Tomonori Moritaka

Interstitial lung disease in Japanese patients with non-small cell lung cancer receiving gefitinib : An analysis of risk factors and treatment outcomes in okayama lung cancer study group

ABSTRACTRisk factors for the development of interstitial lung disease in patients with non-small cell lung cancer receiving gefitinib and the prognostic factors after interstitial lung disease development have not been established. The aim of this study was to retrospectively identify and evaluate these possible factors. PATIENTS AND METHODSWe reviewed the clinical records and radiographs of 365 consecutive patients with non-small cell lung cancer who received gefitinib in West Japan between 2000 and 2003. RESULTSIn total, 330 patients were eligible for interstitial lung disease evaluation, and 15 patients (4.5%) were finally confirmed to have developed interstitial lung disease by blinded expert review. Multivariate analysis revealed that preexisting pulmonary fibrosis, poor performance status, and prior thoracic irradiation were independent risk factors for interstitial lung disease, with odds ratios of 21.0 (95% confidence interval, 5.12–86.3, P < 0.0001), 9.70 (2.27–41.4, P= 0.001), and 4.33 (1.27–14.8, P= 0.019), respectively. Among the 15 patients who developed interstitial lung disease, eight have died of the condition. Short interval from the initiation of gefitinib treatment to the onset of interstitial lung disease, acute interstitial pneumonia pattern, and the presence of pre-existing pulmonary fibrosis were associated with poor prognosis. DISCUSSIONOur results suggest the importance of patient selection for gefitinib treatment based on interstitial lung disease risk factors in the Japanese population identified.

Comparison of the Incidence and Pattern of Interstitial Lung Disease During Erlotinib and Gefitinib Treatment in Japanese Patients with Non-small Cell Lung Cancer: The Okayama Lung Cancer Study Group Experience

Background: Data comparing the incidence and pattern of interstitial lung disease (ILD) in non-small cell lung cancer patients receiving treatment with gefitinib versus erlotinib, both of which are epidermal growth factor receptor tyrosine kinase inhibitors, are scarce. We investigated the incidence of ILD in Japanese patients treated with gefitinib or erlotinib. Methods: We reviewed the clinical records of 209 patients treated with erlotinib in 2008 (cohort A) and 330 treated with gefitinib between 2000 and 2003 (cohort B). Toxicity within the first month of treatment was investigated. Results: The patients in cohort A had fewer known risk factors for ILD (e.g., poor performance status and prior pulmonary fibrosis). ILD was detected in two patients (1.0%) from cohort A and eight patients (2.4%) from cohort B during the first month of treatment. The events were graded as follows: one patient each in grades 1 and 2 (cohort A), and one, one, and six patients in grades 3, 4, and 5, respectively (cohort B). Multivariate analysis revealed that poor performance status and prior pulmonary fibrosis were significantly correlated with the occurrence of ILD, but the type of epidermal growth factor receptor tyrosine kinase inhibitor administered was not. Conclusion: There was a somewhat lower incidence of ILD with erlotinib therapy than with gefitinib therapy, despite no statistically significant difference. Patient selection based on awareness by Japanese physicians of the risk factors for ILD, rather than the type of agent, may explain the difference in ILD incidence between the two treatments.

Second primary cancer in survivors following concurrent chemoradiation for locally advanced non-small-cell lung cancer

Long-term cancer survivors risk development of second primary cancers (SPC). Vigilant follow-up may be required. We report outcomes of 92 patients who underwent chemoradiation for unresectable stage III non-small-cell lung cancer, with a median follow-up of 8.9 years. The incidence of SPC was 2.4 per 100 patient-years (95% confidence interval: 1.0–4.9).

Bronchial atresia: Report of a case and review of the literature

We report herein an unusual presentation of bronchial atresia in a 28-year-old woman, in whom hyperlucency of the ventral segment, distal to a right extrahilar mass found on a routine chest X-ray, was not recognized. Atresia of the medial branch of the ventral segmental bronchus (B3b) with mucoid impaction in the dilated bronchus was finally disclosed by a right upper lobectomy. The patient had been asymptomatic, and physical examination demonstrated no abnormal findings such as decreased breathing sounds over the affected lung. Localized hyperlucency and a mass are the characteristic radiographic features of bronchial atresia. In the present case, however, hyperlucency distal to the mass, which was retrospectively evident on a computed tomogram of the chest, was not recognized. The preoperative diagnosis was also made difficult by the fact that the atresia was located on a subsequential branch (B3b) of the ventral segmental bronchus of the right upper lobe. Since computed tomography and magnetic resonance imaging are able to make an accurate diagnosis of bronchial atresia possible, surgery is often not indicated for asymptomatic patients. Moreover, although surgical intervention is required for patients with complications such as encroachment of normal pulmonary tissue or infection, resection should be as limited as possible to preserve normal lung tissue.

