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

Eight patients with refractory Hodgkin's disease received intensive combination chemotherapy conditioning with cyclophosphamide, carmustine (BCNU), and etoposide (VP 16-213), and allogeneic marrow transplants. All patients achieved complete responses. Three patients relapsed; two died of Hodgkin's disease and one of chronic graft-v-host disease (GVHD) and infection. In all, four patients died due to transplant-related toxicity. One patient developed a fatal B-cell lymphoproliferative disorder soon after transplantation, and died without evidence of Hodgkin's disease. One patient is alive and free of progression 29 months after transplantation. These data indicate that allogeneic marrow transplantation may be considered as therapy for selected patients with advanced Hodgkin's disease and, despite substantial toxicity, will occasionally result in long-term responses. Better patient selection would likely improve results.
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PMID:Allogeneic marrow transplantation for refractory Hodgkin's disease. 247 58

Seventeen patients with advanced stage Hodgkin's disease who relapsed or failed to respond to multiple regimens of combination chemotherapy (mostly Mechlorethamine, Vincristine, Procarbarzine, Prednisone and Adriamycin, Bleomycin, Vinblastine, Dacarbazine) were treated with accelerated hyperfractionated total lymphoid irradiation (TLI) and high-dose chemotherapy followed by autologous bone marrow transplantation (AuBMT). Candidates for the protocol did not have prior radiation therapy and had no evidence of bone marrow involvement. Their bone marrow was initially harvested and cryopreserved. The treatment protocol consisted of reinduction with conventional doses of combination chemotherapy followed by boost local field irradiation to areas of residual disease (1500 cGy within 5 days) and total lymphoid irradiation (2004 cGy given in 12 fractions of 167 cGy each t.i.d. delivered within 4 days). The patients were treated with Etoposide (250 mg/m2/day I.V. X 3 days) and high-dose Cyclophosphamide (60 mg/kg/day I.V. X 2 days). Cryopreserved (unpurged) autologous bone marrow was infused 48 hr after completion of chemotherapy. Of the 17 patients treated, four were in relapse and 13 refractory to multiple regimens of combination chemotherapy. Four patients died during the immediate peritransplant period (2--septicemia, 2--pulmonary complications). Of the 13 surviving patients, 12 entered a complete remission and one had a partial remission and died of disease 6 months later. One patient relapsed 5 months after treatment and is currently alive with disease. Eleven patients (65%) are alive with no evidence of disease 4-35 months (median 20 months) following completion of therapy. Treatment with this protocol results in a high rate of complete remission and a potential for long-term disease-free survival in previously unirradiated patients with advanced stage refractory or relapsed Hodgkin's disease who have exhausted conventional modes of chemotherapy.
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PMID:Total lymphoid irradiation, high-dose chemotherapy and autologous bone marrow transplantation for chemotherapy-resistant Hodgkin's disease. 247 11

To determine whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) can accelerate granulocyte recovery after high-dose combination chemotherapy with autologous bone marrow transplantation (ABMT) in patients with Hodgkin's disease, we performed a nonrandomized phase II study using historical controls as a comparison. Eighteen relapsed/refractory Hodgkin's disease patients who received cyclophosphamide at 1.5 g/m2/day (days -6 to -3), carmustine (BCNU) at 300 mg/m2 (day -6), and etoposide (VP-16) at 125 mg/m2 every 12 hours (days -6 to -4), followed by ABMT (day 0) were treated with rhG-CSF at 60 micrograms/kg/day for a maximum of 28 days beginning on day 1. rhG-CSF dosage was gradually diminished and stopped once an adequate granulocyte count was maintained. rhG-CSF significantly accelerated absolute granulocyte count (AGC) compared with historical controls recovery to the 100/microL level (median, 9 days v 13 days; P = .103 x 10(-4), 500/microL level (median, 13 days v 22 days; P = 0.189 x 10(-2), and 1000/microL level (median, 16 days v 30 days levels; P = .125 x 10(-5). Platelet recovery to 50,000/microL was not significantly altered (P = .370). rhG-CSF was well tolerated, bone pain and myalgia being the only side effects noted. rhG-CSF hastens granulocyte recovery after high-dose chemotherapy with ABMT in patients with relapsed/refractory Hodgkin's disease without significant toxicity.
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PMID:Recombinant human granulocyte colony-stimulating factor hastens granulocyte recovery after high-dose chemotherapy and autologous bone marrow transplantation in Hodgkin's disease. 247 19

