Koops H S, Vaglini M, Suciu S, Kroon B B, Thompson J F, Göhl J, Eggermont A M, Di Filippo F, Krementz E T, Ruiter D, Lejeune F J
Department of Surgical Oncology, University Hospital, Groningen, The Netherlands.
J Clin Oncol. 1998 Sep;16(9):2906-12. doi: 10.1200/JCO.1998.16.9.2906.
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.
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.
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.
Prophylactic ILP with melphalan cannot be recommended as an adjunct to standard surgery in high-risk primary limb melanoma.
厚度≥1.5 mm的原发性皮肤黑色素瘤患者在初次手术治疗时存在区域微转移的高风险。一项III期国际研究旨在评估预防性隔离肢体灌注（ILP）是否可预防区域复发并影响生存。
来自16个中心的832例可评估患者进入该研究；412例被随机分配至单纯广泛切除（WE）组，420例被随机分配至WE联合使用美法仑及轻度热疗的ILP组。中位年龄为50岁，68%的患者为女性，79%的黑色素瘤位于下肢，47%的患者肿瘤厚度≥3 mm。
中位随访时间为6.4年。ILP后无病间期（DFI）有延长趋势。对于未接受选择性淋巴结清扫（ELND）的患者，差异具有显著性。ILP的影响明显体现在作为首个进展部位的移行转移（ITM）的发生上，其发生率从6.6%降至3.3%，区域淋巴结（RLN）转移发生率从16.7%降至12.6%。在远处转移时间或生存方面，ILP并无益处。ILP后的副作用更高，但大多数患者为一过性。ILP后有两例因肢体毒性而行截肢手术。
对于高危原发性肢体黑色素瘤，不推荐将美法仑预防性ILP作为标准手术的辅助治疗。
