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

Five dogs with ostoegenic sarcoma were treated by surgical removal of the primary tumor and by adjuvant chemotherapy. Methotrexate at dosages of 3 to 6 g/m2 was used with leucovorin rescue. All dogs tolerated E g of methotrexate/m2 of body surface, but granulocytopenia precluded escalation beyond this dosage in 4 dogs. The rate and time of appearance of pulmonary metastases were not altered by treatment, with all dogs developing metastases at a median time of 4 months after amputation.
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PMID:High-dose methotrexate and leucovorin rescue in dogs with osteogenic sarcoma. 31 44

Forty-one evaluable patients with malignant melanoma resistant to other chemotherapeutic agents received 9 mg/m2 of piperazinedione every 3 weeks. Two patients had partial responses and one additional patient had stable disease. One of the partial responses occurred in a patient with subcutaneous metastases and the other occurred in a patient with pulmonary and osseous metastases. Both antitumor responses occurred in the 17 patients with a performance status of greater than or equal to 80%. The dose-limiting toxicity was myelosuppression; thrombocytopenia was more frequently observed than granulocytopenia.
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PMID:Phase II trial of piperazinedione in malignant melanoma: a report by the Southeastern Cancer Study Group. 47 10

Thirty-two evaluable patients with metastatic carcinoma of the breast received chemotherapy consisting of BCNU plus cyclophosphamide followed in 18 hours by Adriamycin. Treatments were repeated every 4 weeks. Complete or partial responses were observed in 14 patients (43.7%) and in 12 of 27 drug-resistant patients (44.4%). An additional 26% of patients had objective improvement, for an overall objective response rate of 70.4% in drug-resistant patients. Skin, lymph node, and soft tissue metastases more frequently responded to therapy, while hepatic, peritoneal, and osseous metastases responded with an intermediate frequency. Pulmonary, pleural, and central nervous system metastases did not respond to therapy. The median duration of complete and partial responses was 6.8 months, and the median survival of these patients was 9.6 months. Overall, the median survival of all patients in this study was 6.5 months. The dose-limiting toxicity was myelosuppression, particularly granulocytopenia. Congestive heart failure and stomatitis were rare. This combination of drugs is a reasonably well-tolerated regimen for treating advanced breast carcinoma in an ambulatory setting, and produces a high rate of objective antitumor response of moderate duration.
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PMID:Adriamycin, 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU, NSC 409962) and cyclophosphamide therapy of drug-resistant metastatic breast carcinoma. 90 47

Wy 18,251 (Tilomisole; Wyeth Laboratories, Philadelphia, PA, USA) is a benzimidazole that is structurally similar to the antihelminth levamisole that has recently been approved for the adjuvant treatment of colon cancer. In preclinical models, Tilomisole caused less agranulocytosis than levamisole, but retained immunomodulating capabilities. We examined the effects of Tilomisole administered to cancer patients in four different dose schedules: 60 mg/m2 orally (p.o.) weekly, and 60, 300, or 960 mg/m2 p.o. daily for 1 month. All patients were immunosuppressed when treatment was initiated as defined by standardized assays of phytohemagglutinin, concanavalin A, pokeweed mitogen, and mixed lymphocyte responses. Tilomisole was well tolerated with no significant side effects in 25 patients. There were no antitumor responses noted in this setting of metastatic cancer. There was no improvement in concanavalin A or pokeweed mitogen assays at any dose or schedule, but there was sustained improvement in mixed lymphocyte reaction and phytohemagglutinin assays at the 60 mg/m2 daily dose. This drug may have favorable biological response modifying effects in vivo and be a suitable alternative to levamisole in cancer treatment, especially if agranulocytosis is a significant problem associated with widespread use of levamisole.
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PMID:WY 18,251 (Tilomisole), an analog of levamisole: tolerability, and immune modulating effects in cancer patients. 138 9

The National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a phase II study of weekly oral menogaril as first-line therapy in 51 patients with incurable, metastatic or locally advanced breast cancer. While no prior chemotherapy for metastatic disease was permitted, prior adjuvant chemotherapy was allowed provided that no anthracycline or anthracene had been given. Forty-eight patients were evaluable for response. Two patients (4%) achieved complete remissions, 9 patients (19%) achieved partial remissions, 26 patients (54%) were stable and 11 patients (23%) failed. At the initial menogaril dose of 275 mg/m2 per week, 13 of 14 patients required a dose reduction and/or a treatment delay of one or more weeks. Therefore, the menogaril dose was reduced to 225 mg/m2 per week for the last 37 patients. At that those, 20 of 37 patients developed grade 3 or 4 granulocytopenia and 22 required dosage delays. At the initial starting dose, the average dose intensity actually delivered was 169 mg/m2 per week. At 225 mg/m2 the average dose intensity actually delivered was 197 mg/m2 per week. Toxic effects included mild to moderate nausea and vomiting, diarrhea, hair loss and occasional hyperpigmentation. In summary, menogaril is an anthracycline derivative that has modest activity when administered orally to minimally pretreated patients with breast cancer.
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PMID:Phase II study of oral menogaril as first line chemotherapy for advanced breast cancer: a National Cancer Institute of Canada Clinical Trials Group study. 153 20

