This article is more than 5 years old. Information may no longer be current.

Imatinib mesylate and docetaxel: minimal response in platinum-resistant ovarian cancer

Few patients had sustained response or stable disease.

Add topic to email alerts

Receive an email when new articles are posted on

Please provide your email address to receive an email when new articles are posted on .

Subscribe

Added to email alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

Back to Healio

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

Back to Healio

A combination of imatinib mesylate and docetaxel produced only a modest response in patients with recurrent, platinum-resistant or refractory ovarian cancer, according to the results of a study conducted by the Hoosier Oncology Group at Indiana University Cancer Center.

The platelet-derived growth factor receptors alpha and beta are transmembrane receptor tyrosine kinases. Both are involved in a number of physiologic and pathologic processes including vascular permeability, stroma modulation and cell growth and survival.

Platelet-derived growth factor receptors are also frequently found in fibroblasts, pericytes and endothelial cells, so the researchers hypothesized that inhibiting the receptors could change the tumor microenvironment to enhance chemotherapy and modulate interstitial pressure and angiogenesis.

To test this theory, the researchers screened 34 patients with ovarian cancer for the receptors alpha and c-Kit expression, and enrolled 23 in the trial. All patients were assigned to once daily oral 600 mg imatinib mesylate (Gleevec, Novartis) with once weekly 30 mg/m² IV docetaxel (Taxotere, Sanofi Aventis US) in weeks one through four of a six-week cycle.

The ORR was 21.7%. One patient had complete response and four others had partial responses. Three more patients had stable disease for 4.2 months to nine months. Median PFS was 1.77 months (95% CI, 1.38-3.78 months), and median OS was 9.56 months (95% CI, 9.03-28.16 months).

The researchers concluded that the presence of platelet-derived growth factor receptors alpha and beta had no correlation to clinical response or PFS.

Of the patients who had stable disease or objective response, three tested positive for platelet-derived growth factor receptor alpha-positive tumors, two had c-kit-positive tumors and three patients expressed both.

The researchers said toxicities were generally mild. Fifteen patients developed edema or accumulated pleural or peritoneal fluid. Seven patients developed a rash, two of which were classified as grade 3.

In an accompanying editorial, Robert L. Coleman, MD, and Elise. C. Kohn, MD, note that the regimen of imatinib and docetaxel produced only “modest” results. They went on to say, however, that targeting pericytes, tumor cells and endothelial cells may be the optimal way to combat platinum-resistant ovarian cancer.

“In the current article, metronomic taxanes had demonstrated effects on tumor endothelial cells, and imatinib had demonstrated effects on pericytes and on some tumor cells; and, potentially, combined with an antivascular endothelial growth factor molecule, as hypothesized by Pietras and Hanahan, may provide an optimal approach to microenvironment cytotoxicity,” Coleman and Kohn wrote.

For more information:

• Cancer. 2008;113:723-732.
• Cancer. 2008;113:665-667.
• J Clin Oncol. 2005;23:939-952.