Phase I/II study of docetaxel and cisplatin with concurrent thoracic radiation therapy for locally advanced non-small-cell lung cancer

Abstract

Recent studies have suggested the superiority of concomitant over sequential administration of chemotherapy and radiotherapy. Docetaxel and cisplatin have demonstrated efficacy in advanced non-small-cell lung cancer (NSCLC). This study evaluated the safety, toxicity, and antitumour activity of docetaxel/cisplatin with concurrent thoracic radiotherapy for patients with locally advanced NSCLC. Patients with locally advanced NSCLC (stage IIIA or IIIB), good performance status, age p75 years, and adequate organ function were eligible. Both docetaxel and cisplatin were given on days 1, 8, 29, and 36. Doses of docetaxel/cisplatin (mg m À2 ) in the phase I study portion were escalated as follows: 20/30, 25/30, 30/30, 30/35, 30/40, 35/40, 40/40, and 45/40. Beginning on day 1 of chemotherapy, thoracic radiotherapy was given at a total dose of 60 Gy with 2 Gy per fraction over 6 weeks. In the phase I portion, the maximum tolerated doses (MTD) among 33 patients were docetaxel 45 mg m À2 and cisplatin 40 mg m À2 . The major doselimiting toxicity (DLT) was radiation oesophagitis. The recommended doses (RDs) for the phase II study were docetaxel 40 mg m À2and cisplatin 40 mg m À2 . A total of 42 patients were entered in the phase II portion. Common toxicities were leukopenia, granulocytopenia, anaemia, and radiation oesophagitis, with frequencies of grade X3 toxicities of 71, 60, 24, and 19%, respectively. Toxicity was significant, but manageable according to the dose and schedule modifications. Dose intensities of docetaxel and cisplatin were 86 and 87%, respectively. Radiotherapy was completed without a delay in 67% of 42 patients. The overall response rate was 79% (95% confidence interval (CI), 66 -91%). The median survival time was 23.4 þ months with an overall survival rate of 76% at 1 year and 54% at 2 years. In conclusion, chemotherapy with cisplatin plus docetaxel given on days 1, 8, 29, and 36 and concurrent thoracic radiotherapy is efficacious and tolerated in patients with locally advanced NSCLC and should be evaluated in a phase III study.

Preoperative concurrent chemoradiotherapy with cisplatin and docetaxel in patients with locally advanced non-small-cell lung cancer

“…In several recent reports, preoperative chemoradiotherapy in patients with LA-NSCLC was shown to be feasible and effective, although the new drugs developed in the 1990s such as irinotecan and docetaxel were not included (Albain et al, 1995;Choi et al, 1997;Eberhardt et al, 1998;Thomas et al, 1999). We have already confirmed the feasibility and effectiveness of concurrent chemoradiotherapy using cisplatin and docetaxel in patients with unresectable LA-NSCLC (Kiura et al, 2003), whereas a combination of cisplatin, irinotecan and concurrent thoracic irradiation has been reported to be toxic and unacceptable (Yokoyama et al, 1996). Based on these results, the present study was planned to assess the feasibility and effectiveness of this chemoradiotherapy as preoperative treatment in patients with LA-NSCLC.…”

“…We thus considered that cisplatin plus docetaxel would be an excellent regimen to incorporate in concurrent chemoradiotherapy for LA-NSCLC. We previously reported that combined modality therapy using cisplatin and docetaxel with concurrent thoracic irradiation was feasible and effective in patients with unresectable LA-NSCLC (Kiura et al, 2003). The regimen achieved good control of local tumour and also of distant metastases.…”

Phase II trial of S-1 and cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer

“…However, for many of these newer agents, the dose-limiting toxicities require that lower doses be given during the concurrent phase (Choy et al, 1998;Vokes et al, 2002;Kiura et al, 2003;Belani et al, 2005;Fournel et al, 2005).…”

Clinical and dosimetric factors of radiation-induced esophageal injury: Radiation-induced esophageal toxicity

“…Contrary to the findings of Maguire et al [8] , we did not find any significant association between the incidence of esophagitis and the the longitudinal and circumferential characteristics of the esophagus. However, Kiura et al [12] , reported that concurrent thoracic radiation therapy and chemotherapy are effective and tolerable in patients with advanced NSCLC. Singh et al [13] , found that concurrent chemotherapy is significantly associated with the risk of grade 3-5 esophageal injury in patients with NSCLC.…”