Phase II study of necitumumab plus modified FOLFOX6 as first-line treatment in patients with locally advanced or metastatic colorectal cancer

This single-arm phase II study investigated the EGFR monoclonal antibody necitumumab plus modified FOLFOX6 (mFOLFOX6) in first-line treatment of locally advanced or metastatic colorectal cancer (mCRC). Patients received 800-mg intravenous necitumumab (day 1; 2-week cycles), followed by oxaliplatin 85 mg m −2, folinic acid 400 mg m −2, and 5-fluorouracil (400 mg m −2 bolus then 2400 mg m −2 over 46 h). Radiographic evaluation was performed every 8 weeks until progression. Primary endpoint was objective response rate. Forty-four patients were enrolled and treated. Objective response rate was 63.6% (95% confidence interval 47.8-77.6); complete response was observed in four patients; median duration of response was 10.0 months (7.0-16.0). Median overall survival (OS) and progression-free survival (PFS) were 22.5 (11.0-30.0) and 10.0 months (7.0-12.0), respectively. Clinical outcome was better in patients with KRAS exon 2 wild type (median OS 30.0 months (23.0-NA); median PFS 12.0 (8.0-20.0)), compared with KRAS exon 2 mutant tumours (median OS 7.0 months (5.0-37.0); median PFS 7.0 (4.0-18.0)). The most common grade ⩾3 adverse events were neutropenia (29.5%), asthenia (27.3%), and rash (20.5%). First-line necitumumab+mFOLFOX6 was active with manageable toxicity in locally advanced or mCRC; additional evaluation of the impact of tumour RAS mutation status is warranted

Patients with Endoscopically Visible Polypoid Adenomatous Lesions Within the Extent of Ulcerative Colitis Have an Increased Risk of Colorectal Cancer Despite Endoscopic Resection.

OBJECTIVES: Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer (CRC). Few studies have looked at long-term outcomes of endoscopically visible adenomatous lesions removed by endoscopic resection in these patients. We aimed to assess the risk of developing CRC in UC patients with adenomatous lesions that develop within the segment of colitis compared to the remainder of an ulcerative colitis cohort. METHODS: We identified patients with a confirmed histological diagnosis of UC from 1991 to 2004 and noted outcomes till June 2011. The Kaplan-Meier method was used to estimate cumulative probability of subsequent CRC. Factors associated with risk of CRC were assessed in a Cox proportional hazards model. RESULTS: Twenty-nine of 301 patients with UC had adenomatous lesions noted within the segment of colitis. The crude incidence rate of developing colon cancer in patients with UC was 2.45 (95 % CI 1.06-4.83) per 1000 PYD and in those with UC and polypoid adenomas within the extent of inflammation was 11.07 (95 % CI 3.59-25.83) per 1000 PYD. Adjusted hazards ratio of developing CRC on follow-up in UC patients with polypoid dysplastic adenomatous lesions within the extent of inflammation was 4.0 (95 % CI 1.3-12.4). CONCLUSIONS: The risk of developing CRC is significantly higher in UC patients with polypoid adenomatous lesions, within the extent of inflammation, despite endoscopic resection. Patients and physicians should take the increased risk into consideration during follow-up of these patients

Antiproliferative effects of sapacitabine (CYC682), a novel 2′-deoxycytidine-derivative, in human cancer cells

This study assessed the antiproliferative activity of sapacitabine (CYC682, CS-682) in a panel of 10 human cancer cell lines with varying degrees of resistance or sensitivity to the commonly used nucleoside analogues ara-C and gemcitabine. Growth inhibition studies using sapacitabine and CNDAC were performed in the panel of cell lines and compared with both nucleoside analogues and other anticancer compounds including oxaliplatin, doxorubicin, docetaxel and seliciclib. Sapacitabine displayed antiproliferative activity across a range of concentrations in a variety of cell lines, including those shown to be resistant to several anticancer drugs. Sapacitabine is biotransformed by plasma, gut and liver amidases into CNDAC and causes cell cycle arrest predominantly in the G2/M phase. No clear correlation was observed between sensitivity to sapacitabine and the expression of critical factors involved in resistance to nucleoside analogues such as deoxycytidine kinase (dCK), human equilibrative nucleoside transporter 1, cytosolic 5′-nucleotidase and DNA polymerase-α. However, sapacitabine showed cytotoxic activity against dCK-deficient L1210 cells indicating that in some cells, a dCK-independent mechanism of action may be involved. In addition, sapacitabine showed a synergistic effect when combined with gemcitabine and sequence-specific synergy with doxorubicin and oxaliplatin. Sapacitabine is therefore a good candidate for further evaluation in combination with currently used anticancer agents in tumour types with unmet needs

Surgery with curative-intent in patients treated with first-line chemotherapy plus bevacizumab for metastatic colorectal cancer First BEAT and the randomised phase-III NO16966 trial

BACKGROUND: Complete resection of metastases can result in cure for selected patients with metastatic colorectal cancer. METHODS: First BEAT evaluated the safety of bevacizumab with first-line chemotherapy in 1914 patients. Prospectively collected data from 225 patients who underwent curative-intent surgery were analysed, including an exploratory comparison of resection rate in patients treated with different regimens. NO16966 compared efficacy of oxaliplatin-based chemotherapy plus bevacizumab or placebo in 1400 patients. A retrospective analysis of resection rate was undertaken. RESULTS: In First BEAT, 225 out of 1914 patients (11.8%) underwent curative-intent surgery at median 64 days ( range 42-100) after the last dose of bevacizumab. R0 resection was achieved in 173 out of 225 patients (76.9%). There were no surgery-related deaths and serious post-operative complications were uncommon, with grade 3/4 bleeding and wound-healing events reported in 0.4% and 1.8%, respectively. Resection rates were highest in patients receiving oxaliplatin-based combination chemotherapy (P=0.002), possibly confounded by patient selection. In NO16966, 44 out of 699 patients treated with bevacizumab (6.3%) and 34 out of 701 patients treated with placebo (4.9%) underwent R0 metastasectomy (P=0.24). CONCLUSIONS: The rate of serious post-operative complications in First BEAT was comparable to historical controls without bevacizumab. In NO16966, there were no statistically significant differences in resection rates or overall survival in patients treated with bevacizumab vs placebo

Somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine tumours, current aspects and new perspectives

Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are rare tumours that present many clinical features

Splenic metastasis from gastrointestinal neoplasms: a review.

Spleen metastases from solid tumours are rather exceptional, especially for those located in the digestive tract. Although these lesions are usually associated with multivisceral disease at terminal stage, several cases of isolated lesions have also been described in the literature. Diagnosis of spleen lesions associated with multivisceral disease rarely influences patient's outcome. On the other hand, isolated, only-splenic lesions could be curatively treated, allowing physicians to obtain better patient's survival. The aim of this article is therefore to review and summarize a systematic search of all the literature in English based on a Medline search (Pubmed) carried out from January 2000 to February 2011, focusing on only-spleen lesions secondary to digestive tract cancers, and pointing out diagnostic and treatment challenges medical oncologists have to face in their clinical practice