A multicenter phase II clinical trial using dacarbazine and continuous infusion interleukin-2 for metastatic melanoma. Clinical data and immunomonitoring.
BACKGROUND
Treatment of patients with metastatic melanoma with either dacarbazine or recombinant interleukin-2 (rIL-2) resulted in a response rate of approximately 15%. This study investigates the possible synergism of this chemoimmunotherapy combination.


METHODS
Fifty-seven patients with metastatic malignant melanoma received 135 treatment cycles. Treatment consisted of dacarbazine (Days 1-5) at 250 mg/m2 by a 30-minute slow infusion, and interleukin-2 by constant intravenous infusion (Days 21-25 and 28-32) at 18 x 10(6) IU/m2/24 hours. After this treatment cycle, a 1-week rest was scheduled, and in the absence of undue toxicity or tumor progression, patients received a second cycle as described. Maximum treatment consisted of two induction and four maintenance cycles. In a subgroup of patients, immunoparameters were analyzed to identify prognostic factors. Standard supportive care was given.


RESULTS
Common toxicities included fever, hypotension, nausea/vomiting, anemia, leukopenia, thrombocytopenia, an increase in serum lactic dehydrogenase levels and diarrhea. The objective response rate was 15.8% (one complete response and eight partial responses). In 14 patients, the disease stabilized. For patients who had an objective response, median response duration was 13.9 months (6.3-39.0+), and median survival was 19.0 months (6.3-39.0+); overall survival was 9.3 months (0.8-39.0+). Immunomonitoring did not reveal any relevant prognostic factors for overall response.


CONCLUSIONS
Sequential treatment with dacarbazine and rIL-2 is feasible and produces long-lasting responses in a minority of patients.
Department of Dermatology, University of Zurich Medical School, Switzerland.
R
R
Dummer
M E
ME
Gore
B W
BW
Hancock
P J
PJ
Guillou
H C
HC
Grobben
J C
JC
Becker
R
R
Oskam
J P
JP
Dieleman
G
G
Burg
D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D008875:Middle Aged; D011379:Prognosis; D012044:Regression Analysis; D012074:Remission Induction; D012878:Skin Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
D007376:Interleukin-2; D003606:Dacarbazine