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多机构经验比较上肢和下肢基于美法仑的隔离肢体输注的临床和生理差异。

A multi-institution experience comparing the clinical and physiologic differences between upper extremity and lower extremity melphalan-based isolated limb infusion.

机构信息

Department of Surgical Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.

出版信息

Cancer. 2012 Dec 15;118(24):6136-43. doi: 10.1002/cncr.27676. Epub 2012 Jun 6.

Abstract

BACKGROUND

Although studies of melphalan-based isolated limb infusion (ILI) combine data from upper extremity (UE) treatments with those from lower extremity (LE) treatments, differences between the 2 may be clinically important.

METHODS

Candidates for UE ILI (n = 51) and LE ILI (n = 192) were identified from prospective databases at 2 institutions. The Response Evaluation Criteria in Solid Tumors and Wieberdink toxicity scale were used as appropriate.

RESULTS

The following patients had indications for UE ILI: melanoma, 36 of 47 patients (77%); sarcoma, 5 of 47 patients (11%); Merkel cell sarcoma, 3 of 47 patients (6%), and squamous cell carcinoma, 3 of 47 patients (6%). The patients who underwent UE ILI, as expected, had lower limb volumes (mean, 2.5 L vs 8.6 L; P < .001) and lower mean melphalan doses (20.7 mg vs 49.5 mg; P < .001). On perfusate blood gas analysis, the mean base excess at 30 minutes (-13.9 vs -9.1; P < .001) and the mean pH at 30 minutes (7.06 vs 7.15; P < .001) were lower for UE procedures than for LE procedures, although the mean ischemic time was longer in LE procedures (67.2 minutes) than in UE procedures (61.6 minutes; P = .03). The rate of regional toxicity grade ≥3 for UE ILI was 7% compared with 24% (P = .005) for LE ILI. There was no difference in the complete response rate for melanoma UE procedures (28%; 95% confidence interval, 16%-44%) compared with LE ILI procedures (32%; 95% confidence interval, 25%-39%).

CONCLUSIONS

ILI for UE disease was associated with similar complete response rates but lower toxicity than ILI for LE disease and with different physiologic sequelae despite comparable methods. The UE appears relatively resistant to toxic effects of melphalan-based ILI as currently performed, which suggests a potential for further optimization of drug dosing for UE ILI.

摘要

背景

虽然基于美法仑的孤立肢体灌注(ILI)的研究将上肢(UE)治疗的数据与下肢(LE)治疗的数据结合在一起,但两者之间的差异可能具有临床意义。

方法

从 2 个机构的前瞻性数据库中确定了 UE ILI(n=51)和 LE ILI(n=192)的候选者。适当使用实体瘤反应评估标准和 Wieberdink 毒性量表。

结果

UE ILI 的适应证为:黑色素瘤,47 例患者中的 36 例(77%);肉瘤,47 例患者中的 5 例(11%);默克尔细胞癌,47 例患者中的 3 例(6%)和鳞状细胞癌,47 例患者中的 3 例(6%)。接受 UE ILI 的患者下肢体积较低(平均值,2.5L 与 8.6L;P<0.001),美法仑剂量较低(平均值,20.7mg 与 49.5mg;P<0.001)。在灌注液血气分析中,30 分钟时 UE 手术的平均碱剩余值较低(-13.9 与-9.1;P<0.001),pH 值较低(7.06 与 7.15;P<0.001),而 LE 手术的平均缺血时间较长(67.2 分钟)比 UE 手术(61.6 分钟;P=0.03)。UE ILI 的区域毒性 3 级及以上发生率为 7%,而 LE ILI 为 24%(P=0.005)。UE 黑色素瘤手术的完全缓解率(28%;95%置信区间,16%-44%)与 LE ILI 手术(32%;95%置信区间,25%-39%)相似。

结论

与 LE 疾病的 ILI 相比,UE 疾病的 ILI 与相似的完全缓解率相关,但毒性较低,尽管方法相似,但生理后果不同。UE 似乎对目前实施的基于美法仑的 ILI 的毒性作用具有相对抗性,这表明有进一步优化 UE ILI 药物剂量的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8b2/5161098/57f7f4de2ee7/nihms826073f1.jpg

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