A Phase I trial of escalating doses of trastuzumab combined with daily subcutaneous interleukin 2: Report of cancer and leukemia group B 9661

Gini F. Fleming, Neal J. Meropol, Gary L. Rosner, Donna R. Hollis, William E. Carson, Michael Caligiuri, Joanne Mortimer, Katherine Tkaczuk, Robin Parihar, Richard L. Schilsky, Mark J. Ratain

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: The purpose of this study was to determine the toxicity of escalating doses of trastuzumab when combined with a fixed dose regimen of interleukin (IL)-2. Experimental Design: Eligible patients had nonhematological malignancies for which standard therapy did not exist or was no longer effective and had tumors that over-expressed HER2. IL-2 was initially administered at a dose of 1.25 million IU/m2 (low dose) s.c. daily except for 3 days every 2 weeks, when it was given at a dose of 15 million IU/m2 (intermediate dose). These doses were reduced to 1.0 million and 12 million IU/m2 after the first 18 patients. Trastuzumab was administered i.v. just before the first intermediate IL-2 dose and was escalated in cohorts of six or more patients from 1 mg/kg every 2 weeks to 8 mg/kg weekly. In vitro cytotoxicity testing was performed with patient peripheral blood mononuclear cells and HER2-over-expressing cell lines. Results: Forty-five patients were treated. Dose-related toxicity from trastuzumab was not observed. IL-2-related toxicities such as fever, chills, and fatigue were less common with the reduced doses of IL-2. There were two grade 3 and three grade 4 pulmonary reactions. Four major responses were observed, all in breast cancer patients treated with trastuzumab doses of at least 4.0 mg/kg. Although IL-2 produced expansion of natural killer cell subsets, there was no correlation between in vitro cytotoxicity and clinical response. Conclusions: A regimen of IL-2 combined with trastuzumab is feasible, and response numbers are encouraging. Further testing of this regimen is warranted if the pulmonary toxicity can be ameliorated.

Original languageEnglish (US)
Pages (from-to)3718-3727
Number of pages10
JournalClinical Cancer Research
Volume8
Issue number12
StatePublished - Dec 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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