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

Allergic reaction to an antitumor agent, cis-dichlorodiammineplatinum(II) (DDP) was investigated. A 15-year-old white male with pulmonary metastases from embryonal carcinoma of testis was treated with a combination of DDP, bleomycin, and vinblastine. The dose of DDP varied from 2 to 2.25 mg/kg given i.v. He received 7 doses of DDP in 9 months. An anaphylactic reaction was seen within 3 min of the initiation of i.v. infusion of the 8th dose of DDP. The reaction was due to atopic hypersensitivity, as confirmed by an immediate wheal and flair reaction and increased histamine release from leukocytes with DDP. His serum IgE level was elevated. Neither the presence of chloride nor the amine grouping in DDP was essential for reactivity. The replacement of platinum with palladium abrogated the reactivity. There was no cross-reactivity with 3 other platinum complexes of known antitumor activity (platinum blue, platinum(II) 1,2-diaminocyclohexane malonate, and platinum(II) ethylenediamine malonate). This was also confirmed by the lack of reaction to subsequent i.v. administration of platinum(II) 1,2-diaminocyclohexane malonate (10 mg/kg) in this patient.
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PMID:Atopic hypersensitivity to cis-dichlorodiammineplatinum(II) and other platinum complexes. 5 Aug 81

Forty-seven patients with squamous cell carcinoma of the esophagus were treated with a combination of cis-dichlorodiammineplatinum (II) (cis-DDP) and bleomycin by infusion. cis-DDP at a dose of 3 mg/kg with mannitol and prehydration was given on Day 1. On Day 3, bleomycin was started as a 10--15-unit/m2 loading dose followed by a 10--15-unit/m2 24-hour infusion for 4--7 days. Three groups of patients were treated: group 1 (no clinical evidence of metastatic disease) included 25 patients, all with no prior therapy; group 2 (measurable metastatic disease) included 13 patients, eight previously treated with surgery and/or radiation; group 3 (known nonmeasurable metastatic disease) included nine patients, all previously treated with surgery and/or radiation and/or chemotherapy. A second course of therapy was given on Day 28 to groups 2 and 3, and as soon after surgery as possible in group 1. Nineteen percent of patients had complete or partial responses with another 44% having minor regressions. Toxic effects were mainly renal effects, alopecia, nausea and vomiting, and stomatitis. There were two drug-related deaths. The combination of cis-DDP and bleomycin is useful in the treatment of patients with squamous cell carcinoma of the esophagus.
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PMID:cis-Dichlorodiammineplatinum(II) and bleomycin in the treatment of esophageal carcinomas. 8 Feb 69

A 19-year-old woman with a diagnosis of osteosarcoma was initially treated with amputation of her right leg and adjuvant adriamycin. She developed pulmonary metastases 18 months following diagnosis. She was then given cis-dichlorodiammineplatinum(II) (DDP) at a dose of 100 mg/m2 iv approximately every 4 weeks as the sole drug. Following the fifth dose of DDP, she complained of numbness and tingling in her hands and leg. A distal sensory loss extending to both elbows and her remaining knee was found on examination. Nerve conduction tests were compatible with peripheral neuropathy of the "glove and stocking" type. DDP was withheld and her sensory loss improved over the next 2 months, but became worse after another course of DDP was administered. The temporal relationship between the findings and the administration of DDP implicates this drug as the causative agent in the peripheral neuropathy.
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PMID:Peripheral neuropathy as a complication of cis-dichlorodiammineplatinum(II) treatment: a case report. 20 27

Eight patients with advanced metastatic osteogenic sarcoma were treated with cis-dichlorodiammineplatinum(II) (DDP). Prior to DDP, seven patients had amputations and all had received adjuvant adriamycin (ADR) therapy. In addition, prior to DDP, six patients had received high-dose methotrexate. There was one complete response (pulmonary metastases) and four partial responses (three metastases in the lungs and one in the bone). One additional patient, with local recurrence of osteogenic sarcoma of the mandible following initial resection and adjuvant ADR, was retreated with surgery and DDP and is disease-free for greater than 3 years. The cumulative dose ranged from 300 to 660 mg/m2. Toxicity included irreversible kidney damage in two patients, transient severe hematologic suppression in two patients, and nausea and vomiting in all patients. DDP is a new effective agent in the treatment of osteogenic sarcoma.
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PMID:cis-Dichlorodiammineplatinum (II) in advanced osteogenic sarcoma. 34 12

