title: A phase II study of STEALTH cisplatin (SPI-77) in patients with advanced non-small cell lung cancer.
abstract: Cisplatin-based chemotherapy improves survival in appropriately selected patients with stage IV non-small cell lung cancer (NSCLC). However, cisplatin-based regimens have well-known dose-related toxicities, particularly renal insufficiency and neurotoxicity. On the basis of prior preclinical and phase I studies, we initiated a phase II study of SPI-77 (STEALTH) Liposomal Cisplatin) in patients with stage IIIB and IV NSCLC who failed previous treatment with platinum. Disease in all subjects had progressed during therapy, failed to respond, or progressed within 3 months after discontinuing the platinum-based chemotherapy. Between January and June 1999, 13 patients were enrolled at our institution. Patient characteristics included: seven women, six men; median age, 61 years; median Karnofsky performance status, 80%; median number of prior chemotherapy regimens, two (range, 1-3). All patients had adequate hepatic and renal function. SPI-77 was administered at a dose of 260 mg/m(2) IV every 3 weeks. A median of two cycles (range 1-6) were given; the total number of cycles was 35. Among the 12 patients evaluable for response, two had (17%) stable disease and ten (83%) had progressive disease. The median survival was 24.3 weeks, and the median follow-up was 43.9 weeks. Toxicity could be evaluated in all subjects. Moderate anemia (46% of cycles, <or=grade 2; 3% of cycles, >or=grade 3) with minimal granulocytopenia and thrombocytopenia (26% of cycles grade 1; 0% of cycles, >or=grade 2) were the most notable manifestations of myelosuppression. Grade 3 nonhematological toxicities included dyspnea (8%), fatigue (8%), and pain (8%). There were no grade 4 toxicities. These data suggest that this liposomal cisplatin formulation does not have appreciable activity in this population of patients with NSCLC who had received prior platinum-based chemotherapy. The lack of encouraging results from SPI-77 use in other phase I and II studies resulted in early closure of this trial by the manufacturer.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030-4009, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Kim
authors.forename: C
authors.initials: C
authors.lastname: Lu
authors.forename: F R
authors.initials: FR
authors.lastname: Khuri
authors.forename: M
authors.initials: M
authors.lastname: Tonda
authors.forename: B S
authors.initials: BS
authors.lastname: Glisson
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Jung
authors.forename: W K
authors.initials: WK
authors.lastname: Hong
authors.forename: R S
authors.initials: RS
authors.lastname: Herbst
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008081:Liposomes; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D008081:Liposomes; D002945:Cisplatin