Risk factors for skeletal-related events in patients with non-small cell lung cancer treated by chemotherapy
Introduction
The bone is a preferred site of metastasis in patients with advanced cancer, which is attributable to the abundant blood flow to the red marrow, high expression levels of adhesion molecules on the tumor cells that bind them to marrow stromal cells and the bone matrix, and a large amount of growth factors in the bone that provide fertile ground for tumor cell growth [1]. Bone metastases are encountered in 30–40% of patients with metastatic lung cancer and 30–55% of patients with lung cancer at autopsy [2], [3]. Bone metastases are a serious complication leading to skeletal-related events (SREs), including bone pain requiring radiotherapy, pathologic fractures, and spinal cord compression [2], [3]. There have been few reports on the frequency and risk factors of SREs in patients with advanced non-small cell lung cancer (NSCLC), probably because these patients with bone metastases also show systemic disease progression along with progression of the bone metastases, and had a poor prognosis with an estimated median survival time of less than 6 months [2]. With the recent advances in the systemic treatment of NSCLC, however, the median survival of advanced NSCLC patients has increased to approximately 1 year, increasing the period for which the patients are at risk for SREs. A recent phase III trial of zoledronic acid versus placebo in NSCLC patients with bone metastases showed that the frequency of SREs did not differ between the patients receiving zoledronic acid (42%) and those receiving placebo (45%), however, there was a trend toward a longer median time-to-the first SRE in patients receiving zoledronic acid (5.6 months versus 5.0 months, p = 0.188) [4]. These results suggest that zoledronic acid may delay the appearance of SREs in NSCLC patients with bone metastases, but that this effect may be limited to the subgroup of patients at a high risk for SREs. Thus, we tried to identify the risk factors for SREs in patients with advanced NSCLC who were treated with systemic chemotherapy.
Section snippets
Patient selection
Patients were retrospectively selected for this study according to the following criteria: (1) a histological or cytological diagnosis of NSCLC; (2) stage IV disease or postoperative recurrence with distant metastases; (3) no prior chemotherapy; (4) chemotherapy prescribed by the National Cancer Center Hospital between December 2000 and June 2006. Patients with postoperative local recurrence without distant metastases were excluded.
Data collection and statistical analyses
The patients’ baseline characteristics before the initial
Results
A total of 642 patients fulfilled the eligibility criteria for this study. The first-line chemotherapy was platinum-based chemotherapy in 469 (73.1%) patients, gefitinib in 117 (18.2%) patients, third-generation monotherapy in 47 (7.3%) patients, and non-platinum doublets in 9 (1.4%) patients. Responses to these chemotherapies were complete response in 6 patients and partial response in 177 patients, yielding a response rate of 28.5%. Disease progression was observed in 580 (90.3%) patients.
Discussion
This study showed that the male sex, a poor performance status and presence of multiple bone metastases were associated with a short time-to-the first SRE and poor SRE-free survival. To the best of our knowledge, this is the first study identifying risk factors for the development of SREs in patients with advanced NSCLC treated by administered systemic chemotherapy.
Hypercalcemia of malignancy has been included in the definition of SRE, and we adopted the traditional definition for this study.
Conflict of interest statement
The authors indicated no potential conflicts of interest.
Acknowledgement
The authors would like to thank Mika Nagai for her invaluable assistance in the preparation of this manuscript.
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