Clinical and pharmacogenetic determinants of 5-fluorouracyl/leucovorin/irinotecan toxicity: Results of the PETACC-3 trial.

Purpose: Irinotecan (CPT-11) in combination with 5-fluorouracil (5FU) is widely used in the treatment of colorectal cancer. We assessed potential clinical variables that may predict toxicity and more specifically the role of UGT1A1 polymorphisms associated with irinotecan toxicity. We used data from the PETACC3 trial, which randomised patients in adjuvant setting to 6 months of leucovorin (LV) and 5FU (LV5/FU2) or LV5/FU2 + irinotecan.

Clinical consequences of chemotherapy dose reduction in obese patients with stage III colon cancer: A retrospective analysis from the PETACC 3 study.

Background: Dose reduction in obese cancer patients has been replaced by fully weight-based dosing recommendations. No data, however, are available on the effects of dose reduction in obese stage III colon cancer patients undergoing adjuvant chemotherapy.

Methods: Survival outcomes and toxicity data of obese (body mass index [BMI] ≥30 kg/m), stage III colon cancer patients treated within the phase III PETACC 3 trial comparing leucovorin, 5-FU (LV5FU2) with LV5FU2 plus irinotecan were analysed retrospectively according to chemotherapy dosing at first infusion (i.

Long-term outcome of dasatinib first-line treatment in gastrointestinal stromal tumor: A multicenter, 2-stage phase 2 trial (Swiss Group for Clinical Cancer Research 56/07).

Background: Tyrosine kinase inhibitors (TKIs) have improved the outcome of patients with gastrointestinal stromal tumors (GISTs), but most patients eventually develop resistance and progress. Dasatinib is a potent inhibitor of BCR-ABL, KIT, and SRC family kinases as well as imatinib-resistant cells. In GISTs, response evaluation is routinely done using computed tomography (CT) and F-fluorodeoxyglucose positron emission tomography coupled to CT (FDG-PET/CT) for early response assessment and outcome prediction.

Long-Term Survival with Regorafenib in -Mutated Metastatic Rectal Cancer.

Regorafenib, an oral multikinase inhibitor, was approved in September 2012 by the US Food and Drug Administration for the treatment of patients with metastatic colorectal cancer progressing on standard therapies. Here, we describe the clinical history of a 63-year-old male patient who was treated with regorafenib in the pivotal CORRECT trial. The patient was initially diagnosed in November 2008 with nonmetastatic -mutated (exon 2, codon 12) rectal cancer.

BRAF V600E Mutant Colorectal Cancer Subtypes Based on Gene Expression.

Purpose: Mutation of BRAF at the valine 600 residue occurs in approximately 10% of colorectal cancers, a group with particularly poor prognosis. The response of BRAF mutant colorectal cancer to recent targeted strategies such as anti-BRAF or combinations with MEK and EGFR inhibitors remains limited and highly heterogeneous within BRAF V600E cohorts. There is clearly an unmet need in understanding the biology of BRAF V600E colorectal cancers and potential subgroups within this population.

Rectal outcomes after a liver-first treatment of patients with stage IV rectal cancer.

Background: The treatment of patients with metastatic rectal cancer remains controversial. We developed a reverse strategy, the liver-first approach, to optimize the chance of a curative resection. The aim of this study was to assess rectal outcomes after reverse treatment of patients with metastatic rectal cancer.

Context-dependent interpretation of the prognostic value of BRAF and KRAS mutations in colorectal cancer.

Background: The mutation status of the BRAF and KRAS genes has been proposed as prognostic biomarker in colorectal cancer. Of them, only the BRAF V600E mutation has been validated independently as prognostic for overall survival and survival after relapse, while the prognostic value of KRAS mutation is still unclear. We investigated the prognostic value of BRAF and KRAS mutations in various contexts defined by stratifications of the patient population.

Elective inguinal node irradiation in early-stage T2N0 anal cancer: prognostic impact on locoregional control.

