FORT LAUDERDALE, FloridaModifications 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
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
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
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
"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
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."