Chemotherapy after surgery improves survival in patients with early stage lung cancer

First conclusive proof of chemo's benefits for this type and stage of cancer

June 6, 2004

Adjuvant chemotherapy can improve survival following surgical treatment for early stage lung cancer report researchers at the American Society for Clinical Oncology annual meeting. This is the first study to demonstrate a substantial benefit from chemotherapy for patients with stage 1B non-small-cell lung cancer. The evidence was so powerful that the independent Data Safety Monitoring Board halted the trial early.

The study, which enrolled 344 patients, found that three months of paclitaxel (Taxol®) and carboplatin decreased the risk of dying specifically from lung cancer by 49 percent. After four years, only 15 percent of those who received the chemotherapy compared to 26 percent of those who did not had died of lung cancer. Overall survival at four years was 71 percent in the chemotherapy group and 59 percent in the observation group--a 38 percent reduction in all-cause mortality for those who received adjuvant chemotherapy.

"This was the first study to make a real difference for this group of patients," said Richard Schilsky, MD, professor of medicine at the University of Chicago and chairman of the Cancer and Leukemia Group B (CALGB), which coordinated the study. "It brings a new sense of hope and progress to the treatment of lung cancer, a field that has seen a lot of frustration. Adjuvant chemotherapy should now be considered standard treatment for patients with early stage lung cancer just as for breast and colorectal cancer."

Gary Strauss, MD, MPH, of Rhode Island Hospital and Brown Medical School led the study. Strauss, who is now recommending adjuvant chemotherapy to patients with high-risk early stage disease, said "These figures solidify adjuvant chemotherapy as a proven way to improve cure rates for patients with early stage lung cancer." 

"This is a major breakthrough after several decades of research," said lung cancer specialist Everett Vokes, MD, professor of medicine and chief of hematology/oncology at the University of Chicago. "Many of the previous chemotherapy regimens were effective but they were so toxic that patients left the trial. This regimen not only increased the cure rate, but was also well tolerated. The next step is to find better ways to detect lung cancer at this early stage when it is still curable."

With an estimated 173,770 new cases and 160,440 deaths in 2004, lung cancer remains the leading cause of cancer death in both men and women. The one-year survival rate for all stages combined is 42 percent and five-year survival only 15 percent. Survival rates increase to 49 percent at five years for cases detected when the disease is still localized, but only 16 percent of lung cancers are diagnosed at this early stage.

Stage IB involves a tumor at least 3 cm in diameter or one of any size that invades the surface lining of the lung, but without regional lymph node involvement. These tumors can usually be removed surgically. Previous studies of adjuvant chemotherapy--anticancer drugs given after surgical removal of a tumor--have produced inconsistent results for this group of patients.

In this study, the investigators randomly assigned half of the patients to begin an investigational chemotherapy regimen consisting of approximately three months of paclitaxel and carboplatin within four to eight weeks after surgery, or to receive no chemotherapy following surgery.

Between September 1996 and November 2003, 344 patients were enrolled in the study. Of the 173 patients who received chemotherapy, 71 percent were still alive after an average of four years and 61 percent were alive and apparently cancer free. Of 171 patients who did not receive chemotherapy, 59 percent were alive and 50 percent cancer free.

The chemotherapy was well tolerated, with no deaths related to drug toxicity. The most serious side effect was neutropenia, a temporary reduction in white blood cells that places the patient at high risk for infections. Thirty-six percent of patients receiving chemotherapy had grade III or IV neutropenia.

Future studies will compare different drug combinations as adjuvant therapy in patients with early stage lung cancer to evaluate their relative effectiveness.

This trial was an Intergroup study coordinated CALGB. The Radiation Therapy Oncology Group (RTOG) and the North Central Cancer Treatment Group (NCCTG), large cooperative groups that conduct clinical trials focusing on new cancer treatments, also participated in the study.

In addition to Drs. Strauss, Vokes, and Schilsky, James Herndon, Michael Maddaus, David Johnstone, Heidi Gillenwater, Elizabeth Johnson, Dorothy Watson, David Sugarbaker and Mark Green contributed to this study, which was funded by the National Cancer Institute.