A phase III randomized trial comparing vindesine and cisplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer: long-term follow-up results and analysis of prognostic factors

UNLABELLED In order to evaluate the activity and toxicity of a three-drug combination of vindesine, ifosfamide and cisplatin (VIP) for inoperable non-small-cell lung cancer (NSCLC), we conducted a randomized trial comparing VIP with a two-drug combination of cisplatin and vindesine (VP). Between September 1987 and March 1992, a total of 132 patients with stage III or IV NSCLC were randomly allocated to either VIP or VP. The VIP regimen consisted of vindesine (VDS 3 mg/m(2) on days 1 and 8), ifosfamide (IFX 1300 mg/m(2) on days 1-5), and cisplatin (CDDP 20 mg/m(2) on days 1-5). The VP regimen consisted of VDS and CDDP with the same dose and schedule as the VIP regimen. Both regimens were repeated every 4 weeks. Objective response rates were 49.3% (95% confidence interval: 95%CI, 43.1-55.4%) in the VIP arm and 44.6% (95%CI, 38.4-50.2%) in the VP arm; the difference was not significant (P=0.5390). Median response duration, median survival time, and two-year survival rates were 26.5 weeks, 49.6 weeks, and 14.9% in the VIP arm and 28.7 weeks, 37.1 weeks, and 12.3% in the VP arm, respectively. There were also no significant differences between these two treatment arms. In comparison with the VP regimen, however, a survival advantage of the VIP regimen could be confirmed when the data were evaluated with Coxs multivariate analysis (P=0.0131). In both arms, the principal toxicity was myelosuppression, which was significantly more frequent in the VIP arm, although generally well tolerated. CONCLUSION This study suggested the survival advantage of the VIP regimen over the VP regimen for treatment of patients with advanced NSCLC.

Phase I/II study of altered schedule of cisplatin and etoposide administration and concurrent accelerated hyperfractionated thoracic radiotherapy for limited-stage small-cell lung cancer

To improve the efficacy of a combination of cisplatin and etoposide and concurrent accelerated twice-daily thoracic radiotherapy against limited-stage small-cell lung cancer, we conducted a phase I/II study using an altered schedule of chemotherapy administration. Chemotherapy consisted of four cycles of cisplatin (days 1 and 8) and etoposide (days 1, 2, 8, and 9) every 4 weeks. Accelerated hyperfractionated thoracic radiation (1.5 Gy twice daily x 30 fractions, total dose of 45 Gy) was concurrently given with the first cycle of chemotherapy. The recommended doses of cisplatin and etoposide determined in the phase I study were 40 and 80 mg/m(2), respectively. In the phase II study, the overall response rate was 100% (complete response: 32%, partial response: 68%). By a median follow-up time of 29 months, median radiation-outfield progression-free survival was 13.4 months, while radiation-infield progression-free survival did not reach median value. The median overall survival time was 22.9 months, with survival rate of 48.4% at 2 years. Major toxicities were leukopenia and neutropenia (>/=grade 3, 92% each). The local control and overall survival demonstrated in this study were excellent. However, the insufficient distant control suggests a need for development of more active chemotherapy regimens.

A Case of Pulmonary Mucoepidermoid Carcinoma Responding to Carboplatin and Paclitaxel

A 59-year-old man was admitted to our hospital with dyspnea and cough. A large polypoid tumor was observed in the lower trachea and bronchoscopic polypectomy was performed using a snare to relieve symptoms. The tumor was diagnosed as a high grade mucoepidermoid carcinoma mainly by the histology of piecemeal specimens obtained by bronchoscopic resection. The primary lesion involved the trachea and the main bronchus, and there were multiple metastases in the lung. The patient was treated with the combination of carboplatin and paclitaxel. After four cycles of chemotherapy, the tumors were significantly reduced. He remains well without evidence of tumor progression for 25 months. This case suggests that the combination chemotherapy of carboplatin and paclitaxel can be an option for treatment of pulmonary mucoepidermoid carcinoma.