Interleukin-2 and lymphokine-activated killer cell therapy of solid tumors: analysis of toxicity and management guidelines.
The National Cancer Institute (NCI) Extramural IL2/LAK Working Group treated 93 patients with 114 cycles of high-dose intravenous (IV) interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells in three phase II trials. Thirty-six patients had metastatic melanoma, 35 had metastatic renal cell cancer, and 22 had colorectal cancer. All patients had a Karnofsky performance status greater than or equal to 80% and normal laboratory tests and organ function, and had received no more than one prior form of immunotherapy or chemotherapy. Objective responders were eligible to receive up to two additional courses of therapy at 12-week intervals. The most frequent toxicities were a capillary leak syndrome resulting in marked extravascular fluid shifts, and hypotension requiring treatment with large volumes of IV fluids and vasopressor agents. Laboratory and clinical evidence of hepatic and renal dysfunction were virtually universal. Intensive care-level support was routinely provided and the toxicity observations confirmed the need for this level of care. The life-threatening toxicities were cardiac and pulmonary. Five of the 27 patients who experienced significant respiratory compromise required intubation and mechanical ventilatory support. Twenty patients developed cardiac arrhythmias, the majority of which were supraventricular. There was a single episode of ventricular tachycardia requiring cardioversion. Four patients had transient cardiac ischemia, and an additional four had myocardial infarctions, one of which was fatal. With these exceptions, all toxicities were rapidly reversible. The occurrence of only a single therapy-related death and a very low incidence of other irreversible or life-threatening events is comparable to the level of toxicities often observed in other phase II trials. Although the intensity of this regimen limits this approach to a subset of cancer patients with excellent performance status and adequate organ function, because of the frequency and apparent durability of complete responses, this treatment warrants further investigation.
Margolin
K A
KA
Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA 91010.
Rayner
A A
AA
Hawkins
M J
MJ
Atkins
M B
MB
Dutcher
J P
JP
Fisher
R I
RI
Weiss
G R
GR
Doroshow
J H
JH
Jaffe
H S
HS
Roper
M
M
D000328:Adult; D000368:Aged; D001794:Blood Pressure; D003110:Colonic Neoplasms / Q000628:therapy*; D005260:Female; D006331:Heart Diseases / Q000209:etiology; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000209:etiology; D007680:Kidney Neoplasms / Q000628:therapy*; D007694:Killer Cells, Natural / Q000502:physiology*; D008222:Lymphokines / Q000494:pharmacology*; D008297:Male; D008545:Melanoma / Q000628:therapy*; D008875:Middle Aged; D015337:Multicenter Studies as Topic
D007376:Interleukin-2; D008222:Lymphokines