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)

MOPP (mechlorethamine, vincristine, procarbazine, prednisone) was the first successful regimen for the treatment of Hodgkin's disease. It has the longest period of follow-up and is best studied as to its benefits and acute and long-term side effects. The acute toxicity of the side effects, including nausea and/or vomiting, hair loss, and myelosuppression, may have been reason to modify doses of nitrogen mustard, an agent whose dose intensity may be critical in achieving long-term benefits. The substitution of chlorambucil and vinblastine in the ChlVPP (chlorambucil, vinblastine, procarbazine, prednisone) program has relieved all of these acute toxicities, except myelosuppression. The long-term toxicity of sterility, especially in males, and myelodysplasia is most likely due to alkylating-agent toxicity and would not be influenced by the various MOPP variants, such as MVPP (mechlorethamine, vinblastine, procarbazine, prednisone), ChlVPP, and COPP (chlorambucil-vincristine, procarbazine, prednisone). Doxorubicin-containing regimens, such as ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and ABDIC (doxorubicin, bleomycin, dacarbazine, lomustine, prednisone), have been second-line treatments that have significant antitumor effect and, as such, have resulted in few, if any, long-term cures in most series. ABVD has been incorporated into alternating MOPP/ABVD schemes or in hybrids that attempt to offer all active agents, such as MOPP/ABV. The initial experience has been encouraging with high and durable complete remissions (CRs). MOPP/ABVD x 12(1) and MOPP-2/ABVD-2(2) have been compared with MOPP alone with a significant superiority for the alternating regimens. Other randomized trials have not shown any superiority for the alternating program. The Cancer and Leukemia Group B (CALGB) has compared MOPP with MOPP/ABVD given with a third arm of ABVD alone. The complete response and time-to-treatment failure rates for MOPP/ABVD and ABVD alone were superior to those for MOPP. Significant modifications of MOPP doses may explain the differences, since only 20% of patients were receiving full doses of nitrogen mustard by the sixth dose. ABVD has unique toxicity, and myelodysplasia and sterility are not seen. Pulmonary fibrosis with radiation and bleomycin is unique to ABVD, as shown in the ABVD experience at the NCl (Milan). Can ABVD be improved? The demonstrated single-dose activity of etoposide in Hodgkin's disease has prompted its inclusion in second-line programs, such as EVA (etoposide, vincristine or vinblastine, doxorubicin). The second-line response rates in the St Bartholomew's (London, England) series (where vincristine was used) was 11 of 19 patients (58%);3 in the ongoing CALGB trial of EVA (vinblastine combination), the response rate is 67%. (ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Can MOPP be replaced in the treatment of advanced Hodgkin's disease? 168 9

Between October 1985 and October 1989, 75 previously untreated patients with stage III and IV non Hodgkin's lymphoma, large cell type, were treated with an alternating weekly chemotherapy regimen including the following drugs: week 1: Doxorubicin, vincristine, cyclophosphamide, bleomycin, and intrathecal (i.th.) methotrexate and cytarabine; week 2: Methotrexate with leucovorin rescue; week 3: Doxorubicin, ifosfamide with mesna, etoposide, and i.th. methotrexate and cytarabine; week 4: Methotrexate with leucovorin rescue. Complete responders after three cycles according to this schedule (12 weeks) were given 18 gys cranial irradiation and randomized between one additional cycle or three monthly CHOP (consolidation treatment). Among 66 evaluable patients, 53 achieved a complete remission (CR 80 per cent) and seven a partial remission (11 per cent). There were six failures, and nine early deaths during the initial phase, mostly due to septic problems. Forty-one of the 53 CR patients (77.3 per cent) have remained free of disease with a median follow-up of 15 months (1-49). Eight of the 12 relapses occurred during the first year, the four others at 13, 14, 16 and 38 months respectively. The 2-year survival was 63 per cent for the whole group, and 77 per cent for the CR group. No difference has been observed up until now between the two groups with different consolidation treatment. Therefore, this protocol seems to be able to produce a high rate of complete and durable remission. The analysis of prognostic factors suggests that some high-risk patients should be considered for intensification therapy with the support of autologous bone marrow transplantation.
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PMID:Multicentre combined chemotherapy protocol for large cell advanced non Hodgkin's lymphoma. 172 Jul 59

