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)

Following preliminary studies suggesting that some patients with metastatic renal cell carcinoma had accelerated tumor growth after entry into chemotherapy studies, 73 patients with measurable metastatic disease referred to a tertiary referral center for consideration for experimental treatment protocol have been observed to attempt to establish the incidence of spontaneous regression. Initially, patients went off study if metastases showed greater than 25% increase in products of bidimensional measurement but with increasing confidence patients only went into therapy protocols with the development of symptomatic progression. In this selective series, on observation, three complete (histologically documented) and two partial unexplained "spontaneous" regressions were observed and a further four patients had prolonged stable disease for more than 12 months. On progression, 52 were entered into treatment protocols (BCG n = 19, Mitozantrone n = 12, and Welferon n = 21). A further two complete and five partial responses (14%) and four prolonged stable disease were observed confirming that the previously reported responses with these agents are not totally explicable on the basis of "spontaneous" response.
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PMID:A phase 2 study of surveillance in patients with metastatic renal cell carcinoma and assessment of response of such patients to therapy on progression. 326 68

Mitoxantrone (Novantrone; dihydroxyanthracenedione) is an anthraquinone previously shown to be active in human breast cancer. It appears to have less toxicity than doxorubicin. Results of this phase II-III randomized cross-over trial to determine the relative efficacy and toxicity of mitoxantrone in comparison to doxorubicin, are presented. Patients with measurable, recurrent breast cancer with limited prior chemotherapy with or without radiotherapy for metastatic disease, and who had not been exposed to prior doxorubicin, were randomized to receive either mitoxantrone or doxorubicin every three weeks with cross-over on progression. Response rates, duration of remission, time to treatment failure, and drug toxicity, including cardiac toxicity evaluated with serial radionuclide angiocardiography, were evaluated. Differences in the response rates for the two groups were not statistically significant. Neither time to treatment failure nor duration of response are significantly different (p greater than 0.05). With respect to toxicity, mitoxantrone treated patients consistently exhibited a lower incidence and less severe drug toxicity as compared to their doxorubicin-treated counterparts. Cardiac toxicity was carefully monitored and thus four patients on doxorubicin have had drug related congestive heart failure, as compared to none on mitoxantrone. In summary, mitoxantrone appears to be as active as doxorubicin in patients with stage IV breast cancer previously treated with chemotherapy; however, mitoxantrone causes significantly less nausea, vomiting, stomatitis and alopecia at doses which induce equal or greater myelosuppression than doxorubicin, and appears to be less cardiotoxic.
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PMID:A randomized trial comparing mitoxantrone with doxorubicin in patients with stage IV breast cancer. 389 78

Nineteen patients with advanced, previously treated breast cancer received treatment with vincristine 2 mg i.v., mitomycin-C 6 mg/m2 and mitoxantrone (Novantrone; dihydroxyanthracenedione) 12 mg/m2 i.v. every three weeks. Thirteen patients are evaluable for response and toxicity. Partial remission was seen in six patients, with soft tissue, bone and visceral metastases and static disease in a further four patients. Median duration of response has not yet been reached (8+ months). Toxicity was mild and predictable, with no patient experiencing severe nausea and vomiting, and only four of the patients requiring a wig for alopecia. Malaise and lethargy were common in those patients receiving more than three courses, and an increase in the mean corpuscular volume (MCV) together with a fall in haemoglobin were seen in patients receiving multiple courses of treatment. The study suggests that this combination is active, and may prove useful with other agents in the treatment of breast cancer.
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PMID:Phase II study of vincristine, mitomycin-C and mitoxantrone in advanced breast cancer: a preliminary report of response and toxicity. 392 13

Micro-invasive CT-guided intratumoral therapy (MIC-ITT) when used in combination with sympathectomy can be an excellent palliative treatment with little impairment of the patient. Rapid as well as complete reduction of pain without systemic side effects can be achieved under local anesthesia in patients in advanced tumor stages by the direct instillation of 50 to 96% alcohol and/or a locally efficacious low toxic cytostatic (Mitoxantron) under CT guidance. CT enables not only exact puncture without injuring endangered structures but also a controlled application of medication. The interventions can be performed with special probes with a diameter of 18 to 25 G. The study population consisted of 145 patients who received a total of 434 treatments. Repeated micro invasive intratumoral treatment was performed on 110 patients with bone and soft tissue metastases (Group I, 335 single treatments) and on 35 patients with vertebral metastases (Group II, 109 single treatments). In all patients conventional therapeutic strategies had been exhausted or were no longer applicable on the basis of a reduced Karnofsky Index. Treatment was performed in combination with sympathetic neurolysis at the upper tumor pole in all cases. The maximum follow-up time was 30 months. Pain reduction was estimated on a visual analogic scale. In Group I up to time of death a pain reduction of 75% or better was achieved in 88 patients (80%). A reduction in tumor size concomitant with a stabilization of the tumor region could be shown in 25% in this group, no change in 62% and progression in 13%. In Group II a pain reduction greater than 75% was achieved in 84% as well as a reduction in tumor size (< 50%) in 18% of the patients. Necrotic zones could be shown in 27% and calcification of tumor area in 35%. No change in tumor size was found in 66% of the patients, progression in 16%. All treatments were free of complications. On the whole the results of this therapeutic approach are encouraging. In particular one aspect should be mentioned: with respect to palliative treatment the reduction of tumor size is not crucial. The decisive factor is the improvement in quality of life of the patient using an intervention which impairs the patient only minimally. Furthermore this micro invasive approach should always involve the combination of local tumor treatment with treatment or lysis of the autonomic sympathetic nervous system in tumor vicinity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Microinvasive CT-controlled tumor therapy of soft tissue and skeletal metastases]. 769 78

