The safety and efficacy of weekly paclitaxel in combination with carboplatin for advanced non-small cell lung cancer with idiopathic interstitial pneumonias
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.
References (30)
- et al.
Clinical deterioration in patients with idiopathic pulmonary fibrosis: caused and assessment
Am J Med
(1990) - et al.
Acute exacerbation in idiopathic pulmonary fibrosis: analysis of clinical and pathological findings in three cases
Chest
(1993) - et al.
Outcome of patients with idiopathic pulmonary fibrosis admitted to the ICU for respiratory failure
Chest
(2001) - et al.
Prognosis of patients with advanced idiopathic pulmonary fibrosis requiring mechanical ventilation for acute respiratory failure
Chest
(2001) - et al.
Impact of interstitial lung disease on surgical morbidity and mortality for lung cancer: analyses of short-term and long-term outcomes
J Thorac Cardiovasc Surg
(2003) - et al.
The accuracy of the clinical diagnosis of new-onset idiopathic pulmonary fibrosis and other interstitial lung disease: a prospective study
Chest
(1999) - et al.
Anticoagulant therapy for idiopathic pulmonary fibrosis
Chest
(2005) - et al.
A phase II study of weekly paclitaxel combined with carboplatin for elderly patients with advanced non-small cell lung cancer
Lung Cancer
(2006) - et al.
Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan
Ann Oncol
(2007) - et al.
Cryptogenic fibrosing alveolitis and lung cancer
Thorax
(1980)
Lung cancer and cryptogenic fibrosing alveolitis. Population-based cohort study
Am J Respir Crit Care Med
Lung cancer in patients with idiopathic pulmonary fibrosis
Eur Respir J
International multidisciplinary consensus classification of the idiopathic interstitial pneumonias
Am J Respir Crit Care Med
Clinicopathological characteristics of surgically resected lung cancer associated with idiopathic pulmonary fibrosis
Surg Oncol
CT findings during phase of accelerated deterioration in patients with idiopathic pulmonary fibrosis
AJR (Am J Roentgenol)
Cited by (126)
French practical guidelines for the diagnosis and management of idiopathic pulmonary fibrosis – 2021 update. Full-length version
2023, Respiratory Medicine and ResearchTolerability of sotorasib for KRAS positive lung adenocarcinoma patient with pre-existing interstitial pneumonia; A case report
2023, Respiratory Medicine Case ReportsFrench practical guidelines for the diagnosis and management of IPF – 2021 update, full version
2022, Revue des Maladies Respiratoires