Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

H2-Histamine receptor blocking agents metiamide and cimetidine were assessed in seven patients with Zollinger-Ellison syndrome (serum gastrin greater than 300 microgram/ml, basal acid output greater than 15 meq/h, ratio of basal acid output to maximal acid output greater than 0.5). Intravenous or oral administration of the drugs lowered acid secretion by at least 70% in all cases. Subsequent treatment of six patients for 3 to 15 months (oral therapy) and one patient for 1 month (intravenous therapy) showed that the drugs abolished symptoms in all seven, abolished diarrhea in five, allowed ulcer healing in six, and were well tolerated without adverse effects in seven. No patient failed to respond to the drug, although one died from tumor progression and two required total gastrectomy for complex reasons. The results indicate that patients with Zollinger-Ellison syndrome can be managed medically and, in light of current mortality trends, gain little from the extra risks attending total gastrectomy.
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PMID:H2-Histamine receptor blocking agents in the Zollinger-Ellison syndrome. Experience in seven cases and implications for long-term therapy. 2 4

The effect of local hyperthermia on the prostate using 13.56 MHz radio frequency wave (RF wave) was reported. Firstly, temperature and blood flow of the prostate in normal dogs were measured during local hyperthermia. In most part of the prostate, the temperature reached over 42 degrees C, which was considered as favorable for the hyperthermia therapy. Blood flow of the prostatic tissue rose more slowly than that of muscle tissue. Secondly, the tissue concentration of anticancer agents after local hyperthermia was measured. There was a tendency that drug concentration in the prostate tissue after local hyperthermia was higher than that without local hyperthermia. Histological findings showed interstitial edema and congestion. As a clinical trial, 14 cases of prostatic cancer were treated with local hyperthermia after the administration of anticancer agents. Seven of them were fresh cases and the others were relapsed cases. After treatment, tumor size was reduced in 13 cases. According to "The Response Criteria for Urologic Tumor", one Complete Response, 3 Partial Response and 10 No Change cases were obtained. There was no tumor progression. As for side effects, bone marrow suppression, loss of appetite, diarrhea and skin burns were noted. However, these side effects were mild, and did not interrupt the treatment. Local hyperthermia of the prostate after systemic chemotherapy could be carried out safely and effectively in patients with prostatic cancer.
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PMID:[Basic and clinical studies of local hyperthermia for prostatic cancer]. 137 54

MK-329 is a nonpeptidal, highly specific cholecystokinin (CCK) receptor antagonist, with affinity for pancreatic and gallbladder CCK receptors similar to CCK itself. MK-329 and its progenitor, asperlicin, can inhibit the growth of CCK receptor-positive human pancreatic cancer in athymic mice. Based on these activities and the ability of MK-329 to transiently increase food intake and enhance morphine analgesia in murine models, we conducted an open trial of MK-329 in 18 patients with advanced pancreatic cancer in whom the CCK receptor status of the tumors was unknown. Tumor response, pain control, and nutritional parameters (hunger rating, caloric intake, body weight, and anthropometrics) were serially assessed. The results of the study failed to demonstrate any impact of MK-329 on tumor progression, pain, or nutrition. Toxicity was mild and limited to nausea, vomiting, diarrhea, and abdominal cramps, with 17 of 18 patients able to tolerate treatment. While a role for MK-329 in the management of patients with advanced pancreatic cancer cannot be supported by the results of this trial, additional studies of this agent in patients with known CCK receptor-positive tumors, at escalated doses, and possibly in conjunction with other growth antagonists, appear warranted.
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PMID:A pilot clinical trial of the cholecystokinin receptor antagonist MK-329 in patients with advanced pancreatic cancer. 155 66

Sixty-eight unselected patients with progressive metastatic renal cell carcinoma (RCC) were treated between March 1985 and November 1988 with continuous infusion floxuridine (FUDR). Thirty-seven percent of these patients had previously received and failed systemic treatment. Using implantable pumps for automatic drug delivery, FUDR was continuously infused for 14 days at monthly intervals. The starting dose was 0.15 mg/kg/d (intravenous [IV]; n = 61) or 0.25 mg/kg/d (intraarterial [IA]; n = 7); IV doses were increased or decreased in increments of 0.025 mg/kg/d as permitted by toxicity. Diarrhea (with or without mild abdominal cramping) and nausea/vomiting limited the FUDR IV infusion, and hepatic function abnormalities limited FUDR IA infusion. The use of a circadian-modified infusion schedule permitted high FUDR doses to be safely given as compared with a constant rate infusion schedule. Of 63 patients assessable for response, 56 received systemic FUDR infusion. Four complete responses (CRs; 7.1%); and seven partial responses (PRs; 12.5%) were observed (objective response rate, CR plus PR, 19.6 +/- 5.1% [95% confidence limits] ). The median objective response duration was 10.8 months (range, 1 to 18 months; mean, 9.4 +/- 1.6). Four additional patients had minor tumor responses (MRs; 7.1%). In a subgroup of seven assessable patients receiving hepatic arterial FUDR, we observed one CR and three PRs (57.2 +/- 42.8%). Overall, objective response (CR plus PR) was seen in a quarter of assessable patients treated, 15 of 63, while only 15 of the 63 assessable patients (25.4%) have had objective tumor progression. The median follow-up time for all 68 patients was 28 months (range, 1 to 42), and their median survival duration is 15 months (range, 3 to 37 months). Continuous infusion FUDR is an effective outpatient treatment for progressive metastatic RCC, producing durable tumor response and causing little toxicity.
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PMID:Circadian-shaped infusions of floxuridine for progressive metastatic renal cell carcinoma. 214 18

