PURPOSE: To determine the maximum tolerated dose (MTD) of sunitinib plus gemcitabine/cisplatin for first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). Safety, pharmacokinetics, and antitumor activities were evaluated. METHODS: Patients ≥18 years with Eastern Cooperative Oncology Group performance status 0/1 and stage IIIB/IV NSCLC were included in this open-label, multicenter, dose-escalation phase I study. Treatment was administered in 3-week cycles: oral sunitinib 37.5 or 50mg/day intermittently (Schedule 2/1: 2 weeks on treatment, 1 week off treatment) or 25mg continuous daily dosing (CDD) schedule with intravenous infusions of gemcitabine (1000 or 1250 mg/m(2) days 1, 8) and cisplatin (80 mg/m(2) day 1). RESULTS: A total of 28 evaluable patients were assigned to four dose levels. Most adverse events (AEs) on the Schedule 2/1 MTD were mild to moderate. Dose delays due to myelosuppression occurred on both schedules, limiting treatment to a median of four cycles. Four of 18 evaluable patients (22%) on Schedule 2/1 and 1 of 6 patients (17%) on the CDD schedule had confirmed partial responses. CONCLUSIONS: The MTD was identified as sunitinib 37.5mg (Schedule 2/1), gemcitabine 1250 mg/m(2), and cisplatin 80 mg/m(2), with most AEs being mild to moderate. However, frequent dose delays due to myelosuppression occurred. There was evidence of antitumor activity with this combination.
PURPOSE: To determine the maximum tolerated dose (MTD) of sunitinib plus gemcitabine/cisplatin for first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). Safety, pharmacokinetics, and antitumor activities were evaluated. METHODS:Patients ≥18 years with Eastern Cooperative Oncology Group performance status 0/1 and stage IIIB/IV NSCLC were included in this open-label, multicenter, dose-escalation phase I study. Treatment was administered in 3-week cycles: oral sunitinib 37.5 or 50mg/day intermittently (Schedule 2/1: 2 weeks on treatment, 1 week off treatment) or 25mg continuous daily dosing (CDD) schedule with intravenous infusions of gemcitabine (1000 or 1250 mg/m(2) days 1, 8) and cisplatin (80 mg/m(2) day 1). RESULTS: A total of 28 evaluable patients were assigned to four dose levels. Most adverse events (AEs) on the Schedule 2/1 MTD were mild to moderate. Dose delays due to myelosuppression occurred on both schedules, limiting treatment to a median of four cycles. Four of 18 evaluable patients (22%) on Schedule 2/1 and 1 of 6 patients (17%) on the CDD schedule had confirmed partial responses. CONCLUSIONS: The MTD was identified as sunitinib 37.5mg (Schedule 2/1), gemcitabine 1250 mg/m(2), and cisplatin 80 mg/m(2), with most AEs being mild to moderate. However, frequent dose delays due to myelosuppression occurred. There was evidence of antitumor activity with this combination.
Authors: C Gómez-Martín; R Salazar; C Montagut; M Gil-Martín; J A Núñez; M Puig; X Lin; R Khosravan; J M Tursi; M J Lechuga; J Bellmunt Journal: Invest New Drugs Date: 2012-05-22 Impact factor: 3.850
Authors: Miguel Quintela-Fandino; Maria J Bueno; Luis Lombardia; Marta Gil; Antonio Gonzalez-Martin; Raul Marquez; Raquel Bratos; Juan Guerra; Eugene Tan; Antonio Lopez; Ramon Colomer; Ramon Salazar Journal: Mol Oncol Date: 2014-07-17 Impact factor: 6.603
Authors: Joanna M Brell; Smitha S Krishnamurthi; Linda Rath; Joseph A Bokar; Panayiotis Savvides; Joseph Gibbons; Matthew M Cooney; Neal J Meropol; Percy Ivy; Afshin Dowlati Journal: Cancer Chemother Pharmacol Date: 2012-08-07 Impact factor: 3.333
Authors: Cheol Yong Yoon; Jung Sun Lee; Bo Sun Kim; Seong Jin Jeong; Sung Kyu Hong; Seok Soo Byun; Sang Eun Lee Journal: Korean J Urol Date: 2011-01-24
Authors: M D Michaelson; A X Zhu; D P Ryan; D F McDermott; G I Shapiro; L Tye; I Chen; P Stephenson; S Patyna; A Ruiz-Garcia; A B Schwarzberg Journal: Br J Cancer Date: 2013-03-19 Impact factor: 7.640