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)

Thirteen patients with cancer of the gut, six with hepatocellular carcinoma and three with cancer of the bile duct have been treated with tegafur. All the patients were in an advanced stage of the disease with metastases to lymph-nodes or elsewhere. Each patient was given tegafur (oral daily dose of 600-1200 mg for 15-30 days with a dose-free interval of 25 days). Tegafur with other antiblastic drugs (such as cyclophosphamide, methotrexate, vincristine, doxorubicin, mitomycin) was given to ten patients. The results observed after the first treatment were as follows: partial remission in 14 patients (64%), no change in 4 (18%) and progression of the disease in 4 (18%). Only 10 patients among the 22 who were first treated, underwent one to three subsequent cycles of therapy obtaining with resultant partial remission in four cases, no change in two and progression of the disease in four patients. Side-effects (nausea and vomiting) during the treatment were recorded only in 14% of the patients. No significant impairment of blood functional tests has been documented. A comparison of the results obtained with tegafur and intravenous 5-fluorouracil has been made: the therapeutic effects of these two drugs are similar, but side-effects seem to be less during tegafur treatment.
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PMID:Tegafur chemotherapy for the treatment of gut and liver cancer. 309 13

One hundred twenty-four children and young adults with recurrent tumors, predominantly sarcomas, were treated with the combination of ifosfamide, etoposide, and the uroprotector, mesna (2-mercaptoethane sulphonate), in a phase II trial. The treatment regimen consisted of 12 cycles of therapy administered every 3 weeks. After evaluation of the tumor response to chemotherapy alone, radiation or surgery was used to eradicate residual sites of metastatic disease where possible. At the present time, 77 patients are evaluable for response to the chemotherapy; 43 of the patients have experienced a significant reduction in the tumor size in response to the chemotherapy alone (39 partial responses [PR] and four complete responses [CR]). Sixteen of 17 patients with Ewing's sarcoma, nine of 13 with rhabdomyosarcoma, four of eight with peripheral neuroepithelioma, three of eight with osteosarcoma, and 11 of 31 with other tumors have responded with a PR or CR. The toxicity of the regimen was acceptable. Moderate or severe toxicity evaluated on a per cycle basis included: neutropenia, 97%; thrombocytopenia, 32%; nephrotoxicity, less than 1%; mucositis, 1%; neurologic toxicity, 2%; nausea and vomiting, 13%; hemorrhagic cystitis, less than 1%. Fever was present after 33% of cycles and sepsis following 7%. One patient died due to sepsis and pancytopenia. At the present time, only seven of the 43 patients who responded to the chemotherapy regimen have relapsed, with a median follow-up of 10 weeks after the response. This drug combination is highly active in the treatment of recurrent sarcomas and other tumors in children and young adults.
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PMID:Ifosfamide with mesna uroprotection and etoposide: an effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults. 311 35

We report a Phase I study in 39 cancer patients of the tolerance and biologic activity of 47 intravenous (i.v.), intramuscular (i.m.), and subcutaneous (s.c.) treatments with recombinant methional gamma interferon (IFN-gamma 4A) which most closely resembles the natural material produced by T lymphocytes. Patients were treated with IFN-gamma 4A 5 days a week for 2 weeks. After a 2-week rest period, patients were placed on the same dose of drug three times a week. The most common side effects--fever, chills, malaise, myalgias, and nausea and vomiting--were seen with all routes of administration. Reversible increases in hepatic transaminase and decrease in granulocytes counts were seen. The dose-limiting toxicities observed were malaise and orthostatic hypotension. The maximum tolerated dose was 500-1,000 micrograms/M2/day. The t1/2 of IFN-gamma 4A in the circulation was 20 min after i.v. injection. No blood levels were detected after i.m. or s.c. injection. Antibody against IFN-gamma 4A increased in three patients. A complete response was observed in one patient with pulmonary metastases from renal cell carcinoma.
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PMID:A phase I trial of recombinant human gamma interferon (IFN-gamma 4A) in patients with advanced malignancy. 313 13

Sixty-two women with advanced breast cancer were admitted to a pilot study in which a modified CMF regimen was administered. Cyclophosphamide was administered i.v. at a dosage of 600 mg/m2 on the same day as fluorouracil (600 mg/m2/i.v.) and methotrexate (40 mg/m2/i.v.). The therapy was recycled on the 21st day and in the presence of myelosuppression, the administration of the drugs was delayed for 1-2 weeks recovery of the hematologic values. CR + PR were obtained in 42% of patients and no change in 32% (U.I.C.C. criteria). Metastases to soft tissues showed CR + PR in 55% of the cases, bone in 33% and viscera in 35%. The menopausal status, the disease-free interval and the number of involved sites did not influence statistically the percentage of responses; however, the response rate was influenced statistically by previous treatment. The median duration of response was 7.5 months; the median overall survival of the 60 evaluable patients was 18 months. Due to myelosuppression, CMF i.v. administration was delayed 90/620 times (14%). Toxicity was acceptable and had a lower incidence than that reported in the literature in different series of CMF administered p.o. Nausea and vomiting, in particular, were limited to 24-48 h after administration of the drugs, and alopecia was seldom observed.
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PMID:Intravenous administration of cyclophosphamide, methotrexate and 5-fluorouracil in metastatic breast cancer. A pilot study. 316 24