Twenty-six patients with far-advanced epidermoid carcinoma of the head and neck were treated with cis-dichlorodiammineplatinum(II) (DDP) in high doses, utilizing the technique of concurrent mannitol-induced diuresis. All 26 patients had received prior radical radiotherapy to local disease, 14 had had major ablative surgical procedures, and all but five had been previously treated with chemotherapy. Responses were as follows (duration in months): two complete (2+, 6+), six partial (1, 2, 3, 4, 5+, 8+), ten minor (all but one less than 1.5), and eight no change or progression. Responses were seen in primary tumors, neck nodes, and pulmonary metastases. Nausea and vomiting were seen consistently in all patients but were never dose-limiting. Myelosuppression was mild, with only three patients developing platelet counts less than 50,000/mm3 and no patient with a wbc count less than 2000/mm3. Transient elevations of serum creatinine were common but no patient developed peak levels greater than 2 mg/dl. Transient tinnitus was also common although only four patients developed clinically significant hearing loss during the trial and DDP could be definitely implicated in only one instance. DDP in this dose and schedule is thus effective and safe therapy in a very heavily pretreated group of patients with advanced head and neck cancer and is now being used in combination with other agents in the initial treatment of these patients.
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PMID:CIS-Dichlorodiammineplatinum(II) in the treatment of epidermoid carcinoma of the head and neck. 87 36

An attempt to introduce combined therapy for patients with testicular seminoma in the II degree of clinical advancement was undertaken at the Centre of Oncology. Combined therapy consisted of 3 courses of PVB in the following daily doses: DDP 100 mg/m2 i.v. on the first day; VLB 10 mg i.v. on the first and second day; bleomycin 30 mg i.v. on the second, ninth and sixteenth day every 21 days, and 60Co on lymphatic glands area in which metastases were diagnosed prior to chemotherapy. Twenty three patients were treated that way between January 1985 and June 1989. Mean follow-up period after the treatment was 14 months. One patient died for the tumor, metastases to the lungs were diagnosed in one patient 9 months after completion of the treatment which ameliorated after "second" chemotherapy, and 22 patients (96%) are still free from the symptoms of active disease.
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PMID:[Evaluation of the results of combined treatment of patients with testicular seminoma in the II stage of clinical advancement]. 128 12

One hundred two patients with recurrent and/or metastatic head and neck squamous cell cancer were entered into four consecutive phase II trials, all cisplatinum (C-DDP, 100 mg/m2/cycle)-based. The two combinations tried were C-DDP, bleomycin, and fluorouracil (CFB) on 54 patients, and cisplatinum and vindesin in 36 patients (CV). The CFB combination was given with C-DDP by continuous infusion over 96 hours (23 patients) or on day 1 (31 patients). The CV regimen was also given in two different schedules, with VDS at 3 mg/m2/g weekly (12 patients) or by a 96-hour continuous infusion (0.6 to 1.0 mg/m2/d) in 24 patients. The following variables: sex, age, performance status, previous therapy, local recurrence, length of disease-free interval (DFI), distant metastases, weight loss, primary site, histological differentiation, type of chemotherapy, previous chemotherapy, evaluable/measurable disease, erythrosedimentation rate, and their relation with response to chemotherapy (WHO) and survival were submitted to both univariate and multivariate analysis (Cox). Overall response rate (RR:CR + PR) was 25 (28%) of 90. In the CFB protocols, RR was 12 (22%) of 54 vs. 13 (38%) of 36 (P = 0.15, NS) in the CV combination group. For the four different combinations the RR was CFB C-DDPci 7 (30%) of 23, CFB C-DDP 1 hour 5 (16%) of 31, CV VDS weekly 2 (17%) of 12, CV VDSci 11 (45%) of 24. The patient populations were very different, with the latest combination consisting of metastatic patients exclusively. Univariate analysis of multiple variables showed age less than 60 years, PS:0 or 1, no previous therapy, absence of local relapse, metastatic disease, long DFI, and that measurable disease was significant for the probability of response. Median survival was 7 months for the 90 evaluated patients, 5 months for nonresponders, and 9 months for responders (P = 0.01). In the univariate analysis, significant factors for survival were PS:0 or 1, a weight loss below 10%, long DFI, response to chemotherapy, erythrosedimentation rate (ESR) of less than 30 mm/1st hr, presence of bone metastasis, and the number of metastases. Multivariate analysis shows PS, the absence of local relapse, and disease-free interval as significant prognostic factors for response. Multivariate analysis factors of significance for survival were PS, weight loss, and response to chemotherapy. The analysis of the clinical pattern showed an evolution in RR from 3 (8%) of 36 on previously irradiated local recurrent disease to 8 (73%) of 11 in previously untreated patients with metastatic disease at presentation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recurrent and/or metastatic head and neck squamous cell carcinoma: a clinical, univariate and multivariate analysis of response and survival with cisplatin-based chemotherapy. 170 37

