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)

One hundred sixteen eligible patients with metastatic cancer to the brain were randomized to receive either radiotherapy 3000 rad/10 fractions (treatment 1) or the same radiotherapy plus metronidazole 6 gm/m2 (treatment 2). One hundred eleven patients were either fully or partially evaluable. The response rates (CR + PR) and survival showed no significant differences between treatments. Treatment 1: CR + PR 24%, median survival 14 weeks, Treatment 2: CR + PR 27%, median survival 12 weeks. There were no differences observed in response rates based on primary tumor site, neurologic performance status, or extent of metastatic disease. Metronidazole therapy was associated with substantial nausea and vomiting but no neurotoxicity was observed. Oral metronidazole given every other day during radiation therapy provided no clinical benefit for patients with brain metastases compared to radiotherapy alone.
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PMID:Randomized trial of radiotherapy versus radiotherapy plus metronidazole for the treatment metastatic cancer to brain. A Southwest Oncology Group study. 639 78

We compared the efficacy and safety of the gonadotropin-releasing hormone analogue, leuprolide (1 mg subcutaneously daily), with diethylstilbestrol (DES, 3 mg by mouth daily) in patients with prostate cancer and distant metastases (Stage D2) who had not previously received systemic treatment. Initial therapy (leuprolide or DES) was continued for as long as an objective response was noted; cross-over to the alternative arm occurred at the time of disease progression or intolerable adverse reactions. Ninety-eight patients were randomly assigned to leuprolide, and 101 to DES. Suppression of testosterone and dihydrotestosterone and decreases in acid phosphatase were comparable in the two groups. Patients receiving DES experienced more frequent painful gynecomastia (P less than 0.00001), nausea and vomiting (P = 0.02), edema (P = 0.008), and thromboembolism (P = 0.065) than those receiving leuprolide. The leuprolide group reported more "hot flashes" (P = 0.00001). Overall, 86 per cent of the leuprolide group had an objective response (complete response, 1 per cent; partial response, 37 per cent; stable disease, 48 per cent), as compared with 85 per cent of the DES group (complete, 2 per cent; partial, 44 per cent; stable, 39 per cent). Actual survival rates at one year were 87 per cent for the leuprolide group and 78 per cent for the DES group (P = 0.17). We conclude that leuprolide offers an important alternative treatment that is therapeutically equivalent to and causes fewer side effects than DES for the initial systemic management of metastatic prostate cancer.
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PMID:Leuprolide versus diethylstilbestrol for metastatic prostate cancer. 643

Bisantrene (NSC 337766) is an anthracenedicarboxaldehyde hydrazone demonstrating a wide spectrum of activity in animal tumor model systems with no evidence of cardiotoxicity or alopecia, in contrast to doxorubicin. Thirty-three women with advanced adenocarcinoma of the breast were treated with 260 mg/m2 IV every 3 weeks. All patients had received at least one prior combination chemotherapy regimen for metastatic disease and 32/33 were refractory to doxorubicin. Of 28 patients evaluable for response one had a partial response lasting 10 weeks and three patients had stable disease for 22, 22, and 9 weeks. The most significant toxicities were nonhematologic: nausea and vomiting (41%), phlebitic reactions (38%), hypotension, one fatal anaphylactic reaction, and the development of a 7th cranial nerve palsy during drug infusion. Hematologic toxicity, leukopenia, was dose-limiting but manageable without associated infections or bleeding. These results indicate that bisantrene in this dose and schedule is not a useful drug in heavily pretreated breast cancer patients. The incidence and severity of phlebitic reactions limited venous access and adversely affected patient compliance. Preliminary results of other phase II breast cancer trials indicate a similar spectrum of toxicity but suggest more significant antitumor activity even in patients previously treated with doxorubicin. Trials conducted in patients with minimal prior treatment and with bisantrene administered via central line appear warranted for definitive assessment of the activity of this agent in breast cancer.
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PMID:Bisantrene (NSC 337766) (CL 216,942) in advanced breast cancer. A cancer and leukemia group B study. 648 43

