Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A case report of a patient with metastatic ocular melanoma who experienced a response to treatment with the BRAF inhibitor vemurafenib
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Univ Uppsala Hosp, Dept Oncol, S-75185 Uppsala, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Uppsala Hosp, Dept Oncol, S-75185 Uppsala, Sweden..
Novartis Sverige AB, Kemistvagen 1, S-18379 Taby, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Univ Uppsala Hosp, Dept Oncol, S-75185 Uppsala, Sweden..
2016 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 16, 634Article in journal (Refereed) Published
Abstract [en]

Background: Conjunctival malignant melanoma (CMM) is a rare malignancy and in the advanced setting there is no effective treatment. In contrast, half of cutaneous melanomas have BRAF mutations and treatment with BRAF inhibitors is established for patients with disseminated disease. The most common form of ocular melanoma, uveal melanoma, lacks these mutations, however, their presence has been reported for CMM. Case presentation: We used the BRAF inhibitor vemurafenib to treat a 53 year-old female suffering from a BRAFV600E mutated metastatic CMM. The patient benefited from the treatment, a response was evident within a week and she experienced a progression free survival of four months. Conclusions: To our knowledge, this is the first described case of response to vemurafenib treatment in a patient with ocular melanoma.

Place, publisher, year, edition, pages
2016. Vol. 16, 634
Keyword [en]
BRAF inhibitor, BRAF mutation, Conjunctival malignant melanoma, Ocular melanoma, Vemurafenib
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-305937DOI: 10.1186/s12885-016-2657-7ISI: 000384169800001PubMedID: 27520988OAI: oai:DiVA.org:uu-305937DiVA: diva2:1045895
Available from: 2016-11-11 Created: 2016-10-24 Last updated: 2017-10-15Bibliographically approved
In thesis
1.
The record could not be found. The reason may be that the record is no longer available or you may have typed in a wrong id in the address field.
2. Experimental treatment of patients with disseminated malignant melanoma
Open this publication in new window or tab >>Experimental treatment of patients with disseminated malignant melanoma
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Malignant melanoma (MM) is the deadliest skin cancer with an ever-increasing incidence. New treatments have improved the prognosis for patients with advanced MM. Still, most patients do not respond, and the side effects can be severe, underlining the need for better therapies.

The overall aim of this thesis was to evaluate new means to improve the treatment for patients with advanced MM. Immunostimulatory gene therapy (AdCD40L) was evaluated in a clinical study and BRAF-inhibitory treatment in rare cases of BRAF-mutated MM.

Due to its immunogenicity, MM is an attractive target for immunostimulatory gene therapy. AdCD40L is an adenovirus carrying the human gene for CD40 ligand, which in different ways can stimulate the immune system to combat cancer. We conducted a Phase I/IIa study with AdCD40L in patients with metastatic MM having received established treatments. In cohort 1 (n=6), four weekly, intratumoural AdCD40L injections were given. In cohort 2 (n=9), low dose cyclophosphamide was added to increase the immune response. Since irradiation may act synergistically with immunotherapy, patients in cohort 3 (n=9) also received a single fraction of radiotherapy (8 Gy). This fraction was given towards the lesion selected for injections.

The primary objectives were to assess the feasibility and safety of AdCD40L-treatment and secondarily its anti-tumour effects. Patients were thoroughly assessed for toxicity. The anti-tumour response was evaluated by imaging techniques (FDG-PET/CT, DW-MRI scans), tumour biopsies and blood tests. Plasma protein markers were measured with a multiplex platform. Another objective was to evaluate the potential of DW-MRI and FDG-PET/CT for prediction of AdCD40L treatment response, in terms of overall survival (OS).

AdCD40L was well tolerated with mild transient reactions. Local and distant responses in PET/CT scans along with a significantly better 6-month survival in the cohorts that received cyclophosphamide conditioning were observed. Effector lymphocyte responses were elicited. All patients had an increased T effector/T regulatory-cell ratio and death receptors were significantly up-regulated post therapy. Inflammatory cytokines and other plasma proteins were altered in favourable ways by the AdCD40L treatment. The analyses support that the functional DWI parameters may be better early predictors of OS than the established metabolic and morphologic criteria of FDG-PET/CT and CT/MRI, respectively.

In conclusion, the stimulation of the CD40 pathway to initiate anti-tumour immunity is a promising treatment alternative for MM patients. However, further studies with developed treatment schemes are warranted.

In the first report ever on treatment of a pregnant patient with a BRAF-inhibitor, the therapy was initiated in the second trimester. The treatment with vemurafenib enabled prolonged gestation, hence reducing the risk of immaturity-related complications. Further, we report the first case worldwide of a patient with metastatic conjunctival melanoma who benefitted from treatment with vemurafenib. Additional studies are needed to assess the efficacy of BRAF -inhibitors in the different subtypes of ocular melanoma.

 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 80 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1382
Keyword
Malignant melanoma, AdCD40L, immunotherapy, proteomics, DW-MRI, FDG-PET/CT, prediction, early response, BRAF-inhibitor, vemurafenib
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:uu:diva-330710 (URN)978-91-513-0107-5 (ISBN)
Public defence
2017-12-02, Hedstrandsalen, Akademiska sjukhuset ingång 70, Uppsala, 09:30 (Swedish)
Opponent
Supervisors
Available from: 2017-11-09 Created: 2017-10-15 Last updated: 2017-11-09

Open Access in DiVA

fulltext(907 kB)152 downloads
File information
File name FULLTEXT01.pdfFile size 907 kBChecksum SHA-512
4bdd2489ed1ffd59f961adb26c49f12890203c7823fa5cb4e2bca7860b93e296765badb0aa13c612fd5be4520a7c0e540dab1cd916c37d5ef4a150e0ce975a26
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Maleka, AglaiaÅström, GunnarUllenhag, Gustav J.
By organisation
Experimental and Clinical OncologyRadiology
In the same journal
BMC Cancer
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar
Total: 152 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 550 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf