Phase 1 trial on molecularly targeted radiotherapy published in The Lancet Oncology by researchers from The Norwegian Radium Hospital

Pressrelease April 9th 2010, Kjersti Flatmark and Anne Hansen Ree

Anne Hansen Ree, Svein Dueland, Kjersti Flatmark, and coworkers from The Norwegian Radium Hospital are publishing results from a translational radiotherapy study, entitled “Vorinostat, a histone deacetylase inhibitor, combined with pelvic palliative radiotherapy for gastrointestinal carcinoma: the Pelvic Radiation and Vorinostat (PRAVO) phase 1 study”, in The Lancet Oncology (published online on April 7, 2010). This is the first clinical trial to report on the combination of a histone deacetylase (HDAC) inhibitor with radiotherapy, and the authors found that vorinostat can safely be combined with palliative pelvic radiotherapy with a maximum tolerable dose of 300 mg daily.

Histone deacetylases play important roles in the epigenetic regulation of gene expression, and the therapeutic principle of HDAC inhibition exploits the aberrant epigenetic changes characterizing cancer cells. HDAC inhibitors have demonstrated activity in a variety of malignancies, and currently, a dozen HDAC inhibitors are under investigation in clinical trials. Reports indicating low toxicity and favorable safety profiles suggest HDAC inhibitors as interesting candidates for combinatory regimens with cytotoxic therapy (radiotherapy, chemotherapy). The authors have previously reported that the HDAC inhibitor SAHA (vorinostat) had radiosensitizing activity in preclinical models, as tumor cell radiosensitization was achieved in human colorectal carcinoma cell lines in vitro and in vivo.

The PRAVO phase 1 study was performed to assess whether vorinostat could be administered safely in combination with pelvic palliative radiotherapy. The authors report that, among the 16 patients completing the study (one patient withdrew), most adverse events were grades 1 or 2, with fatigue and gastrointestinal events common to all patients. Grade 3 adverse events included fatigue (five patients), anorexia (three), diarrhea (two), hyponatremia (one), hypokalemia (one), and acneiform rash (one). Dose-limiting toxicities occurred at the 300 mg dose in one of six patients (fatigue and anorexia) and at the 400 mg dose in two of six patients (diarrhea, fatigue, anorexia, hyponatremia, and hypokalemia), suggesting a maximum tolerable daily dose of 300 mg. The researchers observed histone hyperacetylation in tumor biopsies, indicating biological activity of vorinostat in the radiotherapy target volumes.

Strategies for improving therapeutic efficacy in clinical radiotherapy are increasingly focused on targeting molecular mechanisms to increase tumor cell radiosensitivity, and HDAC inhibition is emerging as a promising concept. This study shows that vorinostat can be safely combined with short-term pelvic palliative radiotherapy, emphasizing the potential use of HDAC inhibitors with radiation. Furthermore, these promising results suggest vorinostat to be investigated in combination with long-term curative pelvic radiotherapy, for instance in rectal cancer.

The Norwegian Radium Hospital Research Foundation will also for 2010 distribute resources to photodymamic therapy and photochemical internalisation (PDT/PCI) related research. For 2009 a sum amounting 1.4 mill. NOK was distributed on various research projects within this field. Employees at the Oslo University Hospital are welcome to apply. The closing date for applications is January 15th 2010.

The application, containing a description of the project, is sent to:

Radiumhospitalets Forskningsstiftelse
ved Bente Prestegård
Hoffsveien 70 B
0377 Oslo

Email address: This email address is being protected from spam bots, you need Javascript enabled to view it

Web address: www.radforsk.no

Closing date for applications: January 22th 2010.

INFORMASJONSMØTE
– OSLO CANCER CLUSTER  INNOVASJONSPARK

Oslo Cancer Cluster og Oslo Cancer Cluster Innovasjonspark AS (OCCI) planlegger å etablere en Innovasjonspark som kombinerer næring-, utdanning- og forskning og i umiddelbar nærhet til Kreftklinikken Radiumhospitalet og Institutt for Kreftforskning og i fysisk integrasjon med Ullern videregående skole. Innovasjonsparken tar mål av seg til å huse Kreftregisteret, en eller flere større legemiddelselskaper, 12-18 mellomstore og mindre norske bioteknologi-selskaper og selskaper i oppstartfasen samt en inkubator. Parken vil stå ferdig sommeren 2012.

