Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 9/2012

01-09-2012 | Melanomas

Is Melphalan Dose Adjustment According to Ideal Body Weight Useful in Isolated Limb Infusion for Melanoma?

Authors: Anna M. Huismans, MD, Hidde M. Kroon, MD, PhD, Lauren E. Haydu, BSCHE, MIPH, Peter C. A. Kam, MD, John F. Thompson, MD

Published in: Annals of Surgical Oncology | Issue 9/2012

Login to get access

Abstract

Background

Isolated limb infusion (ILI), introduced in 1992, is a technique used to deliver regional chemotherapy to treat advanced melanoma confined to a limb. Adjusting melphalan dose according to ideal body weight (IBW) has been proposed as a method of decreasing limb toxicity without compromising outcome. The current study analyzed this proposed dose adjustment.

Methods

We reviewed 99 consecutive patients with lower extremity melanomas treated by ILI at our institution between May 1998 and February 2009. Toxicity and outcomes were tested for correlation with differences between administered dose and calculated adjusted dose, both in mg and mg/L, and with differences between actual limb volume and calculated adjusted limb volume.

Results

The median actual body weight was 71 kg, whereas the calculated median IBW was 57 kg (p < .001). Median administered melphalan dose was 7.7 mg/L. The median calculated adjusted dose was 6.5 mg/L (range 3.2–9.3 mg/L, p < .001). None of the three aforementioned parameters correlated with either Wieberdink toxicity grade or outcome. BMI did not correlate with toxicity either. Interestingly, a higher total melphalan dose did not only correlate with higher toxicity, but also with a lower response rate.

Conclusions

Adjusting the melphalan dose for IBW does not appear to reduce toxicity following ILI for melanoma. The effect on outcome remains uncertain. More research is needed to optimize melphalan concentrations in individual patients during ILI to limit toxicity without compromising the response.
Literature
1.
Thompson JF, Waugh RC, Saw RPM, Kam PCA. Isolated limb infusion with melphalan for recurrent limb melanoma: a simple alternative to isolated limb perfusion. Reg Cancer Treat. 1994;7:188–92.
2.
Thompson JF, Kam PC, Waugh RC, Harman CR. Isolated limb infusion with cytotoxic agents: a simple alternative to isolated limb perfusion. Semin Surg Oncol. 1998;14:238–47.PubMedCrossRef
3.
Thompson JF, Ramzan I, Kam PCA, Yau DF. Pharmacokinetics of melphalan during isolated limb infusion for melanoma. Reg Cancer Treat. 1996;9:13–6.
4.
Thompson JF, Siebert GA, Anissimov YG, Smithers BM, Doubrovsky A, Anderson CD, et al. Microdialysis and response during regional chemotherapy by isolated limb infusion of melphalan for limb malignancies. Br J Cancer. 2001;85:157–65.PubMedCrossRef
5.
Roberts MS, Wu ZY, Siebert GA, Thompson JF, Smithers BM. Saturable dose-response relationships for melphalan in melanoma treatment by isolated limb infusion in the nude rat. Melanoma Res. 2001;11:611–8.PubMedCrossRef
6.
Roberts MS, Wu ZY, Siebert GA, Anissimov YG, Thompson JF, Smithers BM. Pharmacokinetics and pharmacodynamics of melphalan in isolated limb infusion for recurrent localized limb malignancy. Melanoma Res. 2001;11:423–31.PubMedCrossRef
7.
Santillan AA, Delman KA, Beasley GM, Mosca PJ, Hochwald SN, Grobmyer SR, et al. Predictive factors of regional toxicity and serum creatine phosphokinase levels after isolated limb infusion for melanoma: a multi-institutional analysis. Ann Surg Oncol. 2009;16:2570–8.PubMedCrossRef
8.
Kroon HM, Moncrieff M, Kam PC, Thompson JF. Factors predictive of acute regional toxicity after isolated limb infusion with melphalan and actinomycin D in melanoma patients. Ann Surg Oncol. 2009;16:1184–92.PubMedCrossRef
9.
Beasley GM, Caudle A, Petersen RP, McMahon NS, Padussis J, Mosca PJ, et al. A multi-institutional experience of isolated limb infusion: defining response and toxicity in the US. J Am Coll Surg. 2009;208:706–15.PubMedCrossRef
10.
Cheng TY, Grubbs E, Abdul-Wahab O, Leu SY, Hung CF, Petros W, et al. Marked variability of melphalan plasma drug levels during regional hyperthermic isolated limb perfusion. Am J Surg. 2003;186:460–7.PubMedCrossRef
11.
McMahon N, Cheng TY, Beasley GM, Spasojevic I, Petros W, Augustine CK, et al. Optimizing melphalan pharmacokinetics in regional melanoma therapy: does correcting for ideal body weight alter regional response or toxicity? Ann Surg Oncol. 2009;16:953–61.PubMedCrossRef
12.
Beasley GM, Petersen RP, Yoo J, McMahon N, Aloia T, Petros W, et al. Isolated limb infusion for in-transit malignant melanoma of the extremity: a well-tolerated but less effective alternative to hyperthermic isolated limb perfusion. Ann Surg Oncol. 2008;15:2195–205.PubMedCrossRef
13.
Klaase JM, Kroon BB, Beijnen JH, van Slooten GW, van Dongen JA. Melphalan tissue concentrations in patients treated with regional isolated perfusion for melanoma of the lower limb. Br J Cancer. 1994;70:151–3.PubMedCrossRef
14.
Thompson JF, Kam PC, Waugh RC, Harman CR. Isolated limb infusion with cytotoxic agents: a simple alternative to isolated limb perfusion. Semin Surg Oncol. 1998;14:238–47.PubMedCrossRef
15.
Thompson JF, Hunt JA, Shannon KF, Kam PC. Frequency and duration of remission after isolated limb perfusion for melanoma. Arch Surg. 1997;132:903–7.PubMedCrossRef
16.
Lindner P, Doubrovsky A, Kam PC, Thompson JF. Prognostic factors after isolated limb infusion with cytotoxic agents for melanoma. Ann Surg Oncol. 2002;9:127–36.PubMed
17.
Sanki A, Kam PC, Thompson JF. Long-term results of hyperthermic, isolated limb perfusion for melanoma: a reflection of tumor biology. Ann Surg. 2007;245:591–6.PubMedCrossRef
18.
Wieberdink J, Benckhuysen C, Braat RP, van Slooten EA, Olthuis GA. Dosimetry in isolation perfusion of the limbs by assessment of perfused tissue volume and grading of toxic tissue reactions. Eur J Cancer Clin Oncol. 1982;18:905–10.PubMedCrossRef
19.
World Health Organization. WHO handbook for reporting results of cancer treatments. Geneva, Switzerland: World Health Organization; 1979.
20.
Devine BJ. Gentamicin therapy. Drug Intell Clin Pharm. 1974;8:650–5.
21.
Kroon HM, Moncrieff M, Kam PC, Thompson JF. Outcomes following isolated limb infusion for melanoma. A 14-year experience. Ann Surg Oncol. 2008;15:3003–13.PubMedCrossRef
22.
Klaase JM, Kroon BB, van Geel AN, van Wijk J, Franklin HR, Eggermont AM, et al. Limb recurrence-free interval and survival in patients with recurrent melanoma of the extremities treated with normothermic isolated perfusion. J Am Coll Surg. 1994;178:564–72.PubMed
23.
Vrouenraets BC, Hart GA, Eggermont AM, Klaase JM, van Geel BN, Nieweg OE, et al. Relation between limb toxicity and treatment outcomes after isolated limb perfusion for recurrent melanoma. J Am Coll Surg. 1999;188:522–30.PubMedCrossRef
24.
Huismans AM, Kroon HM, Kam PC, Thompson JF. Does increased experience with isolated limb infusion for advanced limb melanoma influence outcome? A comparison of two treatment periods at a single institution. Ann Surg Oncol. 2011;18:1877–83.PubMedCrossRef
25.
Kroon HM, Lin DY, Kam PC, Thompson JF. Safety and efficacy of isolated limb infusion with cytotoxic drugs in elderly patients with advanced locoregional melanoma. Ann Surg. 2009;249:1008–13.PubMedCrossRef
26.
Parsons PG, Carter FB, Morrison L, Regius Mary S. Mechanism of melphalan resistance developed in vitro in human melanoma cells. Cancer Res. 1981;41:1525–34.PubMed
Metadata
Title
Is Melphalan Dose Adjustment According to Ideal Body Weight Useful in Isolated Limb Infusion for Melanoma?
Authors
Anna M. Huismans, MD
Hidde M. Kroon, MD, PhD
Lauren E. Haydu, BSCHE, MIPH
Peter C. A. Kam, MD
John F. Thompson, MD
Publication date
01-09-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 9/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2316-4

Other articles of this Issue 9/2012

Annals of Surgical Oncology 9/2012 Go to the issue

Bone and Soft Tissue Sarcomas

A Probabilistic Analysis of Completely Excised High-grade Soft Tissue Sarcomas of the Extremity: An Application of a Bayesian Belief Network

Breast Oncology

Outcome of Pure Mucinous Breast Carcinoma Compared to Infiltrating Ductal Carcinoma: A Population-based Study from China

Bone and Soft Tissue Sarcomas

Technical Considerations in Surgery for Retroperitoneal Sarcomas: Position Paper from E-Surge, a Master Class in Sarcoma Surgery, and EORTC–STBSG

Hepatobiliary Tumors

Diffuse Infiltrative Hepatocellular Carcinoma: Assessment of Presentation, Treatment, and Outcomes

Hepatobiliary Tumors

Impact of Obesity and Body Fat Distribution on Survival After Pancreaticoduodenectomy for Pancreatic Adenocarcinoma

Translational Research and Biomarkers

MicroRNA-10b is a Prognostic Indicator in Colorectal Cancer and Confers Resistance to the Chemotherapeutic Agent 5-Fluorouracil in Colorectal Cancer Cells