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Prophylactic Cranial Irradiation in Small-Cell Lung Cancer: Is It Ever Indicated?

January 2nd 1998

Prophylactic cranial irradiation (PCI) is being reintroduced into multimodality treatment protocols of patients with small-cell lung cancer (SCLC). The history of its use brings interesting insights into clinical evaluations of treatment strategies and design of relevant and informative trials. The critical issues of effectiveness and overall health gains of prophylactic cranial irradiation have been addressed in a series of recently completed clinical trials. These trials tested prophylactic cranial irradiation in small-cell lung cancer patients achieving good response to induction therapy and confirmed the ability of standard prophylactic cranial irradiation schedules to significantly reduce the lifetime risk of brain metastases. A subset of these trials evaluated neurotoxicity in a formal and prospective manner. No sustained or significant detriment in neuropsychometric function could be linked to the use of prophylactic cranial irradiation. In addition, all the large trials have shown a consistent survival advantage in favor of the prophylactic cranial irradiation arm. None of the individual sample sizes were large enough to statistically confirm this survival benefit, but a meta-analysis is in progress and will report on this aspect of evidence shortly. Issues that remain to be answered are the optimal dose and schedule of prophylactic cranial irradiation as well as the timing of this administration. These questions form the nucleus of the next generation of collaborative trials that are being designed.[ONCOLOGY 12(Suppl 2):19-24, 1998]


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The Role of Carboplatin in the Treatment of Small-Cell Lung Cancer

January 2nd 1998

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]


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One-Hour Paclitaxel Plus Carboplatin for Advanced Non-Small-Cell Lung Cancer

January 2nd 1998

We report here the preliminary results of a large phase II multicenter study done in the community setting, using paclitaxel (Taxol) (given by 1-hour infusion) plus carboplatin (Paraplatin) to treat patients with advanced non-small-cell lung cancer (NSCLC). In this study, 155 chemotherapy-naive patients with stage IIIB, stage IV, or recurrent metastatic non-small-cell lung cancer received the two drugs in 21-day cycles. Paclitaxel 225 mg/m² was given by 1-hour intravenous infusion followed immediately by carboplatin at a targeted area under the concentration-time curve of 6.0 (calculated according to the Calvert formula). Colony-stimulating factors were not used routinely. Objective responses occurred in 53 of 155 patients (34%) (53 of 144 [36%] evaluable patients) including three complete responses and 50 partial responses. Fifty-two other patients had stable disease at initial reevaluation. The median survival among all 155 patients was 8 months; the 1-year survival rate was 42%, and the 2-year survival rate was 20%. Leukopenia and cumulative peripheral neuropathy occurred consistently but rarely were severe or affected the course of therapy. One patient died due to sepsis. Other grade 3 and grade 4 toxicities were uncommon. This paclitaxel-carboplatin combination chemotherapy appears to be a relatively convenient, safe, and active regimen in advanced non-small-cell lung cancer.[ONCOLOGY 12(Suppl 2):71-73, 1998]

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