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)

We report a clinical study of the pharmacokinetics, toxicity, and biological activity of i.v.- and i.m.-administered recombinant gamma-interferon (rIFN-gamma) consisting of 143 amino acids. Ten patients with metastatic cancer were given rIFN-gamma at doses of 0.01 to 2.5 mg/sq m by alternating i.m. and i.v. bolus injections with a minimum intervening period of 72 h. After i.v. administration, rIFN-gamma was cleared monoexponentially with a short half-life of 25 to 35 min as determined by bioassay and enzyme immunoassay. After i.m. injection, a longer half-life of 227 to 462 min was measured by enzyme immunoassay. Serum titers were detected by bioassay only at high doses, suggesting partial loss of antiviral activity at the i.m. site. However, other biological effects were retained as evidenced by fever, chills, and fatigue after both routes of administration and granulocytopenia after i.m., but not i.v., doses. Two of ten patients showed objective evidence of tumor regression. These data suggest that further studies with i.m. as well as prolonged i.v. infusions of rIFN-gamma are indicated.
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PMID:Pharmacokinetics, single-dose tolerance, and biological activity of recombinant gamma-interferon in cancer patients. 392 Dec 49

Partially purified interferon alpha (IFN alpha) was administered to 50 patients with metastatic renal-cell carcinoma (RCC) studied for more than two years. Complete or partial remissions were observed in 26% of the patients. Duration of remissions range from two to 16 months (median, six months). No distinct prognostic factors were clearly identified in the responsive patients, but responses occurred more frequently in men with optimal performance status who had undergone nephrectomy and in whom the metastatic disease was confined to the lungs, pleura, or mediastinum. Leukopenia and granulocytopenia were useful markers of biological activity but did not predict tumor response. Side effects and toxicity at the dosage used (3 X 10(6) units intramuscularly daily) were well-tolerated and consisted predominantly of fatigue and asthenia. We concluded that IFN alpha is useful for palliating metastatic RCC, but no impact on survival was demonstrated. Further studies are required to determine the optimal dose, routes of administration, and treatment schedules.
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PMID:Phase II study of interferon alpha in metastatic renal-cell carcinoma: a progress report. 402 Apr 10

A total of 304 patients with limited small-cell carcinoma of the lung were treated with a combination of cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, Ohio), and vincristine (CAV) and elective brain irradiation (3,600 rad TD in 14 fractions). The patients were randomized to either receive or not receive thoracic irradiation (4,000 rad TD, split course). Of the 304 patients, 291 were eligible for the study. Two hundred eighteen (75%) were completely evaluable. In each group, 81% of the patients had a Karnofsky index of 80% or higher and 14% had supraclavicular or scalene lymph nodes. Patients treated with CAV and no thoracic irradiation had a complete response (CR) of 48%, in contrast to 63% for those receiving chest irradiation (P = .05). In the first group, the complete and partial response rate was 70%; in the second, 80%. The median survival for the eligible patients treated with CAV and brain radiation therapy was 49 weeks; for those treated with the same regimen plus thoracic irradiation, the median survival was 60 weeks. The actuarial two-year tumor-free survival is 19% in the first group and 28% in the second group. The median survival for the responders in the CAV plus brain irradiation group was 57 weeks and for those receiving thoracic irradiation, 78 weeks (P = .12). Thoracic failure was 52% in patients not treated with thoracic radiation therapy v 36% in those receiving it (P = .06). The distant metastases incidence was 23% in patients not treated with thoracic radiation and 35% in patients treated with thoracic radiation. Hematologic toxicity was comparable in both groups; 30% of the patients had moderate to severe granulocytopenia and 6%, low homoglobin. Two toxicity-related deaths occurred (one in each group). Moderate gastrointestinal toxicity was noted in 41% and severe in 16% of the patients receiving CAV and brain irradiation without thoracic radiotherapy v 44% and 20% in those irradiated in the thorax. Disease-free survival is enhanced in the patients receiving thoracic irradiation. More effective chemotherapy is critically needed to significantly improve overall survival. These preliminary results suggest that thoracic irradiation should be a primary component in the therapy of these patients, although this combined therapy is moderately toxic.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Randomized trial of radiotherapy to the thorax in limited small-cell carcinoma of the lung treated with multiagent chemotherapy and elective brain irradiation: a preliminary report. 609 55

