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)

Based on laboratory studies showing enhanced cytotoxicity of floxuridine (FUDR) when used with high doses of leucovorin (LV), a pilot study of FUDR and LV through an implantable pump was initiated for the treatment of hepatic metastases from colorectal cancer. The highest dose of LV that could be administered, taking into account the constraints of the capacity of the pump and the solubility of LV, was 120 mg/m2/d. Due to the possibility of added toxicity, 25% of this dose was initially used. Twenty-four patients were treated at three dose levels. Eight patients were treated with the combination of LV (30 mg/m2/d) and FUDR (0.3 mg/kg/d) for a 14-day infusion through the pump, alternating with 2 weeks of saline. All eight patients had a greater than 50% decrease in measurable disease (PR) and a greater than 50% decrease in carcinoembryonic antigen (CEA) value; however, sclerosing cholangitis developed in two of these patients within 4 months. The next seven patients were treated with a lower dose of FUDR (0.2 mg/kg/d) and the same dose of LV, both for 14 days. Four of seven patients had a PR, and toxicity was decreased with no biliary sclerosis. A third regimen explored the combination of FUDR (0.3 mg/kg/d) and LV (30 mg/m2/d) for 7 days, alternating with 1 week of saline, to evaluate a shorter interval of treatment with the same overall dose intensity. Six of nine patients had a PR and all patients had a greater than 50% decrease in CEA value; sclerosing cholangitis developed in three of these patients. The overall response rate was 72%, with 18 of 25 patients alive after 1 year. The median survival time has not been determined, but it is greater than 27 months. FUDR with LV appeared to be effective in the treatment of hepatic metastases from colorectal carcinoma, but hepatic toxicity appeared to be greater than that previously reported with FUDR alone.
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PMID:Continuous intrahepatic infusion of floxuridine and leucovorin through an implantable pump for the treatment of hepatic metastases from colorectal carcinoma. 214 70

Medulloblastoma, pineoblastoma, and cerebral neuroblastoma are malignant embryonal tumors of the CNS that may demonstrate similar histologic features, a propensity for neuraxis dissemination and sensitivity to radiation therapy and, in certain cases, chemotherapy. To evaluate the activity of preirradiation chemotherapy in such tumors, 11 newly diagnosed children with measurable residual disease and characteristics indicative of poor prognosis were treated postoperatively with cisplatin (CDDP) and etoposide (VP-16). Responses graded on the basis of radiographic findings in areas of either macroscopic residual tumor or metastatic disease included two complete responses (CRs), eight partial responses (PRs), and one stable disease (SD). Acute and subacute toxicity consisted of high-frequency hearing loss in four patients, reversible signs and symptoms of increased intracranial pressure in two patients, and transient neutropenia. Seven of eight patients with high-risk medulloblastoma and two of two with pineoblastoma remain free of tumor progression following neuraxis irradiation at 8 to 48 months postdiagnosis (median, 18 months). CDDP and VP-16 is a highly active drug combination when given before irradiation in children with high-risk medulloblastoma and other malignant embryonal tumors of the CNS, producing objective responses in at least one site of measurable disease in 10 of 11 newly diagnosed patients, including all of five with gross neuraxis dissemination.
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PMID:Preirradiation cisplatin and etoposide in the treatment of high-risk medulloblastoma and other malignant embryonal tumors of the central nervous system: a phase II study. 215 66

Twenty-nine patients with metastatic prostate cancer progressing after hormonal therapy (orchiectomy 19, diethylstilbestrol 10) and who had never received cytotoxic therapy were treated with carboplatin. Patients had good clinical performance status (66% PS 0,1) and adequate renal (creatinine less than 2.0 mg/dL) and bone marrow function. The standard dose of carboplatin administered was 400 mg/sq m. Seventeen patients received this dose and 12 either 320 mg/sq m or 250 mg/sq m based on reduced renal function or prior radiation. Five patients had bidimensionally measurable disease: one experienced a partial regression of cervical lymph node metastases of 97 days duration. Twenty-four patients had metastatic disease evaluable by clinical status, bone scan and acid phosphatase. In one patient greater than 50% reduction in number of abnormal areas of bone scan uptake occurred; 3 patients experienced improvement in clinical status; in no patient did an elevated prostate acid phosphatase return to normal. All patients entered on study have progressed and died: median time to progression was 94 days (6 to 625 days); median survival was 297 days (6-1152 days). The primary toxicity of carboplatin was myelosuppression. The median WBC and platelet nadirs after cycle one were 3150/cu mm and 93,000/cu mm, respectively. Dose escalations to grade 2 or greater myelosuppression were mandated. Twenty-six achieved at least grade 2 myelosuppression during carboplatin treatment. We conclude that carboplatin administered at this dose and schedule has no important activity in hormone refractory prostate cancer.
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PMID:A phase II trial of carboplatin (NSC 241240) in advanced prostate cancer, refractory to hormonal therapy. An Eastern Cooperative Oncology Group pilot study. 219 2

