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
Är CTLA-4-inhibitorn ipilimumab bättre som monoterapi eller i kombination med andra läkemedel hos patienter med metastaserat malignt melanom?
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
2016 (Swedish)Independent thesis Basic level (university diploma), 10 credits / 15 HE creditsStudent thesis
Abstract [en]

Malignant melanoma is a growing problem with more and more people in Sweden and the world suffering from this cancer. Malignant melanoma is a disease that when discovered in time can be treated successfully with surgical methods, but the real challenge lies in treating the disease after its spread. Treatment in the past for advanced malignant melanoma has been unsuccessful with no positive effect on overall survival. However, in the last couple of years, new treatment has arrived with focus on priming the immune system to eradicate the tumors. One new drug is the CTLA-4 inhibitor ipilimumab that is given as intravenous infusion. CTLA-4 is a protein located on regulatory T-cells and that is upregulated on activated cytotoxic T-cells. This protein mediates an inhibitory signal that attenuates T-cell-activation.  Treatment with the CTLA-4 inhibitor has been shown to increase overall survival. However, not much is known about how well ipilimumab synergizes with other drugs used for treatment of malignant melanoma.

 

This is a literature study with the aim to evaluate if ipilimumab is used best as monotherapy or if it is of better use as part of a combination therapy. Search was made in PubMed with the key-words "Ipilimumab", "Ipilimumab treatment", CTLA-4 inhibitor" and "treatment malignant melanoma”. Six articles were chosen and each of these analyzed the effect of ipilimumab alone or combined with other agents against malignant melanoma.

 

The combination of ipilimumab and the alkylating agent dacarbazine was shown to have a better impact on overall survival compared with monotherapy with dacarbazine, but this combination also showed an increase in serious adverse events. Ipilimumab also showed to work in synergy with both the PD-1-inhibitor nivolumab and the granulocyte macrophage colony-stimulating factor (GM-CSF) sargramostim. Combination with sargramostim was also shown to decrease the amount of serious adverse events. Combination with a gp100 peptide vaccine failed to show any positive effects on overall survival. Also prophylactic treatment with budesonide showed no further gain in overall survival. The effect of ipilimumab was found to have a dose-ranging effect, with higher dose treatment having a better effect but also with more serious adverse events.

 

The results of this literature study showed that ipilimumab has a better effect with higher dose and that it can work in synergy with other agents such as nivolumab and sargramostim. Results also showed that occurring adverse effects during treatment with ipilimumab may be treated with systemic glucocorticoids that did not affect the tumor-killing ability of ipilimumab. These results should be evaluated in bigger studies and with longer follow up time.

Place, publisher, year, edition, pages
2016. , 34 p.
Keyword [sv]
Ipilimumab, CTLA-4
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:lnu:diva-52662OAI: oai:DiVA.org:lnu-52662DiVA: diva2:930946
Subject / course
Pharmacy
Educational program
Bachelor of Science Programme in Pharmacy, 180 credits
Supervisors
Examiners
Available from: 2016-05-27 Created: 2016-05-25 Last updated: 2016-05-27Bibliographically approved

Open Access in DiVA

fulltext(398 kB)58 downloads
File information
File name FULLTEXT01.pdfFile size 398 kBChecksum SHA-512
d10747404f314e248a64892b7b60877490b06de853a681b4a7af7d78a6c959db004e070fa4901c5ae56bace48171f8cfe7fe1514f0f8f34f2bbb9e99c40a6c3a
Type fulltextMimetype application/pdf

Search in DiVA

By author/editor
Georgsson, Jonathan
By organisation
Department of Chemistry and Biomedical Sciences
Pharmaceutical Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 58 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

urn-nbn

Altmetric score

urn-nbn
Total: 105 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