Ninety-six cancer patients received a total of 280 courses of cis-diamminedichloroplatinum (DDP), alone (20 patients), or in combination with other agents. DDP was given in 20 mg/m2 as a continuous 24-hour infusion daily for 5 consecutive days, repeated every 4 to 6 weeks. Patients were adequately hydrated for 12 hours prior to treatment but no diuretics or mannitol were used. Twenty percent of the patients developed no toxicity. Nausea and vomiting were lacking in 42% of 256 evaluable cycles and were mild in 36%. Nephrotoxicity was observed in four patients (5%) and was reversible on cessation of therapy in all except one. Hypomagnesemia occurred in 4% of 140 evaluable cycles. Mild ototoxicity was noted in two patients. The therapeutic efficacy of this dose schedule could not be adequately assessed, but one patient with thymoma and extensive pulmonary metastases achieved partial remission on DDP alone, and another with progressive mediastinal thymoma achieved stabilization of disease. In conclusion, this study suggests that the toxicity of the 5-day continuous infusion regimen is relatively mild. Randomized trials are indicated to evaluate the therapeutic efficacy of this new regimen, and the role of DDP in the treatment of malignant thymoma should be further explored.
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PMID:Cis-diamminedichloroplatinum (II) by 5-day continuous infusion. A new dose schedule with minimal toxicity. 653 93

Five patients between 72 and 82 years old received 5 to 6 treatments of 50 to 75 mg. per m.2 cisplatin by bilateral internal iliac artery infusion for unirradiated invasive transitional cell carcinoma of the bladder. Of the patients 3 also were diabetics and 1 had congestive heart failure. Treatment was tolerated extremely well, although most courses were associated with moderate to severe nausea and vomiting lasting several hours. Of 4 evaluable patients 3 achieved complete remission and 1 achieved a good partial remission. An additional 55-year-old woman with a large invasive bladder carcinoma fixed to surrounding structures was treated with 4 courses of 100 mg. per m.2 intra-arterial cisplatin. This patient had a marked decrease in tumor size, permitting surgical resection of all known residual tumor. A 49-year-old patient with large pelvic lymph node metastases from a squamous cell carcinoma of the bladder achieved only minimal decrease in tumor size after 3 courses of 100 mg. per m.2 intra-arterial cisplatin. We conclude that intra-arterial cisplatin can be highly effective for localized invasive bladder cancer even when relatively low doses are used. With proper care the regimen can be used safely and effectively in elderly patients with medical contraindications to an operation.
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PMID:Intra-arterial cisplatin treatment of unresectable or medically inoperable invasive carcinoma of the bladder. 653 37

Thirty-four patients with advanced breast cancer, who had not received previous chemotherapy for metastatic disease, were treated with mitoxantrone 14 mg/m2 i.v. every 21 days. Eleven of 33 evaluable patients (33%) achieved a partial response; there were no complete responders. Before commencing mitoxantrone, and 3-monthly thereafter, radionuclide assessment of ventricular performance was obtained at rest and in response to stress. Ten patients showed a deterioration in ejection fraction, two of whom developed congestive cardiac failure. Dose-limiting toxicity was myelosuppression. Nausea and vomiting were generally mild and transient. Alopecia was minimal in most patients. Mitoxantrone is an active, well-tolerated new drug in the treatment of advanced breast cancer, but cardiotoxicity may occur in a proportion of patients. Further investigation is required to determine the precise nature, incidence and prognosis of cardiotoxicity encountered with mitoxantrone.
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PMID:Mitoxantrone in advanced breast cancer--a phase II study with special attention to cardiotoxicity. 654 Jan 79

