Axitinib has proven efficacious in treating advanced renal cell carcinoma (RCC) with or without sunitinib as first line treatment. It is currently being investigated in combination therapies for metastatic colorectal cancer where it appears to be more effective than in sunitinib. Recently we have been working on developing axitinib as an antiangiogenic agent. This means it causes the death of tumour cells by constricting their blood supply. In a phase I study we showed that this drug was well tolerated and induced regression or stabilization of several different types of solid tumours including those of the lung and pancreas.
Axitinib has been approved as an anticancer drug in Japan since 2004 and in Europe and the US since 2007. It was previously reported that axitinib has antiangiogenic activity in preclinical models of cancer, but its exact mechanism of action remains unknown. In a recent study, we observed that axitinib inhibits tumor growth and angiogenesis in vivo and in vitro. The present results suggest that axitinib may be useful in treating proliferative retinal diseases such as diabetic macular edema and age-related macular degeneration.
There were few published clinical trials involving axitinib. The CALGB 229803 study reported significant antitumor activity and manageable toxicity profiles; however, the initial results were subsequently interpreted as showing little response to axitinib therapy.
[Renal cell carcinoma (RCC) accounts for approximately 4.2% of newly diagnosed cases of cancer per year in the United States. Over 1,000 patients die of RCC each year in the United States alone.
The most severe form of carcinoma of the kidney and ureter is renal cell carcinoma. Of all malignant neoplasms arising in the kidney, renal cell carcinoma is the third most common type. It accounts for approximately one half of all cases of all malignant neoplasms of the kidneys. The average life expectancy following diagnosis of renal cell carcinoma is 11 months, but this varies greatly depending on many factors such as the size of the tumor and the extent of spread. Renal cell carcinoma is a progressive disease, and as a consequence, most patients die within 10 years of diagnosis. A significant number of patients have metastatic disease at presentation and may not be candidates for curative surgery.
The 5-year survival rate for carcinoma, renal cell was 92% for Stage I and II tumors, and 89% for Stage III tumors. The overall survival rate was 96%. There were no differences in survival between genders. Most patients were white (94%) and non-Hispanic (88%). The median age at diagnosis was 69 years old. Activation of the phosphoinositide 3'-kinase pathway was associated with the presence of metastases and poor prognosis.
According to our data, the average age a person will get renal cell cancer is 50 years old. The number of people diagnosed with renal cell cancer has increased significantly since 1990. We speculate that this may be caused by earlier detection, better understanding of risk factors, and altered lifestyles. These changes may also suggest that incidence is increasing, possibly because of improved screening methods and/or early recognition.
Axitinib was found to be associated with few adverse events among patients treated with chemotherapeutic agents, but this did not apply to patients receiving targeted treatment. Further data on long-term safety are needed before recommending axitinib as monotherapy in metastatic renal cell carcinoma.
Axitinib was well tolerated in patients treated for metastatic renal cell carcinoma (mRCC). Given the high rates of progressive disease after first-line therapy for mRCC, continued investigation of this drug is warranted.
Findings from a recent study suggests that there may be significant differences between RCCs (ccRCC) and ccSCC in their tumor growth rates and speed of metastasis. This could have important implications for the development of new therapies targeting metastatic tumors.
Axitinib's most common side effects include rash, fatigue, nausea, diarrhea, dyspepsia, headache,/visual disturbances, insomnia, back pain, and non-healing wounds. A recent study reported that this drug also causes an increased risk of cardiovascular events, including MI, stroke, and death, especially in patients who already had cardiovascular disease (CVD). Therefore, patients should be advised about the risks when they start taking axitinib. [Power] In many cases, axitinib is prescribed for patients who do not have CVD, so more studies are needed to determine whether axitinib has any effect on CVD.