One of the most common side effects of many different anti-angiogenic agents, which are felt to decrease the tumor’s blood supply, is high blood pressure, also known as hypertension.   The cause of this isn’t really known, but most patients develop some degree of high blood pressure.  What is interesting is that there is growing evidence that this may not just be an unwanted side effect, but rather a marker of a probability of doing better, similar to the correlation of rash with longer survival in patients receiving EGFR inhibitors.

For this, we can start by looking at results from a recent study of the anti-angiogenic agent sorafenib (nexavar) in renal cell carcinoma (kidney cancer).  Here, patients were classified according to whether they demonstrated evidence of a high blood pressure, which was defined as a systolic blood pressure (the higher number) of 140 or greater, and/or a diastolic blood pressure (the lower number) of 90 or greater over the course of their treatment with sorafenib. The 441 of 534 (83%) who had hypertension had a remarkably higher response rate (54% vs. 10%, p < 0.0001), and a significantly longer median progression-free survival (12.5 vs. 2.5 months, p < 0.0001) and median overall survival (30.5 vs. 7.8 months, p < 0.0001) than the patients with advanced RCC who didn’t have hypertension on the study:

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Sorafenib, or Nexavar, is an oral “multi-kinase inhibitor”. Kinases are specialized proteins that coordinate communitcation networks inside the cell and can modulate cancer cell growth as well as angiogenesis, the tumor blood supply. While many of the molecularly targeted agents I have discussed previously have demonstrated activity in lung cancer and sometimes other tumors, I have been discussing agents that primarily target one important cell process or another. Multi-targeted agents can potentially affect multiple relevant signaling cascades at once, but it isn’t clear yet whether they work better than our single-targeted options, or combinations of several single-targeted drugs together. There may also be the possibility of developing new combinations of side effects from one agent that hits multiple targets at once.

Great, but does it work? Fortunately, it does, at least in some tumor types. Sorafenib is currently approved by the US FDA for treatment of advanced kidney cancer, where it was studied in a randomized, placebo (sugar-pill) controlled trial of over 900 previously treated patients. This trial demonstrated that patients treated with nexavar at 400 mg by mouth twice daily went more than twice as long before developing progression of disease compared to the patients who received a placebo. There was also an improvement in overall survival in patients who received nexavar. It was generally well tolerated, with the main side effects being diarrhea, rash, fatigue, a “hand/foot syndrome” of redness and burning on the palms and soles, hair loss, and nausea/vomiting. Read the rest of this entry »