Monday, June 11, 2012

ASCO - Ovarian Cancer Phase 1 trials

Part two of my ASCO report. This one is about some of the many  phase 1 trials I learned about.

The part of ASCO I liked best were the poster sessions. Many times there was a researcher present at the session to answer questions about the studies being done and most were very happy to share information with patient advocates. In addition to those posters specific to ovarian cancer I also started to look closely at  research that involved solid tumors since ovarian cancer is a solid tumor.

I saw research on small molecules that inhibit different pathways in cancer proliferation and also research combining those therapies with standard chemotherapy drugs.

Here some phase 1 trials I found most intriguing:

Abstract 3082

A phase I study of R04929097, an oral gamma secretase inhibitor, in combination with gemcitabine in patients with advanced solid tumors (PHL-078/CTEP 8575).

"RO4929097 (RO) is an oral inhibitor of gamma-secretase that disrupts Notch signaling." 

Conclusion: "RO and GEM can be safely combined." Notch signaling pathway is a transmembrane ( outside the cancer cell to inside the cell) protein. The protein signals the cell to reproduce. 

Abstract 3088

A phase I study of dovitinib (TKI258) in Japanese patients with advanced solid tumors

"Dovitinib is a tyrosine kinase inhibitor with demonstrated inhibitory activity against FGFRs, VEGFRs, and PDGFRs in vivo."  
Conclusion: Dovitinib(TK1258) was used in this phase I trial and found the MTD (maximum tolerated dose) to be 500mg.

Abstract 3054

A phase I study of chronically dosed, single-agent veliparib (ABT-888) in patients (pts) with either BRCA 1/2-mutated cancer (BRCA+), platinum-refractory ovarian cancer, or basal-like breast cancer (BRCA-wt).

"Veliparib(ABT-888) is an oral, potent inhibitor of PARP 1/2. Preclinically, PARP inhibitors have activity in tumors with defective homologous recombination (HR), particularly those that are BRCA+." 

Conclusion: Veliparib(ABT 888) ,an oral drug, was found to be tolerable at the MTD of 500mg and was also found to show evidence of anti-cancer activity in BRCA1 and 2 patients. I was pleased to see that  researchers in this study included oncologists from CINJ.

Abstract 3044

SORAVE: Phase I study for the treatment of relapsed solid tumors with the combination of sorafenib and everolimus.

"Dual inhibition of signaling pathways interfering with angiogenesis and cell proliferation may increase anti-tumor efficacy. We evaluated the combination of the VEGFR inhibitor sorafenib (S) and the mTOR inhibitor everolimus (E)" 
Conclusion:Relasped patients tolerated a combination of E everolimus at 7.5 mg/day and Sorafenib at 400 mg per day. It was found to be safe and feasible. Sorafenib is a multi-kinase inibitor and everolimus is an mTor inhibitor.

Abstract 3041

Phase I, first-in-human trial of an oral VEGFR tyrosine kinase inhibitor (TKI) x-82 in patients (pts) with advanced solid tumors

"VEGFR TKIs have shown benefit in the treatment of various tumor types. Side effects of the TKIs have affected the duration of therapy pts can tolerate, as well as the combinability with chemotherapy. X-82 is a highly potent VEGFR/PDGFR TKI with a smaller volume of distribution and limited tissue accumulation designed to minimize side effects while maintaining target effect." 
Conclusion:Oral X-82 is well tolerated with reduced the side effects.

Abstract 5061

A phase Ib study of the combination of temsirolimus (T) and pegylated liposomal doxorubicin (PLD) in advanced or recurrent breast, endometrial, and ovarian cancer.

"PLD is active in metastatic breast, endometrial and ovarian cancer. Preclinical studies suggest that mTOR inhibitors (mTORi), such as T, have an additive therapeutic effect to chemotherapy and resistance to doxorubicin can be reversed by adding an mTORi.: 
Conclusion : "The combination of T and PLD is safe and tolerable. The MTD was assessed at PLD 40 mg/m2 once every 4 weeks and T 15 mg weekly. The activity of this combination in breast, endometrial and ovarian cancer pts is promising and warrants further studies. "Temsirolimus is a kinase inhibitor which would be working with a chemotherapy drug.

I understand that many of these treatments may not be effective in terms of increasing overall survival but this very small review depicts that there is a good body of work being conducted to to improve the treatment of Ovarian Cancer.

Every Day is a Blessing!

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