Thirty-one patients affected by recurrent Hodgkin's disease have been treated with an oral combination chemotherapy including lomustine (CCNU 90 mg/sqm, on day 1), melphalan (Alkeran, 7.5 mg/sqm on days 1-5), etoposide (VP-16, 100 mg/sqm on days 6-10) and prednisone (40 mg/sqm on days 1-10). MOPP and ABVD regimens administered sequentially or in alternating fashion had been employed as first choice treatment. The majority of patients had extranodal (80%) and a progressive disease resistant to previous chemotherapy (80%). Complete and partial remission were induced in 8 (26%) and 5 patients (16%), respectively, with an overall response rate of 42%. Median duration of complete remission was 10 months. Patients who did not respond to previous chemotherapies had a significantly lower complete response rate (16%). Myelosuppression was the most frequent complication, with one patient dying of a thrombocytopenic hemorrhage. The oral administration of drugs allowed good patients', compliance with treatment. CAVP is an effective regimen in the management of patients with refractory Hodgkin's disease and the results obtained are comparable with other third-line chemotherapies.
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PMID:Third-line chemotherapy with CAVP (CCNU, melphalan, etoposide and prednisone) in refractory Hodgkin's disease. 251 Oct 96

Etoposide, an epipodophyllotoxin structurally related to vincristine, is active in solid tumors. Trials of etoposide in hematologic malignancies, particularly leukemia and lymphoma, were initiated in 1973. Subsequent studies indicate that etoposide, either as a single agent or in combination with other drugs, is active in acute myelogenous leukemia, non-Hodgkin and Hodgkin lymphoma. Etoposide may be effective in acute lymphoblastic leukemia, but it is inactive in chronic myelogenous leukemia. The major toxicity of etoposide is myelosuppression. Non-hematologic toxicity is relatively mild at doses up to 2000 mg/m2. This feature favors its use in high dose regimens such as those employed before bone marrow transplantation. Preliminary studies of etoposide in autologous bone marrow transplantation in lymphoma and Hodgkin disease are promising. Studies of high dose etoposide in combination with other chemotherapeutic agents or in the context of bone marrow transplantation are in progress.
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PMID:Etoposide in leukemia, lymphoma and bone marrow transplantation. 267 26

A phase I trial of vincristine and etoposide was designed following the identification of a potentially synergistic antitumor effect in a murine model. The dose of vincristine was fixed (0.5 mg daily for 3 days). Etoposide was given at 1 of 3 total dose levels (250, 500, or 750 mg/m2) per treatment. Each dose was given in 3 equal fractions and each fraction was given daily for 3 days, i.e., 83.3 mg/m2/d x 3d, 166.7 mg/m2/d x 3d, or 250 mg/m2/d x 3d. A total of 31 patients were entered into study including 10, 18, and 3 patients treated at the 250, 500, and 750 mg/m2 dose levels, respectively. Dose-limiting toxicity occurred at the 750 mg/m2 level, in which Grade 4 myelosuppression developed in all of the patients. Life-threatening gram negative sepsis occurred in two of these patients and both required platelet transfusions. Grade 3-4 WBC toxicity was observed in 9 of 16 (56%) evaluable patients treated at the 500 mg/m2 level, but reversal of toxicity was generally rapid with repeat courses given at 3 week intervals in most patients. Non-hematologic toxicity was negligible. Objective responses were observed in 2 of 4 patients with Hodgkin's disease. The starting dose of etoposide recommended for phase II trials of this agent in combination with vincristine is 500 mg/m2; dose escalation may be possible in some patients.
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PMID:Phase I study of vincristine and escalating doses of etoposide. 279 73

In an effort to improve the treatment of patients with refractory or recurrent lymphoma, we developed a protocol using cis-platinum combined with two other agents of known efficacy in these disorders but with differing side effects: VP-16 and MGBG. Twenty-six eligible patients were treated with this regimen. There were 15 men and 11 women with a median age of 54 years (22-73), and performance status of 1 (0-3). Their diagnoses were Hodgkin's disease 5 and non-Hodgkin's lymphoma [NHL] 21 which included 11 with diffuse histocytic lymphoma [DHL]. The median number of chemotherapy regimens was 2 (1-5); 12 also received radiotherapy. Twenty patients are evaluable for response: 15 NHL and 5 Hodgkin's disease. Three patients, all of whom had DHL entered complete remission (20%) with a median time to treatment failure of 7 1/2 months. Six NHL (40%) and one Hodgkin's disease (20%) patients entered a partial remission. There were three early deaths: one due to progressive disease, one to acute respiratory failure, and one with disease status undocumented. Toxicity included leukopenia, thrombocytopenia, anorexia, nausea, vomiting, stomatitis, alopecia, renal failure, profound peripheral neuropathy, and hypersensitivity vasculitis. Treatment was stopped because of the latter two. These agents are non-crossresistant with doxorubicin-containing regimens. The drugs are possibly synergistic and modestly active with moderate to severe toxicity.
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PMID:Cisplatin, VP-16-213 and MGBG (methylglyoxal bis guanylhydrazone) combination chemotherapy in refractory lymphoma, a phase II study. 319 89

