An exploratory study investigating the metabolic activity and local cytokine profile in patients with melanoma treated with pazopanib and paclitaxel.

Details

Serval ID
serval:BIB_B287A12518AD
Type
Article: article from journal or magazin.
Collection
Publications
Title
An exploratory study investigating the metabolic activity and local cytokine profile in patients with melanoma treated with pazopanib and paclitaxel.
Journal
The British journal of dermatology
Author(s)
Thurneysen S., Cheng P.F., Nagel H.W., Kunz M., Jaberg-Bentele N., Nägeli M., Ziegler M., Guenova E., Goldinger S.M., Mangana J., Levesque M.P., Dummer R.
ISSN
1365-2133 (Electronic)
ISSN-L
0007-0963
Publication state
Published
Issued date
11/2016
Peer-reviewed
Oui
Volume
175
Number
5
Pages
966-978
Language
english
Notes
Publication types: Clinical Trial ; Journal Article
Publication Status: ppublish
Abstract
There is a medical need for new drugs in patients with BRAF wild-type metastatic melanoma. Pazopanib is a multitarget tyrosine kinase inhibitor with antitumour and antiangiogenic activity.
The primary aim was to investigate the metabolic response to pazopanib monotherapy and pazopanib plus paclitaxel in patients with BRAF wild-type melanoma. Secondary end points were the early cytokine and chemokine profiles and histological findings.
Pazopanib (400 mg twice daily) was administered orally from days 1 to 10 and from days 14 to 70. An intravenous infusion with paclitaxel (150 mg m <sup>-2</sup> body surface) was administered on days 14, 35 and 56. Metabolic response evaluation was performed before treatment, after treatment with pazopanib (day 10) and after treatment with pazopanib and paclitaxel (day 70). Skin biopsy of metastatic tissue for chemokine and cytokine expression analysis and histology and immunohistochemistry (CD68, CD163) evaluation, and blood samples were taken at the same time points.
Two patients failed screening and 17 were dosed. Of 67 adverse events, nine (13%) were grade 3 or 4. Five of 14 evaluable patients had a partial metabolic response at day 10 under pazopanib monotherapy. The response rate at day 70 under combined pazopanib-paclitaxel treatment was 0%. Immunohistochemistry revealed an increase of M2-like macrophages in nonresponders compared with responders. We observed a significant upregulation of five cytokines (CXCL1, CXCL2, CXCL13, CCL22 and SPP1) in responding vs. nonresponding lesions. Overall, the median progression-free survival was 70 days (range 5-331), which did not differ significantly between responders (148 days) and nonresponders (70 days, P = 0·17).
In this patient population pazopanib efficacy was limited. Response is associated with low M2-like macrophage density and increased expression of several chemokines.
Keywords
Administration, Oral, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Cytokines/metabolism, Drug Administration Schedule, Female, Humans, Infusions, Intravenous, Male, Melanoma/drug therapy, Melanoma/metabolism, Paclitaxel/administration & dosage, Pyrimidines/administration & dosage, Skin Neoplasms/drug therapy, Skin Neoplasms/metabolism, Sulfonamides/administration & dosage, Treatment Outcome, Up-Regulation
Pubmed
Web of science
Create date
27/08/2020 14:59
Last modification date
29/09/2020 10:23
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