Skip to main content
SpringerLink
Log in

Isolated Limb Infusion as Palliative Treatment for Advanced Limb Disease in Patients with AJCC Stage IV Melanoma

  • Melanomas
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Introduction

In the treatment of patients with advanced limb melanoma a major treatment dilemma can arise when distant metastases are present also. Isolated limb infusion (ILI) has proved to be a useful limb-saving treatment and could potentially be of palliative value in patients with American Joint Committee on Cancer (AJCC) stage IV melanoma.

Methods

We identified 37 patients with advanced symptomatic limb disease as well as documented distant metastases at the time of their ILI. In all patients a drug combination of melphalan and actinomycin D was used.

Results

Fifty one percent had visceral distant metastases and 49% had cutaneous distant metastases only. The overall response rate in the treated limb was 76% [complete response (CR) rate 22%, partial response (PR) rate 54%]. Median response duration was 11 months (28 months for patients with CR; p = 0.08). Median survival after CR was 22 months, 17 months after PR, and only 4 months for those with stable or progressive disease (p = 0.002). Patients with visceral distant metastases had a significantly decreased survival compared with those with cutaneous distant metastases only (8 and 21 months, respectively; p = 0.03). Limb salvage was achieved in 86% of the patients. The procedure was well tolerated, with only one patient developing Wieberdink grade IV toxicity (threatened/actual compartment syndrome) and none requiring amputation as a result of the procedure (grade V toxicity).

Conclusions

Minimally invasive ILI can effectively be used as palliative treatment to provide local tumor control and limb salvage in stage IV melanoma patients with advanced, symptomatic limb disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Balch CM, Buzaid AC, Soong S-J, Atkins MB, Cascinelli N, Coit DG, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. 2001;19:3635–48.

    PubMed  CAS  Google Scholar 

  2. Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Elashoff R, Essner R, et al. MSLT-group. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006;355:1307–17.

    Article  PubMed  CAS  Google Scholar 

  3. Strobbe LJ, Nieweg OE, Kroon BB. Carbon dioxide laser for cutaneous melanoma metastases: indications and limitations. Eur J Surg Oncol. 1997;23:435–8.

    Article  PubMed  CAS  Google Scholar 

  4. Thompson JF, Kam PCA, de Wilt JHW, Lindnér P. Isolated limb infusion for melanoma. In: Thompson JF, Morton DL, Kroon BBR, editors. Textbook of melanoma. London: Martin Dunitz; 2004. p. 429–37.

    Google Scholar 

  5. Kroon HM, Moncrieff M, Kam PC, Thompson JF. Outcomes following isolated limb infusion for melanoma. A 14-year experience. Ann Surg Oncol. 2008;15:2749–56.

    Google Scholar 

  6. Noorda EM, Takkenberg B, Vrouenraets BC, Nieweg OE, van Geel BN, Eggermont AM, et al. Isolated limb perfusion prolongs the limb recurrence-free interval after several episodes of excisional surgery for locoregional recurrent melanoma. Ann Surg Oncol. 2004;11:491–9.

    Article  PubMed  Google Scholar 

  7. American Joint Committee on Cancer. Malignant melanoma of the skin. In: Kleming I, Cooper J, Henson D, et al., editors. AJCC cancer staging manual. Philadelphia: J.B. Lippincott; 1992. p. 143–8.

    Google Scholar 

  8. Kim CJ, Reintgen DS, Balch CM; AJCC Melanoma Staging Committee. The new melanoma staging system. Cancer Control. 2002;9:9–15.

    PubMed  Google Scholar 

  9. Lindnér P, Doubrovsky A, Kam PCA, Thompson JF. Prognostic factors after isolated limb infusion with cytotoxic agents for melanoma. Ann Surg Oncol. 2002;9:127–36.

    PubMed  Google Scholar 

  10. Lindnér P, Thompson JF, De Wilt JH, Colman M, Kam PC. Double isolated limb infusion with cytotoxic agents for recurrent and metastatic limb melanoma. Eur J Surg Oncol. 2004;30:433–9.

    Article  PubMed  Google Scholar 

  11. Bonenkamp JJ, Thompson JF, de Wilt JH, Doubrovsky A, de Faria Lima R, Kam PC. Isolated limb infusion with fotemustine after dacarbazine chemosensitisation for inoperable loco-regional melanoma recurrence. Eur J Surg Oncol. 2004;30:1107–12.

    Article  PubMed  CAS  Google Scholar 

  12. 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.

    Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. Thompson JF, Kam PC. Isolated limb infusion for melanoma: a simple but effective alternative to isolated limb perfusion. J Surg Oncol. 2004;1:88:1–3.

    Article  Google Scholar 

  15. 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.

    Article  PubMed  CAS  Google Scholar 

  16. Schraffordt Koops H, Lejeune FJ, Kroon BBR, Klaase JM, Hoekstra HJ. Isolated limb perfusion for melanoma: technical aspects. In: Thompson JF, Morton DL, Kroon BBR, editors. Textbook of melanoma. London: Martin Dunitz; 2004. p. 404–9.

    Google Scholar 

  17. 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.

    Article  PubMed  Google Scholar 

  18. 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.

    PubMed  CAS  Google Scholar 

  19. Lai DTM, Ingvar C, Thompson JF. The value of monitoring serum creatine phosphokinase values following hyperthermic isolated limb perfusion for melanoma. Reg Cancer Treat. 1993;6:36–9.

    Google Scholar 

  20. World Health Organization. WHO handbook for reporting results of cancer treatments (WHO offset publication no. 48). Geneva: World Health Organization; 1979.

