Journal of Cancer Research and Clinical Oncology

, Volume 133, Issue 8, pp 533–538

Control of aggressive fibromatosis by treatment with imatinib mesylate. A case report and review of the literature

  • Gabriel Wcislo
  • Katarzyna Szarlej-Wcislo
  • Cezary Szczylik
Original Paper



There has been only one report available that focuses on the treatment with imatinib mesylate of two individual persons with aggressive fibromatosis. The authors concluded that after long-term treatment, for 9 and 11 months, with imatinib mesylate, both patients demonstrated radiographic and clinical responses. The novel therapy should be considered as salvage in patients with aggressive fibromatosis expressed platelet-derived growth factor receptor—alfa, beta (PDGFR-alfa, PDGFR-beta), and/or c-kit, whose tumors are uncontrollable by the standard management. On the other hand, the number of kinases blocked by imatinib mesylate is notching up, for instance the tyrosine kinase, which is associated with macrophage-colony stimulating factor receptor (M-CSFR).


The patient was suffering from aggressive fibromatosis after prior therapy including surgery (R2), radiotherapy, and systemic treatment with combination of tamoxifen and sulindac. The tumor specimen was immunostained for PDGFR-beta and c-kit (CD117), and PDGFR-alfa and cytokines platelet-derived growth factor-alfa and beta were not assessed. The tests for both assessed molecules revealed negative results. In spite of this, the patient underwent a unique treatment with imatinib mesylate at the dose of 400 mg orally once daily for 3 years and 2 months.


After three months of the therapy, radiographic (met criteria of SD but small decrease of the tumor was noted) and clinical responses were recorded for the first time. The same was seen after 6 and 13 months of therapy continuation with imatinib mesylate. Currently, the patient is treated with imatinib mesylate (400 mg orally once daily) without any toxicity effects. The last MRI revealed readily a smaller tumor (35 × 20 mm) after such a therapy lasted more than 3 years.


Treatment with imatinib mesyalte has been a well-accepted therapy for chronic myelagenous leukemia (CML) and gastrointestinal stromal tumors (GIST). There have been established four kinases (p210bcr/abl, c-kit, PDGFR-alfa, PDGFR-beta) suggested as the target for imatinib mesylate. Other potential targets will be discovered as it has lately been determined that M-CSFR kinase activity was blocked by imatinib mesylate. The salvage therapy for aggressive fibromatosis with imatinib mesylate seems to be an attractive opportunity for patients with the advanced disease, whose prior therapy failed.


Aggressive fibromatosis Imatinib mesylate Salvage therapy 


  1. Alman BA, Pajerski ME, Diaz-Cano S et al (1997) Aggessive fibromatosis (desmoid tumor) is a monoclonal disorder. Diag Mol Pathol 6:98–101CrossRefGoogle Scholar
  2. Li M, Cordon-Cardo C, Gerald WL et al (1996) Desmoid fibromatosis is a clonal process. Hum Pathol 27:939–943PubMedCrossRefGoogle Scholar
  3. Bauernhofer T, Stoger H, Schmidt M et al (1996) Sequential treatment of reccurrent mesenteric desmoid tumor. Cancer 77:1061–1065PubMedCrossRefGoogle Scholar
  4. Kulaylat MN, Karakousis CP, Keaney CM et al (1999) Desmoid tumor: a pleiomorphic lesion Eur. J Surg Oncol 40:637–645Google Scholar
  5. Stewart M, Monat T (1924) Fibroma of the abdominal wall. Br J Surg 12:355–377CrossRefGoogle Scholar
  6. Spear MA , Jennings LC, Mankin HJ et al (1998) Individualizing management of aggressive fibromatosis. Int J Radiat Oncol Biol Phys 40:637–645PubMedCrossRefGoogle Scholar
  7. Klein WA Miller HH, Anderson M et al (1987) The use of indomethacin , sulindac, and tamoxifen for the treatment of desmoid tumors associated with familial poliposis. Cancer 60:2863–2868CrossRefGoogle Scholar
  8. Karakousis CP, Berjian RA, Lopez R et al (1978) Mesenteric fibromatosis in Gardner`s syndrome. Arch Surg 113:998–1000PubMedGoogle Scholar
  9. Gardner EJ, Richards RC (1953) Multiple cutaneous and subcutaneous lesions occuringsimultaneously with hereditary polyposis and osteomatosis. Am J Hum Genet 5:139–147PubMedGoogle Scholar
  10. Hoos A, Lewis JJ, Antonescu CR et al (2001) Characterisation of molecular abnormalities in human fibroblastic neoplasms: a model for genotype-phenotype association in soft tissue tumors. Cancer Res 61:3171–3175PubMedGoogle Scholar
  11. Ahman BA, Li C, Pajerski ME et al (1997) Increased beta-catenin protein and somatic APC mutations in sporadic agressive fibromatosis (desmoid tumors). Am J Pathol 151:29–34Google Scholar
  12. Eastman Q, Grosschedl R (1999) Regulation of LEF-1/TCF transcription factors by Wnt and other signals. Curr Opin Cell Biol 11:233–240PubMedCrossRefGoogle Scholar
  13. Cheon SS, Cheah AY, Turley S et al (2002) Beta-catenin stabilization dysregulates mesenchymal cell proliferation, motility and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds. Proc Natl Acad Sci USA 99:6973–6978PubMedCrossRefGoogle Scholar
  14. Alman BA, Greel DA, Ruby LK et al (1996) Regulation of proliferation and platelet-derived growth factor expression in palmar fibromatosis (Dupuytren contracture) by mechanical strain. J Orthop Res 14:722–728PubMedCrossRefGoogle Scholar
  15. Skubitz KM, Skubitz APN (2004) Gene expression in agressive fibromatosis. J Lab Clin Med 43:89–98CrossRefGoogle Scholar
  16. Denys H, De Wever O, Nusgens B et al (2004) Invasion and MMP expession profile in desmoid tumors. Br J Cancer 90:1443–1449PubMedCrossRefGoogle Scholar
  17. Higaki S, Tateishi A, Ohno T et al (1995) Surgical treatment of extra-abdominal desmoid tumors (aggresiive fibromatosis). Int Orthop 9:383–389Google Scholar
  18. Plukker JT, van Oort I, Vermey A et al (1995) Aggressive fibromatosis (non-familial desmoid tumor) : Theraputic problems and the role of adjuvant rodiotherapy. Br J Surg 82:510–514PubMedCrossRefGoogle Scholar
  19. Pritchard DJ, Nascimento AG, Petersen IA et al (1996) Local control of extra-abdominal desmoid tumors. J Bone Joint Surg Am 78:848–854PubMedGoogle Scholar
  20. Dalen BPM, Bergh PM, Gunterberg UP (2003) Desmoid tumors. A clinical review of 30 patients with more than 20 year`s follow up. Acta Orthop Scand 74:455–459PubMedCrossRefGoogle Scholar
  21. Ballo MT, Zagars GK, Pollack A et al (1999) Desmoid tumor: prognostic factors and outcome after surgery, radiotion therapy, or combined surgery and radiation therapy. J Clin Oncol 17:158–167PubMedGoogle Scholar
  22. Catton CN, O`Sullivan B, Bell R et al (1995) Aggressive fibromatosis: optimisation of local management with a retrospective failure analysis. Radiother Oncol 34:17–22PubMedCrossRefGoogle Scholar
  23. Schmitt G, Mills EED, Levin V et al (1992) Radiotherapy of aggressive fibromatosis. Eur J Cancer 28A:832–835PubMedCrossRefGoogle Scholar
  24. Kens R, Bartelnik H (1986) The role of radiotherapy in the treatment of desmoid tumors. Rradiother Oncol 7:1–5CrossRefGoogle Scholar
  25. Ballo MT, Zagars GK, Pollack A (1998) Radiation therapy in the management of desmoid tumors. Int J Radiat Oncol Biol Phys 42:1007–1014PubMedCrossRefGoogle Scholar
  26. Mc Adam WAF, Goligher JC (1970) he occurence of desmoids in patients with familial polyposis coli. Br J Surg 57:618–631CrossRefGoogle Scholar
  27. Havry P, Reitamo JJ, Vihko R et al (1982) The desmoid tumor III. A biochemical and genetic analysis. Am J Clin Pathol 77:681–685Google Scholar
  28. Lim CL, Walker MY, Melita RR et al (1986) Estrogen and antiestrogen binding sites in desmoid tumors. Eur J Cancer Clin Oncol 22:583–587PubMedCrossRefGoogle Scholar
  29. Brooks MD, Ebbs SR, Colletta AA et al (1992) Desmoid tumors treated with tripenylethylenes. Eur J Cancer 28A:1014–1018PubMedCrossRefGoogle Scholar
  30. Lanori A (1983) Effect of progesterone on desmoid tumors (aggressive fibromatosis). N Engl J Med. 309:1523Google Scholar
  31. Barone RM, Shamonki IM, Siteri PKD et al (1979) Inhibition of peripheral aromatization of androstendione et estrone in post-menopausal women with breast cancer using-testolactone. J Clin Endocrinol Metab 49:672–676PubMedCrossRefGoogle Scholar
  32. Waddell WR, Kirsch WM (1991) Testolactone, sulindac, warfarin, and vitamin K1 for unresectable desmoid tumors. Am J Surg 161:416–421PubMedCrossRefGoogle Scholar
  33. Chan TA, Morin PJ, Vogelstin B et al (1998) Mechanisms underlaying non-steroidal antiinflammatory drug-mediated apoptosis. Proc Natl Acad Sci USA 95:681–686PubMedCrossRefGoogle Scholar
  34. Tsukuda K, Church JM, Jagelman DJ et al (1992) Noncytotoxic therapy for intra-abdominal desmoid tumor in patient with familial adenomatous polyposis. Dis Colon Rectum 35:29–33CrossRefGoogle Scholar
  35. Acker JC, Bossen EH, Halperin EC (1993) The management of desmoid tumors. Int J Radiat Oncol Phys 26:851–858CrossRefGoogle Scholar
  36. Fernberg JO, Brosjo O, Larsson O et al (1999) Interferon-induced remission in aggressive fibromatosis of the lower extremity. Acta Oncol 38:971–972PubMedCrossRefGoogle Scholar
  37. Seiter K, Kemeny N (1993) Successful treatment of a desmoid tumor with doxorubicin. Cancer 71:2242–2244PubMedCrossRefGoogle Scholar
  38. Patel SR, Evans HL, Benjamin RS (1993) Combination chemotherapy in adult desmoid tumors. Cancer 72:3244–3247PubMedCrossRefGoogle Scholar
  39. Weiss AJ, Horowitz S, Lackman RD (1999) Therapy of desmoid tumors and fibromatosis using vinorelbine. Am J Clin Oncol 22:193–195PubMedCrossRefGoogle Scholar
  40. Skapiec SX, Hawk BJ, Hoffer FA et al (1998) Combination chemotherapy using vinblastine and methotrexate for the treatment of progressive desmoid tumor in children. J Clin Oncol 16:3021–3027Google Scholar
  41. Janinis J, Patriki M, Vini L et al (2003) The pharmacological treatment of aggressive fibromatosis: a systemic review. Ann Oncol 14:181–190PubMedCrossRefGoogle Scholar
  42. Drucker BJ, Talpaz M, Resta DJ et al (2001) Efficacy and safety of a specific inhibitor of the BCR-Abl tyrosine kinase in chronic myelogenous leukemia. N Engl J Med. 344:1031–1037CrossRefGoogle Scholar
  43. Buchdunger E, Cioffi CL, Law N et al (2000) Abl protein tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther 295:139–145PubMedGoogle Scholar
  44. Carroll M, Ohno-Jones S, Tamura S et al (1997) CGP57148 a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-Abl, TEL-Abl, and TEL-PDGFR fusion proteins. Blood 90:4947–4952PubMedGoogle Scholar
  45. Demetri GD, von Mahren M, Blanke CD et al (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 346:472–480CrossRefGoogle Scholar
  46. Dewar AL., Cambareri AC, Zannettino ACW et al (2005) Macrophage colony stimulating factor receptor, c-fms, is a novel terget of imatinib. Blood 105:3127–3132PubMedCrossRefGoogle Scholar
  47. Mace J, Biermann JS, Sondak V et al (2002) Response to extraabdominal desmoid tumors to therapy with omatinib mesylate. Cancer 95:2373–2379PubMedCrossRefGoogle Scholar
  48. Corless CL, Heinrich MC, Dimitrijevic S et al (2003) Correlation of imatinib response with activation of KIT and PDGF receptors in a variety of cancers: Results of the CSTIB2225 trial. Proc Am Soc Clin Oncol 22:195 (783 a)Google Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Gabriel Wcislo
    • 1
  • Katarzyna Szarlej-Wcislo
    • 1
  • Cezary Szczylik
    • 1
  1. 1.Department of OncologyMilitary Institute of MedicineWarsawPoland

Personalised recommendations