Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This phase I study was designed to develop a high-dose combination of two cycles of mitoxantrone and cyclophosphamide in patients with solid tumors, as an alternative to single-cycle high-dose regimens that use only alkylating agents. Treatment was delivered with granulocyte colony-stimulating factor (G-CSF), but without stem cell support, in order to avoid potential tumor cell reinfusion. Thirty-one patients with advanced solid tumors received two cycles of high-dose mitoxantrone (20-30 mg/m2) plus high-dose cyclophosphamide (3000-4000 mg/m2). All patients received G-CSF until hematologic recovery. Dose-escalation was performed when less than 50% of cycles per level had dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) achieved was mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2. Main dose-limiting toxicities (DLTs) were hematological: grade IV neutropenia lasting more than 7 days and thrombopenia below 20 x 10(9)/l requiring more than one platelet transfusion. Non-hematological DLT consisted predominantly of grade III emesis and asthenia. Follow-up after each cycle was performed in an outpatient setting and there were no toxic deaths. In conclusion, the administration of two cycles of high-dose mitoxantrone and cyclophosphamide with G-CSF support is safe and feasible. MTD was mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2. Evaluation of this regimen is being done in a phase II trial.
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PMID:High-dose mitoxantrone and cyclophosphamide without stem cell support in high-risk and advanced solid tumors: a phase I trial. 1128 78

In a multi-institutional Phase II trial, we evaluated the efficacy of a platelet-derived growth factor receptor (PDGF-r) inhibitor, SU101, in patients with hormonerefractory prostate cancer. The patients received a 4-day i.v. loading dose of SU101 at 400 mg/m(2) for 4 consecutive days, followed by 10 weekly infusions at 400 mg/m(2). The primary study end points were a decline in prostate-specific antigen (PSA) and a decrease in measurable tumor. Secondary end points were time to progression and an effect on pain as measured by the Brief Pain Survey. Expression of PDGF-r was examined in both metastatic and archival primary prostate tumor samples. Forty-four patients were enrolled at four centers. The median age was 72 years, the median PSA was 223 ng/ml, and 21 patients had at least one prior chemotherapy. Thirty-nine patients are evaluable for PSA, and three patients demonstrated a PSA decline >50% from baseline (55-99.9% decrease). The median time to progression was 90 days. Of 19 patients evaluable for measurable disease, 1 patient had a partial response. Nine of 35 evaluable patients had significant improvement in pain. The most frequent adverse events were asthenia (75%), nausea (55%), anorexia (50%), and anemia (41%). PDGF-r expression was detected in 80% of the metastases and 88% of primary prostate cancers. The results of this trial may warrant further clinical studies with other PDGF-r inhibitors.
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PMID:A multi-institutional phase ii study of SU101, a platelet-derived growth factor receptor inhibitor, for patients with hormone-refractory prostate cancer. 1130 25

OBJECTIVE: The recent advances in psycho-neuro-endocrino-immunology have demonstrated the existence of several endogenous neuroendocrine substances, capable of affecting both tumor growth and host anticancer immune defenses. The pineal gland would represent one of the most important organs releasing antiproliferative and immunostimulating substances, the most known of them is melatonin (MLT). However, MLT would not be the only pineal indole provided by antitumor activity. Other pineal indoles, namely 5-methoxytryptamine (5-MTT), would play antitumor effects, by either inhibiting cancer cell proliferation or stimulating the anticancer immunity. Preliminary data have shown that MLT may deserve antitumor activity in the treatment of human neoplasms, whereas at present there are no clear data about 5-MTT. In an attempt to obtain some preliminary data about the anticancer properties of 5-MTT in humans, we have evaluated the efficacy of MLT plus 5-MTT in untreatable advanced cancer patients progressing on MLT alone. METHODS: The study included 73 untreatable advanced solid tumor patients, who had progressed after two months of MLT therapy alone. According to tumor histotype, patients were randomized to receive MLT alone (20 mg/day orally in the evening) or MLT plus 5-MTT (1 mg at noon orally), every day for at least two months. The clinical response was evaluated according to WHO criteria. RESULTS: A partial response (PR) occurred in two patients treated with MLT + 5-MTT and in none of the patients receiving MLT alone. A stable disease (SD) was achieved in only 2/37 patients on MLT therapy alone, and in 8/36 patients receiving MLT plus 5-MTT. Therefore, the percent of non-progressing patients (SD + PR) obtained with MLT plus 5-MTT was significantly higher than that obtained with MLT alone. Moreover, the relief of asthenia and depressant symptoms was significantly higher in patients concomitantly treated with 5-MTT. DISCUSSION: This preliminary study would suggest that the concomitant administration of the less known pineal indole 5-MTT, also provided by antiproliferative and immunomodulating effects, may further amplify the oncostatic activity of the pineal hormone MLT in the palliative and curative therapy of advanced untreatable human solid neoplasms.
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PMID:Oncostatic activity of pineal neuroendocrine treatment with the pineal indoles melatonin and 5-methoxytryptamine in untreatable metastatic cancer patients progressing on melatonin alone. 1145 67

