The Role of Carboplatin in the Treatment of Small-Cell Lung Cancer
Lung cancer is the leading cause of death due to cancer in the United States, and approximately 178,100 new cases were estimated to occur last year. Small-cell lung cancer (SCLC) accounts for approximately 17% to 25% of all lung cancers. Due to its aggressive nature and rapid proliferation rate, small-cell lung cancer is usually widespread at diagnosis. Therefore, chemotherapy is the cornerstone of therapy for this disease. Cisplatin (Platinol) is an active chemotherapeutic agent used to treat small-cell lung cancer, but its toxicity, including nausea and vomiting, nephrotoxicity, neurotoxicity, and ototoxicity, has led to the investigation of combination regimens with different toxicity profiles. Carboplatin (Paraplatin), a derivative of cisplatin, has far less nonhematologic toxicity, although myelosuppression may be slightly greater than that observed with cisplatin. The reduced toxicity and equivalent efficacy of carboplatin have resulted in the increased use of carboplatin-based regimens to treat small-cell lung cancer. Phase I and II trials of carboplatin as single-agent treatment for small-cell lung cancer resulted in overall response rates of approximately 60% for previously untreated patients and 17% for those who had received prior therapy. New combination chemotherapy regimens that include carboplatin may improve survival in patients with small-cell lung cancer and potentially cure those patients with limited disease. Further investigation of carboplatin and other new agents is warranted.[ONCOLOGY 12(Suppl 2):36-43, 1998]
ABSTRACT: Lung cancer is the leading cause of death due to cancer in the United States, and approximately 178,100 new cases were estimated to occur last year. Small-cell lung cancer (SCLC) accounts for approximately 17% to 25% of all lung cancers. Due to its aggressive nature and rapid proliferation rate, small-cell lung cancer is usually widespread at diagnosis. Therefore, chemotherapy is the cornerstone of therapy for this disease. Cisplatin (Platinol) is an active chemotherapeutic agent used to treat small-cell lung cancer, but its toxicity, including nausea and vomiting, nephrotoxicity, neurotoxicity, and ototoxicity, has led to the investigation of combination regimens with different toxicity profiles. Carboplatin (Paraplatin), a derivative of cisplatin, has far less nonhematologic toxicity, although myelosuppression may be slightly greater than that observed with cisplatin. The reduced toxicity and equivalent efficacy of carboplatin have resulted in the increased use of carboplatin-based regimens to treat small-cell lung cancer. Phase I and II trials of carboplatin as single-agent treatment for small-cell lung cancer resulted in overall response rates of approximately 60% for previously untreated patients and 17% for those who had received prior therapy. New combination chemotherapy regimens that include carboplatin may improve survival in patients with small-cell lung cancer and potentially cure those patients with limited disease. Further investigation of carboplatin and other new agents is warranted.[ONCOLOGY 12(Suppl 2):36-43, 1998]
Lung cancer is the leading cause of death due to cancer in the United States. Of the estimated 178,100 new cases that were expected to be diagnosed in 1997,[1] approximately 17% to 25% will be small-cell lung cancer (SCLC).[2] Unfortunately, due to its aggressive nature and rapid rate of proliferation, small-cell lung cancer is usually quite advanced at diagnosis.
The Veterans Administration Lung Group system for classifying small-cell lung cancer is preferred to TNM staging.[2] This system classifies small-cell lung cancer into two stages, limited and extensive disease. In limited disease, tumor growth is confined to one hemithorax and its regional lymph nodes. Involvement beyond these limits is considered extensive disease. Ipsilateral pleural effusion and supraclavicular lymph node involvement are generally considered consistent with extensive disease, although this is controversial.[2]
Combination cytotoxic therapies given at frequent intervals have yielded the best response rates in small-cell lung cancer patients.[2] Overall response rates of 85% to 95% and 75% to 85% can be expected in patients with limited and extensive disease, respectively.[2] Although small-cell lung cancer responds well to chemotherapy, disease will relapse in the majority of patients, who will die within 2 years of diagnosis.[3] These poor survival rates are a result of the advanced disease stage at diagnosis, the high recurrence rates associated with local therapy, and the inability of combination chemotherapy to prolong survival significantly.[4]
Cisplatin (Platinol), an active chemotherapeutic agent in the treatment of lung cancer, is routinely combined with etoposide (VePesid) to treat small-cell lung cancer. The use of cisplatin, however, is limited by toxicity and the need for aggressive hydration support.[5] Adverse reactions associated with cisplatin include nausea and vomiting, nephrotoxicity, neurotoxicity, and ototoxicity.[2,6] This has led to the development and investigation of combination regimens that have more tolerable toxicity profiles.[7] Carbo-platin (Paraplatin), an analogue of cisplatin, has similar activity and a more favorable toxicity profile and is easier to administer.[5,7]
Phase I and II trials of carboplatin as single-agent treatment for small-cell lung cancer resulted in overall response rates of approximately 60% for previously untreated patients and 17% for those who had received prior therapy.[7] The dose-limiting toxicity of carboplatin is myelosuppression, particularly thrombocytopenia.[8] Because carboplatin is associated with less toxicity than cisplatin and exhibits equivalent efficacy, carboplatin-based combination regimens are being used increasingly to treat small-cell lung cancer.[7]
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