Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We conducted a multicenter Phase II study of BMS-181339 in patients with ovarian cancer. The facilities participating were 23 in number. The total number of cases registered for the study were 62; 57 of them entered for evaluation in drug efficacy, and 58 cases were evaluable in drug safety. All the cases were previously treated with chemotherapy including platinum-based drugs. The clinical responses of BMS-181339 were as follows: CR, 1 case; PR, 13 cases; MR, 3 cases; NC, 13 cases and PD, 27 cases. The response rate was 24.6% (95% CI: 14.1-37.8%). Histologically, the drug showed its efficacy on serous adenocarcinoma 28.2% (11/39), mucinous adenocarcinoma 20.0% (1/5) and clear cell adenocarcinoma 20.0% (1/5). In regional evaluation, the drug demonstrated its efficacy not only on endopelvic lesions 19.0% (4/21) and abdominal lesions 14.3% (2/14), but also on remote metastatic lesions such as hepatic metastasis 30.8% (4/13) and lung/pleura 33.3% (2/6). The drug also showed its efficacy on the cases 22.9% (8/35) refractory to the platinum-based drugs. Major adverse reactions were fever 63.8% (37/58), alopecia 59.3% (32/54), peripheral nerve disorders 28.1% (16/57) such as numbness of the extremities, nausea/vomiting 24.1% (14/58), arthralgia 20.7% (12/58) and diarrhea 20.7% (12/58) etc.. Abnormal alterations in laboratory test values were an incidence rates of 100% for both leukopenia and neutropenia. However, these symptoms were clinically manageable by transient withdrawal of medication, dose reduction and administration of antibiotics and G-CSF. In addition, decrease in hemoglobin 93.1% (54/58), decrease in platelet counts 31.0% (18/58), elevation in GOT 27.6% (16/58), in GPT 31.0% (18/58) and in LDH 20.7% (12/58) were seen, but no serious organopathy was observed. Thus, we confirmed that BMS-181339 was a clinically useful chemotherapeutic agent in patients with ovarian cancer.
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PMID:[A phase II study of BMS-181339 in patients with ovarian cancer. BMS-181339 Ovarian Cancer Study Group]. 794 92

Patients given preoperative radiotherapy (31.5 Gy in 18 fractions) in a prospective, randomized trial of presumably operable rectal adenocarcinoma, were examined for a possible relation between bowel toxicity manifested as diarrhoea, and tumour size in the operative specimen, in addition to recurrence rate. The group requiring drugs for diarrhoea had significantly smaller tumours at surgery (2.5 cm versus 3.5 cm, p < 0.05). Patients without significant radiation-induced diarrhoea had also more recurrences (37.5% against 14.3%, p = 0.01). The disease-specific survival rate was also significantly better (p = 0.02) at 1.5 and 10 years in patients with diarrhoea WHO grade 3 and 4; 89.5%, 75.9% and 65.1% compared to 83.5%, 49.3% and 44.4% in patients with no or minimal radiation-induced loose bowels. These results indicate that the reaction of the normal bowel to radiation may correlate to radiation sensitivity of tumours derived from the same tissue.
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PMID:Do acute side-effects during radiotherapy predict tumour response in rectal carcinoma? 801 74

The therapeutic efficacy and toxicity of sequential methotrexate and 5-fluorouracil in 64 inoperable gastric cancer patients are reported. An intermediate-dose treatment was given to 48 patients, and a low-dose treatment to 16 patients. In the intermediate-dose treatment, leukopenia was observed in 11 patients, nausea and vomiting in six patients and diarrhea and stomatitis in two patients each. In the low-dose treatment, no patient developed toxic symptoms of grade 3 or 4. All 9 responders had adenocarcinoma of the poorly differentiated type and the response rate in patients who belonged to this type was 32.1%.
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PMID:Therapeutic efficacy and toxicity of sequential methotrexate and 5-fluorouracil in gastric cancer. 806 96

Between February 1984 and July 1992, six adults with advanced pancreatic adenocarcinoma (n = 1), pancreatic neuroendocrine tumor (n = 2), and cholangiocarcinoma (n = 3) underwent radical foregut resections (n = 3) or radical pancreaticoduodenectomy (n = 3) combined with liver transplantation. The major postoperative complications included diarrhea (n = 4), pancreaticojejunostomy leak (n = 3), infection (n = 7), malnutrition (n = 3), refractory ascites (n = 2), and late hepatic artery thrombosis (n = 1). Tumor recurrence occurred in one patient. The actuarial survival for the group is 82 per cent at 1 year and 55 per cent at 2 years. The results demonstrate that radical pancreaticoduodenectomy/foregut resections combined with liver transplantation offer potential surgical cure of malignancies involving these organs. However, the procedure is formidable, with frequent complications.
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PMID:Radical resection combined with liver transplantation for foregut tumors. 825 33

