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)

Twenty-six patients with metastatic cancer were entered into a phase I trial of concurrent recombinant interleukin-2 (IL-2) and recombinant interferon-gamma (IFN-gamma). IL-2 was administered as a continuous intravenous infusion for 5 days. IFN-gamma was administered by a daily intramuscular (IM) injection during the 5 days of IL-2 administration. Treatment was repeated twice after 9-day rest periods. After a 2-week rest, patients without evidence of tumor progression were retreated. Natural killer (NK)- and lymphokine-activated killer (LAK)-cell activity were assayed in each patient before treatment, on day 1, and on day 5 of each cycle. Constitutional symptoms occurred in most patients but were not dose-limiting. Other toxicities included hypotension responsive to fluids, transient elevations in liver function tests, erythema/pruritus, eosinophilia, and transient leukopenia/thrombocytopenia. The maximum-tolerated dose (MTD) of the combination was 1 x 10(6) U/m2/d of IL-2 combined with 0.50 mg/m2/d of IFN-gamma. The dose-limiting toxicity was pulmonary manifesting as rales and shortness of breath. The dose of the combination that resulted in the optimal generation of in vivo LAK-cell activity was a dose of at least 0.25 mg/m2/d of IFN-gamma combined with 1 x 10(6) U/m2/d of IL-2. Objective clinical responses were seen in five of 26 patients. These included a partial response of 2 months duration in a patient with non-Hodgkin's lymphoma (NHL), mixed responses in a patient with NHL and two patients with renal cell carcinoma (RCC), and an ongoing assessable response in a patient with bone metastases from RCC. The recommended dose for phase II trials of this combination is 0.50 mg/m2 of IFN-gamma and 1 x 10(6) U of IL-2.
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PMID:A phase I trial of recombinant interleukin-2 combined with recombinant interferon-gamma in patients with cancer. 211 71

The purpose of the study was to investigate the antitumour activity and toxicity of high dose (120 mg m-2) single agent epirubicin therapy in untreated extensive small cell lung cancer patients. Out of 80 patients entered, 71 were evaluable for both antitumour activity and toxicity, 4 only for toxicity and 5 were lost for follow-up. The drug possessed a high antitumour activity, the overall response rate was 47.9% (34/71) with 4 complete remissions (CR) and 30 partial remissions (PR). The median remission duration was 3.5 months. Particular drug activity was observed in the primary tumours, lymph nodes and pleural metastases. Toxicity (leukopenia, anaemia, vomiting, reversible rhythmic cardiac disorder, stomatitis) was mild, alopecia was registered less than in adriamycin medication. One fatal congestive heart failure occurred. The actual mean survival time calculated on the basis of the data gained from 64 patients was 7.0 months (range 2-22). The high antitumour activity and no increase in toxicity justify the incorporation of high dose epirubicin into combination therapy.
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PMID:Phase II study of 4'-epi-doxorubicin in patients with untreated, extensive small cell lung cancer. South-East European Oncology Group (SEEOG). 216 33

Fotemustine is a new chloronitrosourea recently developed by the French company Servier. It is chemically characterized by the graft of an aminophosphonic acid on the chloronitrosourea radical, which makes it highly lipophil. The preclinical studies revealed a lower mutagenicity and hepatotoxicity when compared to BCNU. The pharmacokinetic studies showed a high body clearance and a short half-life. The phase I study enabled us to determine the definitive treatment schedule: 100 mg/m2/week during 3-4 consecutive weeks followed by 5 weeks' rest and a maintenance therapy of 100 mg/m2 every 3 weeks for stabilized or responding patients. Fotemustine should be given as a 1-h intravenous infusion, protected from daylight. There was no life-threatening toxicity and positive activity was observed in different tumors and especially melanomas. This indication was thus chosen for the phase II study. Among the 153 evaluable patients, the response rate reached 24.2%. It depended on the location of the metastatic sites, with 25% brain metastases, 19.2% visceral metastases, 8.8% liver metastases and 31.8% skin and lymph node metastases. The median duration of response was 22 weeks. The median overall survival of responding patients reached 85 weeks, while it dropped to 52 weeks in case of minor response or stabilization and 17 weeks in case of progression. The hematological toxicity was moderate (WHO grade III and IV: 46.3% leukopenia and 40.3% thrombopenia) and delayed as for other nitrosoureas (nadir: white blood cells: day 44 and thrombocytes: day 35).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Fotemustine, a new nitrosourea derivative. Current status of development]. 218 26

