Drug Criteria & Outcomes

FDA recently announced these approvals: Novartis' Tasigna® (nilotinib) capsules has been approved by FDA for treating Philadelphia chromosome positive chronic myeloid leukemia in adults whose disease has progressed on or who cannot tolerate other therapies including Novartis' Gleevec® (imatinib). Imatinibis approved for treating newly diagnosed patients with Philadelphia chromosome positive CML.

The approval includes a black box warning for possible life-threatening heart problems that may lead to an irregular heartbeat and possible sudden death.

Nilotinib's effectivesss was assessed on response rates observed in an ongoing clinical trial associated with normalization of blood counts and bone marrow examinations. FDA said follow-up of patients is needed to determine how long these responses will last.

Patients can lower their chances for heart problems by taking nilotinib without food and by avoiding grapefruit products. Patients should consult with health care professionals about avoiding other medications that can cause heart problems while taking nilotinib. Patients with low blood potassium or magnesium should not take nilotinib.

The most common side effects in clinical trials included low blood counts, rash, headache, nausea, and itching. Other possible serious side effects include live damage, fluid accumulation, and pancreas inflammation.

FDA approved Bayer's Nexavar® (sorafenib) for use in patients with inoperable hepatocellular carcinoma. Nexavar was originally approved in 2005 for treating patients with advanced renal cell carcinoma.

The agency said that in a randomized clinical trial, the group of patients with inoperable hepatocellular carcinoma who received sorafenib survived 2.8 months longer than the group of patients who didn't receive the drug.

Sorafenib is a kinase inhibitor that interferes with molecules thought to be involved in chemical messages sent within cancer cells, in forming blood vessels that supply tumors and in cell death.

Approval of sorafenib was based on results of an international randomized placebo-controlled trial in patients with inoperable hepatocellular carcinoma. Some 600 patients were studied, with each patient receiving either sorafenib or a placebo. The trial was stopped after a planned interim analysis showed a statistically significant advantage in overall survival for patients receiving sorafenib. Patients who received sorafenib survived a median of 10.7 months, while patients who received placebo survived a median of 7.9 months. A separate analysis showed that tumors progressed more slowly in patients who received sorafenib compared to patients who received placebo.

The most common adverse reactions in patients taking sorafenib for hepatocellular carcinoma or renal cell carcinoma were fatigue, weight loss, rash or superficial skin shedding, hand or foot skin reaction, hair loss, diarrhea, anorexia, nausea, and abdominal pain. Some 20% or more of patients experienced at least one of these reactions.

In patients with hepatocellular carcinoma, diarrhea was reported in 55% of patients receiving sorafenib. Inadequate blood supply to the heart or heart attack were reported in 2.7% of patients receiving sorafenib, compared to 1.3% for patients who received placebo. New hypertension was reported in 9% of sorafenib patients, compared to 4% of placebo patients. Elevated serum lipase, an enzyme measuring liver function, occurred in 40% of patients who received sorafenib, compared to 37% of patients who received placebo, and hypophosphatemia occurred in 35% of patients who received sorafenib, compared to 11% of patients receiving placebo.