In order to find an effective and suitable chemotherapy regimen for preoperative treatment of esophageal cancer, patients with inoperable or metastatic disease were treated with a combination of etoposide and cisplatin. Of 27 evaluable patients, 13 had squamous cell carcinoma, 13 adenocarcinoma, and 1 muco-epidermoid carcinoma. No complete responses were noted. Nine of 13 patients with squamous cell carcinoma and only one of 13 with adenocarcinoma showed a partial response. Nine of 10 responders achieved a partial response after 2 courses, one after 4 courses. There was one toxic death, due to sepsis during leukopenia. Other toxicities were alopecia, nausea and vomiting, nephrotoxicity, thrombocytopenia and leukopenia.
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PMID:Etoposide and cisplatin in advanced esophageal cancer. A preliminary report. 323 66

Experimental data show that sequencing methotrexate (MTX) and 5-fluorouracil (5-FU) may result in synergistic antitumor activity. Moreover, the effect of 5-FU is increased by folinic acid (FA), and finally, cyclophosphamide (CPA) produces an expansion of tumor growth fraction, suggesting an increased cytotoxic effect of cycle-specific drugs subsequently administered. Based on these premises, we have performed a Phase II study with CPA (600 mg/m2 i.v., day 1), MTX (200 mg/m2 1-h i.v. infusion, day 7), 5-FU (600 mg/m2 i.v., day 8), and FA (500 mg/m2 2-h i.v. infusion, day 8 plus 15 mg p.o. every 6 h on days 8 and 9) administered every 3 weeks. Thirty-six patients with metastatic breast cancer were admitted into the study. Median age was 52 years, and all but two patients were postmenopausal. Dominant sites of metastases were soft tissues in 10 patients, bones in 7 patients, and viscera in 19 patients. All patients were pretreated with chemo- and/or hormone therapy. Sixteen patients achieved an objective response (44.5%: 1 complete response and 15 partial responses), 8 had stable disease (SD) (22.2%), and 12 progressed (33.3%). Twenty-one patients had previously received conventional CMF in an adjuvant setting (15 patients) or for metastases (6 patients): 1 complete response (CR) and 7 partial responses (PR) were obtained in the first group and 1 in the second. Major toxic effects were hair loss (56.4%), nausea and vomiting (72%), mucositis (52.5%), and leukopenia (61%). A randomized study could be useful to assess the role of sequential CMF versus conventional CMF in metastatic breast cancer patients.
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PMID:Sequential administration of cyclophosphamide, methotrexate, 5-fluorouracil, and folinic acid as salvage treatment in metastatic breast cancer. 331 Jun 5

A non-randomized clinical study on systemic combination chemotherapy was conducted by the Japanese Urological Cancer Research Group for Adriamycin to compare the effectiveness of CAP (cyclophosphamide 200-500 mg/m2, adriamycin 30-50 mg/m2 and cisplatin 30-50 mg/m2) and CAF (cyclophosphamide 200-500 mg/m2, adriamycin 30-50 mg/m2 and 5-fluorouracil 250 mg/m2) in 123 patients (104 evaluable) with advanced and/or metastatic cancer of the urinary bladder. Among 96 patients who were non-randomly selected to receive CAP, 4 achieved complete remission, 12 achieved partial remission, 7 achieved minor response, 30 had stable disease, and 43 had disease progression. The response in the 8 patients who received CAF were: partial remission in 1 and progressive disease in 7. The overall response rate to CAP therapy was 17%, as against 13% for CAF therapy. The median duration of survival with CAP was 29 weeks and with CAF, 22 weeks. The differences between the two groups in duration of survival and response rate were not statistically significant. Complete and/or partial remissions were observed in the lymph nodes, lung and liver in 32%, 24%, and 57% of cases, respectively. There was no objective response in bone metastasis. The main side effects of CAP were anorexia (88%), nausea and/or vomiting (81%), alopecia (65%), leukopenia (72%), anemia (48%), and renal dysfunction (17%). No patients died as a result of toxicity of these combination chemotherapy modalities.
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PMID:Phase III trial of the Japanese Urological Cancer Research Group for Adriamycin: cyclophosphamide, adriamycin and cisplatinum versus cyclophosphamide, adriamycin and 5-fluorouracil in patients with advanced transitional cell carcinoma of the urinary bladder. 331 45