Forty-four patients with either metastatic or locally advanced transitional cell carcinoma of the bladder were treated with the MCNO regimen (methotrexate 300 mg/m2 in 1,000 ml normal saline as a 4-hour infusion on days 1 and 14 with leucovorin rescue 15 mg 6-hourly for 6 doses; carboplatin 300 mg/m2 in 250 ml 5% distilled water as a 1-hour infusion on day 1; mitoxantrone (Novantrone) 10 mg/m2 in 100 ml 5% distilled water as a 30-min infusion on day 1, and vincristine (Oncovin) 1 mg/m2 as an intravenous bolus on days 1 and 14. Patients with metastatic disease were treated with 6 cycles, while patients with locally advanced disease were treated with 4 cycles of induction chemotherapy followed by cystectomy or radiotherapy. The overall response rate was 40%, with 15% complete response (CR). The responses were better for patients with locally advanced disease (CR 25%, partial response, PR, 31.25%, response rate, RR, 56.25%) than for those with metastatic disease (CR 8.3%, PR 20.83%, RR 29.1 %). The differences in these results were probably due to the bad performance status and the presence of visceral metastases in patients with generalized disease. The overall median survival was 14 months, with responders living longer (median survival 28.8 months in patients with locally advanced disease and 22.9 months in patients with metastatic disease) than non-responders (median survival 16 months in patients with locally advanced disease and 8.9 months in patients with metastatic disease). The difference in survival between responders and non-responders was statistically significant in both groups of patients. Toxicity was moderate, but manageable. The MCNO regimen appears to have a lower efficacy than that obtained with cisplatin-based regimens for the treatment of metastatic disease and rather similar efficacy for the treatment of locally advanced urothelial-cell cancer. Therapy with this regimen, though less toxic, may not be a reliable alternative in elderly patients with visceral metastases and a performance status of > or = 2.
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PMID:Chemotherapy with methotrexate, carboplatin, mitoxantrone (Novantrone) and vincristine (Oncovin) in transitional-cell urothelial cancer. 949 88

From February 1992 to November 1993, forty patients with operable breast cancer tumors larger than three centimeters were enrolled in this study of accelerated neo-adjuvant chemotherapy. Thirty-seven patients are evaluable: one patient was excluded from the protocol and two refused to continue treatment after the first cycle. Chemotherapy consisted of three presurgical cycles of CNF [cyclophosphamide at 600 mg/m2, mitoxantrone (Novantrone) at 10 mg/m2 and 5-fluorouracil at 600 mg/m2] administered every 2 weeks, plus G-CSF (5 microg/kg s.c./day on days 7-12). Twenty-six of 37 patients (70%) achieved objective tumor response and were submitted to quadrantectomy. Toxicity was easily manageable. After a median 55-month follow-up (range 48-70), no locoregional recurrences were observed. Distant metastases occurred in 12/37 (32%) patients. The five-year disease-free (DFS) and overall (OS) survival were 58% and 80%, respectively. Accelerated CNF plus G-CSF proved to be a safe and tolerable regimen yielding a good clinical response thereby increasing the possibility of breast conservation surgery for patients otherwise candidates for mastectomy.
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PMID:Neoadjuvant chemotherapy with accelerated CNF plus G-CSF in patients with breast cancer tumors larger than three centimeters: a pilot study. 953 46

