A phase II study of outpatient subcutaneous histamine dihydrochloride, interleukin-2 and interferon-alpha in patients with metastatic melanoma.
BACKGROUND
Experimental data had suggested a synergistic effect of histamine with interleukin-2 (IL-2) and interferon-alpha (IFN-alpha).


METHODS
Forty-one patients with metastatic melanoma received IL-2 9 MU subcutaneously (s.c.) twice daily on days 4-8 and 25-29, and once daily on days 11-15 and 32-36. IFN-alpha-2b was given as 5 MU s.c. on days 1-3 and then daily to day 43. Histamine 1 mg s.c. was administered twice daily, following IL-2 and IFN injections starting on day 4. Efficacy and toxicity were compared with those of 42 patients included on exactly the same criteria and receiving the same regimen but without histamine.


RESULTS
Two patients achieved a partial response (PR) for an objective response rate of 5% [95% confidence interval (CI) 1% to 17%]. Median overall survival was 7.8 months (95% CI 6.4-9.1). In the control group, two complete responses and one PR were achieved. Median overall survival was 7.1 months (95% CI 5.4-8.9).


CONCLUSIONS
This IL-2 and IFN regimen was well tolerated on an outpatient basis. However, the applied regimen cannot be recommended because of the low clinical efficacy. Histamine did not add efficacy or toxicity in combination with this moderate-dose schedule of IL-2 and IFN.
Schmidt
H
H
Department of Oncology, Aarhus University Hospital, Denmark. hs@oncology.dk
Larsen
S
S
Bastholt
L
L
Fode
K
K
Rytter
C
C
Von Der Maase
H
H
D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D016009:Chi-Square Distribution; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006632:Histamine / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000556:secondary*; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D011994:Recombinant Proteins; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D006632:Histamine