Preview

Bone and soft tissue sarcomas, tumors of the skin

Advanced search

Isolated regional chemotherapeutic perfusion oflimbs

Abstract

Among patients suffering from diseases such as skin melanoma, skin cancer and soft tissue sarcoma, there is a group with locally advanced forms. Standard treatment options may not be effective. For some patients, limbsparing approach is often not possible. Amputation decrease quality of life. Isolated regional perfusion - the method of temporary isolation of the affected limb with the implementation of cardiopulmonary bypass and chemotherapy agents loaded in it. The method of ILP was developed to be able to achieve regional concentrations of chemotherapeutic agents that are 15 to 25 times higher than can be reached with systemic administration, but without the systemic sideeffects. Melphalanbased ILP is associated with complete response rates of 40-50%, and overall response rates of 75-80%. When Tumor Necrosis Factor-alfa was introduced in the isolated limb perfusion model by Lejeune and Lienard in 1988, complete response rates of 80-90% were reported. Multicenter trials confirmed that TNFbased ILP was a highly effective new method of induction biochemotherapy for extremity soft tissue sarcomas with a 20-30% complete remission rate, a 50% partial remission rate and a limb salvage percentage of 80%. We treated 2 patients in RCRC N.N. Blokhin RAMS with isolated limb perfusion with melfalan and mild hyperthermia. Progression not observed for 9 months.

About the Authors

M. D. Aliev
N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences
Russian Federation


B. I. Dolgushin
N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences
Russian Federation


L. V. Demidov
N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences
Russian Federation


T. K. Charatishvili
N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences
Russian Federation


Y. V. Buydenok
N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences
Russian Federation


B. Y. Narkevitch
N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences
Russian Federation


D. V. Martynkov
N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences
Russian Federation


A. A. Fedenko
N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences
Russian Federation


B. Y. Bokhyan
N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences
Russian Federation


References

1. Benckhuijsen С., Kroon В.В., van Geel A.N. et al. Regional perfusion treatment with melphalan for melanoma in a limb: an evaluation of drug kinetics. Eur. J. Surg. Oncol. 1988, v. 14, p. 157-163.

2. Omlor G., Gross G., Ecker K.W. et al. Optimization of isolated hyperthermic limb perfusion. World J. Surg. 1993, v. 16, p. 1117-1119.

3. Cavaliere R., Ciocatto R.C., Giovanella B.C. et al. Selective heat sensitivity of cancer cells: biochemical and clinical studies. Cancer. 1967, v. 20, p. 1351-1381.

4. Clark J., Grabs A.J., Parsons P.G. et al. Melphalan uptake, hyperthermic synergism and drug resistance in a human cell culture model for the isolated limb perfusions of melanoma. Melanoma Res. 1994, v. 4, p. 365-370.

5. Rosin R.D., Westbury G. Isolated limb perfusion for malignant melanoma. Practitioner. 1980, v. 224, p. 1031-1036.

6. Lejeune F.J., Deloof T., Ewalenko P. Objective regression of unexcised melanoma intransit metastases after hyperthermic isolation perfusion of the limbs with melphalan. Recent. Results Cancer. Res. 1983, v. 86, p. 268-276.

7. Minor D.R., Allen R.E., Alberts D. et al. A clinical and pharmokinetic study of isolated limb perfusion with heat and melphalan for melanoma. Cancer. 1985, v. 55, p. 2638-2644.

8. Skene A.I., Bulman A.S., Williams T.R. et al. Hyperthermic isolated perfusion with melphalan in the treatment of advanced malignant melanoma of the lower limb. Br. J. Surg. 1990, v. 77, p. 765-767.

9. Kettelhack Ch., Kraus Th., Hupp Th. et al. Hyperthermic limb perfusion for malignant melanoma and soft tissue sarcoma. Eur. J. Surg. Oncol. 1990, v. 16, p. 370-375.

10. Lienard D., Eggermont A.M.M., Schraffordt Koops H. et al. Isolated limb perfusion with tumour necrosis factor-alpha and melphalan with or without interferon-gamma forthe treatment of in-transit melanoma metastases: a multicentre randomized phase II study. Melanoma Res. 1999, v. 9, p. 491-502.

