Dacarbazine, cisplatin, and interferon-alfa-2b with or without interleukin-2 in metastatic melanoma: a randomized phase III trial (18951) of the European Organisation for Research and Treatment of Cancer Melanoma Group.
BACKGROUND
Based on phase II trial results, chemoimmunotherapy combinations have become the preferred treatment for patients with metastatic melanoma in many institutions. This study was performed to determine whether interleukin-2 (IL-2) as a component of chemoimmunotherapy influences survival of patients with metastatic melanoma.


METHODS
Patients with advanced metastatic melanoma were randomly assigned to receive dacarbazine 250 mg/m2 and cisplatin 30 mg/m2 on days 1 to 3 combined with interferon-alfa-2b 10 x 10(6) U/m2 subcutaneously on days 1 through 5 without (arm A) or with (arm B) a high-dose intravenous decrescendo regimen of IL-2 on days 5 through 10 (18 x 10(6) U/m2/6 hours, 18 x 10(6) U/m2/12 hours, 18 x 10(6) U/m2/24 hours, and 4.5 x 10(6) U/m2 for 3 x 24 hours). Treatment cycles were repeated in the absence of disease progression every 28 days to a maximum of four cycles.


RESULTS
Three hundred sixty-three patients with advanced metastatic melanoma were accrued. The median survival was 9 months in both arms, with a 2-year survival rate of 12.9% and 17.6% in arms A and B, respectively (P = .32; hazard ratio, 0.90; 95% CI, 0.72 to 1.11). There was also no statistically significant difference regarding progression-free survival (median, 3.0 v 3.9 months) and response rate (22.8% v 20.8%).


CONCLUSIONS
Despite its activity in melanoma as a single agent or in combination with interferon-alfa-2b, the chosen schedule of IL-2 added to the chemoimmunotherapy combination had no clinically relevant activity.
Keilholz
Ulrich
U
Department of Medicine III, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. ulrich.keilholz@medizin.fu-berlin.de
Punt
Cornelis J A
CJ
Gore
Martin
M
Kruit
Wim
W
Patel
Poulam
P
Lienard
Danielle
D
Thomas
Jose
J
Proebstle
Thomas M
TM
Schmittel
Alexander
A
Schadendorf
Dirk
D
Velu
Thierry
T
Negrier
Sylvie
S
Kleeberg
Ulrich
U
Lehman
Frederic
F
Suciu
Stefan
S
Eggermont
Alexander M M
AM
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001707:Biopsy, Needle; D002945:Cisplatin / Q000627:therapeutic use; D003606:Dacarbazine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology / Q000556:secondary; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011336:Probability; D016016:Proportional Hazards Models; D011994:Recombinant Proteins; D012016:Reference Values; 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; D003606:Dacarbazine; D002945:Cisplatin