Phenotypic tumour cell plasticity as a resistance mechanism and therapeutic target in melanoma

Publication date: May 2016
Source:European Journal of Cancer, Volume 59
Author(s): Alexander Roesch, Annette Paschen, Jenny Landsberg, Iris Helfrich, Jürgen C. Becker, Dirk Schadendorf
Despite the recent success of MAPK and immune checkpoint inhibitors in advanced melanoma, intrinsic and acquired resistance mechanisms determine the efficacy of these therapeutic approaches. Therapy resistance in melanoma is not solely driven by genetic evolution, but also by epigenetically driven adaptive plasticity. Melanoma cells are shifting between different transcriptional programs, cell cycle states and differentiation phenotypes reflecting a highly dynamic potential to adapt to various exogenous stressors including immune attack or cancer therapies. This review will focus on the dynamic interconversion and overlap between different melanoma cell phenotypes in the context of therapy resistance and a dynamically changing multicellular microenvironment.



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Polyurethane versus silicone catheters for central venous port devices implanted at the forearm

Publication date: May 2016
Source:European Journal of Cancer, Volume 59
Author(s): Moritz Wildgruber, Claudia Lueg, Sebastian Borgmeyer, Ilham Karimov, Ulrike Braun, Marion Kiechle, Reinhard Meier, Michael Koehler, Johannes Ettl, Hermann Berger
PurposeWe aimed to analyse short and long-term complications of polyurethane (PU) versus silicone catheters used in totally implantable venous-access ports (TIVAPs) implanted at the forearm.MethodsRetrospective analysis of 698 consecutively implanted TIVAPs was performed. Primary end-points were defined as rates of major complications associated with either type of central venous port catheter. Technical success rate, device service interval as well as minor complications not requiring port explantation were defined as secondary end-points.ResultsA total of 698 port devices were implanted in 681 patients, 396 equipped with a PU catheter, 302 with a silicone catheter. The technical success rate was 99.9% with no major periprocedural complications. During follow-up a total of 211 complications in 146 patients were observed (1.0/1000 catheter days), 183 occurred associated with PU catheters (1.8/100 catheter days), 28 (0.3/1000 catheter days) with silicone catheters (log rank test p < 0.0001). Catheter-related bloodstream infections as well as thrombotic complications occurred significantly more frequently with PU catheters, while silicone catheters exhibited a trend towards a higher rate of mechanical failure such as disconnection or catheter rupture. Major complications requiring explantation of the device occurred more frequently with PU-based catheters (10.6%) compared to silicone catheter carrying ports (4.6%, log rank test p < 0.001).ConclusionPU catheters are more susceptible to catheter-related infections and exhibit a higher thrombogenicity, compared to silicone catheters. Silicone catheters instead exhibit a trend towards decreased mechanical stability.



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Ramucirumab: Boon or bane

Publication date: Available online 26 March 2016
Source:Journal of the Egyptian National Cancer Institute
Author(s): Priya Tiwari
Ramucirumab is the recent addition to the list of monoclonal antibodies being tried in various malignancies. It has been approved in non-small cell lung cancer, gastric cancer and colorectal cancer after progression of one or more lines of therapies in the advanced setting. Though randomized trials have shown benefit, cost effectiveness is questionable. Moreover, the benefits shown are marginal, putting a question mark over its clinical usage. This review summarizes the latest evidence on ramucirumab.



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[Perceptual gap between oncologists/oncology nurses and patients in the management and impact of chemotherapy/radiotherapy-induced nausea and vomiting: French results of the GAP survey].

[Perceptual gap between oncologists/oncology nurses and patients in the management and impact of chemotherapy/radiotherapy-induced nausea and vomiting: French results of the GAP survey].

