Cigarette smoking is by far the leading cause of lung cancer. More than 87% of lung cancers are caused directly by smoking. [27] The 3-fold variation in lung cancer mortality rates across the United States more or less parallels long-standing, state-specific differences in the prevalence of cigarette smoking. See chart below.
Average annual age-adjusted lung cancer death rates
(1996-2000) [29]
Second-hand smoke
Second-hand tobacco smoke is also an established cause of lung cancer [29]. Though the absolute concentrations are lower (between 1% and 10%), the same components that are in inhaled mainstream smoke are also in second-hand smoke.
The development of lung cancer is the culmination of multistep carcinogenesis. The carcinogens found in cigarette smoke cause genetic damage and are the driving force behind the multistep process. [29]
Other causes of lung cancer
There are a number of other factors and environmental exposures that have been associated with lung cancer. However, the lung cancer burden due to these exposures is small compared to cigarette smoking.
- Asbestos—asbestos workers are about 7 times more likely to die from lung cancer. The risk is even higher if the worker smokes [27]
- Radon—the lifetime relative risk for residing in a home with EPA action radon level of 4 pCi/L is estimated to be about 1.4 for smokers and 2.0 for nonsmokers. Approximately 10% of all lung cancer deaths and 30% of lung cancer deaths in nonsmokers are due to indoor radon exposure [29]
- Cancer-causing agents in workplace—uranium, inhaled chemical/minerals, gasoline, diesel exhaust
- Air pollution—the risk of lung cancer was observed to increase 14% for each 10-μg/m³ increase in concentration of fine particles [29]
- Personal and family history—recent studies have concluded the susceptibility to lung cancer might reside on chromosome 6. An abnormality on this chromosome may increase a patient’s risk of developing lung cancer. Patients who have had lung cancer also have an increased risk of developing another lung cancer [27]
Important Safety Information
ContraindicationsHycamtin is contraindicated in patients who have a history of hypersensitivity reactions to topotecan or to any of its ingredients. Hycamtin should not be used in patients who are pregnant or breast-feeding, or those with severe bone marrow depression.
WarningsHycamtin should be used only in patients with adequate bone marrow reserves, including baseline neutrophil counts of at least 1,500 cells/mm3 and platelet counts of at least 100,000/mm3. Frequent monitoring of blood counts should be instituted during treatment with Hycamtin.
Patients should not be treated with subsequent courses of Hycamtin until neutrophils recover to >1,000 cells/mm3, platelets recover to >100,000 cells/mm3, and hemoglobin levels recover to 9.0 g/dL (with transfusion if necessary).
Hycamtin may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Hycamtin.
Drug InteractionsConcomitant administration of G-CSF can prolong the duration of neutropenia, so if G-CSF is to be used, it should not be initiated until day 6 of the course of therapy, 24 hours after completion of treatment with Hycamtin.
Myelosuppression was more severe when Hycamtin was given in combination with cisplatin in phase I studies. In a reported study on concomitant administration of cisplatin 50 mg/m² and Hycamtin at a dose of 1.25 mg/m²/day x 5 days, 1 of 3 patients had severe neutropenia for 12 days, and a second patient died with neutropenic sepsis. There are no adequate data to define a safe and effective regimen for Hycamtin and cisplatin in combination.
Adverse EventsFrequently reported nonhematologic adverse events associated with use of Hycamtin included nausea (64%), vomiting (45%), diarrhea (32%), alopecia (49%), fatigue (29%), and dyspnea (22%). Most nonhematologic toxicities were grade 1 or 2.
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