Cardiopulmonary toxicity of treatment with high dose interleukin-2 in 199 consecutive patients with metastatic melanoma or renal cell carcinoma

Cancer. 1994 Dec 15;74(12):3212-22. doi: 10.1002/1097-0142(19941215)74:12<3212::aid-cncr2820741221>;2-i.


Background: Administration of recombinant interleukin-2 (rIL-2) can mediate tumor regression in patients with metastatic melanoma and renal cell carcinoma. In response to recent FDA approval of high dose rIL-2 for use in renal cell carcinoma, the authors recent experience with the cardiopulmonary toxicity associated with high dose IL-2 therapy is reviewed.

Methods: The treatment courses of all patients receiving high dose intravenous bolus rIL-2 from January, 1988, until December, 1992, were evaluated for cardiopulmonary toxicity.

Results: One hundred ninety-nine patients received 310 courses of treatment. There were no treatment-related deaths. Respiratory distress occurred in 3.2% of the courses, requiring intubation in one patient. Three obtunded patients were endotracheally intubated for airway control. Arrhythmias occurred in 6% of the courses (18 patients) with hypotension developing in two of the 199 patients as a result. Eleven of these patients were retreated and recurrent atrial fibrillation developed in two. One episode of significant ventricular tachycardia was noted. Hypotension occurred in 53% of courses; no patients developed hypotension unresponsive to vasopressors. There were no myocardial infarctions; however, 2.5% of patients experienced elevated creatine phosphokinase levels associated with elevated MB isoenzymes attributed to cardiac toxicity. Only one of these patients developed symptoms. Response rates of 19.6% and 15.7% were noted in patients with renal cell carcinoma and melanoma, respectively. Hypotension requiring vasopressors was associated with a significantly improved rate of response in patients with melanoma compared with patients not requiring vasopressors (23.2% vs. 6.5%, P2 = 0.037).

Conclusions: Although high dose intravenous rIL-2 therapy can be associated with cardiopulmonary toxicity, toxic side effects generally are not severe and are rapidly reversible.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arrhythmias, Cardiac / chemically induced
  • Carcinoma, Renal Cell / drug therapy*
  • Cardiomyopathies / chemically induced
  • Cardiovascular Diseases / chemically induced*
  • Child
  • Female
  • Humans
  • Injections, Intravenous
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / adverse effects*
  • Kidney Neoplasms / drug therapy*
  • Male
  • Melanoma / drug therapy*
  • Melanoma / secondary
  • Middle Aged
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Respiratory Insufficiency / chemically induced*


  • Interleukin-2
  • Recombinant Proteins