A total of 83 patients with metastatic transitional cell carcinoma who had previously received no systemic therapy entered a randomized phase II evaluation of carboplatin and cis-dichloro-transdihydroxy-bis-isopropylamine platinum IV (CHIP), administered respectively at 400 and 270 mg./m.2 every 28 days. Among evaluable patients with measurable disease response rates were 3 of 22 (14%, 95% confidence interval 5 to 35%) for carboplatin and 4 of 25 (16%, 95% confidence interval 5 to 36%) for CHIP. Among 17 patients with evaluable but not measurable metastases (10 carboplatin and 7 CHIP recipients) there were no responses. Median survival for 64 evaluable patients was 4.8 months (5.0 months for carboplatin and 4.3 months for CHIP recipients). Independent factors prognostic for survival (p less than 0.01) were performance status (0 or 1 versus 2 or 3), liver metastases, prior radiation therapy and recent weight loss (p = 0.02). Multivariate analysis confirmed that a performance status of 2 or 3 and liver metastases were predictive of shorter survival. A total of 31% of the patients treated with carboplatin and 34% of those who received CHIP experienced severe or life-threatening myelosuppression. While the response rates with carboplatin and CHIP are modest, we believe that the characteristics of these agents indicate that they should be evaluated further.
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PMID:Randomized phase II evaluation of carboplatin and CHIP in advanced transitional cell carcinoma of the urothelium. The Eastern Cooperative Oncology Group. 223 83

Forty-five patients with metastatic germ cell tumour were treated with chemotherapy. Complete remission was achieved in 63% of all cases and in 65% of patients whose primary tumour arose in the testis or ovary. Surgical resection of abdominal masses persisting after chemotherapy was performed in seven patients, two of whom were found to have persistent tumours. Twenty-seven of the 33 patients with teratoma originating in the gonads remain in complete remission. Total serum LDH activity was elevated in 28 of the patients with measurable disease. The increased LDH was not accompanied by significant alteration in other hepatic enzymes nor were hepatic metastases demonstrable in these patients. Fractionation of the LDH demonstrated that the increased LDH in these patients was located in either iso-enzymes 1 or fractions 1 + 2. Alteration of the serum LDH activity correlated with the response to therapy and warrants further study.
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PMID:The management of metastatic germ cell tumours and the clinical utility of lactate dehydrogenase estimations. 241 41

The role of chemotherapy in the management of patients with cancer of the paranasal sinus has not been defined. An analysis of 24 evaluable patients treated with chemotherapy as part of their overall therapy was performed. There were 16 male patients and eight female patients. Sixteen patients were previously untreated and eight had recurrent disease after surgery and/or radiotherapy. Six of the previously untreated patients had metastatic disease on presentation (four central nervous system (CNS) and two lung), and four recurrent patients had CNS involvement. The majority of patients (78%) had squamous cell carcinoma. The chemotherapy regimens included cisplatin (CDDP), vincristine (VCR), and bleomycin (COB), 5-fluorouracil (5-FU) infusion and CDDP, or 5-FU/CDDP and methotrexate (MTX). All patients had computed tomography (CT) measurable disease. Previously untreated patients underwent surgery and/or radiotherapy postchemotherapy. The overall response rate to chemotherapy for previously untreated patients was 82% (complete response [CR] 44%, partial response [PR] 38%) and for recurrent patients 88% (CR 38%, PR 50%). Predominant toxicities were nausea, vomiting, myelosuppression, mucositis, and renal impairment. The median survival of the previously untreated patients, based on response to chemotherapy, was as follows: CR 21+ months (range, 10+ to 81 months), PR 13.5 months (range, 2 to 21 months), and no response (NR) 3 months (range, 1 to 7 months). The median survival of patients with recurrent disease was as follows: CR 16 months, PR 13.5 months, and NR 5 months. We conclude that patients with paranasal cancers are responsive to CDDP-containing combinations. The role of adjuvant chemotherapy in previously untreated, locally advanced patients needs to be demonstrated by future randomized trials.
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PMID:Chemotherapy for paranasal sinus carcinoma. A 10-year experience at Wayne State University. 245 17

