Retrospective study of efficacy and toxicity on patients older than 70 years within a randomized clinical trial of two cisplatin-based combinations in patients with small-cell lung cancer
Introduction
Lung cancer is the first cause of death due to cancer in developed countries. In more than 50% of the cases it is diagnosed in patients older than 65 years and approximately 30% in older than 70. Small-cell lung cancer (SCLC) subtype nearly represents the 20% of all cases [1]. Besides it seems to be more frequent in patients older than 65 years. Additional factors, such as the increase of life expectancy and proportion of smoking women, have lead day after day to a higher number of SCLC elderly patients that require treatment [2].
Since an increase of the response rate and survival of SCLC patients was shown with poly-chemotherapy in the 70s, it became the standard treatment. Although no confirmatory randomized trials are available, it has been historically considered that chemotherapy tolerability may be worse in the elderly patients. This belief has lead to the use of less aggressive diagnostic procedures and treatments, frequently using non-properly validated schedules or doses that are suboptimal. It is also noteworthy that elderly patients have frequently been excluded from clinical trials.
As chemotherapy clearly provides a benefit in terms of symptomatic control and shows high response rates and significant survival increase in SCLC it is important to confirm the efficacy and tolerability of chemotherapy that is being used in the elderly population with this diagnosis. In this regard it is important to assume that aging induces significant changes in body composition, metabolism and hepatic, renal, and bone-marrow dysfunctions which have a negative impact on chemotherapy toxicity [3].
The Spanish Lung Cancer Group (SLCG) conducted a clinical trial comparing the standard chemotherapy regimen, cisplatin (P) plus etoposide (E), with the combination of high-dose epirubicin (Ep) plus cisplatin [4]. Four-hundred and two patients were enrolled, and no significant differences regarding activity, time to progression (TTP) and survival were observed. Lesser haematological toxicity was seen in the Ep arm, and this schedule could be considered then as an effective alternative for SCLC treatment, at least for extended disease patients. With the patients included in both treatment arms of this trial, a retrospective study to evaluate differences concerning efficacy, toxicity, time to progression and overall survival (OS) according to age (younger vs. older than 70 years) was performed.
Section snippets
Inclusion criteria
In the SLCG original study patients with histological or cytological SCLC diagnosis, at least one bidimensionally measurable lesion, aged between 18 and 75 years, expectancy of life more than 3 months and Karnofsky PS greater than 60%, were included. Other inclusion criteria were: adequate liver, renal and bone-marrow function. Radiotherapy was accepted for urgent cases in which the irradiated area did not include target lesions. Patients with symptomatic brain metastases previously treated
Results
In the original SLCG study no significant differences were observed between both treatment arms regarding overall treatment response, time to progression and overall survival when the 402 patients analyzed. In addition, significant differences were not observed between the toxicity profile of both schedules, except for grade 3–4 neutropenia that was more frequent in the EP arm (59.8% vs. 48%; p = 0.002).
Discussion
Theoretically, elderly patients should have worse tolerability to chemotherapy due to organ function impairment related to age and concomitant diseases. There seems to be a trend towards simplified staging work-up and suboptimal treatments without scientific data supporting these practices, particularly the lower chemotherapy benefit in these patients [3]. In most of the clinical trials reported, both in SCLC and also in other tumours, elderly patients are routinely excluded [7], [8], [9]. In
Conflict of interest
None declared.
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