Two Pediatric Intergroup Ewing's Sarcoma studies of patients with metastatic disease (IESS-MD) have used multimodal therapy consisting of intensive combination chemotherapy and radiation therapy (XRT) to areas of gross disease detected at the time of diagnosis. In IESS-MD-I, conducted from 1975 to 1977, 53 eligible patients were entered and received the chemotherapeutic agents vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, and dactinomycin with concomitant XRT (VACA + XRT). In IESS-MD-II, conducted from 1980 to 1983, 69 eligible patients were entered and received 5-fluorouracil (5FU) in addition to the chemotherapeutic agents of IESS-MD-I; initial intensive chemotherapy was given and XRT was delayed until week 10 (VACA + 5FU, delayed XRT). The best response rate (complete and partial remissions combined) was 73% in IESS-MD-I and 70% in IESS-MD-II, so there was no statistical evidence of a difference in response rates (P = 0.62). The length of best response also was similar between studies (P = 0.79), with approximately 30% of the patients on both studies remaining in remission at 3 years. The percentage of patients surviving 5 years or more was 30 on the first study and 28 on the second study (P = 0.49). The major sites of relapse after a response were lung and bone, each occurring with nearly equal frequency. The age of the patient was related to both best response rate and survival: patients 10 years of age or younger had substantially higher response and survival rates than patients 11 years of age or older. The favorable prognosis for younger patients might be explained by a more favorable distribution of primary sites at diagnosis; 39% of patients 10 years of age or younger had rib primary sites, compared with only 16% for patients older than 10 years of age (P = 0.05). The frequency of life-threatening toxicity was substantially higher in IESS-MD-I (30%) than in IESS-MD-II (9%), but the frequency of fatal toxicity was similar (6% to 7%). Fatal complications included Adriamycin-induced cardiomyopathy, Pneumocystis carinii pneumonia, unspecified pneumonitis, and sepsis. The most common toxicity and complications were leukopenia and infections.
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PMID:Ewing's sarcoma metastatic at diagnosis. Results and comparisons of two intergroup Ewing's sarcoma studies. 220 33

A total of 21 untreated patients (5 males, 16 females; median age, 55 years; range, 28-72) with advanced measurable colorectal carcinoma were treated with an association of 5-fluorouracil (1000 mg/weekly) and alpha-2 interferon (three times a week s.c.: 6 x 10(6) U in the 1st month, 9 x 10(6) U in the 2nd month, 12 x 10(6) U in the 3rd month and then 18 x 10(6) U) until maximum response or progression of disease. Sites of disease involved liver in 10 patients, lung in 6, supraclavicular lymph nodes in 3, skin in 1, abdomen in 4, and vagina in 1 patient. Nine responses (42.8%) were documented (4 complete and 5 partial) with metastases confined to the liver, lung, nodes and skin. Median duration of response was 11 months (range, 4-17+) and median survival was 10 months (range, 2-17+). Side effects (fever, flu-like syndrome and leukopenia) required a dose reduction of 5-fluorouracil in 8 patients and interferon in 2 patients.
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PMID:Alpha-2 interferon and 5-fluorouracil in advanced colorectal cancer. 220 28

Sixteen patients with metastatic carcinoma of the colon were treated with a regimen of leucovorin 200 mg/m2, given as a 10-min infusion followed by a median dose of 833 mg/m2 (range 500-1000 mg/m2) 5-fluorouracil every two weeks. For the 16 patients with proven metastatic disease, two-year survival exceeds 50%. Responses were: 2 complete; 4 partial; 4 minor; 3 progression; and 3 not evaluable but without progression to date. Toxicities include: 8 (50%) leukopenia; 9 (56%), 1 severe thrombocytopenia; 9 (56%), 2 severe, diarrhea; 9 (56%), 3 severe, nausea/vomiting; 8 (50%), 1 severe, stomatitis; 7 (44%) conjunctivitis; 6 (38%) alopecia; and 13 (81%), 3 severe, neurotoxicity. Leucovorin appears to exert a dose-dependent beneficial effect on both the response and survival produced by the intermittent high-dose 5-fluorouracil schedule. This benefit first appears to increase substantially when the leucovorin dose is increased from 120 to 200 mg/m2. Findings identify a testable candidate regimen for selected good risk patients. Full selection criteria remain to be identified.
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PMID:Dose-dependent leucovorin efficacy with an intermittent high-dose 5-fluorouracil schedule. 220 56

