Optimal dose of dasatinib determined for advanced, recurrent ovarian cancer

Share this article:

A phase I trial determined that dasatinib 150 mg daily is the optimum dose when dasatinib is combined with paclitaxel and carboplatin to treat patients with advanced or recurrent ovarian cancer.

Dasatinib is an oral SRC-family tyrosine kinase inhibitor. It has promising potential to treat advanced ovarian cancer because the SRC families play a role in the increased activation of cell migration, proliferation, survival, invasion, and angiogenesis. The SRC pathways are frequently dysregulated in solid tumors and can increase chemotherapy resistance.

Previous laboratory studies with ovarian cancer cell lines found that SRC inhibition enhanced the cytotoxic efficacy of both paclitaxel and cisplatin. Studies done in vivo found decreased tumor growth with SRC inhibition. This study sought to determine the maximum tolerated dose of dasatinib when it was combined with paclitaxel and cisplatin.

Administering dasatinib with paclitaxel did not alter the effects of either drug, according to the study's results. Further, dasatinib may be better used in combination with chemotherapy agents for a synergistic effect.

“It may also be better to combine dasatinib with only one cytotoxic therapy to improve tolerability,” study co-author Robert M. Wenham, MD, of the Moffitt Cancer Center explained.

The researchers concluded that finding biomarkers to direct the use of targeted therapies is of the utmost importance. Although SRC gene expression was not correlated with response, the research team found several differentially regulated genes between responders and those with stable disease.

“Unfortunately, a biomarker was unable to be identified to demonstrate which women are most likely to benefit from dasatinib,” said study contributor Johnathan M. Lancaster, MD, PhD, also of Moffitt Cancer Center. “Further study should explore relevant biomarkers and identify a patient population most likely to benefit from the addition of dasatinib.”

This study was published in Clinical Cancer Research (2012; doi:10.1158/1078-0432.CCR-12-0507).
Share this article:
You must be a registered member of ONA to post a comment.

Sign Up for Free e-newsletters


What is this?

Regimen and Drug Listings

GET FULL LISTINGS OF TREATMENT Regimens and Drug INFORMATION

Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Genitourinary Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Rare Cancers Regimens
Skin Cancer Regimens Drugs

More in Web Exclusives

New analysis method finds possible therapeutic targets for drug resistant melanoma

Researchers have developed a new way to identify possible therapeutic targets for patients with drug resistant melanoma.

Fewer cardiac scans in low-risk childhood cancer survivors can safely reduce costs ...

A less frequent screening schedule would both reduce health care charges and still protect low-risk childhood cancer survivors from heart ailments caused by drug therapy, according to recently published findings.

Everolimus does not improve overall survival of advanced liver cancer

Despite strong preclinical data, the drug everolimus failed to improve overall survival in patients with advanced liver cancer, compared to placebo, according to a study.