Sc Cesar Wong

Intermittent versus continuous erlotinib with concomitant modified "XELOX" (q3W) in first-line treatment of metastatic colorectal cancer: correlation with serum amphiregulin and transforming growth factor alpha.

This study evaluated the activity of 2 schedules of erlotinib in combination with chemotherapy, and the prognostic significance of serum amphiregulin (AREG) and transforming growth factor alpha (TGFa) in metastatic colorectal cancer.

Elucidating the prognostic significance of KRAS, NRAS, BRAF and PIK3CA mutations in Chinese patients with metastatic colorectal cancer

The prognostic significance of KRAS, NRAS, PIK3CA and BRAF mutations was evaluated in Chinese patients with metastatic colorectal cancer (CRC).

Prospective evaluation of plasma Epstein–Barr virus DNA clearance and fluorodeoxyglucose positron emission scan in assessing early response to chemotherapy in patients with advanced or recurrent nasopharyngeal carcinoma

BackgroundPlasma Epstein–Barr virus (pEBV) DNA and fluorodeoxyglucose positron emission (PET) reflect tumour burden in advanced NPC. This study hypothesised that a dual endpoint based on assessing pEBV DNA clearance and PET response could predict early drug response.MethodsEligible patients underwent a computed tomography (CT) scan and dual PET-CT at baseline, a PET-CT at 4 weeks, and then a CT scan at 10 weeks after starting palliative or induction chemotherapy. Plasma EBV DNA clearance was determined.ResultsFifty-eight out of 70 enrolled patients completed all imaging and 50/58 had falling pEBV DNA level, which allowed calculation of the clearance. At a median follow-up of 29.1 months, the dual endpoint (pEBV DNA clearance ≤ 10 days and > 50% drop in sum of SUVmax of target lesions) was an independent indicator of overall survival (hazard ratio (HR) = 0.135, 95% CI = 0.039 to 0.466, p = 0.0015) and progression-free survival (HR = 0.136, 95% CI = 0.048 to 0.385, p = 0002). This dual endpoint could predict subsequent response by Response Evaluation Criteria In Solid Tumours (RECIST) criteria at 10 weeks after chemotherapy.ConclusionsEarly PET-CT response and pEBV DNA clearance could predict survival and subsequent response. This dual endpoint is an innovative tool for assessing early drug response.

Randomized phase II study of erlotinib (ERL) in two different schedules with concomitant modified XELOX in the first-line treatment of metastatic colorectal cancer (mCRC): Correlation with serial serum levels of amphiregulin (AMR) and transforming growth factor receptor-alpha (TGFa).

425 Background: This study evaluated the feasibility of combining XELOX with erlotinib in a 2 different schedules, and the prognostic significance of serum AMR and TGFa in previously untreated mCRC. Methods: Eligible patients (Pt) were randomized to the ‘continuous’ arm (Arm CON) [ERL 100mg daily D1-21, oxaliplatin (Ox) 130mg/m2 D1, capecitabine (Xe) 825mg/m2 bd D1-14, q3w], or the ‘intermittent’ arm (Arm INT) [ERL 150mg daily at alternate day on D 1-14, then 150mg daily on D15-21, Ox 130mg/m2 on D1, Xe 750mg/m2bd on D1-14, in a q3w]. Serum levels of AMR, TGFa and CEA were determined serially. KRAS mutation was determined from archived tumors. Results: 60 pts were randomized and there was no difference in the baseline characteristics between the 2 arms. Of the 58 pts evaluated for response, the overall response rates (ORR) were 56.3% (Arm CON) and 66.3% (Arm INT). At a median follow-up of 2.8 yrs, the median overall survival (OS) of pts in Arm CON and Arm INT were 9 m (95% CI: 7.2-18m) and 10.3m (95% CI: ...

Abstract 505: Jagged 2 knockdown inhibits invasion in colorectal cancer cell lines

Background: The notch pathway is involved in control of cell differentiation in various tissues including pancreas, muscle and bone marrow. Jagged 2 (JAG2) is a ligand for the notch pathway and was found to be overexpressed in malignant plasma cells from patients with multiple myeloma, causing the secretion and release of IL-6, VEGF, and IGF-1 in the microenvironment supporting myeloma cell growth. In breast cancers, it was found to be overexpressed at the hypoxic invasive front and was significantly correlated with metastasis free survival. Furthermore, up-regulation of JAG2 expression in mouse lung adenocarcinoma cells promoted its metastasis in mice. However, the expression pattern and function of JAG2 in colorectal cancer (CRC) is not clear. Therefore in this study, we examined the expression of JAG2 in CRC cell lines and determined the effect(s) of JAG2 knockdown by RNA interference in CRC cell lines. Materials and Methods: The expression of JAG2 protein was examined in four CRC cell lines (SW480, SW620, HCT116, DLD-1) and also in 1 normal colon epithelial cell line (CCD18co) using the western blot. To investigate the effects JAG2 knockdown in CRC cell lines, a pool of 4 siRNAs against JAG2 was transfected into the 4 CRC cell lines listed above. The effects on cell growth was then determined by the CellTiter 96® AQueous One Solution Cell Proliferation Assay (the MTS assay) and the Matrigel invasion assay was performed to assess its effects on invasive capability. Results: Western blot results showed that JAG2 protein was expressed in all 4 colorectal cancer cell lines including SW480, SW620, HCT116 and DLD-1 but not in the CCD18co normal colon epithelial cell line. The MTS assay showed that cell growth was not affected by JAG2 knockdown in the CRC cell lines. Interestingly, the invasive capability of HCT116 and DLD-1cells was reduced after JAG2 knockdown. Conclusions: Results from this study suggest that JAG2 may play a role in the invasiveness of CRC cell lines but not in cell proliferation. JAG2 may be a promising therapeutic target for inhibition of metastasis in colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 505. doi:1538-7445.AM2012-505