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Predictive Factors of Regional Toxicity and Serum Creatine Phosphokinase Levels After Isolated Limb Infusion for Melanoma: A Multi-Institutional Analysis

  • Melanomas
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Abstract

Background

Isolated limb infusion (ILI) is a minimally invasive technique delivering regional chemotherapy to treat in-transit extremity melanoma. Determining perioperative factors that could predict toxicity is important to optimize strategies to improve clinical outcomes after regional chemotherapy in melanoma.

Methods

Perioperative factors from 171 ILI patients performed at eight centers from 2001 to 2008 were reviewed. The Wieberdink limb toxicity scale and creatine phosphokinase (CK) levels were used to measure toxicity. Logistic regression analysis was used to estimate the association between toxicity and perioperative parameters.

Results

Mild (grades I–II) and severe (grades ≥III) limb toxicity developed in 68% and 32% of patients, respectively. Melphalan adjusted for ideal body weight (aIBW) and papaverine were used in 47% and 63% of patients, respectively. Median peak CK for all patients was 563 U/l, and median peak occurred at postoperative day 4. On univariate analysis, papaverine and high CK levels (>563 U/l) were significantly associated with higher toxicity. On the contrary, aIBW was significantly associated with a lower risk of severe toxicity. Perfusate blood gas at 30 min [pH, PaO2, and base excess (BE) ], limb temperature, and ischemia time were not predictive of limb toxicity. On multivariate analysis, severe toxicity was associated with female sex (P = 0.01), papaverine (P = 0.01), and high peak CK levels (P < 0.01). Independent predictors of high CK levels included younger age, unadjusted melphalan dose, and low PaO2 at 30 min.

Conclusions

ILI can be performed with an acceptable morbidity. Papaverine use, female gender, and high peak CK were associated with higher limb toxicity. CK levels can be diminished significantly with aIBW.

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Authors and Affiliations

  1. Division of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Alfredo A. Santillan MD, MPH & Jonathan S. Zager MD, FACS

  2. Department of Surgery, Emory University, Atlanta, GA, USA

    Keith A. Delman MD

  3. Department of Surgery, Duke University Medical Center, Durham, NC, USA

    Georgia M. Beasley MD & Douglas S. Tyler MD

  4. Department of Surgery, Lehigh Valley Hospital, Allentown, PA, USA

    Paul J. Mosca MD

  5. Department of Surgery, University of Florida, Gainesville, FL, USA

    Steven N. Hochwald MD & Stephen R. Grobmyer MD

  6. Department of Surgery, University of Utah, Salt Lake City, UT, USA

    Robert H. Andtbacka MD & R. Dirk Noyes MD

  7. Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA

    John M. Kane MD

  8. Department of Surgery, MD Anderson Cancer Center, Houston, TX, USA

    Merrick I. Ross MD

  9. Moffitt Cancer Center, Tampa, FL, USA

    Jonathan S. Zager MD, FACS

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  1. Alfredo A. Santillan MD, MPH
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Correspondence to Jonathan S. Zager MD, FACS.

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Santillan, A.A., Delman, K.A., Beasley, G.M. 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 16, 2570–2578 (2009). https://doi.org/10.1245/s10434-009-0563-9

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  • DOI: https://doi.org/10.1245/s10434-009-0563-9

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