Melatonin (MLT) is the main hormone released from the pineal gland and has proved to have physiological antitumor activity. MLT has been shown to exert anticancer activity through several biological mechanisms: antiproliferative action, stimulation of anticancer immunity, modulation of oncogene expression, and anti-inflammatory, anti-oxidant and anti-angiogenic effects. Several experimental studies have shown that MLT may inhibit cancer cell growth, and preliminary clinical studies seem to confirm its anticancer property in humans. In addition, MLT may have other biological effects, which could be useful in the palliative therapy of cancer, namely anticachectic, anti-asthenic and thrombopoietic activities. On this basis, the present clinical investigation was performed in an attempt at better definition of the therapeutic properties of MLT in human neoplasms. In a first clinical study, we evaluated the effects of MLT in a group of 1,440 patients with untreatable advanced solid tumors, who received supportive care alone or supportive care plus MLT. In a second study, we evaluated the influence of MLT on the efficacy and toxicity of chemotherapy in a group of 200 metastatic patients with chemotherapy-resistant tumor histotype, who were randomized to receive chemotherapy alone or chemotherapy plus MLT. In both studies, MLT was given orally at 20 mg/day during the dark period of the day. The frequency of cachexia, asthenia, thrombocytopenia and lymphocytopenia was significantly lower in patients treated with MLT than in those who received supportive care alone. Moreover, the percentage of patients with disease stabilization and the percentage 1-year survival were both significantly higher in patients concomitantly treated with MLT than in those treated with supportive care alone. The objective tumor response rate was significantly higher in patients treated with chemotherapy plus MLT than in those treated with chemotherapy alone. Moreover, MLT induced a significant decline in the frequency of chemotherapy-induced asthenia, thrombocytopenia, stomatitis, cardiotoxicity and neurotoxicity. These clinical results demonstrate that the pineal hormone MLT may be successfully administered in medical oncology in the supportive care of untreatable advanced cancer patients and for the prevention of chemotherapy-induced toxicity.
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PMID:Is there a role for melatonin in supportive care? 1186 1

Vascular tumors of the stomach represent 0.9%-3.3% of all gastric neoplasms. A 41-year-old man was admitted to our department with a 3-month history of early postprandial epigastric pain, sluggish digestion, nausea, asthenia, and occasional alimentary emesis. Preoperative staging detected a submucosal neoformation in the prepyloric zone, which narrowed the lumen, without any infiltrative features; a wedge gastric resection was performed and the definitive diagnosis was an epithelioid hemangioendothelioma of stomach. An 8-month follow up did not show any relapse of the disease. The term hemangioendothelioma is controversial because of disagreements regarding the nosologic setting and treatment. As a result, the latest WHO classification calls such neoplasms "borderline." The correct diagnosis depends on the histological findings supported by immunohistochemistry. Surgery represents the treatment of choice; however, a conservative approach is preferred whenever possible. However, due to the borderline biological behavior of this neoplasm, it is important that detailed clinical evaluations be carried out for such patients along with a thorough follow-up.
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PMID:Epithelioid hemangioendothelioma of the stomach: clinical-pathological features, nosologic setting, and surgical therapy. Report of a case. 1199 17