We undertook a phase I trial using fixed-dose cisplatin, escalating doses of etoposide, and reinfusion of previously obtained autologous bone marrow in 29 relapsed or refractory small cell and non-small-cell lung cancer patients. Median age was 59 years (range of 38-68 years). Three patients had small-cell and 26 patients had non-small-cell lung cancer. Patients received i.v. cisplatin 200 mg/m2 over 5 days and i.v. etoposide 600 mg/m2/day for 3 days (total of 1,800 mg/m2) that was escalated to 800, 1,000, 1,200, 1,400, and 1,600 mg/m2/day for 3 days (total of 2,400-4,800 mg/m2). Cryopreserved autologous bone marrow was thawed and reinfused through a central venous catheter the second day after the completion of chemotherapy. Toxicities included nausea, vomiting, alopecia, high-tone hearing loss, mucositis, diarrhea, renal insufficiency, metabolic acidosis, and severe myelosuppression. The duration of neutropenia (less than 500 neutrophils/microliter) ranged from 5 to 22 days (median of 11 days) and the duration of severe thrombocytopenia (platelets of less than 20,000/microliters untransfused) ranged from 2 to 19 days (median of 9 days). Reversible renal insufficiency (peak serum creatinines of 6.7, 6.6, 4.3, and 3.5 mg/dl) occurred in four patients who completed the therapy. In three patients, death occurred within 4 weeks of chemotherapy and marrow reinfusion. Three complete and 12 partial remissions (range of 1+(-)22+ months, median of 3 months) were observed. No response was noted in eight patients and tumor progression within 1 month of transplant occurred in two patients. The maximally tolerated dose of etoposide was 1,400 mg/m2/day (total of 4,200 mg/m2), since two of three patients developed life-threatening diarrhea at the 1,600 mg/m2/day (total of 4,800 mg/m2) dose. The encouraging antitumor effects of this regimen suggest that this approach may be useful therapy for lung cancer and other tumors sensitive to VP-16 and cisplatin.
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PMID:Phase I trial of high-dose etoposide, high-dose cisplatin, and reinfusion of autologous bone marrow for lung cancer. 215 15

During a 21-month period, 48 dogs with spontaneous canine transmissible venereal tumor (clinical stage, T1-T3) were presented to the Veterinary Teaching Hospital, Ahmadu Bello University, Zaria, Nigeria, and were divided into one control and four treatment groups to test the efficacy of single-agent chemotherapeutic drugs. The dogs were not randomly assigned to groups because each chemotherapeutic agent was not continuously available during the test period. Group I consisted of four dogs that received oral cyclophosphamide (50 mg/M2 body surface area [BSA]) on the first four days for six weeks. No therapeutic response was noted in any of the four dogs. Group II consisted of ten dogs that received intravenous (IV) cyclophosphamide (50 mg/M2 BSA) for four consecutive days per week for six weeks. Two of the ten had a partial remission. Group III consisted of eight dogs that received oral methotrexate (2.5 mg/M2 BSA) every other day for six weeks. No therapeutic response was noted in any of the eight dogs. Group IV consisted of 20 dogs that were administered IV vincristine sulfate (0.5 mg/M2 BSA) weekly until a response was noted. Complete remission occurred in each of the 20 dogs. One dog had recurrence within 12 months. Group V was the untreated control group, consisting of six dogs among which no spontaneous remission was seen. Instead, tumor progression was noted. Adverse responses to medication, anorexia, vomiting, diarrhea, and weight loss were seen only with dogs treated with cyclophosphamide and methotrexate.
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PMID:Single-drug chemotherapy of canine transmissible venereal tumor with cyclophosphamide, methotrexate, or vincristine. 143 5

