the potential of F3 from S. crispus to prevent metastasis in breast cancer.
MATERIALS AND METHODS: The antimetastatic effects of F3 were first investigated on murine 4T1 and human MDA-MB-231 breast cancer cell (BCC) lines using cell proliferation, wound healing and invasion assays. A 4T1-induced mouse mammary carcinoma model was then used to determine the expression of metastasis tumor markers, epithelial (E)-cadherin, matrix metalloproteinase (MMP)-9, mucin (MUC)-1, nonepithelial (N)-cadherin, Twist, vascular endothelial growth factor (VEGF) and vimentin, using immunohistochemistry, following oral treatment with F3 for 30 days.
RESULTS: Significant growth arrest was observed with F3 IC50 values of 84.27 µg/ml (24 h) and 74.41 µg/ml (48 h) for MDA-MB-231, and 87.35 µg/ml (24 h) and 78.75 µg/ml (48 h) for 4T1 cells. F3 significantly inhibited migration of both BCC lines at 50 μg/ml for 24 h (p = 0.018 and p = 0.015, respectively). Similarly, significant inhibition of invasion was demonstrated in 4T1 (75 µg/ml, p = 0.016) and MDA-MB-231 (50 µg/ml, p = 0.040) cells compared to the untreated cultures. F3 treatment resulted in reduced tumor growth compared to untreated mice (p
CONCLUSION: Anticancer screening of the synthesized compounds using Sulforhodamine B (SRB) assay demonstrated that compounds 2y (IC50 = 0.01 µmol/mL) and 4y (IC50= 0.02 µmol/mL) have high antiproliferative potential against human colorectal carcinoma cancer cell line than the reference drug (5- fluorouracil) and these compounds also showed best dock score with better potency within the ATP binding pocket and may also be used lead for rational drug designing.
MATERIALS AND METHODS: Two EGFR mutation tests, a tissue-based assay (cobas® v1) and a tissue- and blood-based assay (cobas® v2) were used to analyze matched biopsy and blood samples (897 paired samples) from three Asian studies of first-line erlotinib with similar intent-to-treat populations. ENSURE was a phase III comparison of erlotinib and gemcitabine/platinum, FASTACT-2 was a phase III study of gemcitabine/platinum plus erlotinib or placebo, and ASPIRATION was a single-arm phase II study of erlotinib. Agreement statistics were evaluated, based on sensitivity and specificity between the two assays in subgroups of patients with increasing tumor burden.
RESULTS: Patients with discordant EGFR (tissue+/plasma-) mutation status achieved longer progression-free and overall survival than those with concordant (tissue+/plasma+) mutation status. Tumor burden was significantly greater in patients with concordant versus discordant mutations. Pooled analyses of data from the three studies showed a sensitivity of 72.1% (95% confidence interval [CI] 67.8-76.1) and a specificity of 97.9% (95% CI 96.0-99.0) for blood-based testing; sensitivity was greatest in patients with larger baseline tumors.
CONCLUSIONS: Blood-based EGFR mutation testing demonstrated high specificity and good sensitivity, and offers a convenient and easily accessible diagnostic method to complement tissue-based tests. Patients with a discordant mutation status in plasma and tissue, had improved survival outcomes compared with those with a concordant mutation status, which may be due to their lower tumor burden. These data help to inform the clinical utility of this blood-based assay for the detection of EGFR mutations.