FORT LAUDERDALE, FL-The updated treatment guidelines for patients with lung cancer suggest that patients with relatively good performance status can benefit from two, three, or even more courses of chemotherapy.
Although outcomes in patients with recurrent small cell lung cancer are disappointing, doctors recommended continuing to treat patients with chemotherapy even in the face of progressing illness, according to the new treatment algorithms presented here at the 6th annual conference of the National Comprehensive Cancer Network.
The Acting Chairman of the Small-Cell Lung Cancer Panel, Bruce Johnson, MD, Director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School in Boston, said the guidelines incorporated the use of methotrexate and lomustine into salvage therapies, based on clinical trials that indicated that about one in five relapsed patients respond to the regimen, and that patients on the regimen have survival extended about four months. Two of the original 34 patients in the Italian study, survived at least 18 months, Dr. Johnson noted.
The guidelines call for use of topotecan in cases of relapse with small-cell lung cancer. If disease progresses after that regimen, the combination of methotrexate and lomustine could then be used.
Performance Status Key
The revised guidelines list a number of anticancer agents that can be employed in the salvage setting, including topotecan, irinotecan, and taxanes. The key issue is that there is available treatment for even second- or third-line therapy, said Mark Kris, MD, Chief of the Thoracic Oncology Service at Memorial Sloan-Kettering Cancer Center in New York City. The guidelines tried to define the number of treatments that have been published in the literature that they could use.
Studies indicate that if the performance status of the patient is okay, then the patient can handle the additional courses of chemotherapy, said Dr. Johnson,
Dr. Kris noted that this is particularly important in people who have shown a good response to treatment, which does happen frequently in small-cell lung cancer. He said the guidelines also add a recommendation for a second line of treatment for patients with non-small-cell lung cancer who relapse.
Other Recommendations
The newest recommendations in small-cell lung cancer also:
▪ Suggest that patients with solitary pulmonary nodules and no lymph node involved with small-cell lung cancer by mediastinoscopy should undergo a lobectomy with mediastinal lymph node dissection.
▪ Call for irradiation concurrently with chemotherapy with 4,500 cGy given twice daily over a three-week period or at least 5,400 cGy given in daily fractions of 180 cGy.
▪ Incorporate prophylactic cranial irradiation in doses of 2,400 to 3,600 cGy for patients with a complete response to therapy in an attempt to prevent brain metastases. The percentage of people who go on to have brain metastases without irradiation is about 40 to 60 percent, Dr. Johnson said. Prophylactic cranial irradiation can reduce that occurrence by nearly half.
Harm to Mental Facilities?
He said doctors have been reluctant to give radiation to the head for fear of causing mental deficits, but newer studies indicate that is not as much of a problem as once thought.
The use of radiation to prevent the metastases was proposed in the 1970s after observations in children's cancer that prophylactic radiation appeared to reduce recurrence in brain tumors, Dr. Johnson explained. Obviously, radiation to the head doesn't make you any smarter. Clinicians have debated endlessly whether the potential side effects of irradiation would be worth the survival benefit.
Clinical trials to determine if irradiation was superior to placebo were difficult to accomplish, but a meta-analysis of a series of small studies found that patients who got radiation lived longer-an absolute benefit of about five percent over three years.
After three years, 15 percent of small-cell lung cancer patients who had achieved a complete remission but did not receive radiation were still alive compared with nearly 21 percent of patients who received radiation, he said. That's as good as you see in some trials with adjuvant chemotherapy.
In addition, he noted that new studies have found no dramatic differences in the intellectual capabilities of those radiated versus those who did not receive the therapy.
The new NCCN guidelines also recommend radiation therapy after surgical resection of carcinoid tumors and chemotherapy plus chest radiotherapy after resection of atypical carcinoid tumors based on the recurrence pattern.
No PET Yet
Among the recommendations for non-small-cell lung cancer, the algorithm-writing committee said that positron emission tomography (PET) scans are not yet ready for diagnostic purposes, except as an optional practice.
Although PET scans are thought to be potentially more sensitive than CT scans in evaluating lung cancer, it was decided that the PET scanner was too early in its development to recommend it as part of the routine evaluation of non-small-cell lung cancer, Dr. Johnson said.
In addition, the guidelines say that mediastinoscopy could be considered as optional for patients with peripheral T 1-2 Stage 1 disease. However, mediastinoscopy is still considered the gold standard in evaluating mediastinal lymph node involvement and is recommended for clinical Stages I-III disease.
Smoking Counseling
The guidelines also tell doctors to continually counsel patients to stop smoking. A high percentage of lung cancer patients continue to smoke after diagnosis and surgery, said Dr. Kris, Doctors should discuss smoking cessation at every visit. Smoking even in lung cancer patients worsens the outcome, especially if the patient is undergoing some form of radiation therapy.
Government & Industry Team Up to Battle Infectious Diseases
The National Institute of Allergy and Infectious Diseases (NIAID) has launched a new initiative that encourages private-sector involvement in attacking several of the world's most deadly infectious diseases. Through a $19 million Challenge Grants program, it will provide matching grants to companies willing to commit their own funds and resources toward developing new drugs and vaccines against malaria, tuberculosis, influenza, and dengue virus.
Forging partnerships with industry is an important part of NIAID's commitment to research on new ways to prevent and treat these diseases, and to move discoveries quickly from the laboratory to the clinic, said NIAID Director Anthony S. Fauci, MD.
The diseases targeted and the grant recipients are as follows: (1) Malaria-SmithKline Beecham Pharmaceuticals and Pfizer Pharmaceuticals, working in collaboration with researchers at the Walter Reed Army Institute of Research; (2) Tuberculosis-Sequella, Corixa Corporation, and SmithKline Beecham; (3) Influenza-Aviron, Aventis Pasteur, and Novavax; and (4) Dengue-OraVax.
The Challenge Grants recipients will focus on vaccine development, new drugs, and innovative drug combinations.
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