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)

The pyrimidine analog, 5-azacytidine (NSC 102816), was administered by continuous intravenous infusion in Ringer's lactate in increasing doses to sets of patients with metastatic cancer to establish a dose sufficient to produce mild toxicity. Twenty-one patients (23 trials) were treated with doses of 50-200 mg/sq/m/day for 5 days every 2-4 wk. Nausea and vomiting were moderate and easily preventable. Doses of 100-200 mg/sq/m for 5 days every 14 days produced granulocytopenia, usually after two courses. Less toxicity was observed when courses were given every 21-28 days. Forty-five patients with previously treated and refractory acute myeloblastic leukemia were treated. The majority received doses of 150 mg/sq m for 5 days every 2 wk. Eleven (24%) complete remissions and four partial remissions were observed. The number of courses to achieve remission averaged three and required an average of 59 days. Nine patients with blastic crisis of chronic myeloblastic leukemia and four with refractory acute lymphoblastic leukemia failed to respond. 5-Azacytidine administered by continuous infusion is well tolerated and is an active compound in acute myeloblastic leukemia.
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PMID:5-Azacytidine (NSC 102816): a new drug for the treatment of myeloblastic leukemia. 6 Jan 56

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

Twenty-four patients with far advanced malignant tumors, resistent to established chemotherapy,, were treated with the combination of MNU and Cyclophosphamide. The drugs were administered in six-day cycles sequentially. MNU in doses of 4 mg/kg body weight and Cyclophosphamide in doses of 8 mg/kg body weight were given. Results of treatment showed response (greater than 50% tumor regression) in 10 (42%) of the 24 treated patients. Seven remissions were complete and three partial. Patients with Hodgkin's disease, malignant melanoma and breast cancer responded to this combination chemotherapy. Objective remissions were obtained also in five of thirteen patients with primary or metastatic brain tumors and in five of nine patients with pulmonary metastases. Nausea and vomiting were the main toxic effects, especially after injections of MNU. Myelosuppression was noted in about 50% of treated patients. Since this combination of cytostatics showed significant antitumor activity, further investigations are necessary on a larger number of patients and in other types of malignant tumors.
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PMID:Combination chemotherapy with 1-methyl-1-nitrosourea (MNU) and cyclophosphamide in solid tumors. 14 13

This report gives the complete findings at one year of a study comparing radiotherapy (Rt) with radiotherapy followed by 3-drug chemotherapy (RtC3) in the treatment of histologically proven small-cell carcinoma of the lung of limited extent. Over the 12-month period there was a significantly increased survival for the RtC3 patients (P = 0.002) and at 12 months 18% of the 121 Rt but 34% of the 115 RtC3 patients were alive (P = 0.009). The median survival for the Rt series was 25 weeks and for the RtC3 series 43 weeks. There was evidence of recurrence of the primary cancer in 32 (32%) of the 99 Rt and 20 (26%) of the 76 RtC3 patients who died. Distant metastases appeared earlier and were more frequent in the Rt series (P less than 0.0001) and over the 12-month period 79% of the Rt and 57% of the RtC3 patients developed distant metastases (P less than 0.0005). At 12 months only 8% of the Rt but 26% of the RtC3 patients were alive and free of metastases. Adverse reactions occurred much more frequently in the RtC3 series; 32% of the Rt series as against 83% of the RtC3 series had reactions, the most common being nausea and vomiting (13% Rt, 71% RtC3) and the most serious being marrow depression (23% Rt, 54% RtC3). No important differences were found among the survivors in the 2 series at 3, 6 or 12 months, in general condition, physical activity or respiratory function. It is concluded that radiotherapy plus chemotherapy was superior to radiotherapy alone, although chemotherapy did not protect patients from recurrence of primary growth.
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PMID:Radiotherapy alone or with chemotherapy in the treatment of small-cell carcinoma of the lung. Medical Research Council Lung Cancer Working Party. 22 12

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

Hycanthone was given to 15 patients with metastatic cancer in order to determine the maximum tolerable dose. The drug was administered in 5-day courses at 3-week intervals. The starting dose was 30 mg/m2/day and the highest dose level reached was 90 mg/m2/day. The most common (13 patients) side effect was nausea and/or vomiting. The dose-limiting toxicity was toxic hepatitis manifested as elevation in serum transaminases in eight of 15 patients and an increase in serum bilirubin in three patients. Hepatotoxicity was dose-related and was observed in two of 25 courses given at the dose level of less than or equal to 70 mg/m2 compared to seven of nine courses given at the dose level of greater than or equal to 80 mg/m2. Because of an unacceptable incidence of hepatotoxicity at higher doses, 70 mg/m2/day x 5 appears to be a safe dose for phase II studies.
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PMID:Phase I study of hycanthone. 35 76

