A combination regimen involving standard carboplatin chemotherapy and a novel drug may improve overall survival for more than 50% of women with high-grade serous ovarian cancers, according to research published in Precision Oncology (published online May 2017; doi:10.1038/s41698-017-0008-z).
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Platinum-containing chemotherapy drugs, such as carboplatin, are the frontline therapy in high-grade serous ovarian cancers. Though ovarian cancers have demonstrated complete response to carboplatin, some tumors recur and response to carboplatin diminishes over time. Researchers have researched this recurrence and investigated a therapeutic approach that may improve outcomes for patients with recurring ovarian cancer.
In 2015, Sanaz Memarzadeh, MD, PhD, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California at Los Angeles, and colleagues isolated carboplatin-resistant ovarian cancer stem cells and determined that these cells house high levels of cellular inhibitor of apoptosis proteins cIAP. Dr Memarzadeh and her team showed that an experimental drug called birinapant — which degrades cIAPs — increases the effectiveness of carboplatin in some ovarian cancer tumors.
Researchers tested 23 patients with high-grade serous ovarian cancer tumors to assess the combination therapy’s rate of effectiveness. They found that carboplatin alone or birinapant alone had minimal effect in patients, while the drugs in combination successfully eliminated the ovarian cancer tumors in 50% of the samples. The combination therapy demonstrated effectiveness in both carboplatin-resistant and carboplatin-sensitive tumors.
Furthermore, researchers found a strong correlation between cancer stem cells with high levels of cIAP and a positive response to the combination therapy.
High levels of cIAPs have been associated with chemotherapy resistance in multiple other cancer types as well. Upon further study, researchers observed a similar correlation in bladder, cervix, colon, and lung cancer cells.
"I believe that our research potentially points to a new treatment option. In the near future, I hope to initiate a phase 1/2 clinical trial for women with ovarian cancer tumors predicted to benefit from this combination therapy," said Dr Memarzadeh in a press release (May 2, 2017).
Researchers believe that carboplatin plus birinapant may offer an effective therapeutic approach for patients with various types of platinum-resistant carcinomas. — Zachary Bessette
