Dose finding study for the use of subcutaneous recombinant interleukin-2 to augment natural killer cell numbers in an outpatient setting for stage 4 neuroblastoma after megatherapy and autologous stem-cell reinfusion

Ruth Ladenstein, Ulrike Pötschger, Dimitris Siabalis, Alberto Garaventa, Christophe Bergeron, Ian J. Lewis, Jerry Stein, Janice Kohler, Peter J. Shaw, Wolfgang Holter, Vito Pistoia, Jean Michon

Research output: Contribution to journalArticle

Abstract

Purpose: To establish a safe dose of subcutaneous (SC) recombinant interleukin 2 (rIL-2) in an outpatient setting for children with stage 4 neuroblastoma after megatherapy (MGT) and autologous stem-cell reinfusion (ASCR) that is able to sustain an increase of natural-killer cells (NKCs) above the level previously reported for immunomodulatory potency. Patients and Methods: Between August 1997 and November 2000, 33 patients with stage 4 neuroblastoma entered the study from six countries after receiving MGT/ASCR according to national protocols. Dose levels of 3, 6, and 9 × 106 U rIL-2/m2 were given SC in six 5-day cycles every 2 weeks. Results: Median age at registration was 4.1 years (range, 1.8 to 7.4). Median observation time was 5 years (range, 4 to 9.8). Increase of NKCs was achieved in 89% of courses, with more than 100% increase over baseline and/or more than 1,000 NKCs/μL in 58%. On the basis of outpatient dose-limiting toxicity at dose level 3, dose level 2 was chosen for the confirmation stage. At dose level 2, the median increase in absolute NKCs was 1,180 cells/μL for all 83 cycles, corresponding to a median relative NKC increase over baseline of 711%. Fever was frequent but controllable with adequate supportive care; 6.5% of patients were hospitalized. Localized pain was moderate and acceptable. Event-free and overall survival rates at 5 years were 45% (± 9 standard deviation [SD]) and 48% (± 9 SD), respectively. Conclusion: The low toxicity profile and ability to sustain an increase in NKCs of IL-2 at 6 × 106 U/m 2 SC allows its integration in an outpatient setting.

Original languageEnglish
Pages (from-to)441-448
Number of pages8
JournalJournal of Clinical Oncology
Volume29
Issue number4
DOIs
Publication statusPublished - Feb 1 2011

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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