Gemzar (gemcitabine HCL)

Gemzar has been approved for the treatment of locally advanced or metastatic pancreatic cancer.

Gemzar improved median survival in people with advanced and metastatic pancreatic cancer, as demonstrated by data from a study comparing Gemzar with 5-Fluorouracil (5-FU), which has been the most common treatment of pancreatic cancer. A second study followed subjects treated with Gemzar who had previously been treated with 5-FU.

The Phase III study of Gemzar involved 126 pancreatic cancer subjects--63 of these subjects received Gemzar therapy and the other 63 subjects received treatment with 5-FU. Of these subjects, more than 70% entered the study with metastatic disease, the most advanced stage of pancreatic cancer. Gemzar demonstrated a statistically significant advantage in survival over 5-FU. Gemzar subjects had a 5.7 month median survival as compared with 4.2 months for 5-FU subjects. From this trial, the six-month probability estimate for survival of subjects treated with Gemzar is 46% (30 patients), compared with 29% (19 subjects) for 5-FU subjects. After one year, the survival probability estimate was 18% (9 subjects) for Gemzar subject, compared with 2% (two subjects) for 5-FU subjects. (Survival probability estimates take results from the clinical trial and, using a mathematical equation, generalize them to the larger population of pancreatic cancer subjects.)

This study also demonstrated that 24% of previously untreated subjects who received Gemzar experienced a clinical benefit response, compared with 5% of subjects treated with 5-FU. This difference also is statistically significant.

A phase II trial of Gemzar, conducted among 63 subjects who had previously been treated with 5-FU, showed median survival time of 3.9 months. In this trial, 87% of subjects entered the study with metastatic disease. Of these subjects, 31% survived for six months, and 4% survived for one year. In addition, clinical benefit response was observed in 27% of subjects.

Gemzar's side effects were generally manageable with less than 1% of subjects discontinuing their therapy for any of the following side effects. A decrease in some infection-fighting white blood cells, called neutropenia, was observed in 63% of subjects, with moderate to severe decreases in 25% of subjects. This effect on the blood was the most frequent reason for reducing or limiting the dose of Gemzar. Common adverse effects in clinical trials included nausea and vomiting (69%), fever (41%), edema or fluid retention (up to 34%), rash (30%), and flu-like symptoms (19%). Only about 10% of all subjects participating in Gemzar clinical trials discontinued therapy due to side effects.

Hair loss was reported in 15% of subjects. This side effect was reversible, and none of the subjects experienced complete hair loss from their treatment.

Gemzar is a nucleoside analogue that mimics a natural building block of DNA.

Pancreatic cancer, one of the most difficult cancers to treat, is hard to detect because subjects remain asymptomatic until late in the course of the disease. Currently, less than 10% of all pancreatic cancer patients live more than one year after diagnosis. An estimated 26,000 people in the United States will be diagnosed with pancreatic cancer in 1996.

Given the difficulty in diagnosing pancreatic cancer, traditional means for establishing the activity of a chemotherapy agent, such as the rate of tumor growth or shrinkage, often cannot provide a useful measurement of a drug's effectiveness. Recognizing the unique needs associated with caring for pancreatic cancer patients, Lilly designed a clinical endpoint that would provide an objective, quantitative measurement of Gemzar's effect on several important disease-related symptoms experienced by subjects.

Clinical benefit response is a measure of symptomatic improvement based on the following: level of pain; consumption of pain medication; ability to perform daily activities; weight change. Subjects were considered to be clinical benefit responders only if they experienced improvement in at least one measurement without deterioration in any of the others. This improvement must have reached an established level for at least four consecutive weeks.