Seventy metastatic breast adenocarcinoma patients, pretreated with standard hormonotherapy or chemotherapy, received continuous UFT at 10 mg/kg/day, orally, for at least two months. There were one complete response (1.5%), 12 partial responses (17%), one minor response and 37 disease stabilizations. The median duration of response was nine months. A greater efficacy was demonstrated in 29 patients with soft tissue disease, with a rate of 38% objective responses. The major toxicity was gastrointestinal, with 45% of patients developing nausea and vomiting and 30%, diarrhea. Bone marrow toxicity was slight. UFT has shown antitumor activity in our group of pretreated patients, especially these with the cutaneous tumoral and/or inflammatory form of the disease.
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PMID:Phase II trial of UFT activity in pretreated breast cancer patients. 828 90

We report two young men with clinical and laboratory evidence of macroscopic ulcerative colitis, sclerosing cholangitis, and insulin-dependent diabetes mellitus. The first patient presented at age 15 with vomiting, abdominal pain, weight loss, and abnormal liver function test results. Liver biopsy and endoscopic retrograde cholangiopancreatography (ERCP) demonstrated sclerosing cholangitis. Colonoscopy with biopsy revealed ulcerative colitis which responded to sulfasalazine. Diabetes occurred at age 18 and insulin therapy was begun. The second patient was 19 at presentation with diarrhea, hematochezia, and weight loss. Proctosigmoidoscopy revealed ulcerative colitis, and sulfasalazine led to clinical remission. Three months later he developed diabetes requiring insulin therapy. At age 28, he developed elevated alkaline phosphatase, and ERCP revealed sclerosing cholangitis. At age 37 he expired from adenocarcinoma that metastasized to the liver. Literature review revealed only one possible case report of this association with microscopic asymptomatic ulcerative colitis in that patient. Statistical analysis suggests that this association is real rather than a chance occurrence. An autoimmune process may be involved and a specific histocompatibility locus antigen (HLA) type may exert a regulatory influence.
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PMID:Associated ulcerative colitis, sclerosing cholangitis, and insulin-dependent diabetes mellitus. 828 9

For the treatment of pancreatic head cancer, pancreatoduodenectomy is followed by the intraoperative radiation therapy (IORT). The present dose adopted ranged 20 to 30 Gy, however the dose is believed to be insufficient for local control of adenocarcinoma cells. In this study, high dose IORT was performed using rabbit, so histological and nutritional changes were evaluated. Rabbits were divided in three groups; 30 Gy, 50 Gy, 80 Gy. The radiation was performed with electrons focusing base of cranial mesenteric artery (SMA in human). The rabbits were sacrificed at intervals ranging from immediately after to 4 weeks following irradiation. The earliest evidence of histological changes was the loss of endothel, although it was repaired within 1 week. Fragmentation and reduplication of internal elastic lamina were observed after 1 week, however the degree was not dose dependent. Damages of the media was observed in 50 and 80 Gy groups. That is, focal degeneration of smooth muscle cell was demonstrated in 50 Gy group and medial necrosis in 80 Gy group. Degeneration of ganglion cells was observed and its severity was dose dependent. In 80 Gy group, diarrhea occurred more frequently compared with the other groups and body weight loss couldn't recover within 4 weeks. It is concluded that, since necrosis of aortic media and marked degeneration of ganglion cells are inevitable in 80 Gy group, IORT dose should be increased within 50 Gy.
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PMID:[Experimental study on intraoperative irradiation for pancreatic cancer: histological and nutritional changes in early phase after high dose irradiation]. 833 23

In a phase I study, 21 patients with metastatic adenocarcinoma of the gastrointestinal tract received the murine monoclonal antibody D612. This antibody is directed at a M(r) 48,000 antigen restrictively expressed on tumors of the gastrointestinal tract and to a limited degree on normal gastrointestinal mucosa. Patients received total doses of 10-180 mg/m2 administered as single or multiple doses of 1-100 mg/m2 over an 8-day period. Dose-limiting toxicity was secretory diarrhea. A single dose of 100 mg/m2 exceeded guidelines for maximal tolerated dose. Higher total doses were achieved in subsequent patients by using repeated administration of lower doses. Three of five patients receiving 60 mg/m2 for 3 doses (180 mg/m2 total dose) experienced grade 3 diarrhea and could not complete the prescribed course. The dose of 40 mg/m2 administered on days 1, 4, and 8 (total dose, 120 mg/m2) has been selected as the dose for phase II studies. The pharmacokinetics of D612 is best described by a one-compartment model with a mean t1/2 of 48 +/- 3 h (SEM). Eighteen of 21 patients developed human anti-mouse antibody (HAMA). Patients who developed high levels of HAMA demonstrated a more rapid clearance of the day 8 dose than those who developed low levels of HAMA. In all patients studied, a component of HAMA was directed at the D612 variable region. With one exception, serum from all patients with detectable antibody to the D612 variable region demonstrated anti-paratope reactivity. Thirty-four % of known metastatic sites demonstrated uptake of radiolabeled D612. There were no objective antitumor responses in this phase I trial. The antitumor effect of D612 in vitro has been shown to be potentiated by interleukin 2 and recombinant human macrophage colony-stimulating factor. A phase II study of D612 administered in combination with cytokines that enhance human effector function is presently ongoing.
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PMID:A phase I clinical trial of murine monoclonal antibody D612 in patients with metastatic gastrointestinal cancer. 840 27