11. Klaase J.M., Kroon B.B.R., Eggermont A.M.M. et al. A retrospective comparative study evaluating the results of «mild» hyperthermic versus «controlled» normothermic perfusion for recurrent melanoma of the extremities. Eur. J. Cancer. 1995, v.31,p. 73-81.

12. Vaglini M., Andreola S., Attili A. et al. Hyperthermic antiblastic perfusion in the treatment of cancer of the extremities. Tumori. 1985, v. 71, p. 355-359.

13. Bryant P.J., Balderson G.A., Mead P., Egerton W.S. Hyperthermic isolated limb perfusion for malignant melanoma: response and survival. World J. Surg. 1995, v. 19, p. 363-368.

14. Cavaliere R., Calabro A., Di Filippo F. et al. Prognosic parameters in limb recurrent melanoma treated with hyperthermic antiblastic perfusion. Proceedings of the International Conference on Regional Cancer. Treatment. Ulm. 1987, G7, p. 163.

15. Di Filippo F., Calabro A., Giannarelli D. et al. Prognostic variables in recurrent limb melanoma treated with hyperthermic antiblasticperfusion. Cancer. 1989, v. 63, p. 2551-2561.

16. Kroon B.B.R., Klaase J.M., Van Geel A.N., Eggermont A.M.M. Application of hyperthermia in regional isolated perfusion for melanoma of the limbs. Reg. Cancer. Treat. 1992, v. 4, p. 223-226.

17. McBride C.M., Sugarbaker E.V., Hickey R.C. Prophylactic isolation perfusion as the primary therapy for invasive malignant melanoma of the limbs. Ann. Surg. 1975, v. 182, p. 316-324.

18. Schraffordt-Koops H., Vaglini M., Suciu S. et al. Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. J. Clin. Oncol. 1999, v. 16, p. 2906-2912.

19. Hafstrom L., Rudenstam C.M., Blomquist E. et al. Regional hyperthermic perfusion with melphalan after surgery for recurrent malignant melanoma of the extremities. J. Clin. Oncol. 1991, v. 9, p. 2091-2094.

20. Krementz E.T., Carter R.D., Sutherland C.M., Hutton I. Chemotherapy of sarcomas of the limbs by regional perfusion. Ann. Surg. 1977, v. 185, p. 555-564.

21. Muchmore J.H., Carter R.D., Krementz E.T. Regional perfusion for malignant melanoma and soft tissue sarcoma: a review. Cancer. Invest. 1985, v. 3, p. 129-143.

22. Pommier R.F., Moseley H.S., Cohen J. et al. Pharmacokinetics, toxicity, and short-term results of cisplatin hyperthermic isolated limb perfusion for soft tissue sarcoma and melanoma of the extremities. Am. J. Surg. 1988, v. 155, p. 667-671.

23. Klaase J.M., Kroon B.B.R., Benckhuysen C. et al. Results of regional isolation perfusion with cytostatics in patients with soft tissue tumors of the extremities. Cancer. 1989, v. 64, p. 616-621.

24. Eggermont A.M.M., Schraffordt Koops H., Klausner J.M. et al. Limb salvage by isolation limb perfusion with tumor necrosis factor alpha and melphalan for locally advanced extremity soft tissue sarcomas: results of 270 perfusions in 246 patients. Proc. Am. Soc. Clin. Oncol. 1999, v. 11, p. 497 (Abstr).

25. Eggermont A.M.M., Lienard D., Schraffordt Koops H. et al. Treatment of irresectable soft tissue sarcomas of the limbs by isolation perfusion with high dose TNF-α in combination with gamma-interferon and melphalan. In: Fiers W., Buurman W.A. (Eds). Tumor necrosis factor: molecular and cellular biology and clinical relevance. Basel, Karger. 1993, p. 239-243.

26. Eggermont A.M.M., Schraffordt Koops H., Lienard D. et al. Isolated limb perfusion with high-dose tumor necrosis factoralpha in combination with interferon-gamma and melphalan for nonresectable extremity soft tissue sarcomas: a multicenter trial. J. Clin. Oncol. 1996, v. 14, p. 2653-2665.