Purpose: To evaluate the influence of elective inguinal node radiation therapy (INRT) on locoregional control (LRC) in patients with early-stage T2N0 anal cancer treated conservatively with primary RT.

Methods And Materials: Between 1976 and 2008, 116 patients with T2 node-negative anal cancer were treated curatively with RT alone (n=48) or by combined chemoradiation therapy (CRT) (n=68) incorporating mitomycin C and 5-fluorouracil. Sixty-four percent of the patients (n=74) received elective INRT.

Integrated analysis of molecular and clinical prognostic factors in stage II/III colon cancer.

Background: The prognostic potential of individual clinical and molecular parameters in stage II/III colon cancer has been investigated, but a thorough multivariable assessment of their relative impact is missing.

Methods: Tumors from patients (N = 1404) in the PETACC3 adjuvant chemotherapy trial were examined for BRAF and KRAS mutations, microsatellite instability (MSI), chromosome 18q loss of heterozygosity (18qLOH), and SMAD4 expression. Their importance in predicting relapse-free survival (RFS) and overall survival (OS) was assessed by Kaplan-Meier analyses, Cox regression models, and recursive partitioning trees.

A comprehensive characterization of genome-wide copy number aberrations in colorectal cancer reveals novel oncogenes and patterns of alterations.

To develop a comprehensive overview of copy number aberrations (CNAs) in stage-II/III colorectal cancer (CRC), we characterized 302 tumors from the PETACC-3 clinical trial. Microsatellite-stable (MSS) samples (n = 269) had 66 minimal common CNA regions, with frequent gains on 20 q (72.5%), 7 (41.

Identification of a poor-prognosis BRAF-mutant-like population of patients with colon cancer.

Purpose: Our purpose was development and assessment of a BRAF-mutant gene expression signature for colon cancer (CC) and the study of its prognostic implications.

Materials And Methods: A set of 668 stage II and III CC samples from the PETACC-3 (Pan-European Trails in Alimentary Tract Cancers) clinical trial were used to assess differential gene expression between c.1799T>A (p.

Node-negative T1-T2 anal cancer: radiotherapy alone or concomitant chemoradiotherapy?

Purpose: To evaluate the influence of concomitant chemotherapy on loco-regional control (LRC) and cancer-specific survival (CSS) in patients with T1-T2 N0 M0 anal cancer treated conservatively by primary radiotherapy (RT).

Materials And Methods: Between 1976 and 2008, 146 patients with T1 (n=29) or T2 (n=117) N0 M0 anal cancer were treated curatively by RT alone (n=71) or by combined chemoradiotherapy (CRT) (n=75) consisting of mitomycin C±5-fluorouracil. Univariate and multivariate analyses were performed to assess patient-, tumor- and treatment-related factors influencing LRC and CSS.

Survival predictors for second-line chemotherapy in Caucasian patients with metastatic gastric cancer.

Principles: There are very limited data suggesting a benefit for second-line chemotherapy in advanced gastric cancer. Therefore, the number of patients who receive further treatment after failure of first-line chemotherapy varies considerably, ranging from 14% to 75%. In the absence of a demonstrated survival benefit of second-line chemotherapy, appropriate selection of patients based on survival predictors is essential.

Adjuvant radio-chemotherapy for extrahepatic biliary tract cancers.

Background: Extrahepatic biliary duct cancers (EBDC) are uncommon malignancies characterized by a poor prognosis with high rate of loco-regional recurrence. The purpose of the present study is to assess the feasibility and the potential impact of adjuvant radiotherapy (RT) in a series of patients treated in one institution.

Methods: Twenty three patients with non-metastatic bile duct cancer treated surgically with curative intent (4 gallbladder, 7 ampullary and 12 cholangiocarcinoma) received 3D conformal external beam RT to a median total dose of 50.

Successful closure of anal cancer-related fistulas with upfront intra-arterial chemotherapy: a report of 8 cases.

Background: Fistulas arising from the perforation of anal cancer into adjacent organs are a debilitating complication in the course of the disease.