    Google Scholar 

  21. Mann HB, Whitney DR. On a test of whether one of two random variables is stochastically larger than the other. Ann Math Stat. 1947;18:50–60.

    Article  Google Scholar 

  22. Kaplan L, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1985;53:457–81.

    Article  Google Scholar 

  23. Hill S, Thomas JM. Use of the carbon dioxide laser to manage cutaneous metastases from malignant melanoma. Br J Surg. 1996;83:509–12.

    Article  PubMed  CAS  Google Scholar 

  24. Stevens G, Hong A. Radiation therapy in the management of cutaneous melanoma. Surg Oncol Clin North Am. 2006;15:353–71.

    Article  Google Scholar 

  25. Eton O, Legha SS, Bedikian AY, Lee JJ, Buzaid AC, Hodges C, et al. Sequential biochemotherapy versus chemotherapy for metastatic melanoma: results from a phase III randomized trial. J Clin Oncol. 2002;20:2045–52.

    Article  PubMed  CAS  Google Scholar 

  26. Keilholz U, Conradt C, Legha SS, Khayat D, Scheibenbogen C, Thatcher N, et al. Results of interleukin-2- based treatment in advanced melanoma: a case record-based analysis of 631 patients. J Clin Oncol. 1998;16:2921–9.

    PubMed  CAS  Google Scholar 

  27. Hwu WJ. New approaches in the treatment of metastatic melanoma: thalidomide and temozolomide. Oncology. 2000;14:25–8.

    PubMed  CAS  Google Scholar 

  28. Takkenberg RB, Vrouenraets BC, van Geel AN, Nieweg OE, Noorda EM, Eggermont AM, et al. Palliative isolated limb perfusion for advanced limb disease in stage IV melanoma patients. J Surg Oncol. 2005;91:107–11.

    Article  PubMed  CAS  Google Scholar 

  29. Kroon BBR. Regional isolation perfusion in melanoma of the limbs; accomplishments, unsolved problems, future. Eur J Surg Oncol. 1988;14:101–10.

    PubMed  CAS  Google Scholar 

  30. Jacques DP, Coit DG, Brennan MF. Major amputation for advanced malignant melanoma. Surg Gynecol Obstet. 1989;169:1–6.

    Google Scholar 

  31. Klaase JM, Kroon BBR, van Geel AN, van Wijk J, Franklin HR, Eggermont AMM, 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  CAS  Google Scholar 

  32. Sanki A, Kam PCA, Thompson JF. Long-term results of hyperthermic, isolated limb perfusion for melanoma. Ann Surg. 2007;4:591–6.

    Article  Google Scholar 

  33. Eigentler TK, Caroli UM, Radny P, Garbe C. Palliative therapy of disseminated malignant melanoma: a systematic review of 41 randomised clinical trials. Lancet Oncol. 2003;4:748–59.

    Article  PubMed  CAS  Google Scholar 

  34. Grunhagen DJ, de Wilt JH, Graveland WJ, van Geel AN, Eggermont AM. The palliative value of tumor necrosis factor alpha-based isolated limb perfusion in patients with metastatic sarcoma and melanoma. Cancer. 2006;106:156–62.

    Article  PubMed  Google Scholar 

  35. Fraker DL, Alexander HR, Andrich M, Rosenberg SA. Palliation of regional symptoms of advanced extremity melanoma by isolated limb perfusion with melphalan and high-dose tumor necrosis factor. Cancer J Sci Am. 1995;1:122–30.

    PubMed  CAS  Google Scholar 

  36. Thompson JF, Lai DT, Ingvar C, Kam PC. Maximizing efficacy and minimizing toxicity in isolated limb perfusion for melanoma. Melanoma Res. 1994;4(1):45–50.

    PubMed  Google Scholar 

Download references

Acknowledgments

Hidde Kroon is supported by grants from, Haak Bastiaanse-Kuneman Stichting, Stichting Fundatie van de Vrijvrouwe van Renswoude te ‘s-Gravenhage, Stichting Sacha Swarttouw-Heijmans, KWF Kankerbestrijding, Stichting Prof. Michaël-van Vloten Fonds, Amgen Netherlands BV, University Medical Center Groningen/Faculty of Medical Sciences of the University of Groningen, the Melanoma Foundation of the University of Sydney and Melanoma Institute Australia.

Author information

Authors and Affiliations

  1. Sydney Melanoma Unit and Melanoma Institute Australia, Sydney Cancer Centre, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney, NSW, 2050, Australia

    Hidde M. Kroon MD, D-Yin Lin MD & John F. Thompson MD, FRACS, FACS

  2. Department of Anaesthetics, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia

    Peter C. A. Kam MD, FRCA, FANZCA

  3. Disciplines of Anaesthetics, The University of Sydney, Sydney, NSW, Australia

    Peter C. A. Kam MD, FRCA, FANZCA

  4. Disciplines of Surgery, The University of Sydney, Sydney, NSW, Australia

    John F. Thompson MD, FRACS, FACS

Authors
  1. Hidde M. Kroon MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D-Yin Lin MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter C. A. Kam MD, FRCA, FANZCA
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John F. Thompson MD, FRACS, FACS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John F. Thompson MD, FRACS, FACS.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kroon, H.M., Lin, DY., Kam, P.C.A. et al. Isolated Limb Infusion as Palliative Treatment for Advanced Limb Disease in Patients with AJCC Stage IV Melanoma. Ann Surg Oncol 16, 1193–1201 (2009). https://doi.org/10.1245/s10434-009-0326-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-009-0326-7

Keywords

Search

Navigation