Makoto Gega

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

PURPOSE Desmoid tumors are locally aggressive and can be fatal in familial adenomatous polyposis (FAP) patients if they are not suitable for surgery or radiation therapy. Here, we prospectively investigated the efficacy of a chemotherapeutic regimen involving doxorubicin (DOX) and dacarbazine (DTIC) for inoperable FAP-associated desmoid tumors. PATIENTS AND METHODS From an initial group of 120 FAP patients, seven of the 11 individuals with symptomatic unresectable desmoid tumors that were unresponsive to conventional hormone therapy were enrolled onto this study. The general chemotherapy regimen comprised four or five cycles of DOX (20 mg/m2 daily) plus DTIC (150 mg/m2 daily) throughout 4 days of drip intravenous infusion (day 1 through 4) every 28 days, followed by the cyclooxygenase-2 inhibitor meloxicam (10 mg/m2). The primary end point was relapse-free survival. The secondary end points included toxicity, clinical improvement, and tumor regression according to computed tomography. RESULTS Significant tumor regression was observed clinically and radiologically in all seven patients. Three patients showed a complete response. The average progression-free survival period was 74.0 months (range, 32.5 to 107.5 months). Three patients showed grade 3 adverse events with no treatment-related mortality. All seven patients survived and remained without tumor progression. An adenomatous polyposis coli germline-mutation analysis revealed no mutations in the specified regions. CONCLUSION A chemotherapeutic regimen of DOX plus DTIC followed by meloxicam is an effective and safe treatment for FAP-associated desmoid tumors. This modality should be considered for use as first-line chemotherapy in symptomatic desmoid tumors that are unresponsive to conventional medical therapy, due to the absence of useful presymptomatic markers.

Regression of sporadic intra-abdominal desmoid tumour following administration of non-steroidal anti-inflammatory drug.

BackgroundDesmoid tumours or fibromatoses are rare entities characterized by the benign proliferation of fibroblasts, which can be life-threatening due to their locally aggressive properties. Surgery is widely accepted as the first line of treatment for extra-abdominal desmoids; however, it is not recommended for intra-abdominal desmoids because of the high-risk of recurrence and difficulties with the operation. Here, we report on a patient with sporadic intra-abdominal desmoid tumours, who showed partial response following the intake of non-steroidal anti-inflammatory drugs.Case presentationA 73-year-old man presented with swelling and pain of the right leg. Computed tomography showed an abnormal multilocular soft-tissue mass (95 × 70 mm) in the right pelvis, which was revealed by biopsy to be a desmoid tumour. Immunohistochemical analysis showed that the tumour cells expressed vimentin, but not smooth-muscle actin, CD34, or desmin. Very few Ki-67-positive cells were found. Non-cytotoxic treatment with etodolac (200 mg/day) was chosen because of the patients age, lack of bowel obstruction, and the likelihood of prostate cancer. Two years after the commencement of non-steroidal anti-inflammatory drug administration, computed tomography showed a decrease in tumour size (63 × 49 mm), and the disappearance of intratumoural septa.ConclusionOur case report suggests that non-steroidal anti-inflammatory drug treatment should be taken into consideration for use as first-line treatment in patients with sporadic intra-abdominal desmoid tumours.

Postoperative enteroenteric intussusception in patients with Crohn’s disease: Report of two cases

Postoperative enteroenteric intussusception is a rare complication in adult patients with Crohn’s disease. We treated two patients with Crohn’s disease accompanied by an ileal obstruction, each of whom underwent an elective resection. In both, the upper left quadrant of the abdoment became progressively distended following ileocecal resection and each required surgical treatment after diagnosis of postoperative enteroenteric intussusception by abdominal computed tomography scanning, as the intussusception could not be reduced by conservative treatment. There were no Crohn’s lesions found in the intussuscepted specimens, and the condition was thought to have been caused by a segment of thickened and fibrotic intestine that had developed because of long-standing bowel dilatation from obstructive Crohn’s lesions. In one of the patients, the intussusceptum was irreducibly incarcerated and required a resection, whereas it was able to be manually reduced in the other.

Effect of setting of drug holidays on the efficacy of weekly higher shorter plus lower continuous (metronomic) five-fluorouracil (5-FU) concentration regimen in colorectal cancer

13542 Background: Since the advent of various novel (molecular target) agents, it has been inevitable to reassure the dose regimen of 5-FU, a key drug in CRC. Recently, we have achieved good clinical benefits and cost-effectiveness in the treatment of CRC using ‘Pharmacokinetic Modulating Chemotherapy (PMC)’, which was designed as a hybrid of lower continuous (metronomic) and higher shorter plasma 5-FU concentration (Cancer 89: 1228, 2000, Cancer Res 61:1029, 2001, Proc ASCO 22: 1175, 2003). To establish a safer and more efficacious dose and scheduling of 5-FU administration from the perspective of cell cycle regulation, we investigated their anti-tumor efficiency by dose-enhancement and drug holidays, and the adverse events. Methods: First, weekly PMC regimens with or without dose-intensification and drug holidays were designed according to the mathematical model, and, then, experimented on the cell growth in vitro. Secondly, we assessed the clinical effects of the PMC regimens between “Tsunami 7” withou...

A novel distant metastasis-related marker in colorectal cancer

9684 Background: Distant metastasis is one of the major problems in treatment for advanced colorectal cancer. There is growing evidence that Polysaccharide-K (PSK), or Krestin (Sankyo Co., Tokyo, J...

Doxorubicin plus dacarbazine for the treatment of desmoid tumors in association with familial adenomatous polyposis (FAP)

3609 Background: Desmoid tumors are locally aggressive tumors and sometimes fatal for FAP patients with the tumors that are not amenable to surgery or radiation therapy. We investigated the efficac...