15 patients aged between 24 and 66 years with 10 different malignant tumor diseases were treated with a recombinant human tumor necrosis factor preparation PAC-4D in a phase-I trial. The starting dose was 10(5) U PAC-4D as an intravenous short infusion. The maximally tolerable dose is around 18 X 10(5) U/m2. As the main clinical side effects were observed: fever, chills, hypertension with subsequent hypotension, lethargy, transient somnolence, headache, neurological deficiency symptoms, nausea and vomiting. Important laboratory-chemical parameters were the increase in transaminases and, in higher dose levels, leukocytosis with the left shift and lymphopenia in the differential blood picture. As dose-limiting toxicity are estimated hypotension, and neurological side effects and hepatotoxicity. In one female patient who received 27 X 10(5) U PAC-4D there appeared pronounced, histologically verified necroses in the metastases of a malignant fibrous histiocytoma.
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PMID:Human pharmacological investigation of a human recombinant tumor necrosis factor preparation (PAC-4D) a phase-I trial. 337 52

Transcatheter arterial chemoembolization (TAE) and hepatic arterial infusion using totally implantable reservoir were performed for the treatment of liver metastasis of colo-rectal cancers, and their therapeutic effects, side effects and complications were evaluated. Eleven cases of H1 (metastasis in one lobe only), 7 cases of H2 (a few scattered metastases in both lobes), 12 cases of H3 (numerous metastases in both lobes) were entered into the study and underwent TAE 45 times. Gel foam, Ivaron and Lipiodol were used as embolic materials in combination with chemotherapeutic agents such as mitomycin C and adriamycin. Serum CEA level was decreased less than 50% of pre-TAE level 20 out of 32 (61%). The tumor size was regressed in 25% of TAE cases which were evaluated on the basis of CT scan. Abdominal symptoms including abdominal pain, nausea and vomiting and fever, leukocytosis, elevated GOT, LDH and bilirubin level were seen after TAE therapy. Median survival of H1, H2 and H3 cases were 21 months, 8 months and 4.5 months, respectively. Another 21 cases (H1, 5 cases: H2, 3 cases: H3, 13 cases) of liver metastasis of colo-rectal cancers were treated with selective hepatic arterial infusion therapy using totally implantable reservoir. Reservoir catheters were implanted into hepatic artery via gastroduodenal artery under direct vision at laparotomy. Mitomycin C, adriamycin and fluorouracil (5-FU) were used as chemotherapeutic agents. No particular side effect such as leukopenia or liver dysfunction was noted. Median survival of H1, H2 and H3 cases treated with arterial infusion were 4 months, 9 months and 9 months, respectively. Median survival of TAE cases and arterial infusion cases was 10 and 6 months, respectively. Thus, the survival rate of cases treated with TAE was better than that of cases treated with arterial infusion.
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PMID:[Transcatheter arterial chemoembolization and selective hepatic arterial infusion using totally implantable reservoir]. 341 58

Forty-eight patients with metastatic breast cancer previously treated with cytostatics (except anthracyclines) underwent peroral treatment with 4-demethoxydaunorubicin (4-DMDR), a new daunorubicin analogue. Forty-three patients received greater than or equal to 2 cycles and have been evaluated. The mean age was 54 years, with 10 premenopausal and 33 postmenopausal patients. All the patients showed progressive disease. Performance status 0-2 (ECOG score) was recorded in 34, and 3 in 7 patients. Soft tissue metastases were recorded in 23, visceral in 10 and bone in 10 patients. 4-DMDR was administered in the dose of 15 mg/m2 perorally daily, on day 1, 2 and 3 (45 mg/m2 per cycle). Since there was no severe toxicity, after 2 cycles the dosage was increased to 60 mg/m2 per cycle. The patients received 2-6 cycles (median 3) and the total cumulative dose ranged from 90 to 300 mg/m2 (median 140 mg/m2). Objective response was observed in 10 patients (1 complete remission, 9 partial remissions) with a response rate of 23% (10/43). Soft tissue metastases were most responsive (8/23-35%). Two responses were observed in visceral organs. Response lasted 2-6+ months (median 4 months). Toxic side effects have been mild with myelotoxicity (grade I-II) observed in 23% of patients. Alopecia (grade 1-15 patients, grade II and III = 4 patients) was moderate. Nausea and vomiting (grade I-II) was present in 60% of patients. In all the patients MUGA scans (left ventricular ejection fraction) were in normal range, however, reversible ECG changes have been recorded in 4 patients (grade I = 3, grade II = 1). All the changes appeared on the 3rd day of the cycle but became normal before starting a new cycle. In conclusion, it should be emphasized that 4-DMDR administered perorally (45 mg/m2 per cycle) in previously treated (except anthracycline) metastatic breast cancer patients showed antitumor efficacy with a low incidence of toxic side effects. Further clinical studies, possibly with the dose escalation in the schedule we have used, will be needed in previously untreated breast cancer patients to determine exact antitumor activity of this new daunorubicin analogue.
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PMID:Phase II study of oral 4-demethoxydaunorubicin in previously treated (except anthracyclines) metastatic breast cancer patients. 347 33


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