January 12, 2002

New cancer regimen offers extended life

Featured Image

Dr. Kurt Spindler

New cancer regimen offers extended life

A new treatment for a particularly deadly form of lung cancer holds the promise of dramatic improvement in survival for many patients, says a Vanderbilt-Ingram Cancer Center physician.

Dr. Alan Sandler, associate professor of Medicine and director of Vanderbilt-Ingram’s Thoracic Oncology Program, is leading a large U.S. study to further evaluate the treatment’s ability to prolong survival in patients with small-cell lung cancer, following publication of a Japanese trial in this week’s issue of The New England Journal of Medicine.

The research in Japan, involving about 150 patients, found that treatment with CPT-11 (also known as irinotecan or Camptosar) and cisplatin was superior to the standard therapy of cisplatin and etoposide. The combination of CPT-11 with cisplatin extended median survival to 13 months, and also increased the percentage of patients alive at one and two years after diagnosis. More than 58 percent of patients treated with CPT-11 and cisplatin survived for one year, compared to less than 40 percent who received the standard regimen of cisplatin and etoposide. Two year-survival was 19.5 percent for the group receiving CPT-11, versus 5.2 percent for the group receiving standard therapy.

“Up until this study, no treatment had been identified that increases survival to this extent,” said Sandler. “This is the first to show a dramatic difference.”

Small-cell lung cancer makes up 15-20 percent of lung cancer cases, occurring in about 30,000 Americans each year. That is comparable to the incidence of non-Hodgkin’s lymphoma and greater than the occurrence of melanoma, pancreatic cancer or adult leukemia. It is a particularly aggressive form of lung cancer, and two-thirds of patients are diagnosed when the cancer is already spread extensively. As a result, the median survival after diagnosis (the point at which half of patients live longer and half of them live a shorter amount of time) has been only about eight to nine months.

“For the first time, I can look a patient in the eye and say, ‘you have a greater than 50 percent chance of being alive in a year,’” Sandler said. “It may not sound like a lot, but for these patients, it may mean they get to see the next wedding anniversary or the birth of a grandchild or a high school graduation that they otherwise would have missed.”

CPT-11 works by interfering with the multiplication of cancer cells. It blocks an enzyme called topoisomerase that is necessary for the successful replication of a cell’s DNA as it divides into two cells. Based on its approval in April 2000 by the Food and Drug Administration, CPT-11 is the standard of care for the first-line treatment of metastatic or relapsed colon cancer and is being evaluated in earlier stages of that disease.

The Japanese study, conducted by the Japanese Cooperative Group, began in 1995 and was stopped early, three years later, because of the dramatic difference in outcome in patients receiving CPT-11.

The ongoing Phase III trial in the United States is designed to confirm the results of the Japanese study and to ensure that American patients have a comparable response to the drug.

Sandler is the primary national investigator in the study, which is also being led by investigators at the University of Colorado, Indiana University and Fox Chase Cancer Center in Philadelphia. The study, which is funded by Pharmacia, the maker of CPT-11, opened at these and 25 other locations earlier this year.

The study compares CPT-11 and cisplatin with the standard therapy using cisplatin and etoposide. Patients will be assigned by chance to receive one or the other therapy, with two-thirds of the patients receiving the CPT-11/cisplatin therapy.

A total of 300 patients will be enrolled in the trial nationwide.

In addition to Vanderbilt-Ingram in Nashville, the study is or will be available soon at the more than a dozen locations in Vanderbilt-Ingram’s Affiliate Network (VICCAN). The network offers some of the most promising new cancer therapies through clinical trials at centers in Tennessee, Georgia, Alabama and Kentucky.