Temozolomide and interferon alpha 2b in metastatic melanoma stage IV.
BACKGROUND
A multicentre, centrally randomized, open-labelled study with temozolomide and interferon (IFN)-alpha 2b was carried out to study the therapeutic effect in patients with metastatic melanoma stage IV.


OBJECTIVE
The response rate, efficacy, side-effects, reasons for discontinuation of therapy and survival rate of 47 patients treated with temozolomide in combination with two different dosing regimens of IFN-alpha 2b were documented.


METHODS
Twenty-nine male and 18 female patients (mean age 57.6 years, range 34-74) were centrally randomized to two different arms: 20 patients received a treatment schedule with temozolomide 150 mg m(-2) on days 1-5 orally every 28 days in combination with IFN-alpha 2b 10 MIU m(-2) every other day and 27 patients received temozolomide 150 mg m(-2) on days 1-5 every 28 days in combination with IFN-alpha 2b in a fixed dose of 10 MIU every other day.


RESULTS
We observed an overall response rate of 27.6% comprising five complete remissions (10.6%: one patient group A, four patients group B), in two of these five patients at the last follow-up in the study (4.3%, both in group B); and eight partial remissions (17%: six patients in group A, two patients in group B), in three of these eight patients at the last follow-up in the study (6.4%, two patients in group A, one patient in group B). Three patients showed stable disease (6.4%: one patient in group A, two patients in group B). Mean survival was 14.5 months [95% confidence interval (CI) 10-19] with no significant differences between treatment groups. However, there was a significant correlation with response after three cycles (log rank test, P < 0.03). Within the 32 patients who completed at least three cycles of therapy, seven patients (three in group A and four in group B) with a partial or complete response showed a significantly better mean survival of 30.6 months (95% CI 19.1-42) compared with 25 patients who did not respond (13.7 months 95% CI 9.2-18.3). In total, patients with at least one complete remission showed the longest survival (37.1 months 95% CI 26.3-47.9), followed by patients with at least one partial response (17.4 95% CI 10.9-23.9). Major side-effects of the treatment were nausea, vomiting, headache, leucopenia, thrombopenia, elevation of liver function parameters and neurological symptoms. In five patients, the side-effects led to a discontinuation of treatment: neurological symptoms (two patients), sepsis (one patient), brain haemorrhage (one patient) and exanthema (one patient). There were no treatment-related deaths.


CONCLUSIONS
The combination of temozolomide and IFN-alpha 2b can easily be administered and shows tolerable toxicity. When an objective response occurs after three cycles, it indicates a significant survival advantage.
Department of Dermatology, University of Graz, Austria. erika.richtig@uni-graz.at
E
E
Richtig
R
R
Hofmann-Wellenhof
H
H
Pehamberger
Ch
Ch
Forstinger
K
K
Wolff
P
P
Mischer
J
J
Raml
P
P
Fritsch
B
B
Zelger
G
G
Ratzinger
J
J
Koller
A
A
Lang
K
K
Konrad
E
E
Kindermann-Glebowski
A
A
Seeber
A
A
Steiner
R
R
Fialla
W
W
Pachinger
C
C
Kos
G
G
Klein
H
H
Kehrer
H
H
Kerl
H
H
Ulmer
J
J
Smolle
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008875:Middle Aged; D016016:Proportional Hazards Models; D011994:Recombinant Proteins; D012074:Remission Induction; D012878:Skin Neoplasms / Q000188:drug therapy / Q000401:mortality; D015996:Survival Rate; D000077204:Temozolomide
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003606:Dacarbazine; D000077204:Temozolomide