Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. European Organization for Research and Treatment of Cancer Malignant Melanoma Cooperative Group Protocol 18832, the World Health Organization Melanoma Program Trial 15, and the North American Perfusion Group Southwest Oncology Group-8593.
OBJECTIVE
Patients with primary cutaneous melanoma > or = 1.5 mm in thickness are at high risk of having regional micrometastases at the time of initial surgical treatment. A phase III international study was designed to evaluate whether prophylactic isolated limb perfusion (ILP) could prevent regional recurrence and influence survival.


METHODS
A total of 832 assessable patients from 16 centers entered the study; 412 were randomized to wide excision (WE) only and 420 to WE plus ILP with melphalan and mild hyperthermia. Median age was 50 years, 68% of patients were female, 79% of melanomas were located on a lower limb, and 47% had a thickness > or = 3 mm.


RESULTS
Median follow-up duration is 6.4 years. There was a trend for a longer disease-free interval (DFI) after ILP. The difference was significant for patients who did not undergo elective lymph node dissection (ELND). The impact of ILP was clearly on the occurrence-as first site of progression - of in-transit metastases (ITM), which were reduced from 6.6% to 3.3%, and of regional lymph node (RLN) metastases, with a reduction from 16.7% to 12.6%. There was no benefit from ILP in terms of time to distant metastasis or survival. Side effects were higher after ILP, but transient in most patients. There were two amputations for limb toxicity after ILP.


CONCLUSIONS
Prophylactic ILP with melphalan cannot be recommended as an adjunct to standard surgery in high-risk primary limb melanoma.
Koops
H S
HS
Department of Surgical Oncology, University Hospital, Groningen, The Netherlands.
Vaglini
M
M
Suciu
S
S
Kroon
B B
BB
Thompson
J F
JF
Göhl
J
J
Eggermont
A M
AM
Di Filippo
F
F
Krementz
E T
ET
Ruiter
D
D
Lejeune
F J
FJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D010478:Chemotherapy, Cancer, Regional Perfusion; D003131:Combined Modality Therapy; D018450:Disease Progression; D005121:Extremities; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D012307:Risk Factors; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000628:therapy
D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan