A phase II study of neoadjuvant biochemotherapy for stage III melanoma.
BACKGROUND
Phase II studies of biochemotherapy (combining interleukin-2, interferon-alpha, and multiagent chemotherapy) have reported high response rates and a significant number of durable complete responses in patients with metastatic melanoma.


METHODS
A pilot Phase II study was performed to explore the safety and activity of neoadjuvant biochemotherapy in patients with Stage III melanoma. Forty-eight patients were enrolled between April 1996 and May 1999. The median age of the patients was 46 years (range, 19-70 years). Two cycles of biochemotherapy were administered prior to and after complete lymph node dissection. Each cycle was comprised of cisplatin, 20 mg/m2 intravenously (i.v.), on Days 1-4; vinblastine, 1.6 mg/m2 i.v., on Days 1-4; dacarbazine, 800 mg/m2 i.v., on Day 1; interleukin-2, 9 x 10(6) IU/m2/day i.v. over 24 hours, on Days 1-4; and interferon-alpha, 5 x 10(6) IU/m2/day subcutaneously, on Days 1-5, every 3 weeks. Twelve patients did not have measurable disease. All patients were evaluable for toxicity and survival.


RESULTS
Clinical responses were observed in 14 of 36 patients (38.9%) with measurable disease, including 13 partial responses (36.1%) and 1 complete response (2.8%). Complete pathologic responses were noted in 4 patients (11.1%). Toxicity, although severe, was manageable and typically short-lived. There were no treatment-related deaths reported. At a median follow-up of 31 months, 38 of the 48 patients (79.2%) were alive and 31 patients (64.6%) remained free of disease progression.


CONCLUSIONS
Neoadjuvant biochemotherapy appears to have promising activity in patients with Stage III melanoma. A larger multicenter study currently is underway to explore this approach further.
Gibbs
Peter
P
Oncology Department, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Anderson
Clay
C
Pearlman
Nathan
N
LaClaire
Stacy
S
Becker
Maude
M
Gatlin
Kristi
K
O'Driscoll
Martin
M
Stephens
Janet
J
Gonzalez
Rene
R
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D010865:Pilot Projects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D015996:Survival Rate; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects
D016898:Interferon-alpha; D007376:Interleukin-2; D016179:Granulocyte Colony-Stimulating Factor; D014747:Vinblastine; D003606:Dacarbazine; D002945:Cisplatin