Taxol, an antimicrotubule agent, has shown promise for efficacy in treatment of breast cancer, but severe hypersensitivity reactions led to cessation of many phase I clinical trials. Consequently, investigators and the National Cancer Institute recommended that phase I and II studies of this agent use 24-hour infusions and antiallergic medications. Using a premedication regimen effective in preventing hypersensitivity reactions, we have performed a phase II trial of taxol in patients with metastatic breast cancer. Taxol was administered to 25 patients at a dose of 250 mg/m2 by 24-hour infusion every 21 days. These patients had received only one prior chemotherapy regimen, either adjuvant to surgery or for metastatic disease; all but two had received doxorubicin. In 60% of the patients, the dominant site of disease was the viscera. All patients were assessable. In April 1991, at a median time on study of 9 months (range, 5-13+ months), the objective response rate was 56% (12% complete and 44% partial; 95% confidence interval, 35%-76%). Disease progressed in only 8% of the patients. The median number of courses of therapy was 11. Granulocytopenia was the dose-limiting toxic effect, but neutropenia with fever occurred in only 5% of 232 courses. A chronic glove-and-stocking neuropathy developed in most patients, but no allergic reactions occurred. We conclude that taxol is an active agent in the treatment of metastatic breast cancer and that it warrants continued study. Currently, we are conducting a phase I trial of taxol plus doxorubicin. Future trials should address the optimal effective dose, the optimal sequencing of combinations, mechanisms of drug resistance in tumors, and dose-limiting toxic effects (particularly cardiac toxic effects of taxol given as a single agent or in drug combinations).
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PMID:Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer. 168 8

Cyclophosphamide demonstrates enhanced tumoricidal activity with decreased bone marrow toxicity when given on a divided-dose schedule in certain animal models. A total of 22 patients presenting with refractory metastatic cancer were treated in a phase I trial of continuous infusion of cyclophosphamide over 96 h. Granulocytopenia of less than 500/microliters that lasted for greater than 14 days or thrombocytopenia of less than 25,000/microliters that lasted for greater than 14 days was the target dose-limiting toxicity in the absence of nonhematologic grade 4 toxicity. The maximal tolerated dose was 7 g/m2. Three patients died. Of 21 evaluable patients, 9 responded, including 8/9 who had experienced disease progression during prior oxazaphosphorine-containing combination chemotherapy. Clinically meaningful responses were observed in patients who had demonstrated clinical resistance to an oxazaphosphorine drug given at lower doses.
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PMID:A phase I trial of continuous-infusion cyclophosphamide in refractory cancer patients. 174 50

A phase II trial of vinblastine in patients with refractory epithelial ovarian adenocarcinoma of the ovary was conducted by the Gynecologic Oncology Group (GOG) between March 9, 1988 and July 7, 1988. Vinblastine was administered in a dose of 9 mg/m2 intravenously every three weeks until disease progression or toxicity supervened. Twenty patients were entered initially. One was ineligible due to a previous primary cancer. Thus, 19 patients are evaluable for toxicity and response. All patients had cisplatin-combination chemotherapy and four had prior radiotherapy. Median age was 63 years (range 40-75 years). Thirteen patients had disease in the pelvis and six had extrapelvic metastases. Ten patients had grade 3 lesions and seven had grade 2. A median of two courses (range: 1-6) were administered. Toxicity was moderate. Seven patients (36.8%) experienced GOG grade 3 or 4 leukocytopenia and six had grade 3 or 4 granulocytopenia. Median nadir WBC was 2,000 cells/microliters (range 600-3,500) and platelet nadirs for the three patients with thrombocytopenia were 60,000, 116,000, and 147,000. Other toxicity included grade 3 gastrointestinal and renal toxicity in one patient each. Seven patients (36.8%) had stable disease on therapy and 12 had increasing disease. No responses were observed. Vinblastine in this dose and schedule is inactive in patients with resistant epithelial ovarian adenocarcinoma progressing on first-line chemotherapy.
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PMID:Phase II trial of vinblastine in advanced ovarian carcinoma. A Gynecologic Oncology Group study. 208 71

Thirty-six patients with advanced squamous carcinoma of the uterine cervix recurrent after radiotherapy or surgery or first-line chemotherapy were eligible for a phase II study employing vinblastine in a dose of 9 mg/m2 intravenously every 3 weeks until disease progression or toxicity supervened. Two patients were never treated, leaving 34 patients evaluable for toxicity. One patient was inevaluable for response, leaving 33 evaluable for this parameter. Thirty-two patients had prior radiotherapy and 30 had prior chemotherapy. All patients had Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2. Median age was 46 years. Twenty patients had disease in the pelvis and 13 had extrapelvic metastases. Fourteen patients had grade 3 lesions. A median of three courses (range: 1-12 courses) was administered. Ten patients (29.4%) experienced GOG grade 3 or 4 leukocytopenia and 10 had grade 3 or 4 granulocytopenia. Other toxicity included grade 4 gastrointestinal toxicity and anemia in one patient each and two patients with grade 3 neurotoxicity. Twenty patients (60.6%) had stable disease with therapy and 13 had increasing disease. No responses were observed. Vinblastine in this dose and schedule is inactive in previously treated patients with squamous carcinoma of the cervix.
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PMID:Phase II study of vinblastine in previously treated squamous carcinoma of the cervix. A Gynecologic Oncology Group study. 223


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