Our purpose was to determine the maximum tolerated dose and toxicity associated with soluble Chinese hamster ovary [s(CHO)] recombinant human interleukin (IL) 1 receptor (IL-1R; Immunex, Seattle, WA) administration in humans and to determine the effective biological dose and/or maximum tolerated dose of the s(CHO) IL-1R in combination with high-dose IL-2 as determined by reduction in IL-2 toxicity and modulation of its biological effects. Twenty-seven patients with metastatic cancer were treated with escalating doses of s(CHO) IL-1R at 1, 1, 5, 10, 20, 40, and 55 mg/m2 i.v. on days -6 (except cohort 2), 1, and 15 and IL-2 at doses of 300,000 IU/kg (cohort 1) and 600,000 IU/kg (cohorts 2-7) i.v. every 8 h on days 1-5 and 15-19. No toxicity directly attributable to s(CHO) IL-1R was observed. The median number of IL-2 doses was 23. Hypotension and neurotoxicity were the major dose-limiting toxicities for the IL-2/s(CHO) IL-1R combination. Of the 24 patients treated with full-dose IL-2, there were six responses, three complete and three partial (response rate, 25%). Three patients developed thyroid dysfunction, and all 3 responding melanoma patients exhibited vitiligo. The t1/2 of s(CHO) IL-1R alone was 24-30 h and was not significantly altered by coadministration with IL-2. Whole-blood functional assays indicated that sufficient s(CHO) IL-1R was present in the circulation at top dose levels to inhibit the in vitro effects of IL-1beta on IL-8 induction; however, no effect on IL-2-induced IL-8 induction, or on the IL-1beta- or IL-2-induced tumor necrosis factor production, was observed. Suppression of IL-2-mediated tumor necrosis factor alpha and IL-6 induction in vivo during the first 24 h after IL-2 administration was observed, and the neutrophil chemotactic defect normally seen with IL-2 was not observed. IL-1R antagonist induction far exceeded that seen previously with IL-2 alone. No inhibition of either serum C-reactive protein induction or enhanced urinary nitrate excretion and no consistent effect on IL-2-related changes in peripheral blood mononuclear cell phenotype or endothelial adhesion molecule expression were seen. The coadministration of s(CHO) IL-1R produced no apparent reduction in IL-2 clinical toxicity manifested by either the ability to administer more IL-2 than anticipated or a reduction in the toxicity associated with a given amount of IL-2. Therefore, no effective biological dose could be identified for the s(CHO) IL-1R.
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PMID:A two-part phase I trial of high-dose interleukin 2 in combination with soluble (Chinese hamster ovary) interleukin 1 receptor. 960 78

Our purpose was to determine the effective biological dose and/or maximum tolerated dose of recombinant human tumor necrosis factor receptor:IgG chimera (rhuTNFR:Fc; Immunex, Seattle, WA) in combination with interleukin 2 (IL-2) with regard to reduction in IL-2 toxicity and modulation of biological effects of high-dose IL-2 administration. Twenty-four patients with metastatic cancer were treated with escalating doses of rhuTNFR:Fc at 1, 1, 5, 10, and 20 mg/m2 i.v. on days 1 and 15 (dose levels 1-5) or 10, 20, and 30 mg/m2 days 1 and 15 plus 50% dose on days 3, 5, 17, and 19 (dose levels 6-8) prior to IL-2 at doses of 300,000 IU/kg (dose level 1) and 600,000 IU/kg (dose levels 2-8) i.v. every 8 h on days 1-5 and 15-19. The t1/2 of rhuTNFR in patients receiving IL-2 was 72 h. The median number of IL-2 doses was 24, and central nervous system, skin, and cardiac arrhythmias were the major dose-limiting toxicities. TNF bioactivity was inhibited, and the polymorphonuclear leukocyte chemotactic defect normally seen with IL-2 was not observed. Increases in C-reactive protein, IL-6, IL-8, and IL-1 receptor antagonist levels were partially suppressed relative to historical controls, whereas peripheral blood mononuclear cell phenotypes, urinary nitrate, endothelial adhesion molecule expression in skin biopsies, and cellular infiltrates in tumor biopsies were consistent with findings in patients treated with IL-2 alone. Four patients developed thyroid dysfunction. There were five responses: two complete responses (both melanoma) and three partial responses (response rate, 21%). rhuTNFR:Fc may modulate the toxicity and some of the biological effects of IL-2 while preserving antitumor activity. Dose level 6 (10 mg/m2 on days 1 and 15, and 5 mg/m2 on days 3, 5, 17, and 19) has been chosen for a randomized, double-blind, placebo-controlled trial of IL-2 with and without rhuTNFR:Fc.
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PMID:Phase I trial of interleukin 2 in combination with the soluble tumor necrosis factor receptor p75 IgG chimera. 981 6

Twenty patients (13 males, 7 females, median age 61 years, range 27-74) with recurrent adenocarcinoma-like tumors of major (10 patients) and minor (10 patients) salivary gland origin (13 adenoid cystic carcinoma, 5 adenocarcinoma, 1 malignant mixed tumor, 1 undifferentiated carcinoma) were treated with vinorelbine at the dose of 30 mg/m2 i.v. weekly. Sixteen patients had been previously treated with surgery + radiation, 3 with surgery + radiotherapy + Novantrone and 1 with radiotherapy alone. Nine patients had local recurrence, 2 local relapse + metastasis and 9 metastasis alone. Site of metastases are: lung (7), bone (1), lung + bone (2), lung + bone + lymph-node + skin (1). Overall 174 courses were given (median 9, range 6-19). Responses were: PR in 4 patients (20%) with a median duration of 6 months (3-9), 9 NC (45%) with a median duration of 3.5 months and 7 PD (35%). The median survival time was 10 months for PR/NC patients, 4 months for non-responders. Median overall survival was 7 months. Vinorelbine has a moderate activity in these very advanced cases.
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PMID:Vinorelbine treatment of recurrent salivary gland carcinomas. 983 66