Arterial chemoembolization of liver tumors should improve regional treatment by reducing native blood flow of the whole organ and redistributing residual flow toward hypovascular masses. Plasma cisplatin pharmacokinetics and its tissue uptake and relative tumor and liver vascularity were studied during surgical placement of arterial catheters in four patients and in four patients with colorectal metastases given intraoperative arterial cisplatin (DDP, 25 mg/m2), with an without coadministration of 600 mg degradable starch microspheres (DSM). Mean (+/- standard deviation) filterable plasma platinum levels peaked later (2 minutes) and were significantly lower after DDP with DSM (1.23 +/- 0.69 micrograms/ml) than after DDP alone (2.13 +/- 0.43 micrograms/ml, P less than 0.05), with the area under the curve (AUC0-30 min) values of 15.8 +/- 5.5 and 25.1 +/- 3.8 micrograms x min/ml (P less than 0.05), respectively. No differences in urine excretion, total body clearance, or plasma protein binding of platinum were observed. Tissue biopsies were started 15 minutes after DDP administration and completed in all cases within 5 minutes. Tumor platinum concentrations were significantly higher after DDP with DSM (3.03 +/- 1.60 micrograms/g) than after DDP alone (0.67 +/- 0.49 micrograms/ml, P less than 0.05). Liver concentrations and tumor-liver ratios of platinum also were higher, although not significantly, after DDP with DSM. Preoperative vascularization, studied with arterial perfusion scan, influenced individual tissue drug uptake in cases given DDP alone, with the lowest tumor levels in cold masses. Very high and almost superimposable liver and tumor concentrations were measured in those receiving DDP and DSM. The latter phenomenon was irrespective of native vascularization, indicating that DSM administration induced both an increased whole-liver extraction of the drug and a redistribution of blood flow and flow-dependent tissue uptake of platinum.
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PMID:Liver and tumor uptake and plasma pharmacokinetic of arterial cisplatin administered with and without starch microspheres in patients with liver metastases. 191 93

Surgery is considered the mainstay of diagnosis and treatment in early ovarian carcinoma. Only accurate staging laparotomy can detect subclinical metastases remote from the ovary, thus allowing the identification of the truly early tumors. However the complete macroscopic removal of neoplastic disease is not synonymous with cure. Many postoperative treatments have been carried out in order to improve the prognosis of patients with stage I-II ovarian carcinoma. The present paper reviews the main clinical trials on the employment of external radiotherapy, intraperitoneal radioisotope instillation and systemic chemotherapy in the management of early ovarian carcinoma. The patients appear to benefit from adjuvant treatment, with the exception of those with stage I Ai-I Bi well differentiated tumor, even if there is no agreement in literature about the superiority of a particular therapeutic approach. However the high response rates obtained in patients with advanced ovarian carcinoma with DDP containing combination chemotherapy have suggested to clinicians the use of such treatment also in early stage tumors. In our experience none of the 11 stage I ovarian cancer patients, who received 6 courses of DDP-based combination chemotherapy, have developed recurrent disease after a median follow-up of 54 months (with a range from 24 to 72 months).
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PMID:Adjuvant treatment of early stage ovarian carcinoma. 229 41

Fifty-seven patients with stage III and IV (stage-grouping UICC 1987) carcinoma of the head and neck were primarily treated with both chemotherapy and radiotherapy at the same time. Radiation therapy was administered in two series in daily fractions of 2 Gy up to a total dose of 70 Gy. On the first five days of each series a daily dose of 20 mg/m2 body surface Cis-diamino-dichloroplatin (II) (Cis-DDP) was given intravenously. In the group of T3-tumors, there were 78% complete remissions and 89% complete or partial remissions, while in the group of T4-tumors, 46% complete remissions and 92% complete or partial remissions were found. In cases of N2-metastases there were 63% complete remissions and 89% complete or partial remissions, 43% complete remissions and 86% complete or partial remissions occurred in the group of N3-metastases. Complete remissions were obtained in 46%, and complete or partial remissions both of the primary tumor and of eventual metastases were obtained in 79%. However, the disease-free intervals for the majority of the patients were short. Only half of them stayed recurrence-free for longer than six months, while only one-quarter were recurrence-free for longer than 12 months.
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PMID:[Experiences with simultaneous cytostatic and radiotherapy treatment of advanced cancer of the head and neck]. 237 57


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