27. Santinami M., Deraco M., Azzarelli A. et al. Treatment of recurrent sarcoma of the extremities by isolated perfusion using tumor necrosis factor alpha and melphalan. Tumori. 1996, v. 82, p. 579-584.

28. Eggermont A.M.M., Schraffordt Koops H., Klausner J.M. et al. Isolated limb perfusion with tumor necrosis factor and melphalan for limb salvage in 186 patients with locally advanced soft tissue extremity sarcomas: the cumulative multicenter European experience. Ann. Surg. 1996, v. 224, p. 756-764.

29. Gutman M., Inbar M., Lev-Shlush D. et al. High dose tumor necrosis factor-а and melphalan administered via isolated limb perfusion for advanced limb soft tissue sarcoma results in a >90% response rate and limb preservation. Cancer. 1997, v.79,p. 1129-1137.

30. Eggermont A.M.M., Schraffordt Koops H., Klausner J.M. et al. Limb salvage by isolation limb perfusion with tumor necrosis factor alpha and melphalan for locally advanced extremity soft tissue sarcomas: results of 270 perfusions in 246 patients. Proc. Am. Soc. Clin. Oncol. 1999, v. 11, p. 497 (Abstr).

31. Rossi C.R., Foletto M., Di Filippo F. et al. Soft tissue limb sarcomas: Italian clinical trials with hyperthermic antiblastic perfusion. Cancer. 1999, v. 86, p. 1742-1749.

32. Lejeune F.J., Pujol N., Lienard D. et al. Limb salvage by neoadjuvant isolated perfusion with TNFalpha and melphalan for non-resectable soft tissue sarcoma of the extremities. Eur. J. Surg. Oncol. 2000, v. 26, p. 669-678.

33. Lans T.E., de Wilt J.H.W., van Geel A.N., Eggermont A.M.M. Isolated limb perfusion with tumor necrosis factor and melphalan for nonresectable Stewart-Treves lymphangiosarcoma. Ann. Surg. Oncol. 2002, v. 9, p. 1004-1009.

34. Etten van B., van Geel A.N., de Wilt J.H.W., Eggermont A.M.M. Fifty tumor necrosis factor based isolated limb perfusions for limb salvage in patients older than 75 years with limb-threatening soft tissue sarcomas and other extremity tumors. Ann. Surg. Oncol. 2003, v. 10, p. 32.

35. Hill S., Fawcett W.J., Sheldon J. et al. Low dose tumor necrosis factor alpha and melphalan in hyperthermic isolated limb perfusion. Br. J. Surg. 1993, v. 80, p. 995-997.

36. DeWilt J.H.W., Manusama E.R., van Tiel S.T. et al. Prerequisites for effective isolated limb perfusion using tumour necrosis factor-alpha and melphalan in rats. Br. J. Cancer. 1999, v. 80, p. 161-166.

37. Manusama E.R., de Wilt J.H.W. ten Hagen T.L.M. et al. Toxicity and antitumor activity of interferon-gamma alone and in combinations with TNF and melphalan in isolated limb perfusion in the BN175 sarcoma tumor model in rats. Oncol. Rep. 1999, v. 6, p. 173-177.

38. Lienard D., Eggermont A.M.M., Schraffordt Koops H. et al. Isolated limb perfusion with tumour necrosis factor-alpha and melphalan with or without interferon-gamma for the treatment of in-transit melanoma metastases: a multicentre randomized phase II study. Melanoma Res. 1999, v. 9, p. 491-502.


Review

For citations:


Aliev M.D., Dolgushin B.I., Demidov L.V., Charatishvili T.K., Buydenok Y.V., Narkevitch B.Y., Martynkov D.V., Fedenko A.A., Bokhyan B.Y. Isolated regional chemotherapeutic perfusion oflimbs. Bone and soft tissue sarcomas, tumors of the skin. 2010;(4):46-54. (In Russ.)

Views: 108


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2219-4614 (Print)
ISSN 2782-3687 (Online)