New NCCN Recommendations for Small-Cell Lung Cancer

FORT LAUDERDALE, Florida—Modifications in the National Comprehensive Cancer Network’s (NCCN) 2001 guideline for small-cell lung cancer (SCLC) include changes in surgical management of SCLC and carcinoid tumors, as well as treatment modifications involving the timing and dose of chest radiotherapy, use of prophylactic cranial irradiation, and additional drugs available for relapsed patients.

Bruce E. Johnson, MD, of the Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, chaired the SCLC session during the NCCN’s Sixth Annual Conference: Practice Guidelines and Outcomes Data in Oncology.

The surgical change for SCLC concerns patients with solitary pulmonary nodules and no involved nodes by mediastinoscopy. The 2001 guideline says that these patients should undergo lobectomy with mediastinal lymph node dissection.

Dr. Johnson noted that about 2% to 3% of the SCLC population is surgically resected for carcinoid tumors. The guideline now recommends radiation therapy after surgical resection of these tumors, and chemotherapy plus chest radiotherapy after resection of atypical carcinoid tumors based on the recurrence pattern.

The panel presented new information about when and how much chest radiotherapy should be given for limited-stage disease. Dr. Johnson said that chest radiotherapy should start early rather than late and should be given concurrently with chemotherapy in fractionated doses to a total dose of 4,500 cGy to 5,400 cGy.

"If you give radiotherapy and chemotherapy together up front, patients live longer. The difference in average survival is about 5 months in most of the trials. The percentage alive at 5 years is 15% to 25%," Dr. Johnson said.

Prophylactic Cranial Irradiation

Prophylactic cranial irradiation has gone from being controversial to being the standard of therapy in limited-disease patients, Dr. Johnson said. This year’s guideline recommends prophylactic cranial irradiation in doses of 2,400 to 3,600 cGy for patients with a complete response to initial therapy.

"We’ve moved the recommendation to category 1 [uniform consensus based on high-level evidence] for patients with limited-stage disease, although it is still considered controversial by some because of the possibility of long-term neurologic deficits," he said.

Dr. Johnson cited a meta-analysis published in the New England Journal of Medicine in 1999 that found a 6% absolute survival advantage with prophylactic cranial irradiation after 3 years. Most of the patients in the study had limited-stage disease. "The question is, what about extensive-stage patients? A subgroup from the same analysis shows that the magnitude of the benefit appears to be the same in extensive-stage patients, but because it has not been proven, it remains a category 2 recommendation [consensus based on lower-level evidence]," Dr. Johnson said.

The controversy over cranial irradiation stems from studies in the 1970s and 1980s showing that those who received it often suffered severe neurologic deficits as a result. "During the last couple of years, studies have found no dramatic difference in function between irradiated and nonirradiated patients. The caveat to that is that some of the change in intellectual function can show up years later. The studies only looked at patients for 2 or 3 years after their irradiation," Dr. Johnson said.

The number of people affected by the panel’s recommendation for prophylactic cranial irradiation in limited-stage disease is about 6,000 to 7,000 annually, Dr. Johnson said. There are 160,000 persons in the United States diagnosed with lung cancer each year; 20% or about 32,000 have SCLC; about a third of those, or 11,000, have limited-stage disease; and about two thirds of those, or 6,000 to 7,000, achieve a complete response.

Smoking cessation counseling has been added to the surveillance of patients who have a complete or partial response to treatment. Dr. Johnson cited studies showing that patients with SCLC who continue smoking have a ninefold higher risk of developing a second tumor. He also noted that while smoking is always bad, it is particularly dangerous for those undergoing chest irradiation.

New Drug Regimens

The combination of methotrexate and lomustine (CeeNu) has been added to the guideline as medications to treat patients with sensitive relapse of SCLC. The panel added the drugs based on phase II response and survival data.

"The vast majority of SCLC patients relapse," Dr. Johnson said. "A recent study shows that patients given single-agent topotecan [Hycamtin] over 5 days live as long as those given a three-drug regimen, with a slightly better quality of life. So, topotecan has become a standard agent for relapse. The issue is, what do you do for second or third relapse?"

Mark G. Kris, MD, of Memorial Sloan-Kettering Cancer Center, emphasized that "there is treatment available, even for second and third relapse, and the guideline tries to define the regimens in the literature that are most commonly used."