A somatostatin analog (SMS 201-995) was used to treat symptomatic patients with a residual tumor burden of gastrinoma or medullary thyroid carcinoma and pathologic elevations of circulating marker peptides associated with these neuroendocrine tumors. Possible inhibitory effects of the analog on marker peptides, patients' symptoms, or tumor progression were studied in a dose-response protocol and during several months of self-injection of SMS 201-995. Both patients reported remarkable relief of secretory diarrhea and other symptoms, and serum gastrin was successfully suppressed by increasing doses of the analog. However, no effect was seen in reduction of hypercalcitoninemia. Morphologic imaging of residual tumor showed no progression of medullary thyroid carcinoma during treatment and, in the case of hepatic gastrinoma metastases, remarkable tumor regression was confirmed. No toxicity or glucose intolerance was experienced. Somatostatin analog shows promise for palliative management of endocrinologic symptoms due to neuroendocrine tumors, and an inhibitory effect can be measured in some but not all peptide markers. Further evidence of its negative trophic effect on tumor blood flow may suggest an antineoplastic potential, as well as palliative use of this new treatment.
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PMID:Somatostatin analog: effects on hypergastrinemia and hypercalcitoninemia. 243 92

In a prospective study of 103 patients with carcinoid tumors consecutively referred for medical treatment, the most common sites of the primary tumors were the ileum (73%), bronchi (7%), and jejunum (4%). All patients had local metastases, and 96 (93%) also had liver metastases. The most common initial symptoms were diarrhea (32%), ileus (25%), and flush (23%). The overall frequency of diarrhea was 84% and of flush was 75%. Heart insufficiency caused by cardiac valve disease was seen in 33% of the patients. The carcinoid syndrome, including flush, diarrhea, and elevated urinary 5-hydroxyindole acetic acid (5-HIAA) concentrations, was manifested by 69 patients (67%), 64 of whom (93%) had carcinoid tumors of mid-gut origin. Elevated urinary 5-HIAA was found in 91 patients (88%), of which 89 displayed liver metastases. The plasma concentration of the tachykinin neuropeptide K (NPK) was elevated in 67 patients (66%), 63 of whom had tumors of the mid-gut region. Serum pancreatic polypeptide (PP) and human chorionic gonadotrophin alpha levels were elevated in 43% and 28% of the patients, respectively, and the highest levels were found in patients with metastatic bronchial carcinoid tumors. Thirty-nine of the 103 patients are now dead; 18 died of tumor progression, whereas 14 patients died of heart failure secondary to a carcinoid tricuspidal valve insufficiency. The estimated median survival from the time of histologic diagnosis was 14 years, and from the time of carcinoid syndrome was 8 years.
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PMID:Malignant carcinoid tumors. An analysis of 103 patients with regard to tumor localization, hormone production, and survival. 244 Mar 90

Seven patients with progressive ileal or caecal carcinoid tumors and liver metastases were treated with human recombinant alpha-interferon (IFN alfa-2b) at a dosage of 2-4 x 10(6) U daily or every other day subcutaneously. Six patients had symptoms of the carcinoid syndrome. No change of tumor size lasting 4 to 40+ months (median, 18 months) was noted in 6 patients, and 1 patient had hepatic tumor progression. A decrease in urinary excretion of 5-hydroxyindoleacetic acid by more than 50% lasting 2-11 months (median, 4) was observed in 5 patients. Four patients were completely or partially relieved of flushing, diarrhea, obstruction or abdominal pain. The side-effects were negligible with the exception of mild fever, headache and confusion only during the first days of therapy. Treatment with IFN alfa-2b offers good palliation to patients with disseminated ileal or caecal carcinoid tumor and carcinoid syndrome.
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PMID:[Treatment of metastasized carcinoid tumor of the ileum and cecum with recombinant alpha-2b interferon]. 245 Mar 26

We have followed 14 patients with the Zollinger-Ellison syndrome for a median period of 9 years. All patients have suffered from peptic ulcer disease and six of the 14 have had complications such as bleeding or perforated ulcer. Almost half the patients have had diarrhoea as a dominant symptom and 4 patients suffered from multiple endocrine neoplasia. Before 1978, the year when the H2-receptor antagonists were introduced, the majority of the patients were operated with total gastrectomy. After that year there has been no need for gastrectomies, but all but two patients have undergone an explorative laparotomy. We have been able to localize the gastrinoma in 9 of 12 operated patients; in 7 cases it was localized within the gastrinoma triangle. Three of the patients are considered to have been cured after surgery. Eight patients have needed adjuvant acid-reducing medical therapy. Five of these have been failures to high doses of H2-receptor antagonists and have been successfully treated with omeprazole. Five patients have died during the follow-up period and death in two of these cases was related to tumor progression.
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PMID:Long-term follow up of patients with Zollinger-Ellison syndrome (ZES). 257 21


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