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)

Seven patients with advanced cancer underwent whole-body hyperthermia using a nylon and vinyl mesh, water-perfused suit. Treatments were given at 41.8 degrees C for 4 hours. Five patients received concomitant cyclophosphamide with hyperthermia. Compared to baseline (37 degrees C) conditions, there was a significant rise in pulse rate (P less than 0.001), a fall in diastolic pressure (P less than 0.02), and an increase in respiratory rate (P less than 0.001). Toxic effects included fatigue, extremity edema, diarrhea, nausea and vomiting, and respiratory depression in a patient with cerebral metastases. Compared to baseline values, there was a significant increase in serum glucose (P less than 0.02) and decreases in serum calcium (P less than 0.01) and phosphorus (P less than 0.01). Significant elevations in serum LDH and SGOT values occurred 24 hours following hyperthermia, suggesting hepatic sensitivity to heat. The methods used to induce whole-body hyperthermia, as described in this paper, are feasible, permit relatively easy access to the patient, and are potentially applicable in diverse hospital settings such as intensive care units, radiation therapy areas, and conventional rooms. The physiologic alterations that were observed and the toxic effects that were documented indicate that careful monitoring of patients is necessary.
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PMID:Physiologic response and toxicity in patients undergoing whole-body hyperthermia for the treatment of cancer. 723 54

Fifteen adult patients with advanced solid tumors received bruceantin at doses of 1.6-6.0 mg/m2 iv for 30 minutes/week X 4, followed by a 2-week rest. The dose-limiting toxic effect was nausea and vomiting, which was more severe in patients with hepatic metastases or liver function abnormalities. Other sporadic toxic effects included fever, chills, malaise, alopecia, hypotension, thrombocytosis, and leukocytosis. Hematologic toxicity was insignificant. The recommended starting dose for phase II studies is 5 mg/m2/week X 4, every 6 weeks, with a reduction to 3 mg/m2 for patients with hepatic metastases.
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PMID:Phase I study on bruceantin administered on a weekly schedule. 727 23

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

Single-agent chemotherapy for nonmetastatic gestational trophoblastic disease is most successful for patients who have had an antecedent molar pregnancy with a plateau or persistent beta-human chorionic gonadotropin elevation after molar evacuation. Traditionally, single-agent, five-day, intramuscular methotrexate has been associated with high cure rates, as has methotrexate with citrovorum factor rescue, which reduces toxicity. Standard definitions of low-risk gestational trophoblastic disease and response assessment are critical to a comparison of prognostic features related to single-agent therapy success. Methotrexate with folinic acid rescue administered as primary therapy does achieve an excellent therapeutic outcome with limited chemotherapy exposure but at increased cost. The weekly intramuscular methotrexate Gynecologic Oncology Group (GOG) regimen is inexpensive and allows close monitoring of disease status. Single-dose or pulsed actinomycin-D provides a high level of complete response, although gastrointestinal toxicity, mainly nausea and vomiting, is quite common. Management of first-line chemotherapy failures is unclear, although in the GOG methotrexate trial it was evident that another agent, such as actinomycin-D, should be used to provide the highest success rate. The use of a single agent in low-risk metastatic trophoblastic disease (lung and/or vaginal metastases) depends upon restricting it to patients who have not failed prior chemotherapy, have a low World Health Organization score and have no evidence of the presence of choriocarcinoma, but a much higher first-line failure rate should be anticipated than in nonmetastatic disease. Other single-agent regimens have been proposed that are worthy of investigation to create a safer, more efficacious and more convenient regimen for low-risk gestational trophoblastic disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Development of single-agent chemotherapy regimens for gestational trophoblastic disease. 751 17