Bull Cancer. 2016 Mar 22;

Authors: Morin S, Leurs I, Bousquet MN, Scotté F

Abstract
INTRODUCTION: Despite progress in the treatment of chemotherapy/radiotherapy-induced nausea and vomiting (CINV/RINV), their management remains insufficient.
METHODS: In order to evaluate the incidence and impact of CINV/RINV on the quality of life perceived by patients and estimated by clinicians, a declarative, cross-sectional survey was conducted in France through an online questionnaire.
RESULTS: This survey included 187 participants: 75 oncologists, 35 oncology nurses and 77 patients. Clinicians over-estimated the incidence of CINV/RINV, but underestimated their impact on the quality of life of patients. The sub-optimal prescription of anti-emetic treatments was more prominent when the therapy administered had low or medium emetogenic potential. Only 30% of patients rated their nausea and vomiting as controlled from the start. A major proportion of patients (68%) declared poor compliance with their anti-emetic regimen. The acceptance of CINV/RINV as normal side effects of the chemotherapy/radiotherapy (51%) led the patients not to report them, thus limiting their active management. The number of drugs to absorb, and the fear that the action of swallowing the pill would induce nausea or vomiting were also quoted by the patients as compliance-limiting factors.
CONCLUSION: The perceptual gap between clinicians and patients regarding the incidence and impact of CINV/RINV contributes to a sub-optimal level of anti-emetic cover and control. The anti-emetic regimen needs to be regularly assessed and adapted to the patient in order to improve CINV/RINV management.

PMID: 27015797 [PubMed - as supplied by publisher]

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Open surgery versus laparoscopic surgery after stent insertion for obstructive colorectal cancer

Abstract

Purpose

To compare the outcomes of laparoscopic surgery vs. open surgery after insertion of a colonic stent for obstructive colorectal cancer.

Methods

Between April 2005 and August 2013, 58 patients underwent surgery after the insertion of a colonic stent for obstructive colorectal cancer. We analyzed the outcomes of the patients who underwent laparoscopic surgery vs. those who underwent open surgery.

Results

We compared blood loss, operative time, hospital stay, and complications in 26 patients who underwent laparoscopic surgery and 32 patients who underwent open surgery. Blood loss was significantly less in the laparoscopic surgery group, but operative time was significantly shorter in the open surgery group. The length of hospital stay was shorter in the laparoscopic surgery group than in the open surgery group, but the difference was not significant. There was no significant difference in postoperative surgical complications between the groups.

Conclusion

The patients who underwent laparoscopic resection had less blood loss, although no significant difference was found in postoperative morbidity or mortality. Thus, laparoscopic resection after stent insertion is a feasible and safe option for patients with obstructive colorectal cancer.

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Efficacy and safety of febuxostat for prevention of tumor lysis syndrome in patients with malignant tumors receiving chemotherapy: a phase III, randomized, multi-center trial comparing febuxostat and allopurinol

Abstract

Background

Control of serum uric acid (sUA) levels is very important during chemotherapy in patients with malignant tumors, as the risks of tumor lysis syndrome (TLS) and renal events are increased with increasing levels of sUA. We investigated the efficacy and safety of febuxostat, a potent non-purine xanthine oxidase inhibitor, compared with allopurinol for prevention of hyperuricemia in patients with malignant tumors, including solid tumors, receiving chemotherapy in Japan.

Methods

An allopurinol-controlled multicenter, open-label, randomized, parallel-group comparative study was carried out. Patients with malignant tumors receiving chemotherapy, who had an intermediate risk of TLS or a high risk of TLS and were not scheduled to be treated with rasburicase, were enrolled and then randomized to febuxostat (60 mg/day) or allopurinol (300 or 200 mg/day). All patients started to take the study drug 24 h before chemotherapy. The primary objective was to confirm the non-inferiority of febuxostat to allopurinol based on the area under the curve (AUC) of sUA for a 6-day treatment period.

Results

Forty-nine and 51 patients took febuxostat and allopurinol, respectively. sUA decreased over time after initiation of study treatment. The least squares mean difference of the AUC of sUA between the treatment groups was −33.61 mg h/dL, and the 95 % confidence interval was −70.67 to 3.45, demonstrating the non-inferiority of febuxostat to allopurinol. No differences were noted in safety outcomes between the treatment groups.

Conclusion

Febuxostat demonstrated an efficacy and safety similar to allopurinol in patients with malignant tumors receiving chemotherapy.

Trial registry

http://ift.tt/1WRE85R; Identifier: JapicCTI-132398.

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