Toxicity and activity of a twice daily high-dose bolus interleukin 2 regimen in patients with metastatic melanoma and metastatic renal cell cancer.
The standard q8h high-dose interleukin-2 (IL-2) regimen produces clear benefit for a subset of patients, but has limited acceptance because of its substantial acute toxicity including hypotension requiring pressors in 30% to 50%, the schedule is inconvenient for medical staff who must assess patients before each dose, and in some hospitals, the limited availability of monitored beds. We initiated a high-dose IL-2 program with a modified twice daily dosing schedule, limited the total number of doses per course to 8, and treated patients in an oncology ward without cardiac monitoring. Hypotension was managed preferentially with normal saline fluid boluses and/or delay in treatment. We conducted a retrospective chart review of 41 consecutive metastatic melanoma (n=33) and renal cancer (n=8) patients treated with the modified high-dose IL-2 regimen. The median number of IL-2 doses administered in the first cycle was 15. Overall toxicity was similar to published data for the q8h schedule, but only 9.79% of patients required pressors. Twenty-four percent of patients were transferred electively or emergently to the intensive care unit. There were no treatment-related deaths. The objective response rate was 12.5% and 0% in melanoma and renal cancer, respectively. Responses were durable, and 2 additional melanoma patients with mixed responses remain disease-free after resection of residual or recurrent sites of disease. In summary, the twice-daily IL-2 regimen has meaningful activity, may be more convenient to administer, reduces the need for elective monitored beds, and may be preferable for development of combinations with newer immune modulators.
Acquavella
Nicolas
N
Melanoma Program, Yale Cancer Center, Yale New Haven Hospital, 333 Cedar Street, New Haven, CT 06520, USA.
Kluger
Harriet
H
Rhee
John
J
Farber
Leonard
L
Tara
Harold
H
Ariyan
Stephan
S
Narayan
Deepak
D
Kelly
William
W
Sznol
Mario
M
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D060908:CTLA-4 Antigen; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007376:Interleukin-2