Elsevier

Lung Cancer

Volume 71, Issue 1, January 2011, Pages 70-74
Lung Cancer

The safety and efficacy of weekly paclitaxel in combination with carboplatin for advanced non-small cell lung cancer with idiopathic interstitial pneumonias

https://doi.org/10.1016/j.lungcan.2010.04.014Get rights and content

Abstract

Background

Idiopathic interstitial pneumonias (IIPs) are one of the most common complications in patients with lung cancer. In lung cancer patients with IIP, the most serious toxicity is acute exacerbation of IIP caused by anticancer treatment in Japan. However, there has been no consensus and no evidence presented, regarding optimal treatment for advanced lung cancer with IIP.

Patients and methods

Chemotherapy-naïve patients of inoperable stage, or post-operative recurrent non-small cell lung cancer (NSCLC) with IIPs were enrolled. Patients received paclitaxel at a dose of 100 mg/m2 on Days 1, 8, 15, and carboplatin every 28 days at a target dose of area under the curve (AUC) 5.0 on Day 1.

Results

Between May 2004 and October 2008, 18 patients, including 6 with idiopathic pulmonary fibrosis (IPF), were enrolled and treated for a median of four cycles (range, 1–6). One patient (5.6%; 95% confidence interval (CI), 0–17%) with histologically confirmed IPF had acute exacerbation of IIPs associated with the treatment. The overall response rate was 61% (95% CI, 36–86%). The median progression-free survival, median survival time, and 1-year survival rate were 5.3 months, 10.6 months, and 22%, respectively.

Conclusion

This is the first report indicating that advanced NSCLC patients with IIP may benefit from chemotherapy. Weekly paclitaxel and carboplatin combination chemotherapy was as effective as conventional regimens in advanced NSCLC patients without IIP and was safer than previously reported for NSCLC patients with IIP. The results from this study would support, on ethical grounds, the conduct of a large-scale study to confirm the feasibility of this regimen.

Introduction

Idiopathic interstitial pneumonias (IIPs) appear to be associated with lung carcinogenesis. In particular, the incidence of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) is higher than that in the general population, whose relative risk is reportedly 7–14 [1], [2], [3], [4], [5]. Kawasaki et al. [6] reported that IPF was found in 7.5% of surgically resected lung cancer cases. Recently, it has been recognized that IPF is an independent risk factor for lung carcinogenesis [3].

IIPs are usually characterized by slowly progressive respiratory insufficiency. Nevertheless, some IIP patients experience acute exacerbations (AE) generally characterized by suddenly progressive and severe respiratory failure, with new lung opacities and pathological lesions of diffuse alveolar damage (DAD). There are racial differences between Mongolians (including Japanese), and Caucasians in the frequency of AE. Therefore, the concept of AE, which was first proposed in Japan [7], [8], has recently come to be recognized globally [9], [10], [11], [12]. This clinical condition is lethal in many cases and significantly affects the prognosis of patients with IIP, because there is no established treatment for AE. In lung cancer combined with IIP (LC with IIP), idiopathic or iatrogenic AE frequently occurs following various anticancer treatments. There are only a few retrospective reports of exacerbation of a pre-existing IIP after surgery [13], [14], [15], [16], but there are few reports of chemotherapy that are useful in designing a treatment strategy for LC with IIP. At present, there is neither evidence nor consensus around the issue as to whether aggressive treatments such as chemotherapy are appropriate for non-curative NSCLC with IIP.

The results of our retrospective study of LC with IIP suggested that paclitaxel (TXL) in combination with carboplatin (CBDCA) could be a candidate regimen for treatment of NSCLC patients with IIP [17]. We therefore conducted a prospective study of combined chemotherapy with weekly TXL and CBDCA to assess acceptability, in terms of safety and potential efficacy, in treatment of advanced NSCLC with IIP.

Section snippets

Study design

Pathologically confirmed, inoperable stage or post-operative recurrent NSCLC patients with IIP who had never received chemotherapy or radiotherapy were eligible for enrollment. They did not include cases with unstable IIPs and acute/subacute IIPs. Patients receiving oxygen inhalation or using immunosuppressive drugs such as steroids were included. Histological types of lung cancer were defined according to the World Health Organization Classification of 1999. Additional eligibility criteria

Patients characteristics

Between May 2004 and October 2008, a total of 18 Japanese patients (14 males and 4 females) were enrolled in this study and their characteristics are shown in Table 1. All patients were evaluable for toxicity and survival assessments. The median age at the time of diagnosis of lung cancer was 71 years; 12 patients were current smokers. Six patients were clinically or histologically confirmed cases of IPF. Seven patients had histological confirmation of IIP (6: surgical lung biopsy; 1:

Discussion

Optimal chemotherapy for treatment of advanced LC with IIP still remains controversial, because there have been few reports focusing on AE of IIPs related to chemotherapy for lung cancer. This is the first prospective study to analyze the safety and efficacy of a specific regimen for LC with IIP. In this pilot study of weekly TXL combined with CBDCA for advanced NSCLC with IIP, we observed an incidence of treatment-related AE of 5.6%. In the case of chemotherapy, the incidence of

Conflict of interest

None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

Acknowledgement

Author contributions: Drs. Minegishi, Kudoh and Gemma devised the conception of the study and designed the methods. Dr. Minegishi raised funding wrote manuscript drafts, was responsible for data management and statistical analyses. Drs. Minegishi, Sudoh, Kuribayashi, Mizutani, and Seike were responsible for implementing the study. Drs. Azuma and Yoshimura assisted in the trial design, and reviewed the manuscript. Dr. Gemma provided final approval of the version to be published.

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