Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer.
To determine the efficacy and tolerability of SPI-77 (sterically stabilised liposomal cisplatin) at three dose levels in patients with advanced non-small-cell lung cancer (NSCLC). Patients had Stage IIIB or IV NSCLC and were chemo-naïve, and Eastern Oncology Cooperative Group 0-2. The first cohort received SPI-77 at 100 mg m-2, the second 200 mg m-2 and the final cohort 260 mg m-2. Patients had also pharmacokinetics and analysis of leucocyte platinum (Pt)-DNA adducts performed. Twenty-six patients were treated, with 22 patients being evaluable for response. Only one response occurred at the 200 mg m-2 dose level for an overall response rate of 4.5% (7.1% at >or=200 mg m-2). No significant toxicity was noted including nephrotoxicity or ototoxicity aside from two patients with Grade 3 nausea. No routine antiemetics or hydration was used. The pharmacokinetic profile of SPI-77 was typical for a liposomally formulated drug, and the AUC appeared to be proportional to the dose of SPI-77. Plasma Pt levels and leucocyte DNA adduct levels did not appear to rise with successive doses. SPI-77 demonstrates only modest activity in patients with NSCLC.
White
S C
SC
Christie Hospital NHS Trust, Manchester, UK. shane.white@austin.org.au
Lorigan
P
P
Margison
G P
GP
Margison
J M
JM
Martin
F
F
Thatcher
N
N
Anderson
H
H
Ranson
M
M
D000368:Aged; D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics; D018736:DNA Adducts / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009367:Neoplasm Staging; D010984:Platinum / Q000097:blood; D016019:Survival Analysis; D016896:Treatment Outcome
D018736:DNA Adducts; C422270:SPI-77, liposomal; C057270:cisplatin-DNA adduct; D010984:Platinum; D002945:Cisplatin