Fourteen patients with advanced carcinoma of the breast were treated with CAP combination therapy. An objective therapeutic response (partial remissions with a mean duration of 6.3 months) was achieved in 6 of 13 evaluated patients. This response was observed in soft tissue metastases. Nausea and vomiting were found to be the most frequent undesirable side effects in all patients and could not be avoided by administration of antiemetics. In 2 patients mild nephrotoxicity was found without any effects on further therapy. The results of this study were considered as promising; a definitive assessment of the CAP regimen is expected to come from a randomized study which started in the CMEA countries in 1983.
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PMID:CAP (cyclophosphamide, adriamycin, cisplatinum) in the treatment of advanced breast cancer. 654 99

A Phase I trial of tricyclic nucleoside phosphate (1,4,5,6,8-pentaazaacenaphthylene-3-amino-1, 5-dihydro-5-methyl-1-beta-D-ribofuranosyl 5'-phosphate ester; NSC 280594) was conducted using a 5-day continuous infusion schedule. Thirty-seven patients with advanced cancer were entered on the study, of whom 33 patients were evaluable for response and toxicity. Dose levels ranged from 10 mg/sq m/day X 5 days to 40 mg/sq m/day X 5 days. Initially, courses were repeated every 3 to 4 weeks. As cumulative toxicity became manifested, the interval between courses was changed to every 6 weeks. Major toxicities included hyperglycemia, hepatotoxicity, and thrombocytopenia. Patients with a prior history of diabetes mellitus, extensive radiation therapy, or significant liver metastases were prone to severe toxicity. Other toxicities noted were nausea and vomiting, abdominal discomfort, anemia, and reduction in serum calcium, phosphorus, and albumin levels. Rare side effects included hypertriglyceridemia, hyperamylasemia, diarrhea, and stomatitis. Antitumor activity observed include improvement in s.c. metastases in a patient with papillary thyroid carcinoma, stabilization of disease in a patient with mesothelioma, and mixed responses in three patients (colon cancer, sarcoma, and tonsillar squamous cell cancer). Recommended schedule for Phase II studies is 20 mg/sq m/day for 5 days every 6 weeks.
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PMID:Phase I study of tricyclic nucleoside phosphate using a five-day continuous infusion schedule. 674 83

Seventeen patients with advanced breast cancer were treated with cis-diamminedichloroplatinum (DDP) 100 mg per m2 every 21--28 days. Hydration and mannitol or furosemide diuresis was given. Responses were seen in two patients (one complete, one objective) with soft-tissue metastases. There was no difference in peak plasma platinum concentration (3.91 micrograms/ml +/- 1.41 micrograms/ml), terminal plasma half-life (116--288 hours), peak concentration of unbound platinum (0.7 micrograms/ml), or 24-hour urinary platinum excretion (6.7--17.2% of administered dose) between the objective responder and the nonresponders. Toxicities included severe nausea and vomiting, renal insufficiency, high-frequency hearing loss, and peripheral neuropathies. Hematologic toxicity was mild in most patients. DDP has limited activity when used as a single agent in this dose and schedule in patients with metastatic breast cancer.
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PMID:High-dose cis-diamminedichloro-platinum therapy in patients with advanced breast cancer: pharmacokinetics, toxicity, and therapeutic efficacy. 719 82

In a phase II study of methyl-glyoxal bis-guanylhydrazone (methyl-GAG) in patients with bi-dimensionally measurable metastases of renal cell cancer, 30 patients were given 500 mg/m2 weekly for at least 4 treatment cycles and were evaluable for response. Three patients (10%) achieved partial remission (PR) with a duration of 8-12 weeks; in 11 patients the disease was assessed as stable; and in 16 there was progression. A total of 40 patients were evaluable for toxicity. Nausea and vomiting occurred in 17 (43%), neuropathy, myopathy or myalgia in 8 (21%) and mucositis in 6 (14%). In addition to 3 patients taken off treatment before 4 treatment cycles, toxicity precluded further treatment in 3 others after 5, 6 and 7 cycles respectively. Methyl-GAG has minimal activity in renal cell cancer and, in this dose schedule, causes appreciable toxicity.
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PMID:An EORTC phase II study of methyl-glyoxal bis-guanylhydrazone in advanced renal cell cancer. 720 Aug 96


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