Treatment of poor-prognosis extensive disease small-cell lung cancer with an all-oral regimen of etoposide and cyclophosphamide - A Southwest Oncology Group clinical and pharmacokinetic study

Steven M. Grunberg, John Crowley, Kenneth R. Hande, Dori Giroux, Nikhil Munshi, Derick H Lau, Louis E. Schroder, Mark H. Zangmeister, Stanley P. Balcerzak, Harry E. Hynes, David R Gandara

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Purpose: An all-oral regimen of etoposide and cyclophosphamide was developed for use in poor-prognosis extensive disease small-cell lung cancer. Limited pharmacokinetic sampling was used to derive a pharmacodynamic model predictive of myelosuppression early in the course of therapy. Patients and methods: Eligible patients were chemotherapy-naive and had extensive disease small-cell lung cancer with either SWOG performance status 2 or serum albumin < 3.5 g/dl. The first cohort (n = 18) received etoposide orally at 50 mg daily and cyclophosphamide orally at 50 mg daily days 1-14 every 28 days. Due to good hematologic tolerance, the second cohort (n = 39) received both agents orally at 50 mg twice daily days 1-14 every 28 days. Plasma etoposide levels were determined in samples drawn at baseline, and at 1 h, 2 h, and 23.5 h (trough) after the first dose. Linear regression analysis was used to determine pharmacokinetic and demographic parameters predictive of myelosuppression. Results: A total of 173 treatment cycles were delivered. Patients on the daily regimen had a 22% response rate (complete and partial), a 22% unconfirmed response rate, and a 5-month median survival, while patients on the twice-daily regimen had a 28% response rate (complete and partial), a 13% unconfirmed response rate, and a 7-month median survival. Granulocytopenia and alopecia were the most common toxicities seen. Significant granulocytopenia could be predicted for the twice-daily regimen according to the formula ln(AGC nadir)=7.80 - 1.88(trough), with an increased incidence of granulocytopenia if the etoposide trough value was ≥1.49 μg/ml. Conclusion: Oral etoposide and oral cyclophosphamide given days 1-14 every 28 days is well tolerated and results in an acceptable response rate and median survival in poor-prognosis (poor performance status or low serum albumin) extensive disease small-cell lung cancer. A trough etoposide level obtained within 24 h of starting therapy can predict severe granulocytopenia.

Original languageEnglish (US)
Pages (from-to)461-468
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume44
Issue number6
DOIs
StatePublished - 1999

Keywords

  • Cyclophosphamide
  • Etoposide
  • Oral chemotherapy
  • Pharmacodynamics
  • Small-cell lung cancer

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

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