A Phase II Trial of Isolated Limb Infusion With Melphalan and Dactinomycin for Regional Melanoma and Soft Tissue Sarcoma of the Extremity (original) (raw)

A Multi-Institutional Experience of Isolated Limb Infusion: Defining Response and Toxicity in the US

Journal of the American College of Surgeons, 2009

BACKGROUND: Isolated limb infusion (ILI) is a minimally invasive approach for treating in-transit extremity melanoma, with only two US single-center studies reported. Establishing response and toxicity to ILI as compared with hyperthermic isolated limb perfusion is important for optimizing future regional chemotherapeutic strategies in melanoma. STUDY DESIGN: Patient characteristics and procedural variables were collected retrospectively from 162 ILIs performed at 8 institutions (2001 to 2008) and compared using chi-square and Student's t-test. ILIs were performed for 30 minutes in patients with in-transit melanoma. Melphalan dose was corrected for ideal body weight (IBW) in 42% (n ϭ 68) of procedures. Response was determined at 3 months by Response Evaluation Criteria in Solid Tumors; toxicity was assessed using the Wieberdink Limb Toxicity Scale.

Outcomes Following Isolated Limb Infusion for Melanoma. A 14-Year Experience

Annals of Surgical Oncology, 2008

Background: Isolated limb infusion (ILI) is a minimally invasive technique for delivering regional chemotherapy in patients with advanced and metastatic melanoma confined to a limb. It is essentially a low-flow isolated limb perfusion (ILP) performed via percutaneous catheters without oxygenation. Methods: From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1993 and 2007 were identified. In all patients a cytotoxic drug combination of melphalan and actinomycin-D was used. Drug circulation time was 20-30 min under mild hyperthermic conditions (38-39°C). Results: The majority of patients (62%) were female. Their average age was 74 years (range 29-93 years). Most patients had MD Anderson stage III disease (134/185). The overall response rate was 84% [complete response (CR) rate 38%, partial response rate 46%]. Median response duration was 13 months (22 months for patients with CR; P = 0.01). Median follow-up was 20 months and median survival was 38 months. In those patients with a CR, the median survival was 53 months (P = 0.005). CR rate and survival time decreased with increasing stage of disease. On multivariate analysis significant factors for a favorable outcome were achievement of CR, stage of disease, thickness of primary melanoma, the CO 2 level in the isolated circuit, and a Wieberdink limb toxicity score of III (considerable erythema and edema). Conclusion: The response rates and duration of response after ILI are comparable to those achieved by conventional ILP. ILI is a minimally invasive alternative to the much more complex and morbid conventional ILP technique for patients with advanced metastatic melanoma confined to a limb.

Isolated Limb Infusion in a Series of Over 100 Infusions: A Single-Center Experience

Annals of Surgical Oncology, 2013

Introduction-Isolated limb infusion (ILI) is a therapeutic option for patients with recurrent, unresectable extremity malignancies. Methods-A prospectively collected single institution database of patients undergoing ILI was analyzed for preoperative, intraoperative, and postoperative parameters and outcomes. Results-From 5/2007-1/2012, 76 patients successfully underwent initial ILI, and 28 following either previous hyperthermic isolated limb perfusion (HILP) or ILI. Seventy-nine (74%) patients had melanoma, 24 (22%) sarcoma, 3 (3%) Merkel cell and 1 (1%) squamous cell carcinoma. There were 55 (72%) initial and 22 (79%) repeat lower extremity (LE) ILI's, and 21 (78%) initial and 6 (22%) repeat upper extremity (UE) ILI's. Serologic toxicity, measured by serum creatine kinase (CK), peaked higher and later in LE ILI's, median 620 vs. 124 IU/L and postoperative day 4 vs. 2, respectively, P<0.05. LE ILI's had a longer hospital length of stay (LOS), median 6 vs. 5 days (P<0.0001). A median of grade II Wieberdink regional toxicity was observed. Three-month follow-up was available in 94 (90%). A response (ORR) was seen in 72% of ILI's performed for melanoma and 58% for sarcoma. No difference in response was observed between UE vs. LE or between initial vs. repeat ILI's. Repeat UE ILI's, however, appeared to have an improved ORR than repeat LE ILI's, 83% vs. 64%. Conclusion-ILI may be successfully performed for cutaneous and soft tissue malignancies. LE ILI's have higher CK levels and slightly longer LOS. Repeat ILI's are not associated with increased toxicity and similar ORR. UE ILI's may have better overall response rates.

Soft Tissue Cancer Management: Isolated Limb Infusion for Sarcoma

Visceral medicine, 2019

Background: Sarcoma is a heterogeneous group of malignancies comprising almost 80 subtypes of bone and soft tissue cancers. Previously, all subtypes were managed identically. Advancements in biological and genetic studies have revealed that sarcoma subtypes display varying characteristics and therefore require tailored treatments. Locally advanced soft tissue malignancies of both the trunk and the extremities can present significant challenges for treatment. At present, a negative surgical resection margin is the only definitive treatment despite attempts to use neoadjuvant and adjuvant therapies. In patients with locally advanced non-resectable soft tissue sarcoma (STS), the current practice would advocate amputation. However, studies suggest that limb salvage may be possible with radiotherapy or regional chemotherapy using isolated limb perfusion or isolated limb infusion (ILI). An ideal treatment modality for nonresectable STS would strive for preservation of anatomy and functionality as well as improve quality of life. The aim of the study was to investigate the efficacy of isolated limb infusion as an alternative treatment modality for non-resectable locally advanced STS. Methods: The efficacy of ILI was retrospectively investigated in 10 patients with STS. All patients received ILI with melphalan and actinomycin at the North Estonia Medical Centre Foundation, Tallinn, Estonia from September 1, 2014 to May 31, 2018. The procedures were performed in a lower extremity in 8 patients and in an upper extremity in 2 patients. The 6-month overall response rate was 78% and the overall limb salvage rate was 100%. The distant metastatis-free survival was longer for responders than for non-responders. Results and Conclusions: ILI is an alternative treatment modality for regional disease control and limb preservation in patients with cutaneous and soft tissue malignant neoplasms of the extremities. The shortterm response rates are encouraging and the median overall survival shows good results in this highly complex patient population.

Isolated Limb Perfusion in the Treatment of Advanced Soft-tissue Sarcomas

Musculoskeletal Cancer Surgery, 2004

BACKGROUND In 1958, Creech and Krementz 1 introduced a novel method of drug delivery for patients with advanced cancer and named it isolated limb perfusion (ILP). 1 The idea was to apply the newly invented technique of cardiopulmonary bypass to regional chemotherapy. ILP entailed exposing the major blood vessels to an extremity, isolating it temporarily and perfusing the extremity via a heart-lung machine with very high doses of chemotherapeutic drugs (Figure 4.1). The authors believed it would be possible to obtain high tissue concentrations of the drug with minimal systemic exposure and hence few complications. Following the observation that heat has its own antineoplastic properties, Stehlin 2 in 1969 modified the technique to include hyperthermia. The response rates observed with ILP in patients with metastatic melanoma confined to the limb were higher than those associated with any other known modality. This, combined with the fact that some 25% of complete responders have a 10-year disease-free interval, promoted the use of ILP. Since then, ILP has been widely recognized as a standard treatment strategy for advanced melanoma of the extremities. Despite its effectiveness, ILP did not become widely used, and several major cancer centers did not include it in their therapeutic arsenal. There are several reasons for this. ILP is a multidisciplinary procedure. It is surgically demanding and rather long (3-4 h). It necessitates a heart-lung machine and related technician and equipment, and isotopic monitoring. Unlike the reasonable ease with which new operative techniques are implemented through the acquisition of knowledge and skills, ILP requires a thorough knowledge of vascular surgery and a large degree of coordination and dependence on other disciplines outside the realm of general surgery. In addition, the available literature on ILP showed great variability in surgical technique, drugs administered, degree of hyperthermia, indications, and response evaluation. This, coupled with the retrospective nature of most reported patient series, made it difficult to reach valid conclusions as to when and how to use ILP. The situation has gradually changed, mainly because of two advances. First, the standardization of ILP and the conduct of multicenter studies based on principles of modern surgical oncology and consistent with the standards of the National Cancer Institute made it possible to evaluate outcomes in a uniform fashion, and hence to better define the indications for ILP. The second advance was the addition of tumor necrosis factor (TNF), an exciting new cytokine, to the treatment protocols. 3 TNF is a new drug and its potentially serious side-effects necessitated modifications to the ILP technique. Therefore, all centers began to routinely monitor ILP patients for isotope leakage and better standardization was achieved.