Yuko Kawano1, Tomonari Sasaki2, Hiroyuki Yamaguchi3, Katsuya Hirano4, Atsushi Horiike5, Miyako Satouchi6, Shinobu Hosokawa7, Ryotaro Morinaga8, Kazutoshi Komiya9, Koji Inoue10, Yuka Fujita11, Ryo Toyozawa12, Tomoki Kimura13, Kosuke Takahashi14, Kazuo Nishikawa15, Junji Kishimoto16, Yoichi Nakanishi17, Isamu Okamoto18. 1. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. 2. Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. 3. Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. 4. Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, 2-17-77 Higashinaniwa-cho, Amagasaki, 660-8550, Japan. 5. Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan. 6. Department of Thoracic Oncology, Hyogo Cancer Center, 13-70 Kitaoji-cho, Akashi, 673-8558, Japan. 7. Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, 2-1-1 Aoe, Kita-ku, Okayama, 700-8607, Japan. 8. Department of Thoracic Medical Oncology, Oita Prefectural Hospital, 476 Bunyo, Oita, 870-8511, Japan. 9. Division of Hematology, Respiratory Medicine, and Oncology, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan. 10. Department of Respiratory Medicine, Kitakyushu Municipal Medical Center, 2-1-1 Basyaku, Kokurakita-ku, Kitakyushu, 802-0077, Japan. 11. Department of Respiratory Medicine, National Hospital Organization Asahikawa Medical Center, 7-4048, Hanasakicho, Asahikawa, 070-8644, Japan. 12. Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan. 13. Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwakecho, Seto, 489-8642, Japan. 14. Department of Respiratory Medicine, Aichi Cancer Center Aichi Hospital, 18 Kakemachikuriyado, Okazaki, 444-0011, Japan. 15. Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Oita, 879-5593, Japan. 16. Center for Clinical and Translational Research, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. 17. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan; Center for Clinical and Translational Research, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. 18. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. Electronic address: okamotoi@kokyu.med.kyushu-u.ac.jp.
Abstract
OBJECTIVES: Chemoradiation regimens of greater efficacy are needed for patients with locally advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: In a phase I study, escalating doses of weekly nab-paclitaxel (40 or 50 mg/m2) were administered along with weekly carboplatin at an area under the curve (AUC) of 2 mg mL-1 min and concurrent radiotherapy with 60 Gy in 30 fractions to patients with locally advanced NSCLC. This concurrent phase was followed by a consolidation phase consisting of two 3-week cycles of nab-paclitaxel plus carboplatin. In a phase II study, nab-paclitaxel was administered at the recommended dose (RD) together with carboplatin and radiation. RESULTS: In the phase I study, one of six patients experienced dose-limiting toxicity (leukopenia of grade 3 requiring a second consecutive skip in the administration of weekly chemotherapy) with nab-paclitaxel at 50 mg/m2, which was therefore determined to be the RD. Fifty-six patients treated at the RD were evaluable for safety and efficacy. Common toxicities of grade 3 or 4 in the concurrent phase included leukopenia (60.7%) and neutropenia (28.6%). No treatment-related deaths occurred during the study period. The objective response rate was 76.8% (95% confidence interval [CI], 64.2-85.9%), median progression-free survival was 11.8 months (60% CI, 10.6-16.2 months; 95% CI, 8.2-20.8 months), and median overall survival was not reached. CONCLUSION: Our results reveal encouraging feasibility and activity for concurrent chemoradiation with nab-paclitaxel at 50 mg/m2 and carboplatin at an AUC of 2 in patients with locally advanced NSCLC.
OBJECTIVES: Chemoradiation regimens of greater efficacy are needed for patients with locally advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: In a phase I study, escalating doses of weekly nab-paclitaxel (40 or 50 mg/m2) were administered along with weekly carboplatin at an area under the curve (AUC) of 2 mg mL-1 min and concurrent radiotherapy with 60 Gy in 30 fractions to patients with locally advanced NSCLC. This concurrent phase was followed by a consolidation phase consisting of two 3-week cycles of nab-paclitaxel plus carboplatin. In a phase II study, nab-paclitaxel was administered at the recommended dose (RD) together with carboplatin and radiation. RESULTS: In the phase I study, one of six patients experienced dose-limiting toxicity (leukopenia of grade 3 requiring a second consecutive skip in the administration of weekly chemotherapy) with nab-paclitaxel at 50 mg/m2, which was therefore determined to be the RD. Fifty-six patients treated at the RD were evaluable for safety and efficacy. Common toxicities of grade 3 or 4 in the concurrent phase included leukopenia (60.7%) and neutropenia (28.6%). No treatment-related deaths occurred during the study period. The objective response rate was 76.8% (95% confidence interval [CI], 64.2-85.9%), median progression-free survival was 11.8 months (60% CI, 10.6-16.2 months; 95% CI, 8.2-20.8 months), and median overall survival was not reached. CONCLUSION: Our results reveal encouraging feasibility and activity for concurrent chemoradiation with nab-paclitaxel at 50 mg/m2 and carboplatin at an AUC of 2 in patients with locally advanced NSCLC.
Authors: Allison N DuRoss; Megan J Neufeld; Shushan Rana; Charles R Thomas; Conroy Sun Journal: Adv Drug Deliv Rev Date: 2019-07-04 Impact factor: 15.470