Dose intensity defined as the amount of drug used per unit time, expressed as mg/m2/week, was reported to be a significant determinant of antitumor activity of single or combined drugs in cancer chemotherapy. We formulated a 12 week high dose intensity chemotherapy (CAMBO-VIP) for the treatment of advanced non Hodgkin's lymphoma with aggressive histology. The treatment consists of weekly alternate administration of myelosuppressive and non-myelosuppressive agents. Doxorubicin was administered every other week in combination with either cyclophosphamide, etoposide or ifosfamide. On the weeks in between, non-myelosuppressive vincristine was given with either methotrexate with leucovorin rescue or bleomycin. Prednisolone was given for the first and the last 4 weeks. Dose reduction and treatment delay were kept minimal for the purpose not lowering dose intensity. As of February 1990, 32 patients (pts), median age 52, entered the study, 29 of whom completed the treatment. There were 3 incomplete cases, in which 2 were due to interruption of the treatment at 5 and 6 weeks, respectively and 1 due to a half dose given because of the old age. CR was obtained in 29 pts (90.6%). Relapse occurred in 3 (10.4%) with the median follow-up of 12 months. Two year disease-free survival (DFS) was estimated to be 76.0% for all the patients and 83.9% for CR patients. Toxicity of CAMBO-VIP was moderate with no chemotherapeutic death. Myelosuppression was severe but of short duration, requiring virtually no dose reduction. Treatment delay was 3 days, median, and maximally 28 days. The average actual dose intensity calculated from given amount of drugs and treatment duration was as high as 90% of the protocol dose intensity. Dose intensity of CAMBO-VIP protocol is highest, equaling to that of MACOP-B, among representative series of reported lymphoma protocols. A highly significant correlation was observed between 9 drug relative dose intensity and DFS of the patients treated with each protocol. Significance of dose intensity as an independent prognostic factor, however, should be determined, by a prospective carefully designed stratified randomized studies.
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PMID:[Alternating non-cross resistant multi-drug chemotherapy against malignant lymphoma (CAMBO-VIP)--consideration of the dose intensity]. 222 23

Doxorubicin (adriamycin) has a very wide antitumour spectrum, compared with other anticancer drugs; however, except for Hodgkin's disease, it is not associated with curative chemotherapy. Doxorubicin has been in clinical use for more than 2 decades, and only recently has it been recognised that the cytotoxic effect is produced at the cellular level by multiple mechanisms which have not yet been conclusively identified. Key factors are a combination of doxorubicin-induced free radical formation due to metabolic activation, deleterious actions at the level of the membrane, and drug-intercalation into DNA. Multiple aspects of the clinical pharmacokinetics of this drug have been described. Wide interpatient variations in plasma pharmacokinetics have been noted, but without firm relation to clinical outcome. An apparent volume of distribution of approximately 25 L/kg points to extensive uptake by tissues. Up to several weeks after administration, significant concentrations of doxorubicin have been found in haematopoietic cells and in several other tissues. The maximum cellular doxorubicin concentrations reached in vivo remain significantly below those at which all clonogenic leukaemic cells are killed in vitro. Doxorubicin has been administered as frequent (weekly) low doses, single high doses, and as a continuous infusion. The optimal schedule with respect to tumour cytotoxicity and dose-limiting side effects such as myelosuppression or cardiotoxicity, has never been investigated in a prospective, randomised manner. Clinical trials large enough to study optimal, and possibly individualised, doxorubicin chemotherapy need to be performed. This review summarises pharmacological and pharmacodynamic data of doxorubicin, and discusses these in relation to possible improvement of its therapeutic index. Furthermore, drug interactions, dose-response relationships, mechanisms of action, multidrug resistance, and treatment scheduling are discussed in the perspective of the development of novel treatment strategies.
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PMID:Clinical pharmacokinetics of doxorubicin. 304 44