This study was designed to assess the role of dosage of chemotherapy for treatment of metastatic breast cancer. One hundred thirty-three patients without prior chemotherapy for metastatic disease were randomly allocated to receive two different dose levels of cyclophosphamide (C), methotrexate (M), and fluorouracil (F), administered intravenously (IV) every 3 weeks. Patients were stratified by sites of disease (visceral, bone, or soft-tissue dominant) and by interval from primary surgery to first recurrence. Doses on the higher-dose arm were 600 mg/m2 (C,F) and 40 mg/m2 (M) with escalation if possible; doses on the lower-dose arm were 300 mg/m2 (C,F) and 20 mg/m2 (M) without escalation. Patients who failed to respond to lower-dose CMF were crossed over to the higher-dose arm. Patients randomized to the higher-dose arm had longer survival measured from initiation of chemotherapy (median survival, 15.6 months v 12.8 months, P = .026 by log-rank test), but the effect of dose was of borderline significance (P approximately 0.12) when adjusted for a chance imbalance between the two arms in the time from first relapse to randomization, using the Cox proportional hazards model. Response rates (International Union Against Cancer [UICC] criteria) for patients with measurable disease were higher-dose arm: 16/53 (30%) and lower-dose arm: 6/53 (11%), (P = .03). Only one of 37 patients responded on crossover from the lower- to the higher-dose arm. Patients experienced more vomiting, myelosuppression, conjunctivitis, and alopecia when receiving higher doses of chemotherapy. A series of 34 linear analogue self-assessment scales were used to make detailed quality of life assessments on a subset of 49 patients. These scales confirmed greater toxicity in the immediate posttreatment period, but also a trend to improvement in general health and some disease-related indices, in patients receiving higher-dose chemotherapy. This trial suggests that better palliation is achieved by using full-dose chemotherapy.
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PMID:A randomized trial of two dose levels of cyclophosphamide, methotrexate, and fluorouracil chemotherapy for patients with metastatic breast cancer. 291 36

We treated 41 patients with transitional cell carcinoma with methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy. Median patient age was 56 years. Of the patients 33 had either distant metastases or locoregional disease that could not be cured by an operation or radiation. Of these patients 30 had measurable disease and 12 responded (4 complete and 8 partial responses, response rate 40 per cent, 95 per cent confidence limits 23 to 59 per cent). Only 2 of these patients remain with an unmaintained complete response at 34 and 52 months. Of 5 patients 3 responded who were treated with neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin for locally advanced bladder cancer before radiation or cystectomy, and only 1 of these patients is free of disease. The remaining 3 patients were treated postoperatively because they were at high risk for recurrence and all are well. Toxicity of the regimen was severe: 41 per cent of the patients experienced neutropenic sepsis and 54 per cent required hospitalization for management of toxic complications. Three patients experienced pulmonary embolism and 1 had deep vein thrombosis. There was 1 drug-related death of sepsis. Although a patient occasionally may have long-term benefit from this chemotherapy our results suggest caution in the widespread application of this protocol.
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PMID:M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) chemotherapy for transitional cell carcinoma: the Princess Margaret Hospital experience. 274 45

Sixteen patients with metastatic cancer, each with bidirectionally measurable disease, were treated with a total of 24 membrane UltraPheresis procedures each to remove a low molecular weight (less than 150,000 daltons) plasma fraction. No other oncologic treatment was applied during the 2 months of study. The procedure was generally well tolerated, and no clinically significant adverse effects were observed from the procedure. A consistent tumor-specific inflammatory response was observed following the UltraPheresis procedure and was associated with lymphocytic infiltration of tumor and tumor necrosis that was demonstrated in those patients evaluable by repeat biopsy. In some patients, anergy was reversed and Karnofsky status improved. Six of the 16 patients had reduction of the sum of mean cross-sectional diameters of measureable lesions by 50% or more.
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PMID:Continuous whole blood UltraPheresis procedure in patients with metastatic cancer. 279 94

Serial serum CA-125 levels were measured in fifteen patients with recurrent or advanced endometrial carcinoma during treatment with chemo- or hormonal therapy. All patients had measurable disease by physical examination, chest X-ray or CT scan. Serum CA-125 levels were invariably elevated, and generally reflected, response to therapy in all patients with intraperitoneal or pulmonary metastases. Levels were normal in two of three patients with isolated vaginal metastases prior to and following response to progesterone.
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PMID:Use of serum CA-125 levels to monitor therapy of patients with advanced or recurrent endometrial carcinoma. 280 20


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