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World J Surg Oncol. 2005 Apr 18;3(1):20. doi: 10.1186/1477-7819-3-20.

Feasibility of chemosensitivity testing in soft tissue sarcomas.

World journal of surgical oncology

Marcus Lehnhardt, Thomas Muehlberger, Cornelius Kuhnen, Daniel Brett, Hans U Steinau, Hamid Joneidi Jafari, Lars Steinstraesser, Oliver Müller, Heinz H Homann

Affiliations

  1. Department of Plastic Surgery, Burn Center, Hand surgery, Sarcoma Reference Center, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bürkle-de-la Camp Platz 1, 44789 Bochum, Germany. [email protected].

PMID: 15836792 PMCID: PMC1087896 DOI: 10.1186/1477-7819-3-20

Abstract

BACKGROUND: Soft tissue sarcomas comprise less than 1% of all solid malignancies. The presentation and behavior of these tumors differs depending on location and histological characteristics. Standard therapy consists of complete surgical resection in combination with adjuvant radiotherapy. The role of chemotherapy is not clearly defined and is largely restricted to clinical trials. Only a limited number of agents have proved to be effective in soft tissue sarcomas. The use of doxorubicin, epirubicin and ifosfamide allowed response rates of more than 20%. In addition, recent chemotherapy trials did not demonstrate any significant differences in efficacy for various histological subtypes. METHODS: The objective of this study was to gain additional information about the chemosensitivity of soft tissue sarcomas to seven 7 different chemotherapy agents as single drugs and 4 combinations. Therefore we used an established ATP based in-vitro testing system and examined 50 soft tissue sarcomas. Chemosensitivity was assessed using a luciferin-luciferase-based luminescence assay providing individual chemosensitivity indices for each agent tested. RESULTS: The sensitivity varied widely according to the histological subtypes. The tumors state of cellular dedifferentiation played a crucial role for the efficiency of the chemotherapeutic agents. The sensitivity also depended on the presentation of the sarcoma as a primary or recurrent tumor. The highest sensitivity was demonstrated for actinomycin D as a single agent, with 74% of the tumor samples exhibiting a high-grade sensitivity (20% low sensitivity, no resistance). The combination of actinomycin D and ifosfamide yielded a high sensitivity in 76% (2% resistance). Doxorubicin as a mono-therapy or in combination with ifosfamide achieved high sensitivity in 70% and 72%, respectively, and resistance in 6% of the samples. CONCLUSION: Chemosensitivity testing is feasible in soft tissue sarcomas. It can be used to create sensitivity and resistance profiles of established and new cytotoxic agents and their combinations in soft tissue sarcomas. Our data demonstrate measurable discrepancies of the drug efficiency in soft tissue sarcomas, sarcoma subtypes and tumor recurrencies. However, current therapeutic regime does not take this in consideration, yet.

References

  1. J Ky Med Assoc. 2002 Jan;100(1):10-6 - PubMed
  2. Anticancer Drugs. 1999 Jun;10(5):431-5 - PubMed
  3. Anticancer Drugs. 2002 May;13 Suppl 1:S7-9 - PubMed
  4. Anticancer Drugs. 2003 Jun;14(5):369-75 - PubMed
  5. Presse Med. 1995 Sep 16;24(26):1214-20 - PubMed
  6. J Clin Oncol. 2001 Mar 1;19(5):1238-47 - PubMed
  7. Eur J Cancer. 2002 Mar;38 Suppl 4:S138-41 - PubMed
  8. Ann Oncol. 1993 Sep;4(8):669-72 - PubMed
  9. Chirurg. 2000 Jul;71(7):787-94 - PubMed
  10. Oncology. 2003;65 Suppl 2:80-4 - PubMed
  11. Anticancer Drugs. 1997 Sep;8(8):756-62 - PubMed
  12. Chirurg. 2001 May;72(5):501-13 - PubMed
  13. Eur Cytokine Netw. 2001 Apr-Jun;12(2):239-43 - PubMed
  14. Int J Radiat Oncol Biol Phys. 2003 Jul 15;56(4):1117-27 - PubMed
  15. Recent Results Cancer Res. 2003;161:146-58 - PubMed
  16. Paediatr Drugs. 2002;4(1):21-8 - PubMed
  17. Anticancer Drugs. 2003 Jul;14(6):397-403 - PubMed
  18. Cancer Res. 1995 Nov 15;55(22):5276-82 - PubMed
  19. Anticancer Res. 1998 Sep-Oct;18(5B):3699-704 - PubMed
  20. Eur J Cancer. 2001 Sep;37(13):1599-608 - PubMed
  21. Curr Oncol Rep. 2003 Nov;5(6):505-9 - PubMed
  22. Eur J Cancer. 2002 Mar;38(4):556-9 - PubMed
  23. Invest New Drugs. 2002 Feb;20(1):129-32 - PubMed
  24. Hematol Oncol Clin North Am. 1995 Aug;9(4):909-25 - PubMed
  25. Acta Oncol. 2003;42(1):55-61 - PubMed
  26. J Clin Oncol. 1999 Dec;17(12):3706-19 - PubMed
  27. Eur J Cancer. 2001 Sep;37(13):1609-16 - PubMed
  28. Clin Cancer Res. 2001 Feb;7(2):231-42 - PubMed
  29. Invest New Drugs. 2003 Nov;21(4):481-6 - PubMed
  30. Bull Cancer. 1988;75(5):483-92 - PubMed
  31. Cancer Chemother Pharmacol. 2002 May;49 Suppl 1:S4-8 - PubMed
  32. Tumori. 2003 Jul-Aug;89(4 Suppl):267-8 - PubMed
  33. Oncology. 2003;65 Suppl 2:31-6 - PubMed
  34. Recent Results Cancer Res. 2003;161:221-30 - PubMed
  35. Oncologist. 2002;7(6):531-8 - PubMed
  36. Curr Treat Options Oncol. 2003 Dec;4(6):433-9 - PubMed
  37. Cochrane Database Syst Rev. 2003;(3):CD003293 - PubMed
  38. Cancer. 1991 Dec 1;68(11):2354-8 - PubMed
  39. Geburtshilfe Frauenheilkd. 1996 Feb;56(2):70-8 - PubMed
  40. Surg Gynecol Obstet. 1986 Feb;162(2):149-52 - PubMed
  41. Lancet Oncol. 2000 Oct;1:75-85 - PubMed
  42. Crit Rev Oncol Hematol. 2002 Feb;41(2):157-67 - PubMed
  43. BMC Cancer. 2003 Jul 03;3:19 - PubMed
  44. Oncology. 2003;65 Suppl 2:76-9 - PubMed
  45. Anticancer Res. 2001 Nov-Dec;21(6A):4147-51 - PubMed
  46. Cancer Invest. 2000;18(3):223-41 - PubMed
  47. Cancer. 1972 Dec;30(6):1632-8 - PubMed
  48. Zhonghua Zhong Liu Za Zhi. 1997 May;19(3):231-4 - PubMed
  49. Bull Cancer. 2002 Jan;89(1):100-7 - PubMed
  50. Gynakol Geburtshilfliche Rundsch. 1993;33 Suppl 1:311-3 - PubMed
  51. Br J Cancer. 2003 Dec 15;89(12):2299-304 - PubMed

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