Advertisement

Skin Cancer pp 475-485 | Cite as

Systemic Therapy for Rare Tumours of the Skin and Soft Tissue Tumour

  • Bruno Vincenzi
  • Anna Maria Frezza
  • Daniele Santini
  • Giuseppe ToniniEmail author
Chapter
Part of the Current Clinical Pathology book series (CCPATH)

Abstract

The role of systemic therapy in the management of soft tissue sarcoma and rare tumours of the skin is still extremely important. Even if the principal therapeutic approach in the localised disease is represented by surgery, in the metastatic setting, the role of surgery is still poorly defined, and a systemic approach becomes mandatory. Furthermore, the possible use of systemic therapies both in the adjuvant setting, with the aim of consolidating the results obtained through surgery, and in the neoadjuvant setting, in order to optimise the local control of the disease, has been recently assessed.

For years, standard chemotherapy has represented the only systemic approach available in the treatment of soft tissue sarcoma and rare tumours of the skin: however, given the poor results obtained up today, newer compounds and target therapies are currently under active investigation.

Keywords

Overall Survival Soft Tissue Sarcoma Synovial Sarcoma Merkel Cell Carcinoma Ewing Sarcoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Glossary

Adjuvant chemotherapy

Additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back.

Neoadjuvant chemotherapy

Treatment given as a first step to shrink a tumour before the main treatment, which is usually surgery, is given.

Overall survival

The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. The overall survival rate is often stated as a 5-year survival rate, which is the percentage of people in a study or treatment group who are alive 5 years after diagnosis or treatment.

Progression-free survival

The length of time during and after treatment in which a patient is living with a disease that does not get worse.

Soft tissues

Non-epithelial extraskeletal tissue, including muscle, fat and fibrous supporting structures, arising mainly from embryonic mesoderm, with some neuroectodermal contribution.

