Will antiangiogenic agents be a future for mesothelioma therapy?

Our plain-English summary of Will antiangiogenic agents be a future for mesothelioma therapy?, by C. Belli, S. Anand, M. Panella, et al (Current Medicinal Chemistry, 2010).

The study

• Authors: C. Belli, S. Anand, M. Panella, M. Giovannini, G. Tassi, D. Fennell, L. Mutti
• Journal: Current Medicinal Chemistry
• Published: 2010;17(27):3069-79
• Type of article: Review
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Malignant mesothelioma (MM) is an aggressive disease that is diagnosed mostly in locally advanced or metastatic stage. In this condition chemotherapy with the combination cisplatin and pemetrexed or ralitrexed represents the standard treatment as supported by a phase III study. However, chemotherapy has very limited effect on the improvement of survival of patients and very few of the MM patients survive more than 2 years. A better understanding of molecular mechanisms and pathways involved in angiogenesis in MM is the basis for the development of new drugs targeted against these pathways responsible for the proliferation and survival of tumor cells.

Objective: This review discusses the role of angiogenic factors in tumourigenesis with a particular focus on MM and it summarizes the results of clinical trials on the drugs targeting angiogenic pathways in MM.

Methods: We have used original research articles, abstracts and oral presentations from ASCO (American Society of Clinical Oncology) and the website of clinical trials http://www.ClinicalTrials.gov.

Results/conclusions: This review summarizes the results of antiangiogenic agents under evaluation in clinical trials. A better understanding of the angiogenic pathways activated in MM will hopefully provide new therapeutic options for these patients in the future.

In plain English

This was a review, not a new study. The authors described how tumors grow new blood vessels (angiogenesis) and the growth factors involved (VEGF, PDGF, FGF and TGF-beta). They summarized trials of drugs that block these pathways in malignant mesothelioma, mostly malignant pleural mesothelioma (MPM). In one cited phase II trial in 108 MPM patients, adding bevacizumab to gemcitabine and cisplatin gave progression-free survival of 6.9 months, against 6.0 months with placebo (p = 0.88). Median overall survival was 15.6 against 14.7 months (p = 0.91). Patients with higher baseline blood VEGF levels had shorter survival. Other cited trials reported partial responses in 15% of patients given sunitinib after earlier chemotherapy, a response rate of 11% with vatalanib, 4.4% with sorafenib, and negative results with imatinib alone. The authors concluded that these drugs might be a step forward for a subgroup of MPM patients. They noted that no reliable markers yet predict who will respond. Asbestos appeared as background on the cause of mesothelioma and in a cited 1989 mouse experiment by other researchers, in which new blood vessels grew rapidly around injected crocidolite asbestos fibers.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of the biology of angiogenesis in mesothelioma and of clinical trials of antiangiogenic drugs
• Who was studied: Published research articles, conference abstracts and oral presentations (ASCO), and trial listings on ClinicalTrials.gov, mostly on patients with malignant pleural mesothelioma
• Exposure: Antiangiogenic drugs: bevacizumab, semaxanib, sunitinib, vatalanib, sorafenib, thalidomide and imatinib, with cediranib and pazopanib under study. Asbestos appears as background on the cause of mesothelioma and in a cited mouse experiment by other researchers using injected crocidolite asbestos fibers.
• Main results:
  • In a cited phase II trial of 108 MPM patients given gemcitabine and cisplatin with bevacizumab or placebo, progression-free survival was 6.9 months with bevacizumab and 6.0 months with placebo (HR 0.93, p = 0.88). Median overall survival was 15.6 against 14.7 months (p = 0.91).
  • In the same bevacizumab trial, higher baseline plasma VEGF levels were associated with shorter progression-free survival (p = 0.02) and shorter overall survival (p = 0.0066).
  • In a cited phase II study of sunitinib in MPM patients who had failed platinum plus pemetrexed, 15% had partial responses and 55% had stable disease. Median overall survival was 5.9 months.
  • In a cited phase II study of vatalanib in chemotherapy-naive MPM patients, the response rate was 11%, median overall survival 10 months and progression-free survival 4.1 months.
  • In a cited phase II study of sorafenib in MPM patients, the overall response rate was 4.4% and the disease-stabilization rate was 38.8%.
  • Cited phase II studies of imatinib alone reported negative results. In an Italian study there was no objective response, and the best response was disease stabilization in 4 patients (36.3%).
  • In cited parallel phase II studies of thalidomide alone or with gemcitabine and cisplatin, median survival was 11 months in both arms.
  • In a cited 1989 experiment by Branchaud and colleagues (not the review authors), crocidolite asbestos fibers were injected into the peritoneum of mice, and new blood vessels grew rapidly around the fibers.
• The authors' conclusion: The authors concluded that antiangiogenic drugs might be a step forward in treating a subgroup of MPM patients, and that ongoing studies should show which patients benefit most.
• Limitations the authors state:
  • The authors stated that no reliable biological markers have yet been identified that predict how mesothelioma will respond to antiangiogenic drugs.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Chemotherapy, Cisplatin, Pemetrexed (Alimta), Angiogenesis, Clinical Trial.

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• Targeting the vasculature: anti-angiogenic agents for malignant mesothelioma — P.L. Chia, P.A. Russell, et al. (2016)
• Pemetrexed Maintenance Therapy Following Bevacizumab-Containing First-Line Chemotherapy in Advanced Malignant Pleural Mesothelioma: A Case Report and Literatures Review — X.Q. Jing, L. Zhou, et al. (2016)
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