Visjonen for Innovasjonsparken er å bidra til at Oslo Cancer Cluster utvikler seg til å :
- Bli det mest attraktive, forskningsbaserte industricluster i Europa innenfor utvikling av ny kreftdiagnostikk og kreftbehandling.
- Utvikle ny kreftbehandling til pasienter på verdensbasis gjennom tett samarbeid med Institutt for Kreftforskning ved Radiumhospitalet og biotekbedriftene i Innovasjonsparken
- Å bli Norges ledende læringsmiljø innen realfag, bioteknologi og helsefag gjennom en partnerskapsavtale mellom Ullern vgs, Radiumhospitalet, OCC og Universitet i Oslo

Innovasjonsparken vil som verdens første bygg forene klinisk kreftforskning, biotekbedrifter innen kreft og en videregående skole med spesialisering i realfag, entreprenørskap m.m.

All erfaring og forskning viser at en samlokalisering av de enkelte elementer i et cluster gir betydelige synergier. Et Comprehensive Cancer Cluster innebærer en samlokalisering av virksomheter nært opptil sykehuset (pasientbehandling) og forskningsbygget (forskning). Du inviteres nå til å bli en del av dette spennende miljøet. Informasjonsmøtet vil gi deg mer informasjon om byggeprosessen, utformingen av bygget og prosessen videre i forhold til potensielle leietakere.

Unik samarbeidsavtale i havn (Oslo Kommune, 15.09.2008)

Nylig undertegnet Utdanningsetaten og Oslo Cancer Cluster Innovation (OCCI) en skolefaglig avtale som vil bidra til et toppkompetent fagmiljø og høy kvalitet i opplæring og undervisning for elever og lærlinger på Ullern videregående skole.

The Oslo-region and Oslo Cancer Cluster is on the list of Genome Technology´s “20 best places for biotech”. Oslo is the only European region on the list, and the only one outside the US apart from India and China.
 
« To be appointed one of the 20 best places to do biotech in the world today is a real acknowledgment of the hard work we have been doing since the Oslo Cancer Cluster was launched internationally only one year ago. That this highly renowned magazine says we are among the nine emerging clusters in the world is great», says Bjarte Reve, CEO of the Oslo Cancer Cluster.

See the list in June issue

IMPRESSIVE EFFORT
Genome Tecnology made the overview of the 20 best places to do biotech for the BIO conference in San Diego in mid June. Eleven of the places are well-established clusters, and nine are emerging. The list is made on basis of several recognized sources like Ernst & Young’s Global Biotechnology Report from 2007, and several others.

Genome Technology writes on Oslo; «it’s certainly not the biggest of the biotech clusters, but for it’s size, the efforts to cement a bioscience segment here in Norway is truly impressive».

« Oslo is the only place in Europe on the emerging clusters –list in this overview, and we are the only one outside of USA besides India and China. That makes me really proud on behalf of both the 40 members of Oslo Cancer Cluster and all the others involved in life science in the capitol of Norway», says Reve.

A delegation from Oslo Cancer Cluster and The Norwegian Radium Hospital attended from June 3rd to 6th the Global Oncology Programs Conference in Houston.

Physicians, scientists, nurses and administrators from the Sister Institution network joined MD Anderson Cancer Center in Houston to discuss relevant topics for the community.  As in past years, Norway will be represented with an outstanding group of physicians and scientists; delegations from Stavanger University Hospital, the Norwegian Radium Hospital Comprehensive Cancer Center and the Norwegian Cancer Registry will be present at the conference.

The University of Texas MD Anderson Cancer Center is one of the best research centers in the United States, and has since 2007 had a formal agreement of collaboration with the Norwegian Cancer Consortium - consisting of the Norwegian Radium Hospital Comprehensive Cancer Center, the Norwegian Cancer Registryand Stavanger University Hospital.

The relationship between the Norwegian organizations and MD Anderson in Houston has been an important tool for joint research and proliferation of knowledge since 2001.