Sequential cis-platinum and fludarabine with or without arabinosyl cytosine in patients failing prior fludarabine therapy for chronic lymphocytic leukemia: A phase II study

Francis J. Giles*, Susan M. Obrien, Valeria Santini, Varsha Gandhi, William Plunkett, John F. Seymour, Lester E. Robertson, Hagop M. Kantarjian, Michael J. Keating

*Corresponding author for this work

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Patients with chronic lymphocytic leukemia (CLL) who fail fludarabine (Fluda) therapy have a poor response to subsequent salvage regimens and a poor prognosis. This study was undertaken to determine the efficacy and toxicity of a cis-platinum, (cis-p)fluda and arabinosyl cytosine (ara-C) combination in patients who were refractory to fluda or had relapsed following prior fluda therapy for CLL. Forty-one patients who had progressive CLL were treated on study. Eleven patients (27%) were sensitive to fluda and thirty (73%) refractory prior to study entry. Therapy consisted of cis-p 100 mg/m2 continuous intravenous (IV) infusion over 4 days, fluda 30 mg/m2 IV over 15 minutes on Days 3 and 4 either given alone (PF) or with ara-C 500 mg/m2 IV over 1 hour on Day 4 (PFA). The median number of PF or PFA courses received was two. No patient achieved a complete response. Eight patients (19%) achieved a partial response (PR), 28 were taken off study with progressive or refractory disease and 5 had induction deaths. The overall median survival was 6 months, 15 months in responding patients, and 4 months in non-responding patients. Rai stage I-II patients had a median survival of 7 months and stage III-IV patients had a median survival of 3 months. Major toxicities (myelosuppression, sepsis, renal failure and tumor lysis syndrome) were frequent. In conclusion, it can be said that the PF and PFA regimens have equivalent modest activity in patients with progressive CLL following prior fluda therapy, predominantly among patients whose disease was sensitive to fluda at last prior exposure. Ara-C did not add to the activity of the cis-p/fluda combination in this study group.

Original languageEnglish (US)
Pages (from-to)57-65
Number of pages9
JournalLeukemia and Lymphoma
Volume36
Issue number1-2
DOIs
StatePublished - Jan 1 1999

Keywords

  • Arabinosyl cytosine
  • CLL
  • Chronic lymphocyte leukemia
  • Combination chemotherapy
  • Failire regimen
  • Fludarabine
  • Resistant disease
  • cis-platinum

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Giles, F. J., Obrien, S. M., Santini, V., Gandhi, V., Plunkett, W., Seymour, J. F., Robertson, L. E., Kantarjian, H. M., & Keating, M. J. (1999). Sequential cis-platinum and fludarabine with or without arabinosyl cytosine in patients failing prior fludarabine therapy for chronic lymphocytic leukemia: A phase II study. Leukemia and Lymphoma, 36(1-2), 57-65. https://doi.org/10.3109/10428199909145949