Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 58-year-old male patient was admitted to the hospital complaining of weight loss. Abdominal computerized tomographic (CT) scan disclosed a mass shadow in the left kidney. From the results of further examination, including drip infusion pyelography (DIP) and angiography, he was preoperatively diagnosed as having a left renal tumor. Left radical nephrectomy was performed on March 15, 1990. The lesion was histologically diagnosed as renal cell carcinoma (clear cell subtype, grade 2) confined by the renal capsule (stage I). No distant metastases were detected. Interferon-alpha was administered every other day as adjuvant chemotherapy. After the patient experienced muscle pain in his thighs and shoulders after exercise on February 11, 1991, the serum creatine phosphokinase (CPK) level progressively increased up to 2,329 U/l. On the basis of the results of various examinations reflecting thyroid gland function, he was diagnosed as having primary hypothyroidism due to Hashimoto's disease. Thyroid function improved after administration of triiodothyronine and thyroxine. Interferon has been reported to influence thyroid function, and, in this case, interferon-alpha therapy may have induced the primary hypothyroidism associated with Hashimoto's disease.
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PMID:[Hypothyroidism followed by interferon-alpha as adjuvant therapy of renal cell carcinoma: a case report]. 148 77

This phase I study investigated flavone acetic acid (FAA) given as a 12-h intravenous infusion every 3 weeks in the absence of urinary alkalinisation. Cohorts of three patients were treated at doses of 7, 10 and 13 g/m2. One subject had colon cancer; 5, renal cancer; and 3, lung cancer. The Eastern Cooperative Oncology Group (ECOG) performance status was 0 in four patients, 1 in two subjects and 2 in three cases. The maximum tolerated dose was 13 g/m2. The dose-limiting toxicities were WHO grade 3 hypotension and grade 3 diarrhoea. Other toxicities included lethargy and dizziness, nausea, temperature fluctuation, myalgia and dry mouth, but no significant myelosuppression was encountered. One patient receiving 10 g/m2 for renal cancer showed a partial response that lasted for 3 months and included the resolution of pulmonary and cutaneous metastases. The pharmacokinetics showed large interpatient variability. At 12-16 h post-infusion, the plasma elimination profile entered a plateau phase, with frequent increases in concentration suggesting enterohepatic recycling. Neither peak FAA levels nor AUC values were dose-dependent at the doses studied. Peak plasma levels were 101-402 micrograms/ml and AUC (0-48 h) values were 75-470 mg ml-1 min. Plasma protein binding varied with total concentration. Two metabolites were detected in the plasma, and both also underwent apparent enterohepatic recycling. Repeat dosing resulted in decreases of up to 48% in peak levels and AUC values for FAA in three of six patients. Of the total FAA dose, 39%-77% was excreted in the urine as FAA or metabolites within 2 days. The dose recommended for further phase II studies is 10 g/m2.
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PMID:A phase I and pharmacokinetic study of 12-h infusion of flavone acetic acid. 155 Nov 73

Lonidamine revealed synergistic effects with anthracyclines and alkylating agents in experimental investigations. It differs from conventional cytostatics by acting on the cell energy metabolism and also lacks their typical side effects; therefore it may be valuable to be combined with established chemotherapeutic regimens. Because in unselected patients the results of randomized studies may be influenced by differences in type and combination of prognostic factors, we defined strict entry criteria: no previous systemic palliative treatment, disease-free interval less than or equal to 2 years, measurable visceral metastases, number of tumor sites less than or equal to 2, no brain or bone metastases, World Health Organization performance status less than or equal to 2, age less than or equal to 55. In an ongoing rate, remission duration, time to treatment failure, and survival time in patients treated with vindesin 3 mg/m2 plus epirubicin 100 mg/m2 plus cyclophosphamide 600 mg/m2 (day 1, intravenous, repeated every 3 weeks) +/- lonidamine 600 mg/day orally. Eight of 12 patients achieved an objective remission (complete response 4, partial response 4), 1 patients had a stable disease, 2 patients experienced tumor progression; 1 patient is not yet evaluable for response. In spite of the intensity of the therapy no treatment interval prolongation was necessary. Main toxicities were myelosuppression, nausea, emesis, alopecia, and in patients treated with lonidamine, mild myalgia. The addition of lonidamine to polychemotherapy did not affect myelosuppression. Differences in remission rates or remission duration due to lonidamine could not yet be demonstrated.
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PMID:Lonidamine in high-risk breast cancer patients. 203 Nov 99

