Results of a multicenter randomized study to evaluate the safety and efficacy of combined immunotherapy with interleukin-2, interferon-{alpha}2b and histamine dihydrochloride versus dacarbazine in patients with stage IV melanoma.
BACKGROUND
The safety and efficacy of immunotherapy with histamine dihydrochloride (HDC), interleukin-2 (IL-2) and interferon-alpha2b (IFN) compared with dacarbazine (DTIC) in adult patients with stage IV melanoma was evaluated.


METHODS
Two hundred and forty-one patients were randomized to either receive repeated 4-week cycles of IFN [3 MIU, s.c., once daily for 7 days], IL-2 (2.4 MIU/m(2), s.c., twice a day for 5 days) and HDC (1 mg, s.c., twice a day for 5 days) or DTIC 850 mg/m(2) i.v. every 3 weeks. The primary endpoint was overall survival.


RESULTS
Median survival was longer for patients receiving HDC/IL-2/IFN (271 days) than for patients receiving DTIC (231 days), but this did not achieve statistical significance. Four patients receiving HDC/IL-2/IFN and nine receiving DTIC experienced at least one grade 4 adverse event. Striking differences in overall survival were observed between countries participating in the study.


CONCLUSIONS
Treatment with HDC/IL-2/IFN was safely administered on an outpatient basis, but this immunotherapeutic regimen did not improve upon the response rate and overall survival seen with DTIC.
Middleton
M
M
Department of Medical Oncology, Christie Hospital, Manchester, UK.
Hauschild
A
A
Thomson
D
D
Anderson
R
R
Burdette-Radoux
S
S
Gehlsen
K
K
Hellstrand
K
K
Naredi
P
P
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006632:Histamine / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007167:Immunotherapy; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011994:Recombinant Proteins
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D003606:Dacarbazine; D006632:Histamine