Lung function changes and pulmonary complications in patients with stage III non-small cell lung cancer treated with gemcitabine/cisplatin as part of combined modality treatment
Introduction
Lung cancer is one of the leading causes of cancer mortality in both men and women [1].Worldwide far more than half a million cases of lung cancer are diagnosed annually [2]. About 80% of these tumors are of non-small cell histological type [3]. Surgery is the treatment of choice, but only about 20% of tumors are suitable for potentially radical resection. A well known meta-analysis showed that neoadjuvant chemotherapy (NCT) as part of combined modality treatment, increased survival in patients with stage III non-small cell lung cancer (NSCLC) [4]. The American Society of Clinical Oncology states that NCT, preferably platinum-based, is appropriate for selected patients with locally advanced stage III NSCLC who have a good performance status [5].
However, NCT as part of combined modality treatment can increase morbidity and mortality after surgery and/or radiotherapy in stage III NSCLC, because it is associated with more postoperative complications like respiratory insufficiency/adult respiratory distress syndrome and postpneumonectomy bronchopleural fistulas [6], [7], [8].
Lung function is an important prognostic factor in patients with NSCLC who are treated with surgery or radiotherapy. Increased mortality after radiotherapy is reported in patients with poor lung function. A reduced pre-operative lung function is associated with major complications or a death rate of more than 15% after surgery in thoracic patients [7]. A low pre-operative DLco (<45%) is associated with an increase in postoperative morbidity and mortality and predicts a poor quality of life [10]. A decrease of more than 20% in DLco suggested that toxic effects of pulmonary tissue may occur [11].
Several studies have described changes in lung function due to chemotherapy. Some authors demonstrated a significant decline in DLco and the CO transfer coefficient (Kco) but others could not confirm these findings [11], [12], [13]. Unfortunately, one of these studies included various combinations of chemotherapy and in others, the sample sizes were (frequently) small [11], [13].
Cisplatin combined with gemcitabine has proved to be a highly efficacious chemotherapy regimen with a high response rate and is frequently used in combined modality treatment [14]. We studied the effects of cisplatin and gemcitabine on lung function changes and complications after NCT followed by surgery and/or radiotherapy in patients with locally advanced (stage III) NSCLC.
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Patients
We conducted a retrospective study in 44 patients with stage III NSCLC treated with gemcitabine and cisplatin, who presented to our department between November 1996 and December 2001. Inclusion criteria were age ranging from 18 to 80 years, normal renal, hepatic, and bone marrow function, and locally advanced NSCLC stage IIIA or IIIB. The following data were recorded:
(1) Age, sex, tobacco smoke exposure, presence of chronic obstructive pulmonary disease (COPD), stage of NSCLC, response to
Statistical analysis
Differences between pre- and post-chemotherapy in lung function parameters were evaluated using repeated measurement ANOVA. The effect of chemotherapy on lung function was assessed for the influence of the response status, sex, the presence and the severity of COPD and the number of chemotherapy cycles. Differences in complication rates after surgery and/or radiotherapy were analysed in relation to DLco or Kco changes. α-Value was 0.05 and data are depicted as standard deviation or standard
Patient characteristics
Forty-four patients with stage III NSCLC were included. Patient characteristics between the IIIA and IIIB group were not significantly different (Table 1).
Thirty-five (79%) patients were diagnosed with COPD, seven (15%) were diagnosed with mild COPD, and 28 (64%) with moderate COPD. Patients with severe COPD were not included in the study. The average amount of chemotherapy cycles which could be administered was 2.85, 38 (86%) patients could be treated with three cycles of NCT (Table 1). The
Discussion
More than 80% of the patients with NSCLC are potential candidates for systemic chemotherapy at some time during the course of their disease [16]. Patients with stage III (locally) advanced NSCLC are often treated with a combination of platinum-based NCT followed by surgery and/or thoracic radiotherapy [5], [17]. In this study, we have examined the lung function changes due to cisplatin and gemcitabine as part of combined modality treatment. We consider this study important because lung function
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