Kyoichi Kaira1,2, Yoshio Tomizawa3, Hisao Imai4, Reiko Sakurai5,3, Masana Matsuura6, Akihiro Yoshii3, Mai Ochiai3, Mie Kotake3, Takeshi Ebara7, Jun-Ichi Saitoh8, Noriaki Sunaga5,9, Koichi Minato4, Ryusei Saito3, Takeshi Hisada5. 1. Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. kkaira1970@yahoo.co.jp. 2. Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. kkaira1970@yahoo.co.jp. 3. Department of Respiratory Medicine, Shibukawa Medical Center, Shibukawa, Gunma, Japan. 4. Department of Respiratory Medicine, Gunma Prefectural Cancer Center, Maebashi, Gunma, Japan. 5. Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. 6. Department of Radiology, Shibukawa Medical Center, Shibukawa, Gunma, Japan. 7. Department of Radiation Oncology, Gunma Prefectural Cancer Center, Maebashi, Gunma, Japan. 8. Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. 9. Oncology Center, Gunma University Hospital, Maebashi, Gunma, Japan.
Abstract
BACKGROUND: The aim of our study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin in combination with thoracic radiotherapy for patients with locally advanced stage III non-small cell lung cancer (NSCLC). METHODS: Weekly nab-paclitaxel plus carboplatin was administered intravenously for 6 weeks. Doses of each drug were planned as follows: level 1, 40/2; level 2, 60/2; level 3, 80/2 (nab-paclitaxel [mg/m2]/carboplatin [area under the plasma concentration time curve mg/ml/min]). Concurrent thoracic radiotherapy was administered in 2-Gy fractions 5 times weekly, to a total dose of 60 Gy. RESULTS: Fourteen patients were enrolled in the present study. Eleven (78%) patients received full cycles (6 cycles) of chemotherapy, and 12 (86%) patients received 60 Gy of thoracic radiotherapy. At level 1, none of 3 patients experienced a dose-limiting toxicity (DLT). At level 2, 2 of 7 patients developed grade 3 diarrhea, grade 3 hyponatremia, grade 3 fatigue, and grade 3 esophagitis. Therefore, 4 patients were started at dose level 3 and none developed a DLT. No pulmonary toxicities, such as interstitial pneumonitis and treatment-related deaths, were observed at either level. Therefore, level 3 was considered the MTD and level 3 was defined as the RD. An objective response was observed in 71.4% of all patients. CONCLUSIONS: This regimen is feasible and well tolerated for the treatment of patients with unresectable locally advanced NSCLC.
BACKGROUND: The aim of our study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin in combination with thoracic radiotherapy for patients with locally advanced stage III non-small cell lung cancer (NSCLC). METHODS: Weekly nab-paclitaxel plus carboplatin was administered intravenously for 6 weeks. Doses of each drug were planned as follows: level 1, 40/2; level 2, 60/2; level 3, 80/2 (nab-paclitaxel [mg/m2]/carboplatin [area under the plasma concentration time curve mg/ml/min]). Concurrent thoracic radiotherapy was administered in 2-Gy fractions 5 times weekly, to a total dose of 60 Gy. RESULTS: Fourteen patients were enrolled in the present study. Eleven (78%) patients received full cycles (6 cycles) of chemotherapy, and 12 (86%) patients received 60 Gy of thoracic radiotherapy. At level 1, none of 3 patients experienced a dose-limiting toxicity (DLT). At level 2, 2 of 7 patients developed grade 3 diarrhea, grade 3 hyponatremia, grade 3 fatigue, and grade 3 esophagitis. Therefore, 4 patients were started at dose level 3 and none developed a DLT. No pulmonary toxicities, such as interstitial pneumonitis and treatment-related deaths, were observed at either level. Therefore, level 3 was considered the MTD and level 3 was defined as the RD. An objective response was observed in 71.4% of all patients. CONCLUSIONS: This regimen is feasible and well tolerated for the treatment of patients with unresectable locally advanced NSCLC.
Authors: David A Mahvi; Rong Liu; Mark W Grinstaff; Yolonda L Colson; Chandrajit P Raut Journal: CA Cancer J Clin Date: 2018-10-17 Impact factor: 508.702