Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Navelbine (NVB) is a new semi-synthetic Vinca alkaloid selected on the basis of its affinity for tubulin. NVB inhibits the polymerisation of tubulin and it has significant antitumor activity on P388 and L1210 leukemias and some other experimental tumors. In the present study, 20 patients (9 carcinomas, 10 lymphomas and 1 blastic crisis of chronic myeloid leukemia) received a median of 4 weekly i.v. doses of NVB. Two patients at least received each dose level: 3.6 mg/m2 (1/10 of the LD10 dose/kg in BDF1 mice), 7.2, 12, 18, 32.4, 35 and 43 mg/m2 per week. A total of 89 doses were administered. All patients had been first heavily pretreated and 17 of them had received a Vinca alkaloid. Leukopenia (neutropenia) was the dose-limiting toxicity. There was no thrombocytopenia. Leukopenia was dose-related and first seen at 32.4 mg/m2 per week. The maximal tolerated dose appears to be about 43 mg/m2. At that dose, 2 out of 3 patients developed severe leukopenia and neutropenia. One localized allergic reaction, one case of transient hepatic dysfunction, and 2 reversible peripheral neuropathies were seen. Pharmacokinetics, studied with a radioimmunoassay (RIA) method, suggested an elimination half-life of 30 h and a plasma clearance of 75 l/h. Four patients with Hodgkin's disease and two patients with non-Hodgkin's lymphoma, all of them refractory to vincristine (VCR) and/or vinblastine (VBL), showed minor responses lasting 2-8 weeks. They had received between 4 and 12 doses of 30 and 43 mg/m2. We recommend for phase 11 trials the dose of 40 mg/m2 per week.
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PMID:Phase I pharmacologic study of a new Vinca alkaloid: navelbine. 401 23

Thirty-eight patients with advanced, progressive Hodgkin's disease who had relapsed from or who had not responded to treatment with at least two potentially curative combination chemotherapy regimens were entered into this phase 2 study. All patients received 131I antiferritin antibody administered intravenously (IV) at a dose of 30 mCi on day 0 and 20 mCi on day 5. Antibody was derived from rabbit, pig, and monkey species. Objective partial remission of measurable disease was recorded in 40% of patients. Symptomatic response was recorded in 77% of patients. Toxicity was restricted to bone marrow depression with thrombocytopenia greater than leukopenia. These responses are comparable to other reported phase 2 drugs in this patient population and subsequent trials of antibody free of radioactivity and antibody using a beta emitting isotope are being carried out to expand upon these results.
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PMID:Isotopic immunoglobulin: a new systemic therapy for advanced Hodgkin's disease. 404 23

Eleven patients with established Hodgkin's disease were treated with vinblastine sulfate. Each patient received from 0.15 to 0.20 mg./kg. of body weight intravenously in 10 divided doses over a five-hour period as initial therapy. All had received one or more of the more established forms of treatment before being given vinblastine. The response to treatment with vinblastine was excellent in three patients, good in one, and poor in three; there was no response in four. The longest remission was 15 months. Two of the patients were father and son. The side effects of treatment in this series included alopecia, leukopenia, and septicemia.
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PMID:Clinical experience with vincaleukoblastine sulfate in the treatment of 11 patients with Hodgkin's disease. 582 97

Vincristine 0.25 mg/m2 by IV push and bleomycin 5 units daily by continuous infusion were given on days 1, 2, 3 and 4, together with prednisone 1,000 mg/m2 po in 4 divided doses either on days 1, 3, 5, and 7 (6 patients) or on days 1 and 3 (11 patients) to 17 patients with various lymphoproliferative diseases who had failed their previous treatment program. Fourteen were leukopenic and/or thrombocytopenic. Of 10 patients with non-Hodgkin's lymphoma 2 achieved complete remission and 5 a partial response. Both patients with Hodgkin's disease achieved partial response. A decrease in plasma M protein (median decrease 51%) was observed in 3/3 patients with multiple myeloma and 2/2 with Waldenstrom's macroglobulinemia. Decrease in tumor cell infiltration by 48%, 58% and 100% was observed in 3 patients (2 with macroglobulinemia and 1 with myeloma) in the bone marrow. Leukopenia of less than 3,600/mm3 and thrombocytopenia of less than 70,000/mm3 reverted to normal in 5/7 and 7/10 patients, respectively. Remission duration ranged from 4 to 35+ weeks (median 17 weeks). Three patients had severe GI bleeding. Psychosis controlled by phenothiazines was observed in one, and bleomycin toxicity (anaphylaxis, skin rash, and lung toxicity, one each) was observed in 3 patients. No severe neurotoxicity was observed.
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PMID:Treatment of refractory lymphoproliferative diseases with daily, low-dose vincristine, continuous infusion of bleomycin, and high-dose prednisone. 620 45