We conducted a trial of a murine monoclonal antimelanoma antibody-ricin A chain immunotoxin (XOMAZYME-MEL) in 22 patients with metastatic malignant melanoma. The dose of immunotoxin administered ranged from 0.01 mg/kg daily for 5 days to 1 mg/kg daily for 4 days (total dose: 3.2 to 300 mg). Side effects observed in most patients were a transient fall in serum albumin with an associated fall in serum protein, weight gain, and fluid shifts resulting in edema. In addition, patients experienced mild to moderate malaise, fatigue, myalgia, decrease in appetite, and fevers. There was a transient decrease in voltage on electrocardiograms without clinical symptoms, change in serial echocardiograms or elevation of creatine phosphokinase MB isozyme levels. Symptoms consistent with mild allergic reactions were observed in three patients. The side effects were related to the dose of immunotoxin administered and were generally transient and reversible. Encouraging clinical results were observed, even after a single course of a low dose of immunotoxin. In addition, localization of antibody and A chain to sites of metastatic disease was demonstrated by immunoperoxidase staining of biopsy specimens. Additional studies are being conducted to continue the evaluation of safety and efficacy of immunotoxin therapy for malignancy.
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PMID:Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody-ricin A chain immunotoxin. 349 66

15 patients with metastatic cancer were treated with Lonidamine, a substituted indazole carboxylic acid active against the Lewis lung and Sarcoma 180 tumors. Single doses of 600 mg (350-400 mg/m2) mostly induced somnolence and gastro-intestinal side effects. Toxicity occurring during chronic administration of Lonidamine at doses ranging between 45 and 275 mg/m2 twice daily, mainly consisted of somnolence, myalgias, hyperesthesia and mild hair loss. Myalgias and hyperesthesias were markedly relieved with prednisone 5 mg twice daily. No laboratory abnormalities were seen. In 1 patient with breast cancer resistant to standard chemotherapeutic agents, a 30% reduction of measurable tumor masses was seen. In view of the lack of overlapping toxicity between Lonidamine and other chemotherapeutic drugs, and of its potential activity, it is suggested that phase II studies of Lonidamine be initiated at a dose of 135 mg/m2 twice daily.
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PMID:Phase I toxicologic study of Lonidamine in cancer patients. 671 96

12 patients with metastatic cancer were treated with the substituted indazole carboxylic acid Lonidamine at oral daily doses of 270 mg/m2. Toxicity, consisting mainly of myalgias, somnolence, hyperesthesia, anorexia and vomiting, generally decreased or disappeared over time despite continuing drug administration at unmodified dosage. Myalgias and hyperesthesias were markedly relieved with prednisone 5 mg twice daily. No laboratory abnormalities were seen. Partial responses were observed in a patient with hypernephroma and in a patient with breast cancer. Disease-oriented phase II studies with this new anticancer agent are warranted.
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PMID:Phase II study of Lonidamine in cancer patients. 671 98

In a phase II study of methyl-glyoxal bis-guanylhydrazone (methyl-GAG) in patients with bi-dimensionally measurable metastases of renal cell cancer, 30 patients were given 500 mg/m2 weekly for at least 4 treatment cycles and were evaluable for response. Three patients (10%) achieved partial remission (PR) with a duration of 8-12 weeks; in 11 patients the disease was assessed as stable; and in 16 there was progression. A total of 40 patients were evaluable for toxicity. Nausea and vomiting occurred in 17 (43%), neuropathy, myopathy or myalgia in 8 (21%) and mucositis in 6 (14%). In addition to 3 patients taken off treatment before 4 treatment cycles, toxicity precluded further treatment in 3 others after 5, 6 and 7 cycles respectively. Methyl-GAG has minimal activity in renal cell cancer and, in this dose schedule, causes appreciable toxicity.
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PMID:An EORTC phase II study of methyl-glyoxal bis-guanylhydrazone in advanced renal cell cancer. 720 Aug 96

An ongoing phase I and pharmacokinetic trial of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with carboplatin is evaluating the maximum tolerated dose (MTD) of a 3-hour paclitaxel infusion combined with fixed doses of carboplatin in previously treated and untreated patients with a variety of advanced cancers. A patient's previous treatment status determines the fixed carboplatin dose: target area under the concentration-time curves of 4.0 and 4.5 mg.min/mL in previously treated and untreated patients, respectively. Studies 1 and 2 entered previously treated patients to establish the paclitaxel MTD without and with cytokine support: study 1 established 135 mg/m2 paclitaxel as the MTD without such support. In study 2, granulocyte colony-stimulating factor is administered, and the MTD has not yet been reached with paclitaxel doses of 135 mg/m2 to 230 mg/m2 assessed thus far and 250 mg/m2 now being evaluated. Objective responses have been seen in three of five patients with squamous cell carcinoma of the head and neck and in patients with non-small cell lung cancer and metastatic cancer of unknown primary site as well. Myelosuppression has been the dose-limiting toxicity, although significant nausea and vomiting and myalgia have been documented occasionally. Paclitaxel apparently has nonlinear pharmacokinetics with a beta half-life of 6.7 hours (SD +/- 1.3 hours). Future trials of paclitaxel/carboplatin will address the management of squamous cell carcinoma of the head and neck and non-small cell carcinoma of the lung.
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PMID:Phase I study of paclitaxel and carboplatin: implications for trials in head and neck cancer. 748 55

