title: Phase I/II trial of low dose cyclosporin A with EP for advanced non-small cell lung cancer.
abstract: We and others have shown that cyclosporin A (CsA) reverses resistance to etoposide (E) and cis-platinum (P) in vitro and in vivo. To assess the clinical relevance of combined therapy, we studied CsA with EP in patients with advanced non-small cell lung cancer in a phase I/II clinical trial in a University setting. Patients were treated between July 1989 and June 1994 and included 10 females and 34 males with a median age of 61 years and a mean Karnofsky performance status of 80. CsA was given at escalating doses of 1-6 mg/kg per day on days 1-4 of each 21 day cycle with cis-platinum 25 mg/m2 per day and etoposide 100 mg/m2 per days on days 1-3. Response was assessed after each 2 cycles by measuring index lesions. A total of 44 patients received 133 cycles, 22.7% of patients had a partial response and 36.4% had stable disease with 8% 2-year survival. Patients receiving 1-2 mg/kg CsA had a PR rate of 37.5 and 50% SD compared to 19.4 and 33.3% for doses of 3 mg/kg or more. Although no conclusions should be drawn from this small study, the Kaplan-Meier survival curves were statistically significant different for these two groups by the log-rank test (P = 0.047). The 2-year survival of the former group was 25% compared to 4% for the latter. In light of the potential importance of immunomodulation in cancer control, it seems prudent to balance the effects of CsA on P-glycoprotein and other drug resistance pumps against its dose-dependent immunosuppressive activity. Further studies are needed to validate the activity of low dose CsA in combination with standard chemotherapy for lung cancer.
authors.affiliation: University of California, Irvine Department of Medicine/Hematology Oncology 92697-4060, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Ross
authors.forename: J
authors.initials: J
authors.lastname: Cho
authors.forename: K
authors.initials: K
authors.lastname: Osann
authors.forename: S F
authors.initials: SF
authors.lastname: Wong
authors.forename: N
authors.initials: N
authors.lastname: Ramsinghani
authors.forename: J
authors.initials: J
authors.lastname: Williams
authors.forename: N
authors.initials: N
authors.lastname: Downey-Hurtado
authors.forename: L M
authors.initials: LM
authors.lastname: Slater
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015996:Survival Rate
chemical_list: D005047:Etoposide; D016572:Cyclosporine