The effects of recombinant DNA-produced leukocyte interferon (IFLrA) were studied in 37 patients with metastatic cancer who received sequentially escalating doses of 9-86 million units (MU) of IFLrA by im injection twice weekly. The IFLrA was absorbed rapidly and reached a peak serum concentration 6-8 hours after injection. Serum concentration of IFLrA increased proportionately with the dose. The most common side effects included fever, chills, asthenia, anorexia, and weight loss, and leukopenia, granulocytopenia, and lymphopenia occurred frequently. Elevation of serum glutamic-oxaloacetic transaminase was frequent above doses of 50 MU. All side effects were reversible by discontinuation of the drug. Antibodies to IFLrA were detected in 3 patients while on treatment. The presence of antibodies coincided with drastic reduction in serum IFLrA concentration and, in 1 patient, with relapse of disease. Objective tumor responses were documented in patients with lymphomas but not in other groups of patients.
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PMID:Clinical study of recombinant DNA-produced leukocyte interferon (clone A) in a intermittent schedule in cancer patients. 619 33

Partially purified human leukocyte (alpha) interferon was administered i.m. at a dose of 3 x 10(6) units/day to 19 patients with metastatic renal cell carcinoma. Five patients (26%) showed partial responses; two patients (10.5%), objective minor responses; three patients (16%), mixed effects (evidence of biological effect with regression of some lesions but concomitant progression); two patients (10.5%), disease stabilization; and seven patients (37%), progressive disease. All tumor responses were seen in lung or mediastinal metastases. Tumor response significantly correlated with interferon-induced leukopenia and granulocytopenia and with pretreatment performance status. Antibodies to interferon were found in one patient prior to treatment. We concluded that interferon is a potential active antitumor agent in patients with renal cell carcinoma.
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PMID:Renal cell carcinoma: antitumor effects of leukocyte interferon. 633 62

A trial of combination chemotherapy using mitoxantrone-cyclophosphamide was started in 1983. Sixteen patients with widely metastatic cancer of the breast, including one man, received mitoxantrone, 10 mg/m2 intravenously (IV) over 30 minutes on day 1, followed by cyclophosphamide, 200 mg/m2 by mouth (PO) daily in divided doses on days 3 to 6. It is too early to evaluate four patients at present. The remaining 12 received three or more courses of treatment, and three of these patients achieved a complete response. Another four patients went into partial remission, amounting to an overall response rate of 58%. The other evaluable patients showed stable disease with improved symptoms. Hematologic toxicity was mainly granulocytopenia, but thrombocytopenia occurred in two patients. Alopecia, nausea, and vomiting were attributed to the cyclophosphamide component of the therapy. Mitoxantrone appeared to have no cardiac toxicity. It was concluded that mitoxantrone-cyclophosphamide is an effective chemotherapeutic combination with minimal toxicity and should be further studied in larger controlled trials.
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PMID:Mitoxantrone and cyclophosphamide in advanced breast cancer: a pilot study. 638 60

Fifty-five patients with newly diagnosed, estrogen receptor negative, metastatic breast cancer were entered in a trial of mitoxantrone, 10 mg/m2 intravenous (IV), cyclophosphamide, 500 mg/m2 IV, and 5-fluorouracil, 1000 mg/m2 IV, which were given on day 1 of a 21-day treatment interval. This trial was designed to test the efficacy of substituting mitoxantrone for doxorubicin as part of a combination that has proved to be effective in inducing remission. The trial was also intended to evaluate the response of resistant disease and of stable metastatic disease to a combination of doxorubicin and vinblastine sulfate. The cardiotoxic potential of mitoxantrone was evaluated in all the patients by serial measurements of ejection fraction and by endocardial biopsy of the right ventricle. Patients who achieved a complete response or a partial response (with bone as the only site of disease) on the three-drug combination were continued on this treatment for 2 years, or for 1 year following a complete response, whichever was shorter or as cardiac monitoring permitted. Therapy with doxorubicin, 25 mg/m2/d for two days, followed by continuous infusion vinblastine sulfate, 1.4 mg/m2/d for four days, was given to all patients who progressed after two courses or were stable after six courses of three-drug therapy. The preliminary results from 50 patients show that 4 attained a complete response and 30 a partial response, giving a total response rate of 68%. The median duration of response was more than 7 months (range greater than 5 to greater than 15 months). One patient in complete remission relapsed after 8 months and failed reinduction therapy with doxorubicin-vinblastine sulfate. Myelosuppression, principally granulocytopenia, was the major side effect of cyclophosphamide-mitoxantrone-5-fluorouracil. Mild to moderate vomiting occurred in 76% of patients and alopecia in 88%. This therapy was discontinued in four patients because of a decreased cardiac ejection fraction and/or symptoms of heart failure. No cardiac biopsy score, however, has been greater than 1.0. These results suggest that a combination of cyclophosphamide-mitoxantrone-5-fluorouracil is effective in untreated, estrogen receptor negative, metastatic breast cancer and is comparable to the doxorubicin combination. Myocardial injury occurs with mitoxantrone, and a safe cumulative dose has yet to be established.
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PMID:Mitoxantrone, cyclophosphamide, and 5-fluorouracil in the treatment of hormonally unresponsive metastatic breast cancer. 638 62

