Combination of Gemcitabine and New CHK1 Inhibitor Is Effective in Soft Tissue Sarcomas
The new drug, GDC-0575 inhibits CHK1, which prevents cancer cells from recovering from DNA damage leading to cell death. The combination of GDC-0575 and gemcitabine significantly reduced tumor growth compared with just one drug in laboratory tests and in mice.
In a phase 1 clinical trial (ClinicalTrials.gov Identifier: NCT01564251), 2 patients had a meaningful response despite that the dose of gemcitabine used in the combination was significantly lower dose than when the drug is used alone. The patients were given gemcitabine 250 mg/m3 weekly intravenously and GDC-0575 orally with a range of different doses.
Both patients achieved rapid and substantial tumor shrinkage that was unusually long-lasting. One patient, who had a leiomyosarcoma with extensive metastases in the peritoneum, had a partial response that lasted for 1 year. The other patient, who had lung metastases, achieved a complete response that is ongoing 9 months after initiating treatment.
This trial is no longer accepting new patients; however, based on these results, the researchers are looking to set up a phase II clinical trial to assess safety and efficacy of a gemcitabine-CHKI inhibitor combination for soft-tissue sarcoma.
1. Advanced soft tissue sarcomas respond to a new drug GDC-0575 combined with gemcitabine [news release]. EurekAlert! web site. https://www.eurekalert.org/pub_releases/2016-12/eeco-ast112916.php. December 1, 2016. Accessed December 5, 2016.