Phase II multicenter trial of maintenance biotherapy after induction concurrent Biochemotherapy for patients with metastatic melanoma.
OBJECTIVE
Biochemotherapy improves responses in metastatic melanoma, but not overall survival, in randomized trials. We developed a maintenance biotherapy regimen after induction biochemotherapy in an attempt to improve durability of responses and overall survival.


METHODS
One hundred thirty-three chemotherapy-naïve patients with metastatic melanoma without CNS metastases were treated at 10 melanoma centers. The biochemotherapy induction regimen included cisplatin, vinblastine, dacarbazine, decrescendo interleukin-2 (IL-2), and interferon alfa-2b with granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine support. Patients not experiencing disease progression were eligible for maintenance biotherapy with low-dose IL-2 and GM-CSF followed by intermittent pulses of decrescendo IL-2 over 12 months. Patients were observed for response, progression-free survival, toxicity, and overall survival.


RESULTS
The response rate to induction biochemotherapy was 44% (95% CI, 35% to 52%; complete response, 8%; partial response, 36%; stable disease, 29%). The median number of biochemotherapy cycles was four, and the median number of maintenance biotherapy cycles was five. The median progression-free survival was 9 months, and the median survival was 13.5 months. The 12-month and 24-month survival rates were 57% and 23%, respectively. Twenty percent of patients remain alive (12 without disease), with median follow-up of 30 months (95% CI, 25+ to 45+ months). Thirty-nine percent of patients developed CNS metastases. The median times to CNS progression and death were 8 months and 5 months, respectively.


CONCLUSIONS
Maintenance biotherapy after induction biochemotherapy seems to prolong progression-free survival and improve overall survival compared with recent multicenter trials of biochemotherapy or chemotherapy. The regimen should be studied in a randomized clinical trial in patients with advanced metastatic melanoma. CNS progression remains a formidable challenge.
O'Day
Steven J
SJ
Melanoma Program, The Angeles Clinic and Research Institute, 2001 Santa Monica Blvd, Suite 560 W, Santa Monica, CA 90404, USA. soday@theangelesclinic.org
Atkins
Michael B
MB
Boasberg
Peter
P
Wang
He-Jing
HJ
Thompson
John A
JA
Anderson
Clay M
CM
Gonzalez
Rene
R
Lutzky
Jose
J
Amatruda
Thomas
T
Hersh
Evan M
EM
Weber
Jeffrey S
JS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012074:Remission Induction; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D016019:Survival Analysis; D014747:Vinblastine / Q000008:administration & dosage; D055815:Young Adult
D007376:Interleukin-2; D014747:Vinblastine; D003606:Dacarbazine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002945:Cisplatin