BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a Cremophor EL-free formulation of paclitaxel newly designed to avoid solvent-related toxicities. We have evaluated the safety, tolerability, pharmacokinetics, and tumor response profile of weekly nab-paclitaxel (100 mg/m(2)) infusion together with administration of carboplatin at an area under the curve (AUC) of 6 every 3 weeks in Japanese patients with advanced non-small cell lung cancer (NSCLC). METHODS: Nab-paclitaxel (100 mg/m(2)) was administered without steroid or antihistamine premedication as a 30-min intravenous infusion once a week in combination with carboplatin at an AUC of 6 on day 1 of repeated 21-day cycles. The pharmacokinetics of both drugs were analyzed, and both adverse events and treatment response were monitored. RESULTS: Eighteen patients were enrolled in the study. The most frequent treatment-related toxicities of grade 3 or 4 were neutropenia (67%), leukopenia (50%), and anemia (22%). No severe hypersensitivity reactions were observed despite the lack of premedication, and no unexpected or new toxicities were detected. Pharmacokinetics analysis did not reveal any substantial drug-drug interactions. Seven partial responses were observed among the 18 evaluable patients, yielding a treatment response rate of 38.9%. CONCLUSIONS: The combination of nab-paclitaxel (100 mg/m(2)) administered weekly and carboplatin at an AUC of 6 every 3 weeks was well tolerated in Japanese patients with advanced NSCLC. This combination therapy also showed promising antitumor activity and was not associated with relevant pharmacokinetic interactions.
BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a Cremophor EL-free formulation of paclitaxel newly designed to avoid solvent-related toxicities. We have evaluated the safety, tolerability, pharmacokinetics, and tumor response profile of weekly nab-paclitaxel (100 mg/m(2)) infusion together with administration of carboplatin at an area under the curve (AUC) of 6 every 3 weeks in Japanese patients with advanced non-small cell lung cancer (NSCLC). METHODS:Nab-paclitaxel (100 mg/m(2)) was administered without steroid or antihistamine premedication as a 30-min intravenous infusion once a week in combination with carboplatin at an AUC of 6 on day 1 of repeated 21-day cycles. The pharmacokinetics of both drugs were analyzed, and both adverse events and treatment response were monitored. RESULTS: Eighteen patients were enrolled in the study. The most frequent treatment-related toxicities of grade 3 or 4 were neutropenia (67%), leukopenia (50%), and anemia (22%). No severe hypersensitivity reactions were observed despite the lack of premedication, and no unexpected or new toxicities were detected. Pharmacokinetics analysis did not reveal any substantial drug-drug interactions. Seven partial responses were observed among the 18 evaluable patients, yielding a treatment response rate of 38.9%. CONCLUSIONS: The combination of nab-paclitaxel (100 mg/m(2)) administered weekly and carboplatin at an AUC of 6 every 3 weeks was well tolerated in Japanese patients with advanced NSCLC. This combination therapy also showed promising antitumor activity and was not associated with relevant pharmacokinetic interactions.
Authors: David W Nyman; Kimberley J Campbell; Evan Hersh; Kristen Long; Kelly Richardson; Vuong Trieu; Neil Desai; Michael J Hawkins; Daniel D Von Hoff Journal: J Clin Oncol Date: 2005-11-01 Impact factor: 44.544
Authors: Y Ohe; Y Ohashi; K Kubota; T Tamura; K Nakagawa; S Negoro; Y Nishiwaki; N Saijo; Y Ariyoshi; M Fukuoka Journal: Ann Oncol Date: 2006-11-01 Impact factor: 32.976
Authors: Thomas E Stinchcombe; Mark A Socinski; Christine M Walko; Bert H O'Neil; Frances A Collichio; Anastasia Ivanova; Hua Mu; Michael J Hawkins; Richard M Goldberg; Celeste Lindley; E Claire Dees Journal: Cancer Chemother Pharmacol Date: 2007-02-07 Impact factor: 3.333
Authors: Naiyer A Rizvi; Gregory J Riely; Christopher G Azzoli; Vincent A Miller; Kenneth K Ng; John Fiore; Gloria Chia; Martin Brower; Robert Heelan; Michael J Hawkins; Mark G Kris Journal: J Clin Oncol Date: 2008-02-01 Impact factor: 44.544
Authors: R B Weiss; R C Donehower; P H Wiernik; T Ohnuma; R J Gralla; D L Trump; J R Baker; D A Van Echo; D D Von Hoff; B Leyland-Jones Journal: J Clin Oncol Date: 1990-07 Impact factor: 44.544