Kyoichi Kaira1,2, Noriaki Sunaga3, Hisao Imai3, Yosuke Kamide3, Yasuhiko Koga3, Akihiro Ono3, Tomohito Kuwako3, Tomomi Masuda3, Takeshi Hisada3, Tamotsu Ishizuka3,4, Masanobu Yamada3. 1. Department of Oncology Clinical Development, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan. kkaira1970@yahoo.co.jp. 2. Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan. kkaira1970@yahoo.co.jp. 3. Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan. 4. Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Abstract
BACKGROUND: We conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD), the recommended dose (RD) and the safety profile of amrubicin (AMR) plus paclitaxel (PTX) combination regimen for patients with previously treated non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: PTX was administered at a fixed dose of 150 mg/m(2)/day on day 1 and AMR was intravenously administered at a starting dose of 25 mg/m(2)/day on days 1-3, and this was repeated every 4 weeks. Doses of each drug were planned as follows-level 0, 20/150; level 1, 25/150; level 2, 30/150; level 3, 30/180 AMR mg/m(2) per day/PTX mg/m(2) per day. RESULTS: Twelve patients were enrolled in this study. The dose-limiting toxicity (DLT) of the regimen was assessed during the first cycle. At level 1, all three patients developed a DLT due to grade 4 neutropenia lasting >4 days, grade 4 thrombocytopenia and grade 3 febrile neutropenia. Therefore, level 1 was considered the MTD and level 0 was selected as the RD. Objective responses were seen in two patients (response rate 16.7 %). Overall disease control rate was 91.7 %. CONCLUSIONS: The combination of AMR and PTX is a feasible and well-tolerated regimen for the treatment of patients with previously treated advanced NSCLC. Although our study included a small number of patients, encouraging disease control and progression-free survival were achieved at the recommended doses. Further clinical trials are warranted.
BACKGROUND: We conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD), the recommended dose (RD) and the safety profile of amrubicin (AMR) plus paclitaxel (PTX) combination regimen for patients with previously treated non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: PTX was administered at a fixed dose of 150 mg/m(2)/day on day 1 and AMR was intravenously administered at a starting dose of 25 mg/m(2)/day on days 1-3, and this was repeated every 4 weeks. Doses of each drug were planned as follows-level 0, 20/150; level 1, 25/150; level 2, 30/150; level 3, 30/180 AMR mg/m(2) per day/PTX mg/m(2) per day. RESULTS: Twelve patients were enrolled in this study. The dose-limiting toxicity (DLT) of the regimen was assessed during the first cycle. At level 1, all three patients developed a DLT due to grade 4 neutropenia lasting >4 days, grade 4 thrombocytopenia and grade 3 febrile neutropenia. Therefore, level 1 was considered the MTD and level 0 was selected as the RD. Objective responses were seen in two patients (response rate 16.7 %). Overall disease control rate was 91.7 %. CONCLUSIONS: The combination of AMR and PTX is a feasible and well-tolerated regimen for the treatment of patients with previously treated advanced NSCLC. Although our study included a small number of patients, encouraging disease control and progression-free survival were achieved at the recommended doses. Further clinical trials are warranted.
Entities:
Keywords:
Amrubicin; Class III β-tubulin; NSCLC; Paclitaxel; Phase I; Topoisomerase II
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: J Jassem; T Pieńkowski; A Płuzańska; S Jelic; V Gorbunova; Z Mrsic-Krmpotic; J Berzins; T Nagykalnai; N Wigler; J Renard; S Munier; C Weil Journal: J Clin Oncol Date: 2001-03-15 Impact factor: 44.544
Authors: Nasser Hanna; Frances A Shepherd; Frank V Fossella; Jose R Pereira; Filippo De Marinis; Joachim von Pawel; Ulrich Gatzemeier; Thomas Chang Yao Tsao; Miklos Pless; Thomas Muller; Hong-Liang Lim; Christopher Desch; Klara Szondy; Radj Gervais; Christian Manegold; Sofia Paul; Paolo Paoletti; Lawrence Einhorn; Paul A Bunn Journal: J Clin Oncol Date: 2004-05-01 Impact factor: 44.544
Authors: Peter Fritz; Cristina M Cabrera; Jürgen Dippon; Andreas Gerteis; Wolfgang Simon; Walter E Aulitzky; Heiko van der Kuip Journal: Breast Cancer Res Date: 2005-03-21 Impact factor: 6.466
Authors: K Shimizu; K Kaira; Y Tomizawa; N Sunaga; O Kawashima; N Oriuchi; H Tominaga; S Nagamori; Y Kanai; M Yamada; T Oyama; I Takeyoshi Journal: Br J Cancer Date: 2014-03-06 Impact factor: 7.640