Search results for "colorectal"

Trifluridine/tipiracil : an emerging strategy for the management of gastrointestinal cancers

2018

Fluoropyrimidines are currently the backbone of treatment for gastrointestinal (GI) cancers but development of resistance to these agents remains a major problem. Trifluridine/tipiracil is an oral chemotherapeutic agent recently approved for third-line treatment of chemorefractory metastatic colorectal cancer. This article reviews the clinical value of trifluridine/tipiracil as a monotherapy, including recent trials in GI cancers, and the potential benefit of combining it with other agents in patients with GI cancers, including the preclinical rationale for combination therapy and recently completed and ongoing clinical trials. Data gathered so far suggest that trifluridine/tipiracil has t…

Increased efficacy of stereotactic ablative radiation therapy after bevacizumab in lung oligometastases from colon cancer.

2018

Aim: Metastases from colorectal cancer are poorly responsive to stereotactic ablative radiation therapy (SABR) due to intratumoral hypoxia. Intratumoral oxygenation is improved by administration of angiogenesis inhibitors. Thus, there could be a clinical synergistic effect of SABR with bevacizumab on metastases from colorectal cancer. The aim of this study was to evaluate the feasibility and efficacy of SABR after bevacizumab in lung oligometastases from colon cancer. Methods: The data of patients with lung metastases from colon cancer who underwent SABR were retrospectively evaluated according to the following inclusion criteria: number of metastases ≤3; lung oligometastases from colon can…

A phase I dose-escalation of trifluridine/tipiracil in combination with oxaliplatin in metastatic colorectal cancer.

2017

TPS3626 Background: Trifluridine/tipiracil, also known as TAS‐102, is a combination of an antineoplastic thymidine‐based nucleoside analogue (trifluridine) and a thymidine phosphorylase inhibitor (tipiracil hydrochloride). The antitumor activity of combined trifluridine/tipiracil and oxaliplatin has been studied in gastrointestinal tumor xenografts, including a 5‐FU resistant subline, using a nude mouse model. This study demonstrated increased antitumor activity for the combination compared to trifluridine/tipiracil or oxaliplatin alone (p < 0.001) (Nukatsuka et al., Anticancer Res 2015). These data support the rationale for clinical use of the combination. We describe a phase 1, intern…

The McCAVE Trial: Vanucizumab plus mFOLFOX‐6 Versus Bevacizumab plus mFOLFOX‐6 in Patients with Previously Untreated Metastatic Colorectal Carcinoma …

2019

Abstract Background Bevacizumab, a VEGF‐A inhibitor, in combination with chemotherapy, has proven to increase progression‐free survival (PFS) and overall survival in multiple lines of therapy of metastatic colorectal cancer (mCRC). The angiogenic factor angiopoetin‐2 (Ang‐2) is associated with poor prognosis in many cancers, including mCRC. Preclinical models demonstrate improved activity when inhibiting both VEGF‐A and Ang‐2, suggesting that the dual VEGF‐A and Ang‐2 blocker vanucizumab (RO5520985 or RG‐7221) may improve clinical outcomes. This phase II trial evaluated the efficacy of vanucizumab plus modified (m)FOLFOX‐6 (folinic acid (leucovorin), fluorouracil (5‐FU) and oxaliplatin) ver…

CanStem303C trial: A phase III study of napabucasin (BBI-608) in combination with 5-fluorouracil (5-FU), leucovorin, irinotecan (FOLFIRI) in adult pa…

2017

TPS3619 Background: Cancer stem cells are considered to be fundamentally important for resistance to therapy, recurrence and metastasis. Napabucasin is a first-in-class cancer stemness inhibitor in development identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al, PNAS 112(6):1839, 2015). Preclinically, napabucasin sensitizes cancer cells to chemotherapeutics, including 5-FU and irinotecan. Encouraging anticancer activity in advanced CRC was observed in a phase Ib/II (Bendell et al, GI ASCO 2017) study of 63 pts with disease control rate (DCR) of 93% (28/30) and overall response rate (ORR) of 33% (10/30) in FOLFIRI-naïve pts w…

Copy number variations inDCC/18q andERBB2/17q are associated with disease-free survival in microsatellite stable colon cancer

2017

We conducted a prospective study to assess the prognostic impact of selected copy number variations (CNVs) in stage II-III microsatellite stable (MSS) colon cancer. A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8 selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q, ERBB2/17q, and STK6/20q, were detected using a quantitative multiplex polymerase chain reaction of short fluorescent fragment (QMPSF) method. The primary end-point was the impact of the CNVs on the 4-year disease-free survival (DFS). The recurrence rate at 4 years was 20.9%, corresponding to 14% stage II patients vs 31% stage III patients (p<0.0001). The 4-year DFS was significan…

Phase I multicenter, open-label study to establish the maximum tolerated dose (MTD) of trifluridine/tipiracil (TAS-102) and oxaliplatin combination i…

2018

816 Background: Preclinical evidence suggests improved efficacy when combining trifluridine/tipiracil with oxaliplatin compared to each monotherapy (Nukatsuka, 2015). The primary objective was to determine the MTD and the safety profile of the doublet among mCRC pts who have progressed after at least one prior line of treatment. Methods: Using a 3+3 design, eligible pts received escalating trifluridine/tipiracil doses from 25, 30 to 35 mg/m² bid, days 1–5 q14, together with a fixed dose of oxaliplatin 85 mg/m² (day 1). An intermediate cohort with a lower dose of oxaliplatin (65 mg/m²) plus 35 mg/m² of trifluridine/tipiracil was also tested. Results: Fifteen of 17 enrolled pts were evaluabl…

Neoadjuvant score in locally advanced rectal cancer: integrating downstaging in risk assessment and looking for new valuable end points

2018

Involvement of non-coding RNAs in chemo- and radioresistance of colorectal cancer

2016

Despite recent progress in understanding the cancer signaling pathways and in developing new therapeutic strategies, however, the resistance of colorectal cancer (CRC) cells to chemo- and radiotherapy represents the main hurdle to the successful treatment, leading to tumor recurrence and, consequently, a poor prognosis. Therefore, overcoming drug and radiation resistance, enhancing drug and radiation sensitivity of CRC cells, and improving the effi cacy of chemo- and radiotherapy have an important signifi cance in the treatment of CRC. The identifi cation of new molecular biomarkers which can predict therapy response and prognosis is one of the most signifi cant aims in pharmacogenomics and…

Dual targeting of HER3 and MEK may overcome HER3-dependent drug-resistance of colon cancers

2016

// Giulia Bon 1, * , Rossella Loria 1, * , Carla Azzurra Amoreo 2 , Alessandra Verdina 1 , Isabella Sperduti 2 , Arianna Mastrofrancesco 3 , Silvia Soddu 1 , Maria Grazia Diodoro 2 , Marcella Mottolese 2 , Matilde Todaro 4 , Giorgio Stassi 4 , Michele Milella 5 , Ruggero De Maria 6 , Rita Falcioni 1 1 Department of Research, Advanced Diagnostic, and Technological Innovation, IRCCS Regina Elena National Cancer Institute, Rome, Italy 2 Department of Research, Advanced Diagnostic, and Technological Innovation, IRCCS Regina Elena National Cancer Institute, Rome, Italy 3 Physiopathology Laboratory of Skin, IRCCS San Gallicano Dermatological Institute, Rome, Italy 4 Surgical and Oncological Scien…