Successful Chemotherapeutic Modality of Doxorubicin Plus Dacarbazine for the Treatment of Desmoid Tumors in Association With Familial Adenomatous Polyposis

Gega, Makoto; Yanagi, Hidenori; Yoshikawa, Reigetsu; Noda, Masafumi; Ikeuchi, Hiroki; Tsukamoto, Kiyoshi; Oshima, Tsutomu; Fujiwara, Yoshinori; Gondo, Nobuhisa; Tamura, Kazuo; Utsunomiya, Joji; Hashimoto-Tamaoki, Tomoko; Yamamura, Takehira

doi:10.1200/jco.2005.02.1923

Cited by 170 publications

(111 citation statements)

References 22 publications

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“…Anti-inflammatory agents, hormonal blockade, and cytotoxic chemotherapy also may be useful in selected patients, but overall response rates to these modalities remains modest at best. [23][24][25][26] Investigation of FAP-related desmoids has led to the identification of a potential role for ␤-catenin deregulation in desmoid tumorigenesis. 27 ␤-Catenin is a cadherin-binding protein involved in cell-cell adhesion, but also functions as a transcriptional activator when complexed in the nucleus with members of the T-cell factor/lymphocyte enhancer factor family of proteins.…”

mentioning

confidence: 99%

Specific Mutations in the β-Catenin Gene (CTNNB1) Correlate with Local Recurrence in Sporadic Desmoid Tumors

Lazar

Tuvin

Hajibashi

et al. 2008

The American Journal of Pathology

414

375

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Desmoid fibromatosis is a rare, nonmetastatic neoplasm marked by local invasiveness and relentless recurrence. Molecular determinants of desmoid recurrence remain obscure. ␤-Catenin deregulation has been commonly identified in sporadic desmoids although the incidence of CTNNB1 (the gene encoding ␤-catenin) mutations is uncertain. Consequently, we evaluated the prevalence of CTNNB1 mutations in a large cohort of sporadic desmoids and examined whether mutation type was relevant to desmoid outcome. Desmoid specimens (195 tumors from 160 patients, 1985 to 2005) and control dermal scars were assembled into a clinical data-linked tissue microarray. CTNNB1 genotyping was performed on a 138-sporadic desmoid subset. Immunohistochemical scoring was performed per standard criteria and data were analyzed using Kaplan-Meier and other indicated methods. CTNNB1 mutations were observed in 117 of 138 (85%) of desmoids. Three discrete mutations in two codons of CTNNB1 exon 3 were identified: 41A (59%) , 45F (33%) , and 45P (8% , excluded from further analysis because of rarity). Five-year recurrence-free survival was significantly poorer in 45F-mutated desmoids (23% , P < 0.0001) versus either 41A (57%) or nonmutated tumors (65%). Nuclear ␤-catenin expression was observed in 98% of specimens and intensity was inversely correlated with incidence of desmoid recurrence (P < 0.01). In conclusion, CTNNB1 mutations are highly common in desmoid tumors. Furthermore, patients harboring CTNNB1 (45F) mutations are at particular risk for recurrence and therefore may especially benefit from adjuvant therapeutic approaches. (Am J Pathol

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mentioning

confidence: 99%

Specific Mutations in the β-Catenin Gene (CTNNB1) Correlate with Local Recurrence in Sporadic Desmoid Tumors

Lazar

Tuvin

Hajibashi

et al. 2008

The American Journal of Pathology

414

375

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“…Reports have suggested that therapy might be associated with an initial benefit but the long-term clinical improvement is minimal [39][40][41] . Cytotoxic chemotherapy (doxorubicin, dacarbazine, and carboplatin) may be effective in treating aggressive, rapidly growing and unresectable abdominal desmoids [42,43] . Radiation therapy might be effective in selected cases but it is frequently limited by the presence of the small bowel in the radiation field in mesenteric and pelvic desmoids [44,45] .…”

Section: Managementmentioning

confidence: 99%

Updates on abdominal desmoid tumors

Rampone

Pedrazzani²,

Marrelli³

et al. 2007

WJG

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Desmoid tumor is a monoclonal, fibroblastic proliferation arising in musculoaponeurotic structures. This connective tissue hyperplasia infiltrates locally, recurs frequently after resection but does not metastasize. Abdominal desmoid occurs sporadically, in association with some familial syndromes and often represents a clinical dilemma for surgeons. The enigmatic biology and anatomical location of abdominal desmoids make treatment recommendations difficult. This distinct pathological entity is reviewed with a specific focus on aetiology and management.

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“…Dacarbazine (DTIC)-doxorubicin (DOX) therapy (D-D therapy) is a hopeful therapeutic option against desmoid tumors, providing a high clinical response (8)(9)(10)(11)(12). DOX interferes with the function of topoisomerase II and DTIC is an N-methyl-type compound that produces alkylating species.…”

Section: Introductionmentioning

confidence: 99%

Low-dose dacarbazine-doxorubicin therapy against intra-abdominal desmoid tumors

et al. 2013

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Abstract. Intra-abdominal desmoid tumor is a lifethreatening disease. Studies have shown that dacarbazine (DTIC)-doxorubicin (DOX) (D-D) therapy is the most effective treatment. However, myelosuppression is a major problem, and cardiac muscle disorders due to DOX limit the number of administration cycles, whereas it usually requires a long time to achieve tumor shrinkage. To resolve these issues, we introduced low-dose D-D therapy to 3 patients employing 50 mg/m 2 DOX and 600-700 mg/m 2 DTIC per cycle, which permits repeated administration cycles up to 10-11 times. Case 1 was a 23-year-old female with a sporadic recurrent mesenterium desmoid tumor located in the pelvis (maximum diameter, 8 cm). Cases 2 and 3 were a 33-year-old female and a 36-year-old male. Both patients had intra-abdominal mesenterium desmoid tumors (maximum diameter 9.6 and 9.0 cm, respectively) that were generated after proctocolectomy due to familial adenomatous polyposis. No severe adverse events occurred during the therapy. With the aid of sulindac and tamoxifen after low-dose D-D therapy, the first two patients achieved a complete response, and the third patient achieved a partial response and awaits further tumor shrinkage. Our experience indicates that low-dose DT-D therapy is a safe and effective regimen for patients with intra-abdominal desmoid tumors.

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Successful Chemotherapeutic Modality of Doxorubicin Plus Dacarbazine for the Treatment of Desmoid Tumors in Association With Familial Adenomatous Polyposis

Cited by 170 publications

References 22 publications

Specific Mutations in the β-Catenin Gene (CTNNB1) Correlate with Local Recurrence in Sporadic Desmoid Tumors

Specific Mutations in the β-Catenin Gene (CTNNB1) Correlate with Local Recurrence in Sporadic Desmoid Tumors

Updates on abdominal desmoid tumors

Low-dose dacarbazine-doxorubicin therapy against intra-abdominal desmoid tumors

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