Between 1980 and 1992, 68 patients with clinical indications of involvement of the gastrointestinal (GI) tract with metastatic melanoma were treated at Roswell Park Cancer Institute. Presenting symptoms were anaemia, abdominal pain, nausea and vomiting. Sites commonly involved were the small bowel (75%), the large intestine (25%), and the stomach (16%). Twenty-one patients were considered unsuitable for surgery; their median survival after diagnosis of GI metastases was 2.9 months. Forty-seven patients underwent abdominal surgery; effective palliation was achieved in most of them. Complete resection of GI metastases was accomplished in 47% of patients. The median survival after operation was 27.6 months for patients with complete resection of GI metastasis and no other disease, 5.1 months for patients with resection of involved GI tract and other metastases present, and 1.9 months for patients who had a by-pass procedure only. The 5-year survival for patients with complete resection of GI metastases and no other evidence of disease was 28.3%. The other groups had only 1-year survivors. Surgical intervention is justified on the basis of these findings, and extended palliation can be achieved in patients with complete resection of metastatic disease.
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PMID:Gastrointestinal metastases from malignant melanoma. 755 Dec 58

A phase II trial was performed to assess the efficacy and toxicity of the combination mitoxantrone (MXN) and vinorelbine (VNR) as first-line chemotherapy for metastatic breast cancer. Forty-one patients with metastatic disease or local relapse recruited between March 1991 and April 1993 received a first-line chemotherapy treatment consisting in 12 mg/m2 intravenous (IV) bolus of MXN on day 1 followed by a 20-minute perfusion of 25 mg/m2 of VNR on days 1 and 8. Cycles were repeated every 21 days until evidence of disease progression or of severe toxicity. Thirty-seven patients were evaluable for response and all 41 for toxicity. An objective response was observed in 19 patients (51%; 95% confidence interval, 45 to 74%). The response was complete in a further 11 (30%). Median time to treatment failure was 9 months. Median survival was 14 months. There were no treatment-related deaths. Limiting toxicity was myelosuppression. Leukopenia occurred in 29 patients (71%) and was grade 3 or 4 in nine of these (15%). Grade 2 or 3 anemia was encountered in six patients (15%), grade 1 thrombocytopenia in one, neurotoxicity (constipation) in two, and grade 2 or 3 alopecia in 12 (29%). Nausea/vomiting requiring antiemetic treatment was experienced by only two patients (5%). There were two cases of septicemia treated by antibiotic therapy in hospital.
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PMID:[Combination of mitoxantrone-vinorelbine as first-line chemotherapy for metastatic breast carcinoma]. 765 48

In an effort to evaluate the toxicities and anti-tumor efficacy of the combination of high-dose cyclophosphamide (CY) and carboplatin, we undertook a phase I-II trial with autologous bone marrow (BM) or peripheral blood stem cell (PBSC) rescue for patients with solid tumors. Forty three patients, 39 of whom had either high risk stage II or III or metastatic breast cancer were treated with escalating doses of carboplatin 1200-1800 mg/m2 and cyclophosphamide 4800-6000 mg/m2 over 3 days followed by autologous BM or PBSC infusion. No life-threatening or fatal toxicities were observed. Reversible congestive heart failure was seen in two patients. Transient hepatotoxicity, characterized primarily by elevation of transaminase levels, and nausea and vomiting, adequately managed with anti-emetic therapy, were seen in 39 and 40 of 43 patients, respectively. The 14 month post-transplant probability of relapse-free survival for 26 patients with high risk II-III breast cancer was 79%; for 13 patients with metastatic disease, the 22 month relapse-free survival probability was 23%. High-dose carboplatin and CY at maximally administered doses of 1800 mg/m2 and 6000 mg/m2 is a well tolerated preparative transplant regimen for autologous BM or PBSC transplantation. It appears to have similar anti-tumor activity and an improved safety profile when compared with other commonly employed transplant preparative regimens.
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PMID:Phase I-II trial of high-dose cyclophosphamide, carboplatin and autologous bone marrow or peripheral blood stem cell rescue. 765 78