Our phase II study results demonstrating high efficacy and low toxicity for a weekly schedule of high-dose, 24-hour infusional 5-fluorouracil(5-FU)/folinic acid (HD5-FU/FA) in intensively pretreated patients with metastatic breast cancer prompted addition of paclitaxel (Taxol) to the regimen, for a phase I/II study of outpatient second-line treatment of metastatic breast cancer. That study further prompted the addition of cisplatin (Platinol) to the regimen for first-line treatment. So far, 28 patients with metastatic breast cancer have been evaluated. Pretreatment comprised adjuvant chemotherapy in 24 of 28 patients, but no prior chemotherapy for metastatic disease. Patients were treated with HD5-FU 2 g/m2 (24-hour infusion) plus FA 500 mg/m2 (2-hour infusion prior to FU) weekly for 6 weeks (days 1, 8, 15, 22, 29, and 36); in addition, paclitaxel 175 mg/m2 (3-hour infusion) was administered on days 0 and 21 and cisplatin 50 mg/m2 (1-hour infusion) on days 1 and 22 prior to HD5-FU/FA, repeated every 50 days. Patients were treated as outpatients using Port-a-Cath systems and portable pumps. Neutropenia was common (67% World Health Organization grade 3) but mild to moderate in most patients and was of short duration. No hospitalizations were required because of febrile neutropenia, and no granulocyte colony-stimulating factor support was used. Aside from common total alopecia, nonhematologic toxicities consisted mainly of moderate myalgia, diarrhea, mucositis, and nausea and vomiting. Hand-foot syndrome and peripheral neuropathy were cumulative and occurred most commonly during the third treatment cycle, with mild-to-moderate expression. In 28 patients with bidimensionally measurable disease, 25% (7/28) attained a complete response, 57% (16/28) achieved partial response, 11% (3/28) had stable disease, and 7% (2/28) had disease progression. Overall response was 82% (95% confidence interval, 66% to 100%). Eight of 28 patients are still receiving treatment. It is concluded that the combination of paclitaxel/cisplatin with weekly HD5-FU/FA appears to be effective in the first-line treatment of metastatic breast cancer. Preliminary results must be confirmed by the final analysis of response duration, time to progression, and survival.
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PMID:Infusional 5-FU, folinic acid, paclitaxel, and cisplatin for metastatic breast cancer. 914 90

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), the first taxane used in routine clinical practice, has aroused considerable interest for its high single-agent activity against breast cancer and for its novel mechanism of action. Epirubicin, the 4' epimer of doxorubicin, is another agent with a high activity against breast cancer and is known for its lower rate of toxic side effects, especially toxic cardiac events, compared with its mother compound. The combination of paclitaxel and doxorubicin yielded response rates between 63% and 93% in phase I/II studies. In these studies, however, the investigators reported severe cardiac toxic events. The rationale for the current study was therefore to evaluate the combination of paclitaxel/epirubicin, focusing mainly on cardiac toxicity. In two groups, 85 patients with metastatic breast cancer entered the study. Approximately 20% of the patients had primary metastatic breast cancer with large tumors at the primary site. Half of the patients had received adjuvant chemotherapy. Study medication in group A consisted of epirubicin 60 mg/m2 given intravenously over 1 hour, followed by paclitaxel 175 mg/m2 administered as a 3-hour intravenous infusion after premedication with steroids, antihistamines, and H2-blockers. In group B, epirubicin 90 mg/m2 was combined with paclitaxel 175 mg/m2, given in the same manner as in group A. Dose escalation to 225 mg/m2 paclitaxel was planned in both groups. The main toxicity in both groups was neutropenia (73% World Health Organization grade 3/4 in group A and 93% in group B). Other hematologic side effects were rare. No febrile neutropenia was reported in group A, but two episodes occurred in group B. Peripheral neuropathy, arthralgia, and myalgia were mild (only World Health Organization grades 1 and 2). Alopecia was universal. In group A, the paclitaxel dose could be escalated to 200 mg/m2 in 15 patients and to 225 mg/m2 in seven patients. Dose reduction due to severe neutropenia was necessary in 11 patients. No cardiac events were reported in group A. In group B, the paclitaxel dose could be escalated to 200 mg/m2 in only one patient, and no patient reached 225 mg/m2. Three patients needed a dose reduction. In this group, one patient had a greater than 10% decrease in the left ventricular ejection fraction with no clinical signs. In group A, 43 patients were evaluable for response; in group B, 25 patients were evaluable. Thirteen patients were out of protocol with only bone metastasis, and two patients had more than one prior chemotherapy for metastatic disease. The response rate was identical in both groups, with five complete remissions and 24 partial remissions in group A and three complete responses and 14 partial remissions in group B. The duration of response was 8.2 months in both groups. The median cumulative epirubicin dose was 420 mg/m2 in group A and 630 mg/m2 in group B. The combination of paclitaxel 175 mg/m2 and epirubicin 60 or 90 mg/m2 can be administered safely to patients with metastatic breast cancer. Although response was not the primary end point of this trial, the response data are nonetheless encouraging and suggest that further evaluation of this combination-line treatment of metastatic breast cancer is warranted.
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PMID:Phase II study of paclitaxel and epirubicin as first-line therapy in patients with metastatic breast cancer. 937 90


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