title: A phase I study of STEALTH cisplatin (SPI-77) and vinorelbine in patients with advanced non small-cell lung cancer.
abstract: STEALTH  cisplatin (SPI-77) is a liposomal formulation of cisplatin that has activity in animal models of non  small-cell lung cancer (NSCLC). Vinorelbine has documented clinical activity in NSCLC. The purpose of this study was to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of SPI-77 when administered in combination with a fixed dose of vinorelbine to patients with stage IIIB or IV NSCLC refractory to or recurrent following previous chemotherapy. SPI-77 was given on day 1 in combination with vinorelbine at a fixed dose of 25 mg/m2 on days 1 and 8 of a 3-week treatment cycle. Dose escalation of SPI-77 progressed as follows: 20, 40, 80, 100, 120, and 140 mg/m2. Twenty patients were entered (11 men and nine women; median age, 63 years). Sixty-four complete cycles of therapy were administered, and 19 of 20 patients completed at least 1 cycle of combination chemotherapy. Neutropenia was dose limiting at a SPI-77 dose of 140 mg/m2. Neuropathy and nephrotoxicity were minimal and not dose related. A partial response was observed in three of 17 patients eligible for a response evaluation and response duration ranged from 6 weeks to 5 months. In conclusion, treatment with combination SPI-77 and vinorelbine was well tolerated, and our recommended phase II dose is 120 mg/m2 of SPI-77 in combination with vinorelbine at 25 mg/m2. Activity was observed in this patient population, and additional phase II testing of this regimen in a less extensively pretreated cohort of patients with NSCLC is indicated.
authors.affiliation: University of Chicago, Section of Hematology/Oncology, and Cancer Research Center, Chicago, Illinois 60637-1470, USA. evokes@medicine.bsd.uchicago.edu
authors.forename: E E
authors.initials: EE
authors.lastname: Vokes
authors.forename: G S
authors.initials: GS
authors.lastname: Gordon
authors.forename: A M
authors.initials: AM
authors.lastname: Mauer
authors.forename: C M
authors.initials: CM
authors.lastname: Rudin
authors.forename: S A
authors.initials: SA
authors.lastname: Krauss
authors.forename: L
authors.initials: L
authors.lastname: Szeto
authors.forename: H M
authors.initials: HM
authors.lastname: Golomb
authors.forename: P C
authors.initials: PC
authors.lastname: Hoffman