One hundred sixty-nine patients with histologic evidence of disseminated malignant melanoma, including patients with cerebral metastases, were entered into a Phase II study of the nitrosourea fotemustine. The treatment regimen consisted of a 100 mg/m2 1 hour IV infusion every week for 3 consecutive weeks, followed by a 4- to 5-week rest period (induction therapy). In responding or stabilized patients, maintenance therapy consisted of 100 mg/m2 every 3 weeks until the disease progressed. One hundred fifty-three patients were evaluable for response. Three complete responses and 34 partial responses were observed (according to the World Health Organization criteria), leading to an objective response rate of 24.2% (95% confidence interval: 17.4% to 31.0%). Responses were also documented on cerebral (25.0%), visceral (19.2%), or nonvisceral (31.8%) metastatic sites. The median duration of response was 22 weeks (range, 7 to 80 weeks). The objective response rate in previously untreated patients was 30.7% (19 of 62 patients). The main toxicity was hematologic with delayed and reversible leukopenia and/or thrombopenia. The objective response rate observed (especially in untreated patients), the activity on cerebral metastases, and the small amount of extra-hematologic toxicity encountered suggest that fotemustine is an effective drug in disseminated malignant melanoma.
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PMID:Final report of the French multicenter phase II study of the nitrosourea fotemustine in 153 evaluable patients with disseminated malignant melanoma including patients with cerebral metastases. 222 83

A total of 70 patients presenting with a disseminated malignant melanoma were entered into a multicentric study of combination chemotherapy using dacarbazine and fotemustine. In all, 63 patients were evaluable, 31.8% of whom had previously received cytotoxic chemotherapy. The protocol consisted of induction treatment with a weekly infusion of 100 mg/m2 fotemustine on days 1 and 8 and a daily infusion of 250 mg/m2 dacarbazine on days 15/18 followed by a 4- to 5-week rest period. Responding and stabilized patients were given maintenance treatment comprising fotemustine (100 mg/m2, day 1) and dacarbazine (250 mg/m2, days 2/5) every 3 weeks. The response rate was 33.3% (9 complete responses (CRs) and 12 partial responses (PRs)) and was outstanding among pretreated patients (34.9%). Responses were also documented in cerebral (28.6%), visceral (23.1%) and nonvisceral (43.3%) metastatic sites. Toxicity was mainly hematologic (22.2%, grade III/IV leukopenia; 20.3%, grade III/IV thrombocytopenia) and was acceptable. These results are encouraging in terms of the antitumor activity against nonvisceral metastases (43.3%) and the percentage of CRs obtained (23.3%), and they confirm the activity of fotemustine in cerebral metastatic sites.
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PMID:Combination chemotherapy of dacarbazine and fotemustine in disseminated malignant melanoma. Experience of the French Study Group. 224 37

Sixteen patients with hepatic metastases of histologically documented breast cancer were treated with etoposide (VP 16-213) and cyclophosphamide. Previously, 6 had shown relapse in the liver after adjuvant chemotherapy, 2 had failed to respond to another chemotherapy combination, and 8 had never undergone chemotherapy. Fifty percent responded to treatment, including 1 complete remission and 7 partial responses. Median survival was 16 months and median duration of response was 13 months. All patients showed alopecia and moderate leukopenia; 13 experienced moderate gastrointestinal toxicity; there was 1 mild case of anemia and 1 case of moderate hemorrhagic cystitis. This study suggests that the combination of VP 16-213 and cyclophosphamide is a well-tolerated and effective treatment in advanced breast cancer patients with liver metastases.
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PMID:Combination chemotherapy with oral etoposide plus intravenous cyclophosphamide in liver metastases of breast cancer. 231 88

Thirty-four consecutive patients with measurable advanced gastric cancer were treated in a disease oriented Phase II study with high-dose folinic acid (HDFA) 300 mg/m2 10 min. inf., followed immediately by etoposide 120 mg/m2 50 min. inf., followed immediately by 5-fluorouracil (5-FU) 500 mg/m2 10 min. inf., given on day 1,2,3 (ELF). Courses were repeated every 22-28 days. All patients who entered this study were older than 65 years or had underlying cardiac disease. Thirty-three patients were evaluable for response and toxicity (greater than or equal to 1 course). One patient was lost to follow up. The overall response rate was 48% (16/23) including 12% (4/33) complete remissions. Eight patients had minor responses or no change and 9 had progressive disease. Five of six patients with locally advanced and non-resectable disease had an objective response (1 CR, 4 PR's). The response rate in patients with metastatic disease was 41% (11/27). After a median observation time of 6.5 months, the median survival time was 10.5 months, with a median remission (CR + PR) duration of 8 months. Toxicity was manageable and included mild to moderate myelosuppression and gastrointestinal toxicities. One episode of life-threatening (Grade IV) leukopenia, and two episodes of severe diarrhea requiring hydration were noted. No treatment related death occurred. ELF is an effective combination in advanced gastric cancer and can be safely administered to elderly patients and patients with cardiac risk.
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PMID:High dose folinic acid/etoposide/5-fluorouracil in advanced gastric cancer--a phase II study in elderly patients or patients with cardiac risk. 234 71


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