OBJECTIVE: Combined paclitaxel and carboplatin is a standard regimen for inoperable non-small cell lung cancer (NSCLC). Although an every-3-week schedule is common, weekly paclitaxel is clinically effective for various cancers. A Phase I clinical trial was conducted to determine maximum-tolerated doses (MTDs) for weekly combined paclitaxel and carboplatin, and to evaluate anti-tumor response, toxicity and pharmacokinetics of paclitaxel in patients with inoperable NSCLC. METHODS: Twenty patients with inoperable NSCLC received weekly carboplatin at area under the curve (AUC) = 2 mg/ml min and paclitaxel. Paclitaxel was escalated if MTD was not reached. Three patients each were entered at levels 1 and 2 (level 1, paclitaxel 50 mg/m(2) and carboplatin AUC = 2 mg/ml min; level 2, 60/2), six at level 3 (70/2), five at level 4 (80/2) and three at level 5 (90/2). RESULTS: One patient had grade 4 (G4) neutropenia at level 2, one had G3 hepatic toxicity at level 3 and one had G3 cardiac toxicity at level 4. MTD was not reached for all dose levels. Response rate (RR) was 35% (7/20) and median survival was 11.1 months. Severe neutropenia (G3 and G4) was seen in seven patients associated with greater AUC, peak concentration (C(max)) and the duration of plasma concentration >50 ng/ml of paclitaxel. CONCLUSIONS: Weekly combined paclitaxel (up to 90 mg/m(2)) and carboplatin (AUC = 2 mg/ml min) was well tolerated. A higher dose intensity of paclitaxel can be given, and RR and survival are not less than the every-3-week protocol. The weekly regimen is an alternative for untreated inoperable NSCLC patients.
OBJECTIVE: Combined paclitaxel and carboplatin is a standard regimen for inoperable non-small cell lung cancer (NSCLC). Although an every-3-week schedule is common, weekly paclitaxel is clinically effective for various cancers. A Phase I clinical trial was conducted to determine maximum-tolerated doses (MTDs) for weekly combined paclitaxel and carboplatin, and to evaluate anti-tumor response, toxicity and pharmacokinetics of paclitaxel in patients with inoperable NSCLC. METHODS: Twenty patients with inoperable NSCLC received weekly carboplatin at area under the curve (AUC) = 2 mg/ml min and paclitaxel. Paclitaxel was escalated if MTD was not reached. Three patients each were entered at levels 1 and 2 (level 1, paclitaxel 50 mg/m(2) and carboplatin AUC = 2 mg/ml min; level 2, 60/2), six at level 3 (70/2), five at level 4 (80/2) and three at level 5 (90/2). RESULTS: One patient had grade 4 (G4) neutropenia at level 2, one had G3 hepatic toxicity at level 3 and one had G3 cardiac toxicity at level 4. MTD was not reached for all dose levels. Response rate (RR) was 35% (7/20) and median survival was 11.1 months. Severe neutropenia(G3 and G4) was seen in seven patients associated with greater AUC, peak concentration (C(max)) and the duration of plasma concentration >50 ng/ml of paclitaxel. CONCLUSIONS: Weekly combined paclitaxel (up to 90 mg/m(2)) and carboplatin (AUC = 2 mg/ml min) was well tolerated. A higher dose intensity of paclitaxel can be given, and RR and survival are not less than the every-3-week protocol. The weekly regimen is an alternative for untreated inoperable NSCLCpatients.
Authors: Ana M Gonzalez-Angulo; Ian Krop; Argun Akcakanat; Huiqin Chen; Shuying Liu; Yisheng Li; Kirk S Culotta; Emily Tarco; Sarina Piha-Paul; Stacy Moulder-Thompson; Vivianne Velez-Bravo; Aysegul A Sahin; Laurence A Doyle; Kim-Anh Do; Eric P Winer; Gordon B Mills; Razelle Kurzrock; Funda Meric-Bernstam Journal: J Natl Cancer Inst Date: 2015-02-16 Impact factor: 13.506
Authors: Janice M Mehnert; Antoinette R Tan; Rebecca Moss; Elizabeth Poplin; Mark N Stein; Mika Sovak; Kelly Levinson; Hongxia Lin; Michael Kane; Murugesan Gounder; Yong Lin; Weichung Joe Shih; Eileen White; Eric H Rubin; Vassiliki Karantza Journal: Mol Cancer Ther Date: 2011-06-16 Impact factor: 6.261