21 patients with squamous oesophageal carcinoma were treated with a new regimen designed in our unit and effective in treating gastric adenocarcinoma, consisting of continuous venous infusion of 5-fluorouracil for up to 24 weeks (200 mg/m2/day) with epirubicin (50 mg/m2) and cisplatin (60 mg/m2) every 3 weeks. 12 patients (57%) had an objective response. The median relapse free period was 7 months, median survival from start of chemotherapy 8.4 months, and median survival from diagnosis, 14 months. Symptomatic improvements were reported by 10/11 patients with pain (91%), 8/9 with anorexia (89%), 8/10 with reflux (80%) and 10/14 with dysphagia (71%). Grade 3 or 4 toxicity was reported by 11 patients: 5 had haematological toxicity, 3 vomiting, 2 infection and 1 diarrhoea. One patient developed peripheral neuropathy, 1 renal impairment and another peripheral vascular disease. Following chemotherapy, surgery was attempted in 5 patients. One remains well 3 years on, 2 had macroscopic clearance of tumour but died of postoperative complications. In 2, disease was irresectable. This regimen of moderate toxicity is effective at improving symptoms in the majority of patients. In some patients, tumours are briefly downstaged so that inoperable tumours may become operable.
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PMID:Squamous oesophageal cancer can be downstaged using protracted venous infusion of 5-fluorouracil with epirubicin and cisplatin (ECF). 865 44

Amsacrine is an antineoplastic drug used in the treatment of acute adult leukemias. To assess its carcinogenic potential, groups of 50 male and 50 female rats were administered amsacrine by lateral tail vein injection at 0 (vehicle control), 0.25, 1, or 3 mg/kg once daily for 5 days, followed by a 23-day recovery period. This cycle of dosing and recovery was repeated a total of six times. The animals were then maintained without dosing for an 18-month observation period. During the dosing phase, signs of toxicity were limited to the 3 mg/kg animals and included alopecia, diarrhea, injection site lesions, and skin and subcutaneous nodules. Statistically significant reductions in body weight gain and food consumption also occurred at 3 mg/kg during each 5-day dosing period followed by recovery during the latter 3 weeks of each cycle. Except for skin and subcutaneous nodules, signs of toxicity in the 3 mg/kg animals ultimately disappeared during the 18-month observation phase. Survival at study termination for the vehicle control, 0.25, 1, and 3 mg/kg groups was 56, 52, 34, and 0%, respectively, in males, and 64, 48, 54, and 4%, respectively, in females. Mortality was primarily due to bone marrow suppression during the dosing phase, chronic progressive nephropathy, or development of tumors. Incidences of the following tumors were significantly increased in the 3 mg/kg groups of both sexes (Fisher exact test, two-tailed, p < 0.01): all malignancies; all tumors of the small intestine, adenocarcinoma and adenoma of the small intestine, all tumors of the skin, and squamous cell papilloma. Other tumor incidences that were significantly increased in the 3 mg/kg males were thymoma and multiple neoplastic histotypes of the skin and adnexa including basal cell tumor, fibroma, sebaceous gland adenoma, and squamous cell carcinoma. A disproportionate number of the skin tumors were located on the tail, suggesting a localized tissue concentration effect. In the 3 mg/kg females, significantly increased tumor incidences also included all tumors of the mammary gland, adenocarcinoma of the mammary gland, all tumors of the uterine horn, and endometrial stromal polyps of the uterine horn. The 1 mg/kg males had significantly increased incidences of all tumors of the small intestine and skin, adenocarcinoma of the small intestine, and fibroma of the skin. Fibroma of the skin was also significantly increased in the 0.25 mg/kg males. Incidences of all tumors and all benign tumors were significantly increased in the 1 mg/kg females. There were no significantly increased tumor incidences in the 0.25 mg/kg females. The results of this study show that amsacrine is carcinogenic in Wistar rats. Target organs for tumorigenicity include small intestine, skin, mammary gland, thymus, and uterus.
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PMID:Carcinogenicity of the anticancer topoisomerase inhibitor, amsacrine, in Wistar rats. 881 22


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