During a 3-year period 39 evaluable patients with stage III and IV non-Hodgkin's lymphomas and unfavorable histologies were treated with a unique chemotherapeutic regimen based on a modified CHOP combination to which was added the nitrosourea, CCNU. Complete response was observed in six of 15 (40%) patients with diffuse poorly differentiated lymphocytic lymphoma (DPDL), four of 11 (36%) with diffuse mixed histiocytic lymphocytic (DML), and seven of 13 (54%) with diffuse histiocytic lymphoma (DHL). Of the 17 patients who achieved complete response, nine (53%) have remained continuously disease-free for greater than 2.5 years (2.7-4.1 years) from the onset of therapy: four of six with DPDL, two of four with DML, and three of seven with DHL. Median survival was 18.9 months for all patients, 18.9 months for those with DPDL, 17.4 months for those with DML, and 9.7 months for those with DHL. The median survival has not been reached for patients who attained a complete response, and will exceed 3.3 years. Central nervous system relapse was observed in three patients. In general, toxicity was moderate and consisted primarily of leukopenia, nausea, vomiting, and neurotoxicity. There were no drug-related deaths. The addition of CCNU to a modified CHOP combination resulted in an effective, generally well-tolerated out-patient regimen. However, it did not appear to decrease the rate of CNS relapse or improve current treatment results observed with other adriamycin-containing regimens for similar patients.
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PMID:CCNU in combination chemotherapy for advanced histologically unfavorable non-Hodgkin's lymphoma. 635 17

Mitoxantrone is an anthracenedione, showing structural similarities to doxorubicin. This drug has been proved active against several tumor systems, including some tumors resistant to doxorubicin, and also against human breast xenografts. It is also less cardiotoxic than doxorubicin. Mitoxantrone has been given to 335 patients in an i.v. perfusion of 12 mg/m2 or 14 mg/m2 every 3 weeks. Two hundred and sixty-three patients with advanced disease were evaluable for response: breast (94 patients), head and neck (40), kidney (20), bronchial (19), lymphomas (13) and various sites (77). Most of the patients had been previously treated with radiotherapy and chemotherapy, including/not including doxorubicin. In breast cancer three complete remissions (CR) and 16 partial remissions (PR) have been achieved (20%). The therapeutic activity was higher in patients who had not received any prior chemotherapy: 35 vs 15% (P = 0.06). The response rate observed at 14 mg/m2 (32%) was superior to the response rate observed at 12 mg/m2 (15%). However, no response has been reported in lung metastases (0/22). The median duration of response is 8 months. Mitoxantrone shows borderline activity in head and neck tumors (one CR and two PR out of 40 patients) but no activity in squamous cells of the lung (0/19). One CR and three PR have been seen out of 13 malignant lymphomas (four Hodgkin's disease and nine non-Hodgkin's lymphomas). The duration of response ranges from 10 to 24+ months. Myelosuppression was moderate and no severe leukopenia has been reported. Nausea and vomiting were seen in 50% of the patients. Four patients presented cardiac events associated with mitoxantrone, such as reversible congestive heart failure or a significant decrease in the ventricular ejection fraction. Alopecia was observed in 17 and 48% of the patients treated with 12 and 14 mg/m2 respectively. Due to its anti-tumoral activity, mainly in breast cancer, and its low hematological and cardiac toxicity, mitoxantrone must be considered as a major antimitotic.
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PMID:An EORTC phase II study of mitoxantrone in solid tumors and lymphomas. 654 6