References

  1. 1.
    Ries LAG, Melbert D, Krapcho M, Stinchcomb DG, Howlader N, Horner MJ, Mariotto A, Miller BA, Feuer EJ, Altekruse SF, Lewis DR, Clegg L, Eisner MP, Reichman M, Edwards BK (editors). SEER Cancer Statistics Review, 1975–2005. Bethesda: National Cancer Institute; 2008. http://seer.cancer.gov/csr/1975_2005/, based on November 2007 SEER data submission, posted to the SEER web site.
  2. 2.
    Cormier JN, Pollock RE. Soft tissue sarcomas. CA Cancer J Clin. 2004;54(2):94–109.PubMedCrossRefGoogle Scholar
  3. 3.
    Fong Y, Coit DG, Woodruff JM, Brennan MF. Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients. Ann Surg. 1993;217:72–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Criscione VD, Weinstock MA. Descriptive epidemiology of dermatofibrosarcoma protuberans in the United States, 1973 to 2002. J Am Acad Dermatol. 2007;56:968–73.PubMedCrossRefGoogle Scholar
  5. 5.
    Rutgers EJ, Kroon BB, Albus-Lutter CE, Gortzak E. Dermatofibrosarcoma protuberans: treatment and prognosis. Eur J Surg Oncol. 1997;18:241–8.Google Scholar
  6. 6.
    Patel KU, Szabo SS, Hernandez VS, Prieto VG, Abruzzo LV, Lazar AJ, et al. Dermatofibrosarcoma protuberans COL1A1-PDGFB fusion is identified in virtually all dermatofibrosarcoma protuberans cases when investigated by newly developed multiplex reverse transcription polymerase chain reaction and fluorescence in situ hybridization assays, Hum Pathol. 2008;39(2):184–93.PubMedCrossRefGoogle Scholar
  7. 7.
    Rollison DE, Giuliano AR, Becker JC. New virus associated with Merkel cell carcinoma development. J Natl Compr Canc Netw. 2010;8(8):874–80.PubMedGoogle Scholar
  8. 8.
    Medina-Franco H, Urist MM, Fiveash J, Heslin MJ, Bland KI, Beenken SW. Multimodality treatment of Merkel cell carcinoma: case series and literature review of 1024 cases. Ann Surg Oncol. 2001;8(3):204–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Allen PJ, Bowne WB, Jaques DP, Brennan MF, Busam K, Coit DG. Merkel cell carcinoma: prognosis and treatment of patients from a single institution. J Clin Oncol. 2005;23(10):2300–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Lorigan P, Verweij J, Papai Z, Rodenhuis S, Le Cesne A, Leahy MG, et al. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 2007;25(21):3144–50.PubMedCrossRefGoogle Scholar
  11. 11.
    Frustaci S, Gherlinzoni F, De Paoli A, et al. Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles: results of the Italian randomized cooperative trial. J Clin Oncol. 2001;19:1238–47.PubMedGoogle Scholar
  12. 12.
    Pervaiz N, Colterjohn N, Farrokhyar F, Tozer R, Figueredo A, Ghert M. A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma. Cancer. 2008;113(3):573–81.PubMedCrossRefGoogle Scholar
  13. 13.
    Le Cesne A, Van Glabbeke M, Woll PJ, Bramwell VH, Casali PG, Hoekstra HJ, Reichardt P, Hogendoorn PC, Hohenberger P, Blay JY. The end of adjuvant chemotherapy (adCT) era with doxorubicin-based regimen in resected high-grade soft tissue sarcoma (STS): Pooled analysis of the two STBSG-EORTC phase III clinical trials. J Clin Oncol (ASCO Annual Meeting). 2008;20(15S):10525.Google Scholar
  14. 14.
    Shapira J, Gotfried M, Lishner M, Ravid M. Reduced cardiotoxicity of doxorubicin by a 6-hour infusion regimen: a prospective randomized evaluation. Cancer. 1990;65:870–3.PubMedCrossRefGoogle Scholar
  15. 15.
    Judson I, Radford JA, Harris M, Blay JY, van Hoesel Q, le Cesne A, et al. Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2001;37(7):870–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Edmonson JH, Ryan LM, Blum RH, Brooks JS, Shiraki M, Frytak S, et al. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol. 1993;11(7):1269–75.PubMedGoogle Scholar
  17. 17.
    Garcia-Carbonero R, Supko JG, Manola J, et al. Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy. J Clin Oncol. 2004;22:1480–90.PubMedCrossRefGoogle Scholar
  18. 18.
    Le Cesne A, Blay JY, Judson I, et al. Phase II study of ET-743 in advanced soft tissue sarcomas: a European Organisation for the Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group Trial. J Clin Oncol. 2005;23:576–84.PubMedCrossRefGoogle Scholar
  19. 19.
    Yovine A, Riofrio M, Blay JY, et al. Phase II study of ecteinascidin-743 in advanced pretreated soft tissue sarcoma patients. J Clin Oncol. 2004;22:890–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Grosso F, Dileo P, Sanfilippo R, Stacchiotti S, Bertulli R, Piovesan C, et al. Steroid premedication markedly reduces liver and bone marrow toxicity of trabectedin in advanced sarcoma. Eur J Cancer. 2006;42(10):1484–90.PubMedCrossRefGoogle Scholar
  21. 21.
    Maki RG, Wathen JK, Patel SR, Priebat DA, Okuno SH, Samuels B, et al. Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002. J Clin Oncol. 2007;25(19):2755–63.PubMedCrossRefGoogle Scholar
  22. 22.
