Phase I/II trial of low dose cyclosporin a with EP for advanced non- small cell lung cancer

Helen J. Ross, Jonathan Cho, Kathryn Osann, Siu Fun Wong, Nilam Ramsinghani, James Williams, Nancy Downey-Hurtado, Lewis M. Slater

Research output: Contribution to journalArticle

13 Scopus citations

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 significantly 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.

Original languageEnglish (US)
Pages (from-to)189-198
Number of pages10
JournalLung Cancer
Volume18
Issue number2
DOIs
StatePublished - Oct 1 1997

Keywords

  • Chemotherapy
  • Cis-platinum
  • Cyclosporine
  • Etoposide
  • Immunomodulation
  • Non-small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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    Ross, H. J., Cho, J., Osann, K., Wong, S. F., Ramsinghani, N., Williams, J., Downey-Hurtado, N., & Slater, L. M. (1997). Phase I/II trial of low dose cyclosporin a with EP for advanced non- small cell lung cancer. Lung Cancer, 18(2), 189-198. https://doi.org/10.1016/S0169-5002(97)00061-5