Original articleCarboplatin—etoposide combination in small cell lung cancer patients older than 70 years: a phase II trial
Introduction
Demographic trends in Western countries show a steady ageing of the population: from 1950 to 1990, the over-65 years group has grown from 8 to 13% of the population and is expected to reach 20% in 2030. Close to 60% of all cancer deaths arise in persons aged more than 65 years [1]. Lung cancer is the leading cause of cancer-related mortality in these populations, and occurs in greater than 60% of cases in patients older than 65 years. This proportion should enhance with the increasing life expectancy [1], [2] and is certainly underestimated since elderly patients with respiratory symptoms have less investigations than their younger counterparts [3], [4]. Small cell lung cancer (SCLC) accounts for 25% of all newly diagnosed cases of lung cancer beyond 70 years [4], [5]. Although modest but sure advances were recently allowed in SCLC by combined modality treatment with radiation therapy and systemic chemotherapy [6], older patients have not yet benefited from these improvements, and SCLC remains of poor prognosis in this group [4], [5], [7]. A physiologic decline in the function of vital organs, especially the liver and the kidneys, as comorbidities and polymedications frequently associated with ageing, might result in a greater toxicity of cytotoxic agents [5], [8], [9].
Carboplatin, an active analogue of cisplatin, has the advantages of easier administration, and less gastrointestinal, renal, auditive and neurologic toxicities. Its haematological toxicity remains limiting, particularly in elderly patients [10], [11], but can be reduced by individual dose adaptation, using Calvert's formula [12].
Single-agent etoposide is also highly active in SCLC, producing tumor regression in more than 50% untreated patients [13]. The efficacy of etoposide is schedule-dependent, with a greater antitumoral activity of a same dose given over 5 consecutive days rather than a single continuous infusion [14]. Oral administration is possible with proven efficacy and good tolerance in elderly SCLC patients [15], [16], [17].
We therefore designed a phase II study evaluating the combination of carboplatin and oral etoposide in the treatment of elderly patients with SCLC.
Section snippets
Patient selection
Selection criteria were age ≥70 years, SCLC confirmed by histology or cytology, limited or extensive disease (including cerebral metastasis), no previous chemotherapy or radiation therapy, no history of prior malignant disease, and a WHO performance status (PS) ≤2. Patients with uncontrolled severe heart disease, neutrophil count <1.5×109/l, platelet count <100×109/1, or a creatinine clearance <20 ml/min were excluded. The study protocol was approved by the local ethics committees and all
Patients characteristics
From june 1994 to October 1997, 34 previously untreated patients with SCLC entered the study. Among them, 27 patients were included in three of the participating study centres. Their main characteristics are listed in Table 1. The median age was 73.7 years (range 70–79). Most patients were men (88%). Eighteen patients (53%) had a WHO PS of zero or one, and the remaining 16 patients (47%) had PS 2. Despite the minimal investigations carried out, only six patients (18%) were defined as having LD,
Discussion
Most of prospective trials about SCLC treatment have systematically excluded elderly patients in the past, resulting in a relative lack of data in this population. Single agent therapy with etoposide has shown significant activity and mild toxicity, and so has first been considered as an interesting option for such patients, specially with its oral form [16]. However, two recent randomized studies in elderly or poor-prognosis SCLC patients demonstrated the superiority of intravenous combination
Conclusion
Despite a confirmed activity in SCLC of aged people, the combination of carboplatin and oral etoposide showed in this study lower response rates, shorter survival and higher toxicity than expected. With regards to these disappointing results, such a schedule, although presumed adapted, is certainly not a gentle treatment, and cannot be recommended for such aged patients, and particularly those with poor PS and extensive disease. Optimal modalities of administration have to be specified, and
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