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

Lung cancer is the most lethal cancer in the United States, with 143,000 deaths predicted for 1991. The cure rate is extremely low (approximately 13%), in part because the propensity for early spread precludes surgical cure in most patients. Thus, chemotherapy or other systemic therapies are the only way to improve the dismal results. Cisplatin is an active agent in small cell lung cancer (SCLC) and perhaps the most active agent in nonsmall cell lung cancer (NSCLC). The toxicities and inconvenience of cisplatin make it less than ideal for lung cancer therapy. Carboplatin was developed to provide a less toxic, more convenient alternative to cisplatin. The data presented in this review suggest that carboplatin may be substituted for cisplatin in the treatment of extensive-stage SCLC. In limited-stage SCLC, there are insufficient data to determine whether it should replace cisplatin when used simultaneously with chest irradiation and etoposide. It may be substituted for cisplatin in cycles not using irradiation. In NSCLC, carboplatin may be used alone or with etoposide for the palliative management of metastatic disease. Its role in earlier stages of NSCLC needs investigation.
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PMID:Clinical experiences with carboplatin (paraplatin) in lung cancer. 132 16

Cisplatin/etoposide/bleomycin (DEB) was given as an outpatient regimen in a novel weekly schedule to 27 patients with recurrent and/or widely metastatic cancer of the head and neck region. Six of these patients also received mitomycin (DEB/M) when their disease failed to respond after at least three weekly DEB doses. All but three patients had been treated previously with radiotherapy directed to the primary site and regional nodal disease; four had also received chemotherapy with cisplatin or carboplatin. Before treatment with DEB, 19 patients had distant metastases. Of an intended 12 doses per patient, a mean of 8.2 was achieved. Myelosuppression was the major toxicity, with neutropenia in 45% of patients and significant anemia in 26%. The overall response rate to DEB in 27 patients was 59%, increasing to 70% after the addition of mitomycin. There were two complete and 17 partial responses. The median duration of response was 12 weeks and median survival was 6 months, with 20% of patients surviving 1 year. We conclude that the relatively short survival time together with the significant toxicity of the DEB/M regimen does not warrant its routine use in clinical practice. However, this regimen, or one patterned on it, should be evaluated in combination with radiotherapy as the initial treatment for selected patients with previously untreated head and neck cancer.
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PMID:Treatment of recurrent and metastatic head and neck cancer with cisplatin/etoposide/bleomycin. 138 40

Therapy for metastatic breast cancer can palliate disease and prolong life, but cannot cure. New drugs will be required if this is to change. Cisplatin and its analogue carboplatin offer new approaches to the treatment of metastatic breast cancer. Cisplatin has significant single-agent, front-line activity in metastatic breast cancer. In combination with other agents (eg, etoposide or 5-fluorouracil), it provides response rates equivalent to other front-line combinations. The activity of carboplatin as a single agent is reportedly less than that of cisplatin in single-agent trials, and few combination trials have been reported. Both cisplatin and carboplatin, when used in high doses in the setting of autologous bone marrow transplantation, appear to be useful agents for the treatment of metastatic disease. Further research is needed to define the role of these compounds in the treatment of breast cancer.
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PMID:Cisplatin and platinum analogues in breast cancer. 141 30

From 1984-1990, 143 patients with squamous cell or adenocarcinoma of the esophagus were enrolled in a Phase I/II study of neoadjuvant chemotherapy followed by concurrent chemotherapy plus radiotherapy with or without subsequent esophagectomy. Patients received one cycle of Cisplatin or Carboplatin plus Etoposide for squamous cell carcinoma, or Cisplatin or Carboplatin plus 5FU for adenocarcinoma, followed by two cycles of the same chemotherapy given concurrently with 44-46 Gy over 5 weeks. Operable patients then underwent esophagectomy. Inoperable patients and those with positive surgical margins received additional irradiation (16-18 Gy). Twelve percent of the surgical group received preoperative radiotherapy doses > or = 50 Gy. Seventy-two percent (103) had clinical Stage I-III tumors and 28% (40) were clinical Stage IV (1983 American Joint Committee on Cancer criteria). Only clinical Stage I-III patients were analyzed with respect to patterns of failure. Isolated local failure occurred in 19/103 (18%) of clinical Stage I-III patients. Both local and distant relapse occurred in 15/103 (15%), and distant metastases alone occurred in 25/103 (24%). The 3-year actuarial rates of local and distant failures were 45% and 60%, respectively. Among the clinical Stage I-III patients who underwent surgery (n = 58) versus those who did not (n = 45), the 3-year actuarial local and distant failure rates were 30% versus 60% and 45% versus 45%, respectively. Multivariate analysis was performed to identify significant predictors of local control. For all clinical Stage I-III patients, treatment with surgery (p = 0.001) and with three or more cycles of chemotherapy (p = 0.02) were significant predictors of improved local control. Patients who underwent surgery were significantly younger and had a better performance status than those who did not. The improvement in local control with surgery did not translate into better survival, likely on account of a high operative mortality rate in older patients and those receiving > or = 50 Gy preoperatively. We conclude that local control remains poor with concurrent chemotherapy + radiotherapy for esophageal cancer. The addition of surgery improved local control, but distant metastases remain a problem both in this group of patients as well as those treated without esophagectomy. Efforts to improve local control appear warranted, but it remains to be demonstrated that improved local control translates into improved survival in esophageal cancer because of a high rate of distant metastases in patients whose disease is controlled in the esophagus.
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PMID:Patterns of failure following combined modality therapy for esophageal cancer, 1984-1990. 142 85


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