A 77-year-old woman was found accidentally to be in atrial fibrillation. Two-dimensional echocardiography revealed the presence of a mass attached to the anterior papillary muscle of the mitral valve. She was mildly symptomatic for dyspnea and asthenia. The patient was successfully operated on to excise the left ventricular mass and preserve the mitral valve apparatus. Morphological examination of the excised tissue led to a diagnosis of papillary fibroelastoma. Surgical treatment must be considered when such a tumor is diagnosed, even though asymptomatic, and especially if left-sided because of the high risk of systemic embolization.
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PMID:Case report: fibroelastoma of the papillary muscle of the mitral valve: diagnostic implications and review of the literature. 1200 Jan 74

The maximum tolerated dose of the multitargeted antifolate drug pemetrexed is 600 mg/m(2) every 3 weeks in heavily pretreated patients without folic acid supplementation. However, with folic acid supplementation, higher doses have been given without limiting side effects. The dose-limiting toxicities of pemetrexed are neutropenia, asthenia, and thrombocytopenia. Other adverse effects include anemia, anorexia, rash, nausea, vomiting, peripheral edema, diarrhea, mucositis, and reversible elevations of transaminase and creatinine levels. Multiple pemetrexed combination phase I trials have been completed or are underway. Without folic acid supplementation, pemetrexed doses of 400 to 600 mg/m(2)could be safely administered with full therapeutic doses of irinotecan, gemcitabine, cisplatin, carboplatin, oxaliplatin, and 5-fluorouracil. Preliminary data from other ongoing trials (with folic acid and vitamin B(12) supplementation) have similarly shown that pemetrexed doses of at least 400 to 500 mg/m(2) can be safely administered with therapeutic doses of vinorelbine, docetaxel, and paclitaxel. Combination studies of pemetrexed with agents active in breast cancer (doxorubicin, epirubicin, and cyclophosphamide) and chest radiotherapy are also now underway. Adverse effects of these combinations have included neutropenia, anemia, thrombocytopenia, asthenia, vomiting, diarrhea, rash, nausea, anorexia, mucositis, and reversible transaminase elevation. The phase I trials of pemetrexed have consistently shown activity against a broad range of tumor types, including colorectal cancer, pancreatic cancer, breast cancer, non-small cell lung cancer, and mesothelioma. This activity has been noted not only in the combination trials, but when pemetrexed is given as a single agent as well. Pemetrexed is a promising drug. It is active against a broad range of cancers, and it has manageable side effects that seem to be lessened with folic acid and vitamin B(12) supplementation.
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PMID:Phase I trials of pemetrexed. 1202 87

Pfeifer-Weber-Christian's panniculitis is a rare syndrome characterized by fever, arthralgias, fatigue and recurrent nodular panniculitis. It has been associated with pancreatic diseases, trauma, connective tissue diseases, alpha-1-antitrypsin deficiency, systemic lupus erythematosus, infections, lymphoproliferative diseases and neoplasias. We report the case of a 43-year-old obese male patient who presented with asthenia, arthralgias, intermittent fever, skin erythema and a large hard-elastic tumor of the right calf. Laboratory analysis revealed increased values of the immunophlogosis parameters and positivity for serum antinuclear antibodies. Surgical drainage of the abscess-like tumor mass, revealed leakage of a sterile, subflavious, oily and thick liquid; a skin biopsy showed intra and perivascular infiltration by neutrophils, diagnostic for leukocytoclastic vasculitis. Treatment with prednisone induced clinical improvement and normalization of the laboratory data. The clinical picture, laboratory data and efficacy of prednisone therapy confirmed that the patient developed Pfeifer-Weber-Christian's panniculitis in the clinical setting of an antinuclear antibody-positive leukocytoclastic vasculitis.
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PMID:Pfeifer-Weber-Christian's panniculitis in an obese patient with antinuclear antibody-positive leukocytoclastic vasculitis. 1215 46

