Elsevier

Lung Cancer

Volume 41, Issue 3, September 2003, Pages 345-351
Lung Cancer

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

https://doi.org/10.1016/S0169-5002(03)00237-XGet rights and content

Abstract

Introduction: Lung cancer is the leading cause of cancer mortality. Chemotherapy, ideally a platinum-based regimen as part of combined modality treatment, is appropriate for selected patients with locally advanced stage III non-small cell lung cancer (NSCLC) who have a good performance status. However, chemotherapy can induce side effects including lung function changes. Aim of the study: Retrospective analysis of lung function changes in 44 patients with stage III NSCLC treated with neoadjuvant chemotherapy (NCT) followed by surgery and/or radiotherapy. Patients and methods: NCT consisted of three cycles of gemcitabine/cisplatin. The following data were analysed: age, sex, the presence of chronic obstructive pulmonary disease (COPD), smoking behaviour, response, complications after surgery and/or radiotherapy, and VC, FEV1, DLco and Kco before and after chemotherapy. DLco values were corrected for haemoglobin concentrations. Results: We found a significant decline of Kco (−13.5% of pred; 95% CI: −16.6 to −10.4; P<0.0001), independent of tumor response or presence and severity of COPD. FEV1 and FEV1/VC showed significant increases irrespective of tumor response. Significantly more pulmonary complications were recorded in the radiotherapy group after NCT (P=0.009) compared to patients who underwent surgical therapy after NCT. Conclusions: Patients diagnosed with NSCLC stadium III who were treated with NCT consisting of cisplatin and gemcitabine showed a significant decline of DLco and Kco, irrespective of tumor response, presence and severity of COPD, sex and number of cycles of chemotherapy. Significantly more pulmonary complications were seen in patients treated with NCT and radiotherapy compared with patients treated with NCT and surgery. Questions concering the pathophysiological mechanisms of lung function changes and long term follow-up of pulmonary toxicity due to NCT remain still unanswered and have to be subject of future studies.

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.

Section snippets

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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