A pharmacokinetic study was performed with partially pure immune (gamma) interferon (IFN-gamma) in patients with metastatic cancer. Nine patients were given IFN-gamma by the i.m. route in doses ranging from 1.5 X 10(5) to 9.6 X 10(6) antiviral units. There was no detectable antiviral activity in patients' serum, and only minimal side effects were observed. Fifteen patients were given IFN-gamma by i.v. bolus infusion in doses ranging from 1.5 X 10(5) to 54 X 10(6) units. Serum clearance of antiviral activity was described by a monoexponential disappearance curve. The serum half-life was dose dependent (3 min at the lower doses and 34 min at the highest doses). There were few consistent biological effects observed in the patients. Based on these pharmacokinetic data, eight patients were treated by a 6-hr continuous infusion consisting of 3 X 10(6) units by i.v. bolus followed by 4 X 10(6) units/hr for 6 hr. This regimen resulted in consistent serum levels of IFN-gamma ranging from 40 to 60 units over the 6-hr period. Marked granulocytopenia occurred within 24 hr and was sustained during the 10-day infusion period. There was marked increase in serum beta 2-microglobulin. We conclude that, in order to induce consistent serum antiviral activity, partially pure IFN-gamma, because of its rapid serum disappearance curve, must be administered by continuous i.v. infusion.
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PMID:Pharmacokinetic study of partially pure gamma-interferon in cancer patients. 643 May 57

One hundred twenty pathologically confirmed operable Stage III (T3N0-2) breast cancer patients were randomized to receive either postoperative radiotherapy or chemotherapy, or a combination of these, with or without levamisole immunotherapy. Radiotherapy was given to regional lymph node areas and chest wall. Chemotherapy consisted of 6 cycles of Adriamycin (doxorubicin) (45 mg/m2), vincristine (1.2 mg/m2) intravenously, and cyclophosphamide (200 mg/m2 for 5 days) perorally every 4 weeks. Peroral levamisole, 150 mg a day, 2 days weekly, was given as an immunotherapy. The 3-year results are described in this article. The effect of levamisole on the prognosis cannot be evaluated yet because of the short follow-up period. The disease-free survival was almost equal in each patient group, however, some benefit was achieved by levamisole (a shift of disease-free survival from 12 to 18 months). The patients receiving radiotherapy alone had the poorest prognosis: 68% had a recurrent tumor, and 57% were alive. In the chemotherapy group, the figures were 53% and 72%, respectively. Patients who received a combined treatment had the best prognosis: 13% had a recurrent tumor, and 90% survived 3 years. There was a statistically significant difference in the recurrence rate between any single therapy and the combined treatment (radiotherapy to combined treatment, P less than 0.001, chemotherapy to combined treatment, P less than or equal to 0.01 chi-square test). In overall survival, a statistically significant difference was reached between radiotherapy and combination treatment groups (P less than 0.01, chi-square test). Radiotherapy gave a good local control of the tumor, and chemotherapy decreased the number of metastases. The nonmetastatic axillary lymph node status and secondary amenorrhea or severe menstrual disturbances were of positive prognostic value. The side effects due to radiotherapy and chemotherapy were moderate and tolerable. The dose of Adriamycin had to be reduced only in four patients. All of the patients receiving chemotherapy had a transient total alopecia. Three of them had nonlethal arrhythmias, and one had skin rash. Levamisole was found very toxic with 9 cases of transient agranulocytosis, leading to the discontinuation of immunotherapy in 22 of 59 patients. Our results show that radiotherapy controls the tumor only locally and chemotherapy systematically, but the best patient-saving results are achieved with a combination of radiotherapy and chemotherapy. The disease-free and overall survival are statistically significant, and favor the combined therapy.
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PMID:Adjuvant postoperative radiotherapy, chemotherapy, and immunotherapy in stage III breast cancer. 674 3

A case of rarely occurring rhabdomyosarcoma of the urinary bladder in a boy of 2 is presented. The period from the first clinical manifestations (pyuria, macrohematuria) to death was 4 months. Urological examinations were done at the period of manifest clinical signs of disuria. A tumour of the urinary bladder almost completely filling the lumen was found in the form of numerous papillary-polyplike formations, with uropassage disorders. On the materials of operation biopsy the histological conclusion of urinary bladder rhabdomyosarcoma was reached. The death occurred with urogenic infection and manifestations of drug agranulocytosis (cytostatic therapy). The tumour outgrew into the posterior wall, no metastases were found. Histologically the tumour was characterized by random arrangement of mono- and multinuclear polymorphic cells with oxiphilic cytoplasm. The granularity and fibrous pattern of the cytoplasm were discernible. Typically, an argirophilic framework was observed. By its histological structure the tumour belongs to the embryonal type.
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PMID:[Rhabdomyosarcoma of the bladder in a 2-year-old boy]. 732 25


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