Objective: We studied intra-arterial chemotherapy as a strategy to close such fistulas before the initiation of standard chemoradiation.

Design: This study was based on a retrospective chart review.

Value of contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography in detection and presurgical assessment of pancreatic cancer: a prospective study.

Background And Aim: Positron Emission Tomography (PET) using (18)F-fluorodeoxyglucose (FDG) associated with computed tomography (CT) is increasingly used for the detection and the staging of pancreatic cancer, but data regarding its clinical added value in pre-surgical planning is still lacking. The aim of this study is to investigate the performance of FDG PET associated with contrast-enhanced CT in detection of pancreatic cancer.

Methods: We prospectively evaluated FDG PET/CT studies obtained in patients with suspicion of operable pancreatic cancer between May 2006 and January 2008.

Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial.

Purpose: Mutations within the KRAS proto-oncogene have predictive value but are of uncertain prognostic value in the treatment of advanced colorectal cancer. We took advantage of PETACC-3, an adjuvant trial with 3,278 patients with stage II to III colon cancer, to evaluate the prognostic value of KRAS and BRAF tumor mutation status in this setting.

Patients And Methods: Formalin-fixed paraffin-embedded tissue blocks (n = 1,564) were prospectively collected and DNA was extracted from tissue sections from 1,404 cases.

Neoadjuvant chemotherapy and radiotherapy followed by surgery in selected patients with stage IIIB non-small-cell lung cancer: a multicentre phase II trial.

Background: Stage IIIB non-small-cell lung cancer (NSCLC) is usually thought to be unresectable, and is managed with chemotherapy with or without radiotherapy. However, selected patients might benefit from surgical resection after neoadjuvant chemotherapy and radiotherapy. The aim of this multicentre, phase II trial was to assess the efficacy and toxicity of a neoadjuvant chemotherapy and radiotherapy followed by surgery in patients with technically operable stage IIIB NSCLC.

Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3.

PURPOSE The primary objective of this randomized, multicenter, phase III trial was to investigate whether the addition of irinotecan to the de Gramont infusional fluorouracil (FU)/leucovorin (LV) adjuvant regimen (LV5FU2) would improve disease-free survival (DFS) in patients with stage III colon cancer. PATIENTS AND METHODS After curatively intentioned surgery, patients with stage II and III colon cancer were randomly allocated surgery to receive LV5FU2 (LV 200 mg/m(2) as a 2-hour infusion, followed by FU; as a 400 mg/m(2) bolus and then a 600 mg/m(2) continuous infusion over 22 hours, days 1 and 2, every 2 weeks for 12 cycles: de Gramont regimen) with or without irinotecan (180 mg/m(2) as a 30- to 90-minute infusion, day 1, every 2 weeks). In total, 260 (7.

'Liver first' approach in the treatment of colorectal cancer with synchronous liver metastases.

Background: In patients with synchronous colorectal liver metastases, an approach reversing the traditional therapeutic order - i.e. starting with chemotherapy first, doing the liver surgery second, and performing the colorectal surgery last - is theoretically appealing as it avoids the risk of metastatic progression during treatment of the primary tumor.

Improved long-term outcome of surgery for advanced colorectal liver metastases: reasons and implications for management on the basis of a severity score.

Background: The outcome of liver resection for colorectal liver metastases (CRLM) appears to be improving despite the fact that surgery is offered to patients with more-severe disease. To quantify this assumption and to understand its causes we analyzed a series of patients on the basis of a standardized severity score and changes in management occurring over the years.

Methods: Patients' characteristics, operative data, chemotherapies and follow-up were recorded.

Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research.

Purpose: This randomized phase II trial evaluated two docetaxel-based regimens to see which would be most promising according to overall response rate (ORR) for comparison in a phase III trial with epirubicin-cisplatin-fluorouracil (ECF) as first-line advanced gastric cancer therapy.

Patients And Methods: Chemotherapy-naïve patients with measurable unresectable and/or metastatic gastric carcinoma, a performance status View Article and Find Full Text PDF