    Hensley ML, Maki R, Venkatraman E, Geller G, Lovegren M, Aghajanian C, et al. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol. 2002;20(12):2824–31.PubMedCrossRefGoogle Scholar
  23. 23.
    Tai PT, Yu E, Winquist E, Hammond A, Stitt L, Tonita J, et al. Chemotherapy in neuroendocrine/Merkel cell carcinoma of the skin: case series and review of 204 cases. J Clin Oncol. 2000;18(12):2493–9.PubMedGoogle Scholar
  24. 24.
    Poulsen M, Rischin D, Walpole E, Harvey J, Macintosh J, Ainslie J, et al. Analysis of toxicity of Merkel cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group Study. Int J Radiat Oncol Biol Phys. 2001;51(1):156–63.PubMedCrossRefGoogle Scholar
  25. 25.
    Pectasides D, Pectasides M, Psyrri A, Koumarianou A, Xiros N, Pectasides E, et al. Cisplatin-based chemotherapy for Merkel cell carcinoma of the skin. Cancer Invest. 2006;24(8):780–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Labropoulos SV, Razis ED. Imatinib in the treatment of dermatofibrosarcoma protuberans. Biologics. 2007;1(4):347–53.PubMedGoogle Scholar
  27. 27.
    McArthur GA, Demetri GD, van Oosterom A, Heinrich MC, Debiec-Rychter M, Corless CL, et al. Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225. J Clin Oncol. 2005;23(4):866–73.PubMedCrossRefGoogle Scholar
  28. 28.
    Okuno S. Mammalian target of rapamycin inhibitors in sarcomas. Curr Opin Oncol. 2006;18:360–2.PubMedCrossRefGoogle Scholar
  29. 29.
    Magenau JM, Schuetze SM. New targets for therapy of sarcoma. Curr Opin Oncol. 2008;20:400–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Campistol JM, Schena FP. Kaposi’s sarcoma in renal transplant recipients—the impact of proliferation signal inhibitors. Nephrol Dial Transplant. 2007;22 Suppl 1:i17–22.PubMedCrossRefGoogle Scholar
  31. 31.
    Montaner S. Akt/TSC/mTOR activation by the KSHV G protein-coupled receptor: emerging insights into the molecular oncogenesis and treatment of Kaposi’s sarcoma. Cell Cycle. 2007;6:438–43.PubMedCrossRefGoogle Scholar
  32. 32.
    Guenova E, Metzler G, Hoetzenecker W, Berneburg M, Rocken M. Classic Mediterranean Kaposi’s sarcoma regression with sirolimus treatment. Arch Dermatol. 2008;144:692–3.PubMedCrossRefGoogle Scholar
  33. 33.
    Merimsky O, Jiveliouk I, Sagi-Eisenberg R. Targeting mTOR in HIV-negative classic Kaposi’s sarcoma. Sarcoma. 2008;2008:825093.PubMedCrossRefGoogle Scholar
  34. 34.
    Chawla SP. Results of the phase III, placebo-controlled trial (SUCCEED) evaluating the mTOR inhibitor ridaforolimus (R) as maintenance therapy in advanced sarcoma patients (pts) following clinical benefit from prior standard cytotoxic chemotherapy (CT). J Clin Oncol (ASCO Annual Meeting). 2011;29(15 suppl):10005 (abstract).Google Scholar
  35. 35.
    Sleijfer S, Ray-Coquard I, Papai Z, Le Cesne A, Scurr M, Schöffski P, et al. Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European Organisation for Research and Treatment of Cancer-soft Tissue and Bone Sarcoma Group (EORTC study 62043). J Clin Oncol. 2009;27(19):3126–32.PubMedCrossRefGoogle Scholar
  36. 36.
    Wilhelm SM, Carter C, Tang L, et al. BAY43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004;64:7099–109.PubMedCrossRefGoogle Scholar
  37. 37.
    Levy AP, Pauloski N, Braun D, et al. Analysis of transcription and protein expression changes in the 786-O human renal cell carcinoma tumor xenograft model in response to treatment with the multi-kinase inhibitor sorafenib (BAY 43–9006). Proc Am Assoc Cancer Res. 2006;47:213–4.Google Scholar
  38. 38.
    Maki RG, D’Adamo DR, Keohan ML, Saulle M, Schuetze SM, Undevia SD, et al. Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. J Clin Oncol. 2009;27(19):3133–40.PubMedCrossRefGoogle Scholar
  39. 39.
    Leahy M, Ray-Coquard I, Verweij J, Le Cesne A, Duffaud F, Hogendoorn PC, et al. Brostallicin, an agent with potential activity in metastatic soft tissue sarcoma: a phase II study from the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2007;43(2):308–15.PubMedCrossRefGoogle Scholar
  40. 40.
    Krasagakis K, Fragiadaki I, Metaxari M, Krüger-Krasagakis S, Tzanakakis GN, Stathopoulos EN, et al. KIT receptor activation by autocrine and paracrine stem cell factor stimulates growth of Merkel cell carcinoma in vitro. J Cell Physiol. 2011;226(4):1099–109. doi: 10.1002/jcp.22431.PubMedCrossRefGoogle Scholar
  41. 41.
    Samlowski WE, Moon J, Tuthill RJ, Heinrich MC, Balzer-Haas NS, Merl SA, et al. A phase II trial of imatinib mesylate in Merkel cell carcinoma (neuroendocrine carcinoma of the skin): a Southwest Oncology Group Study (S0331). Am J Clin Oncol. 2010;33(5):495–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Bruno Vincenzi
    • 1
  • Anna Maria Frezza
    • 1
  • Daniele Santini
    • 1
  • Giuseppe Tonini
    • 1
    Email author
  1. 1.Medical OncologyUniversity Campus Bio-MedicoRomeItaly

Personalised recommendations