Forty patients with measurable disseminated malignant melanoma and no prior chemotherapy received monthly DHAC, 5 g/m2/24 h, as a continuous infusion. Among 26 "good risk patients" (ECOG performance score 0, 1 and no prior biological therapy), we observed 3 objective regressions. Among 14 "poor-risk patients" (ECOG PS 2 or prior biological therapy), we observed no objective regressions. For all patients, median time to progression and survival were 1 month and 6.7 months, respectively. Transient pleuritic chest pain and mild nausea and vomiting were the most common complications. We were especially impressed with a complete response (CR) for 11+ months in a 43-year-old woman with extensive visceral metastases and another CR lasting > 4.7 months in a 36-year-old woman with nonvisceral metastatic disease. The absence of myelosuppression raises intriguing possibilities for combination regimens including DHAC in the management of malignant melanoma.
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PMID:A phase II study of 5,6-dihydro-5-azacytidine hydrochloride in disseminated malignant melanoma. 768 19

Methoxymorpholinyldoxorubicin (FCE 23762) is a novel, highly lipophilic doxorubicin analogue. It possesses potent in vitro and in vivo antitumor activity including efficacy in multidrug-resistant tumor cell lines. It is also metabolically activated in vivo resulting in an 80-fold increase in potency over the parent drug. In this phase I study the drug was administered by i.v. bolus injection at 3-week intervals. Fifty-three patients with refractory solid tumors were treated; 133 courses of FCE 23762 were administered at doses ranging from 30 to 2250 micrograms/m2. The dose limiting toxicity was reversible myelo-suppression (granulocytopenia and thrombocytopenia), demonstrating a delayed nadir and recovery in comparison to doxorubicin. Other toxicities included transient elevation of hepatic transaminases, delayed and prolonged nausea and vomiting, mucositis, anorexia, fatigue, and diarrhea. Heavily pretreated patients demonstrated more myelosuppression than previously untreated patients at 1250 micrograms/m2. No cardiotoxicity was observed. Four objective tumor responses were seen: one complete response in a patient with pelvic recurrence of cervical cancer; one partial response in a patient with cutaneous and lymph gland metastases from head and neck cancer; and two minor responses in patients with liver metastases from colorectal cancer. Plasma concentrations of FCE 23762 and its 13-dihydro metabolite, FCE 26176, were measured in 20 patients at doses > or = 675 micrograms/m2, using HPLC with fluorescence detection. The area under the plasma concentration-time curve ranged from 30 to 80 ng/h/ml; plasma data suggested linear kinetics in the range of tested doses (although there was considerable interpatient variability). The maximum tolerated dose defined in this study using this schedule is 1500 micrograms/m2. A safe phase II dose for previously untreated patients using this schedule is 1250 micrograms/m2; however, this may actually be below the optimal dose for this patient population.
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PMID:Phase I clinical and pharmacokinetic study of 3'-deamino-3'-(2-methoxy-4-morpholinyl)doxorubicin (FCE 23762). 774 8

Two female patients with an adenocarcinoma of the colon (Duke stages B and C) underwent colectomy followed by adjuvant chemotherapy combining 5 fluorouracil (5 FU) and levamisole. Secondary neurological manifestations occurred in both patients including vertigo, nausea and vomiting, dizziness with loss of balance, slow ideation, impaired memory, headache and, on one case, central origin facial paralysis. Symptoms appeared between the 11th and 34th week of treatment. The patients had received 9 to 30 g 5 FU and 2.7 to 7.6 g levamisole. CT scan and/or MRI first suggested cerebral metastases then demyelinisation. The clinical signs disappeared spontaneously in less than one month. The brain images were unchanged. The 5 FU/levamisole combination was undoubtedly responsible for the neurological manifestations. Levamisole may have potentialized the effect of 5 FU leading to demyelinisation. Whether chemotherapy should be stopped or not is debated.
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PMID:[Multifocal inflammatory leukoencephalopathy: a complication of chemotherapy by fluorouracil and levamisole]. 774 17


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