Twenty-six patients with disseminated malignant melanoma were treated with intermittent bolus DTIC and actinomycin D in an escalating dose schedule, starting at 650 and 1 mg/m2 respectively. Courses were repeated at 3--4-week intervals. Twenty four patients were evaluable for toxicity and 22 were evaluable for response. Two patients (9%) had a complete remission lasting 7+ and 14 months, and three patients (14%) had a partial remission lasting 2+, 5+, and 14+ months. Nausea and vomiting, lasting 24 hours, was observed in 88% of patients, while diarrhea was noted in 17%. Stomatitis and alopecia were less frequently observed. All responses occurred at nonmyelosuppressive doses and in patients with visceral-predominant metastases. This schedule offers the patient the convenience of single-day treatment and less prolonged gastrointestinal intolerance. Further evaluation of this drug combination and schedule would appear to be indicated.
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PMID:Phase I--II study of intermittent bolus administration of DTIC and actinomycin D in metastatic malignant melanoma. 35 80

In 409 sufferers from various malignant tumours, we used the cytostatic Ifosfamide (ASTAZ4942) in fractionated doses. The total i.v. dose averaging 300 mg/kg bodyweight, was either spread over 5 consecutive days (5 X 60 mg/kg i.v.) or over 10 consecutive days (10 X 30 mg/kg). At the same time, most patients were irradiated, the radiation dose usually being only one tenth the antitumour dose. Infections and electrolyte imbalance were first treated before Ifosfamide therapy was instituted. Cases of advanced cerebral sclerosis, thrombopenia below 75,000/cmm, cerebral metastases, impaired renal function and inadequate cooperation of the patient were excluded from the studies. To prevent and control side effects, various premedications and adjuvants are required: Antiemetics, prevention of cystitis and infections, cardiovascular agents etc. Corticosteroids are contraindicated. Out of 360 assessable patients 101 had a full remission, 150 a partial remission, 79 were failures; 30 cases were not evaluated. Good results were seen especially in ovarian carcinoma, mammary carcinoma and microcellular bronchial carcinoma. Particularly striking is the drug's effectiveness in testicular tumours including teratomas, osteosarcomas, chondrosarcomas and myosarcomas as well as in some adenocarcinomas of the gastro-intestinal tract, particularly pancreatic carcinoma. In lymphoreticular tumours and haemoblastoses, its potency is less pronounced. The side effects of Ifosfamide are the same as those of other alkylating agents. They are reversible and can usually be controlled or even avoided by adequate preventive measures. In the order of incidence we observed: Alopecia, leukopenia, fall in haemoglobin, cystitis, intercurrent infections, nausea and vomiting as well as cerebral disorders. Since haemorrhagic cystitis considerably interferes with Ifosfamide treatment, its prevention is of essential importance. Because of possible complications and specific premedication and adjuvant measures for their control, this type of treatment should for the present only be carried out by oncologists or special cancer centres.
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PMID:Results obtained with fractionated ifosfamide massive-dose treatment in generalized malignant tumours. 78 66

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

Chromomycin A3 was given to 43 patients with metastatic cancer in order to determine the tolerable dose when the drug was administered on an every-other-day dose schedule for a total of five iv push injections, with the course of therapy being repeated every 4 weeks. At least three patients were entered at each dose level, graduated in 0.1-mg/m2 increments between 0.7 and 1.6 mg/m2. The most common (19 patients) side effect was nausea and/or vomiting, but this was usually mild, lasted for a few hours, and diminished in severity with repeated injections. Skin necrosis due to drug extravasation was a problem early in the study, but was eliminated by injecting the drug through iv tubing. Transient elevations in SGOT and alkaline phosphatase levels were observed, but proved not to be of serious consequence. Renal toxicity proved to be the limiting factor in therapy. However, a dose level of 1.3 mg/m2 was found to be a tolerable level of drug administration in previously untreated patients. Objective tumor responses were noted in four patients (Hodgkin's disease, embryonal rhabdomyosarcoma, adenocarcinoma of the lung, and malignant melanoma).
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PMID:Phase I alternate-day dose study of chromomycin A3. 103 32


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