Forty-two cases of Toxoplasma gondii infection were analyzed, 25 in patients with neoplastic disease and 17 in apparently normal patients. Infection in normal hosts was usually manifested by adenopathy and ran a benign course. Infection in patients with neoplastic diseases was usually manifested by fever and/or neurologic symptoms. Patients with leukemias and lymphomas, particularly Hodgkin's Disease, were at highest risk for infection. Most, but not all, patients developed serologic titers indicative of infection. T. gondii infections were fatal in all eight cases with central nervous system involvement despite treatment in five cases. Leukopenia was a significant complication of treatment with sulfadiazine and pyrimethamine despite the use of folinic acid.
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PMID:Toxoplasmosis. Problems in diagnosis and treatment. 661 13

Thirty-three patients with advanced malignancy were treated with Wellferon. Doses ranging from 0.75 X 10(6) to 50 X 10(6) U were administered intramuscularly every 12 h for a 7-day course of therapy. Courses were repeated every 4 weeks as a function of tumor response. Toxicity resulted in fever, chills, malaise, leukopenia, thrombocytopenia, nausea and/or vomiting, diarrhea, hepatocellular damage, and, in a single case, gastrointestinal bleeding (which was a possible cause of patient death). Toxicity tended to increase with increasing dose, and 30 X 10(6) units every 12 h for 7 days was considered to be the maximally tolerated dose. Partial responses were seen in three patients with diagnoses of renal cell carcinoma, diffuse histocytic lymphoma, and Hodgkin's disease. Minimal responses were seen in four patients with diagnoses of chronic lymphocytic leukemia, multiple myeloma (two patients), and breast cancer. Positive response to therapy did not correlate with dose level.
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PMID:Phase I study of Wellferon (human lymphoblastoid alpha-interferon) as cancer therapy: clinical results. 664 35

A phase II trial was conducted to determine the clinical activity of amsacrine (m-AMSA) in patients with heavily pretreated solid tumors, myeloma, and lymphoma at the University of Arizona Cancer Center. Additionally, m-AMSA was evaluated at other Southwest Oncology Group institutions in breast cancer, myeloma, melanoma, and oat cell cancer of the lung. At a dose of 120 mg/m2 given iv every 28 days, 12 partial responses were observed in 221 patients evaluable for response. Some antitumor activity was observed in breast cancer (four responses of 65 patients), non-Hodgkin's lymphoma (three of nine), Hodgkin's disease (two of five), and sarcoma (two of 15). A partial response was also documented in one of two patients with cervical cancer. Among the 135 patients treated at the University of Arizona who were extensively evaluated for toxic effects, only myelosuppression and anemia were seen in a significant number of patients. At this dose and schedule, 29% of patients developed leukopenia of less than 3000 cells/mm3, 16% developed a thrombocytopenia of less than 100,000 cells/mm3, and 29% had an acute fall in hemoglobin of greater than or equal to 2 g/100 ml. In addition, two patients suffered grand mal seizures which were not clearly drug-related. These results suggest that further study of m-AMSA in lymphoma, sarcoma, and cervical cancer is warranted.
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PMID:Phase II evaluation of amsacrine (m-AMSA) in solid tumors, myeloma, and lymphoma: a University of Arizona and Southwest Oncology Group Study. 668 99

Eighty-one patients with a variety of refractory disseminated malignant neoplasms have been treated in the first multiple fixed-dose phase I trial of recombinant leukocyte A interferon (IFL-rA). Each patient received IFL-rA by intramuscular injection, three times weekly for 28 days. Dosages were escalated in different patients from 1 to 136 x 10(6) units per injection. The toxic reactions seen with IFL-rA resembled those of nonrecombinant leukocyte interferon and included fever, chills, fatigue, anorexia, myalgia, headache, occasional nausea and vomiting, and dose-dependent reversible leukopenia and hepatic transaminase elevations. The pharmacokinetics of IFL-rA were also comparable with nonrecombinant leukocyte interferon. Objective evidence of antitumor activity was seen in non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's disease, breast cancer, and melanoma, indicating that IFL-rA, the first genetically engineered biological response modifier available for testing in cancer patients, is biologically active in vivo.
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PMID:A multiple-dose phase I trial of recombinant leukocyte A interferon in cancer patients. 675 47


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