Cachexia is one of the most devastating symptoms of cancer, afflicting up to 75% of all cancer patients. Cachexia deprives patients of their energy, quality of life, and ultimately their sense of independence. Most patients afflicted with cancer cachexia have non-small-cell lung cancer or cancers of the gastrointestinal tract (esophagus, stomach, colon, and pancreas). The foremost sign of cachexia is drastic weight loss, typically greater than 10% of total body weight. This includes loss of both fatty tissue and muscle mass. Commensurate with this weight loss is a profound loss of appetite. Patients often complain that they have no desire to eat. Drastic weight loss is an independent risk factor for poor survival. Cachectic patients have worse outcomes with surgery, chemotherapy, and radiation therapy. Cachexia is also an under-recognized cause for distress and anxiety among patients and their family members as changes in body image are readily noticeable.
An estimated 32% of all cancer patients experience fatigue on a daily basis, 21% experience fatigue on most days, and 78% are fatigued on a monthly basis. Furthermore, 28% of patients with cancer stop going to work altogether because of fatigue. Although cancer management has seen improvements in many areas including pain, depression, nausea, and vomiting, fatigue remains under-treated with 77% of physicians in the United States doing nothing or prescribing rest alone. Fatigue tends to be all-encompassing, and affects the daily lives of cancer patients even more than nausea, pain, or depression. Attempts have been made to emphasize the vital importance of fatigue management in cancer patients, as studies have shown that patients do not simply experience fatigue, they suffer with it. Cancer-related fatigue typically is characterized by rapid onset, intense severity, and an overwhelming reduction in energy, causing social, spiritual, psychological, and cognitive distress in cancer patients.
Cancer-related anemia is a cytokine-mediated disorder resulting from complex interactions between tumor cells and the immune system. Increased expression of certain inflammatory cytokines results in shortened survival of red blood cells, suppression of erythroid progenitor cells, impaired iron utilization, and inadequate erythropoietin production. Approximately 39% of the total cancer patient population is anemic (hemoglobin <12.0 g/dl).
Low hemoglobin levels correlate with poor performance for cancer patients, yet only about 40% of patients who are anemic receive treatment for their anemia. A growing body of clinical evidence indicates that the treatment of anemia can significantly improve a patient's quality of life and may also improve the clinical outcome. Due to recent concerns over the use of erythropoietin in cancer patients, the only remaining treatment option at present is blood transfusion.
ALD518, targeted for the treatment of cancer, entered Alder's therapeutic pipeline with Phase I clinical testing in 2008. Initial Phase II studies were completed in 2009, with additional studies planned for the near future.