Treatment of Elderly Patients with Small Cell Carcinoma of the Lung
ABSTRACT & COMMENTARY
Synopsis: Intergroup Trial 0096 was conducted in patients with limited stage small cell carcinoma of the lung to compare the effects of once or twice daily concurrent thoracic radiation therapy. All patients received cisplatin and etoposide. Three hundred eighty-one patients were entered, 50 of whom were older than 70 years of age. There were no differences in response rate, five-year event-free survival, or duration of response, but overall survival was lower in patients older than the age of 70. However, toxicity was more severe in the older population. Poorer performance status was strongly associated with increased toxicity in the elderly population.
Source: Yuen AR, et al. Cancer 2000;89:1953-1960.
Approximately one-half of all patients with lung cancer are diagnosed when older than the age of 65. Small cell carcinoma of the lung accounts for approximately 20% of these patients with as many as 25% being older than the age of 70. Treatment decisions for metastatic non-small cell carcinoma of the lung are more straightforward since cure is not possible and palliation is typically the major objective. However, in a potentially curable disease, such as limited stage small cell carcinoma of the lung, determining the appropriate aggressiveness of therapy is more problematic. Treatment of the elderly becomes an even greater issue as more aggressive and intensive treatment regimens are developed. Intergroup Study 0096 compared once vs. twice daily thoracic radiation when combined with four cycles of cisplatin and etoposide in patients with limited stage small cell carcinoma of the lung.1 The study demonstrated improved overall survival at two and five years for those patients who received twice daily radiotherapy. Esophagitis was more pronounced in the twice-daily radiation therapy group while other toxicities were similar. Of 381 eligible patients accrued to this study, 50 were age 70 or older. This article is a retrospective review comparing the treatment outcomes of patients who are younger than 70 with those who were 70 or older. There were no significant differences in patient characteristics with respect to treatment assignment, performance status, history of weight loss, or mediastinal involvement. Neutropenia less than 500 cells/mm3 and thrombocytopenia less than 50,000 cells/mm3 were significantly more frequent among the older patients (neutropenia, 82% vs 58%, P < 0.01; thrombocytopenia, 36% vs 21%, P = 0.03). Fatal toxicity occurred in 10% of the older patients compared to 1% of younger patients. However, there was no difference in the incidence of esophagitis, Grade 3-4 vomiting, pulmonary, neurologic, or cardiac toxicities. Ninety percent of the younger patients and only 78% of the older patients received target 4 cycles of chemotherapy. Ten (20%) of the older patients received just one or two cycles of chemotherapy. Despite the difference in the amount of chemotherapy delivered, there was no difference in either the complete or partial response rates for older vs. younger patients. Fifty-two percent of both older and younger patients achieved a complete remission. However, the overall survival at five years favored the younger patients (22% vs 16%; median overall survival 21.6 vs 14.4 months, P = 0.051). Interestingly, the Kaplan-Meier curves separated within the first six months of the study and remained roughly parallel after that time. Only five of the patients older than the age of 70 had a performance status of 2. However, two of these five patients died of treatment-related toxicity.
COMMENT BY MICHAEL J. HAWKINS, MD
Other studies in patients with limited stage small cell carcinoma of the lung have not reported a significant difference in toxicity in patients 70 years or older.2 However, in this study older patients received significantly less chemotherapy, primarily due to omissions of doses. However, in the Intergroup Trial 0096 the dose of chemotherapy was not modified during cycles 1 and 2 and probably is the reason for increased toxicity and treatment-related mortality seen in this study. Clearly elderly patients make up a heterogenous group. Rarely are there not coexistent diseases which would effect patients’ ability to metabolize or tolerate full doses of chemotherapy. However, in diseases that are potentially curable, it is important that elderly patients be treated with an appropriate degree of aggressiveness while remaining mindful of underlying organ compromise. Because there may be limited normal tissue reserves, performance status may be a particularly important factor when selecting doses of chemotherapy for the elderly population.
References
1. Turrisi AT, et al. N Engl J Med 1999;340:265-271.
2. Siu LL, et al. J Clin Oncol 1996;14:821-828.
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