Etoposide (VP-16), 150 mg/M2, given intravenously daily for 3 days every 3 weeks resulted in 3 complete responses and 6 partial responses in 154 patients with a spectrum of recurrent malignant solid tumors. There was evidence of disease control in an additional 37 patients (27 mixed responses and 10 stable disease). These responses occurred primarily in patients with Ewing's sarcoma, Hodgkin's disease, neuroblastoma and rhabdomyosarcoma. Most of the patients had every extensive prior therapy; however prior therapy with teniposide (VM-26), the congener of VP-16, did not seem to preclude responses to the latter drug. Myelosuppression was the principal form of toxicity. Neutropenia characterized by absolute neutrophil counts of 0.5 to 0.9 x 10(9)/L occurred in one-half of the patients, and thrombopenia with platelet counts of less than 25 to 49 x 10(9)/L in one-fourth. These results demonstrate a favorable therapeutic index for VP-16 in several recurrent childhood solid tumors, supporting its use as a component of primary therapy for these diseases.
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PMID:Clinical trial of etoposide (VP-16) in children with recurrent malignant solid tumors. A phase II study from the Pediatric Oncology Group. 341 Jun 65

We examined the effects of various concentrations of etoposide (20-125 microM, 2-h incubation) on normal bone marrow and seven malignant cell lines: HL-60, K562, Namalva, MOLT-3, CEM-7, and the Hodgkin's cell lines L428KS and L428KSA. Tumor cell log-kill was dose dependent and greater than 4 for all cell lines but L428KSA (log-kill, 3.73). Median recovery of CFU-GM after purging with 75, 100, and 125 microM etoposide was 3.6%, 1.3%, and 1% of the controls, respectively. After one week of long-term marrow culture (LTMC), recovery increased 10-20 times/10(5) cells plated, reaching median values of 33.6%, 23.5%, and 20.7% of the controls in samples purged with 75, 100, and 125 microM etoposide, respectively. Flow cytometry for cell-cycle analysis and RNA content, and chromosomal studies of one-week-old LTMC from healthy donors detected no significant abnormalities in purged as compared to control cultures. After 3-4 weeks of LTMC, both control and etoposide-treated cells formed confluent monolayers. Using a panel of seven monoclonal antibodies (S3.13, S16.144, S4.7, S8.6, RIB-19, anti-HLA-DR, and VIL-A1), we investigated the expression of early and late differentiation antigens on LTMC after various culture times (0, 1, 2, 3, and 4 weeks). None of the early antigens S3.13, S16.144, and S8.6 was significantly reduced following etoposide treatment, either in nonadherent cells collected from the supernatant or in the adherent cell population obtained from trypsinized monolayers. Etoposide treatment dose dependently delayed the expression of RIB-19 (a late myeloid antigen) and, to a lesser extent, of S4.7 (an "intermediate" myelomonocytic marker). VIL-A1 expression was not affected by etoposide treatment. We conclude that etoposide purging of bone marrow in the 75-125 microM range spares a sufficient number of functionally intact stem cells to allow adequate in vivo reconstitution following autologous transplantation.
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PMID:Etoposide as an in vitro purging agent for the treatment of acute leukemias and lymphomas in conjunction with autologous bone marrow transplantation. 352 2

Thirty-two patients with recurrent Hodgkin's disease have been treated with an oral regimen employing lomustine (CCNU, 100 mg/m2 orally on Day 1); etoposide (VP-16, 100 mg/m2 orally on Days 1-3 and 21-23); and methotrexate (30 mg/m2 orally on Days 1, 8, 21, and 28). The regimen was repeated every 6 weeks. Most patients had been treated with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine); 20 had had prior irradiation. Lymph node was the predominant site of disease and the majority of patients had B symptoms. Four patients achieved complete response (13%), with a median duration of 33+ months, and 11 achieved partial response (34%), with a median duration of 5 months, for an overall response rate of 47%. The major toxic effect was severe myelosuppression, which occurred in six patients; there were no treatment-related deaths. This oral regimen was easy to administer in heavily pretreated patients with poor venous access and had minimal toxicity.
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PMID:Third-line chemotherapy for resistant Hodgkin's disease with lomustine, etoposide, and methotrexate. 356 72


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