One hundred consecutive isolated limb perfusions with TNF-alpha and melphalan in melanoma patients with multiple in-transit metastases.
OBJECTIVE
The aim of this study is to describe the experience with 100 TNF-based ILP for locally advanced melanoma and to determine prognostic factors for response, time to local progression, and survival.


METHODS
One hundred TNF-based ILPs were performed between 1991 and 2003 in 87 patients for whom local control by surgery of in-transit melanoma metastases was impossible. In total, 62 iliac, 33 femoral, and 5 axillary ILPs were performed in mild hyperthermic conditions with 2 to 4 mg of TNF and 10 to 13 mg of melphalan per liter of limb volume.


RESULTS
Overall response was 95%, with 69% complete response, 26% partial response, and 5% no change. Complete response rate differed significantly for patients with IIIA disease versus IIIAB and IV. Local and systemic toxicity was mild to moderate in almost all cases, with no treatment-related death and one treatment-related amputation. Five-year overall survival was 32%; local progression occurred in 55% after a median of 16 months. In complete response patients, 5-year survival was 42% with local progression in 52% at a median of 22 months. Response rate and survival were significantly influenced by stage of disease; (local progression free) survival was influenced by response rate.


CONCLUSIONS
TNF-based ILP results in excellent response rates in this patient population with unfavorable characteristics. Response on ILP predicts outcome in patients and reflects aggressiveness of the tumor.
Grünhagen
Dirk J
DJ
Department of Surgical Oncology, Daniel den Hoed Cancer Center, PO Box 5201 3008, Rotterdam, Netherlands.
Brunstein
Flavia
F
Graveland
Wilfried J
WJ
van Geel
Albertus N
AN
de Wilt
Johannes H W
JH
Eggermont
Alexander M M
AM
D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000627:therapeutic use; D001366:Axillary Artery; D010478:Chemotherapy, Cancer, Regional Perfusion; D005121:Extremities; D005260:Female; D005263:Femoral Artery; D006801:Humans; D007083:Iliac Artery; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008558:Melphalan / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000627:therapeutic use
D018906:Antineoplastic Agents, Alkylating; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan