sulindac and Fibromatosis--Aggressive

Desmoid fibromatosis (desmoid tumor, DT) is a soft tissue neoplasm prone to recurrence despite complete surgical resection. Numerous small retrospective reports suggest that non-cytotoxic chemotherapy using tamoxifen and sulindac may be effective for DT. We evaluated the safety and efficacy of tamoxifen and sulindac in a prospective phase II study within the Children's Oncology Group.. Eligible patients were <19 years of age who had measurable DT that was recurrent or not amenable to surgery or radiation. The primary objective was to estimate progression-free survival (PFS). Patients received tamoxifen and sulindac daily for 12 months or until disease progression or intolerable toxicity occurred. Response was assessed by magnetic resonance imaging.. Fifty-nine eligible patients were enrolled from 2004 to 2009; 78% were 10-18 years old. Twenty-two (38%) were previously untreated; 15 (41%) of the remaining 37 enrolling with recurrent DT had prior systemic chemotherapy and six (16%) had prior radiation. No life-threatening toxicity was reported. Twelve (40%) of 30 females developed ovarian cysts, which were asymptomatic in 11 cases. Ten patients completed therapy without disease progression or discontinuing treatment. Responses included four partial and one complete (5/59, 8%). The estimated 2-year PFS and survival rates were 36% (95% confidence interval: 0.23-0.48) and 96%, respectively. All three deaths were due to progressive DT.. Tamoxifen and sulindac caused few serious side effects in children with DT, although ovarian cysts were common. However, the combination showed relatively little activity as measured by response and PFS rates.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Disease-Free Survival; Female; Fibromatosis, Aggressive; Humans; Male; Sulindac; Tamoxifen

Aim of this study is to evaluate the outcome of long-term conservative treatment with sulindac and high-dose selective estrogen receptor modulators (SERMs) for sporadic and FAP-associated desmoid tumors. Desmoids are very rare tumors in the general population but occur frequently in FAP patients, being encountered in 23-38 %. Treatment of desmoids is still most controversial since response cannot be predicted and they are prone to develop recurrence. This study included all desmoid patients that were treated and followed at our institution and had completed at least 1 year of treatment. Response was defined as stable size or regression of desmoid size between two CT or MRI scans. A total of 134 patients were included. 64 (47.8 %) patients had a confirmed diagnosis of FAP, 69 (51.5 %) patients were sporadic. Overall 114 (85.1 %) patients showed regressive or stable desmoid size. Patients with previous history of multiple desmoid-related surgeries showed less-favorable response. The mean time to reach at least stable size was 14.9 (±9.1) months. After regression or stabilization, medication was tapered in 69 (60.5 %) of the treated patients with only one long-term recurrence after >10 years. The results of this study fortify the role of sulindac and high-dose SERMs as an effective and safe treatment for both, sporadic and FAP-associated desmoid tumors. While invasive treatment frequently results in high recurrence rates, high morbidity and high mortality, this conservative treatment is successful in most patients. The recurrence rate is negligible with no desmoid-related mortality in this large series. Therefore surgical resection, especially for mesenteric desmoids, should be deferred favoring this convincingly effective, well tolerated regimen.

Topics: Abdominal Neoplasms; Adenomatous Polyposis Coli; Adult; Antineoplastic Combined Chemotherapy Protocols; Female; Fibromatosis, Aggressive; Humans; Male; Middle Aged; Selective Estrogen Receptor Modulators; Sulindac; Treatment Outcome

Intra-abdominal desmoid disease is one of the most common extra-intestinal manifestations of familial adenomatous polyposis. Small bowel obstruction occurs frequently in affected patients and is notoriously difficult to treat. The aim of this study was to review the management and outcome of desmoid-related small bowel obstruction.. This was a retrospective, descriptive study of patients with familial adenomatous polyposis and intra-abdominal desmoid disease who developed small bowel obstruction. Demographic data and data concerning the presentation, diagnosis and treatment of the bowel obstructions were abstracted from the polyposis database or patients' records. Patients with obstruction unrelated to desmoid disease were excluded.. There were 47 patients (30 women and 17 men). Median age at first bowel obstruction was 24.2 (interquartile range 19.2-34.2) years. The median time from index surgery to first bowel obstruction was 4.1 (interquartile range 1.5-9.0) years. Twenty-two patients had a colectomy and ileorectal anastomosis and 21 a proctocolectomy and ileoanal pouch. Obstruction was treated medically in 29% of cases and surgically in 69%. Thirteen patients had total parental nutrition. Thirty (63.8%) had a second episode of small bowel obstruction at a mean of 5.3 years after the first, 50% of which were treated medically. Eighteen (37.5%) patients had more than two episodes of bowel obstruction. There were 118 operations, including lysis of adhesions (29), small bowel resection (14), bypass (12), ileostomy (12), desmoid excision (9) and stricturoplasty (2).. Desmoid-related small bowel obstruction in familial adenomatous polyposis patients requires multiple surgical strategies to restore a patent gastrointestinal tract. WHAT DOES THIS PAPER ADD TO THE LITERATURE?: This is the only series in the literature specifically addressing small bowel obstruction in patients with familial adenomatous polyposis and intra-abdominal desmoid disease. The data show that small bowel obstruction is common, tends to recur, but can be successfully managed by a combination of medical and well selected surgical treatment.

Topics: Abdominal Neoplasms; Adenomatous Polyposis Coli; Adolescent; Adult; Antineoplastic Agents; Cohort Studies; Colectomy; Duodenal Obstruction; Female; Fibromatosis, Aggressive; Humans; Ileal Diseases; Ileostomy; Intestinal Obstruction; Jejunal Diseases; Male; Middle Aged; Parenteral Nutrition, Total; Proctocolectomy, Restorative; Recurrence; Retrospective Studies; Sulindac; Time Factors; Young Adult

Familial adenomatous polyposis (FAP) is a rare syndrome characterized by the presence of hundreds to thousands of colorectal adenomas and is responsible for less than 1% of all colorectal cancers. The syndrome is also characterized by extra-colorectal features including amongst others upper gastrointestinal tract polyps and desmoid tumors. The syndrome is inherited by an autosomal dominant gene, the adenomatous polyposis coli (APC) gene. We present the physical history, clinical presentation, diagnosis and treatment of a patient with a novel germline APC mutation, the W421X mutation, which resulted in FAP presenting with about a hundred colorectal polyps, gastric hyperplastic polyps and multiple aggressive intra-abdominal and extra-abdominal desmoid tumors.

Topics: Adenomatous Polyposis Coli; Adult; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Hormonal; Biopsy; Colonoscopy; Fatal Outcome; Female; Fibromatosis, Aggressive; Gastroscopy; Germ-Line Mutation; Humans; Laparotomy; Mutation; Sulindac; Tamoxifen

Topics: Abdominal Neoplasms; Adenomatous Polyposis Coli; Antineoplastic Agents; Fibromatosis, Aggressive; Humans; Sulindac; Tamoxifen; Treatment Outcome

Topics: Abdominal Neoplasms; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cohort Studies; Dose-Response Relationship, Drug; Female; Fibromatosis, Aggressive; Humans; Male; Maximum Tolerated Dose; Prognosis; Risk Assessment; Sulindac; Survival Analysis; Tamoxifen; Treatment Outcome

A 54-year-old man was evaluated for symptoms of bladder outlet obstruction. Evaluation revealed a 10 by 9.8-cm tumor composed of bland, fibroblastic, poorly cellular material adjacent to the prostate. Administration of a course of antiestrogen (tamoxifen) and a nonsteroidal anti-inflammatory agent (sulindac) resulted in prompt relief of symptoms and a slow decrease in the size of the tumor as measured by computed tomography. After 54 months of therapy, the tumor was undetectable clinically and dramatically reduced in size as seen on computed tomography. Data on the natural history of desmoid tumors and the efficacy of various therapeutic strategies are reviewed.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Estrogen Antagonists; Fibromatosis, Aggressive; Humans; Male; Middle Aged; Pelvic Neoplasms; Remission Induction; Sulindac; Tamoxifen

Desmoid tumors (DTs), the result of an abnormal proliferation of connective tissue, occur frequently in familial adenomatous polyposis. Treatment of DT is difficult because of the high rate of recurrence after operation. Recently, antiestrogens and nonsteroidal antiinflammatory drugs have been used with good results as inhibitors of DT cell proliferation.. In this report we performed in vitro studies on cultured desmoid cells and skin fibroblasts of four patients who underwent surgical resection of DT and normal skin biopsy. We evaluated the expression of estrogen receptors and the mitogenic effect of 17 beta-estradiol and sulindac, a nonsteroidal antiinflammatory compound, on cell proliferation and collagen synthesis of desmoid cells.. Proliferation and collagen synthesis of desmoid cells were stimulated by 17 beta-estradiol, and tamoxifen, an antiestrogenic compound, inhibited this effect. Desmoid cells also expressed estrogen receptors. Moreover, growth of desmoid cells from one of the patients was inhibited by sulindac.. The in vitro evaluation of drug responsiveness in patients operated on for DT could be used as both a prognostic tool in the natural history of DT and in addressing pharmacologic therapy in this disorder.

Topics: Adenomatous Polyposis Coli; Adolescent; Adult; Cell Division; Child; Collagen; Estradiol; Fibromatosis, Aggressive; Humans; Receptors, Estrogen; Sulindac; Tumor Cells, Cultured