SU5416 is a small molecule antiangiogenic agent that inhibits vascular endothelial growth factor (VEGF) stimulation of the KDR tyrosine kinase receptor. In this Phase I dose escalation trial, a weekly dose schedule of SU5416 was tested whereby an initial 5-day loading dose was followed by weekly maintenance infusions. The start dose was 20 mg/m(2) for the loading dose followed by 65 mg/m(2) for the weekly infusions. Dose escalations occurred at 33% until a final dose of 65 mg/m(2) (loading dose) and 190 mg/m(2) (weekly infusion) was obtained. Twenty-two patients were treated at five dose levels; tumor types included gastrointestinal (8), breast (3), lung (4), sarcoma (2), and other (5). The most common serious drug-related toxicity was headache, often associated with nausea and vomiting. Grade 1 and 2 toxicities included headache, nausea, vomiting, asthenia, pain at the infusion site, phlebitis, change in voice, and fevers. Of 19 evaluable patients, 4 obtained clinical benefit as defined by tumor regression (1) or disease stabilization for at least 12 weeks (3). Pharmacokinetic data revealed that the weekly infusion schedule prevented the reported 50-60% induction in SU5416 clearance observed with either daily or twice weekly dosing. Higher baseline levels of urine VEGF were observed in the 4 patients who gained clinical benefit, suggesting this may be a useful marker for predicting response to anti-VEGF therapies. Our results suggest that a weekly schedule of SU5416 shows signs of biological activity and is well tolerated at doses up to 145 mg/m(2).
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PMID:Results of a Phase I dose-escalating study of the antiangiogenic agent, SU5416, in patients with advanced malignancies. 1223 19

Complications of oral contraceptives (OCs) affecting the gastrointestinal tract, liver and pancreas are rare but potentially serious. Hepatobiliary complications are by far the most frequent and varied. Hepatic lesions will probably decline in frequency as low-dose OCs replace higher dosed pills. Intrahepatic cholestasis induced by OCs resembles that of pregnancy. There may be a genetic predisposition to both conditions involving a dose-dependent estrogen effect of decreasing bile secretion. Intrahepatic cholestasis appears within 6 cycles of OC use. Symptoms include pruritus with anorexia, asthenia, vomiting, and weight loss without fever, rash or abdominal pain. Termination of OCs clears the condition without sequelae within 1-3 months, sometimes after a temporary aggravation. A moderate and asymptomatic cytolysis may appear when OC treatment is begun. Sinusoidal dilatation has been conclusively linked to OCs although few cases have been published. Clinical manifestations other than hepatomegaly are variable. Abdominal pain and fever are the most common. The condition is not related to duration of use and disappears 5-15 days after OC use is terminated. The relative risk of Budd-Chiari syndrome in OC users is estimated at 2.37. OCs increase the prevalence of hepatic adenomas as a function of duration of treatment. They are usually discovered fortuitously but may be revealed by vague abdominal pains. Hemorrhagic complications are more likely in OC users. It may be difficult to distinguish between adenomas, hepatocellular carcinoma, and focal nodular hyperplasia. A puncture biopsy guided by sonography may aid diagnosis. The natural history of adenomas is poorly understood and treatment remains controversial. OCs do not appear to increase the risk of focal nodular hyperplasia but they increase the size of the tumor and the risk of hemorrhage. OCs should be terminated because of risk of hemorrhage. Surgical resection is not indicated unless there are complication or diagnostic doubts. While hepatocellular carcinoma is very rare, its risk is increased by a factor of 7-20 in women using OCs for 8 years or more. Use of combined OCs appears to speed development of lithiasis in predisposed women. Risk of lithiasis is linked to estrogen content in women under 30. Several cases of acute pancreatitis in the 1st 3 months of treatment have been reported in women with preexisting lipid metabolic anomalies. Cases of ischemic lesions of the small intestine or colon have been reported in OC users with A positive blood type. Such lesions can be fatal without early diagnosis and termination of OCs. Gastric esophageal reflux is increased by progestins. Preexisting constipation may be aggravated and the incidence of Crohn's disease increased by OCs. It is advisable to rule out preexisting hepatic pathology before prescribing OCs. OCs should be stopped in case of viral hepatitis.
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PMID:[Contraception and hepatogastroenterology]. 1231 76


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