Mitoxantrone is similar to Adriblastin in its mechanism of action and antitumor activity. Objective remissions were obtained in 20-30% pretreated patients and in 23-44% of untreated patients by single-drug treatment of patients suffering from metastatic breast cancer. The objective response rates to Mitoxantrone in combination with CTX, 5-FU, MTX, VCR, MMC. Prednimustine or Vindesine were 16-46% in treatment and 38-89% in primary treatment. Randomized studies comparing Mitoxantrone with Adriblastin in single-drug and combination treatment did not show any significant differences in efficacy. However, Mitoxantrone was significantly less toxic. Remission rates of between 24 and 54% were achieved by single-drug treatment in pretreated patients suffering from non-Hodgkin lymphoma. Mitoxantrone appears to be active in ovarian cancer, lung cancer and hepatocellular carcinoma.
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PMID:Mitoxantrone: mechanism of action, antitumor activity, pharmacokinetics, efficacy in the treatment of solid tumors and lymphomas, and toxicity. 332 53

Doxorubicin is an anthracycline widely used in the treatment of leukaemias, lymphomas and solid tumors. Doxorubicin cannot pass into the cerebrospinal fluid. Nitrosoureas are known to be lipophilic and to be able to penetrate the blood-brain barrier. CCNU is a nitrosourea used to treat Hodgkin's disease, brain tumors and other solid tumors. The authors have previously reported on the nephrotoxicity and hepatotoxicity of these drugs; the present paper reports their findings on haematotoxicity in female Wistar rats. In one group 40 rats received 10 mg/kg doxorubicin. In a second group 40 rats received 20 mg/kg CCNU, and a further 40 rats received 50 mg/kg CCNU. In a third group 60 rats received the association doxorubicin 10 mg/kg plus CCNU 20 mg/kg. Blood counts were performed on days 4, 8, 15, 21 and 28 after treatment. Leucopenia and severe thrombocytopenia were noted after doxorubicin administration. A biphasic decrease in the leucocyte count was observed after CCNU treatment. More severe alterations were observed when doxorubicin and CCNU were combined. Very few data on haematological abnormalities following treatment of human patients have been published. Similarities can be seen between the haematological side-effects noted in rats and those occurring in humans treated with these cytotoxic drugs. Female Wistar rats seemed to be a good model to evaluate the haematological tolerance of anthracycline, nitrosoureas or of their association. If multiple courses of these drugs have to be administered, the evolution of haematological alterations must be known: the decrease phase of blood cells is followed by a rebound phase. The drug should be avoided during this phase of granulocyte activation.
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PMID:Haematotoxicity of doxorubicin and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and of their association in rats. 342 23

In Caucasians, Hodgkin's disease demonstrates constant incidence rates, with a first peak occurring in adolescents and in young adults, and a second peak in the elderly. Age is an important risk factor for overall survival of patients; staging strategies and treatment expose elderly patients to an even higher risk arising from surgical complications, death from secondary cancer and leukemia or lethal cardiac complications. In contrast to non-Hodgkin's lymphoma, optimal staging and treatment procedures have not yet been defined for this disease in elderly patients. However, due to the very poor prognosis of inadequately treated patients, treatment recommendations at present must be based on those for younger patients while keeping the individual risk profile in mind. If staging laparotomy is omitted, most patients will require a combined modality treatment. While in low-risk patients a reduced number of cycles with full-dose chemotherapy like ABVD (Adriblastina, bleomycin, vinblastine, dacarbazine) or of six cycles with less toxic drugs like VBM (vinblastine, bleomycin, methotrexate) followed by limited field radiotherapy may suffice, patients with well-defined risk factors will require a more prolonged chemotherapy. Currently, there is no evidence that C(M)OPP [cyclophosphamide (mustargen), vincristine, procarbazine, prednisone]/ABVD or ABVD may successfully be replaced by less toxic regimens. Therefore, further studies are required on the specific definition of biological age, the cost/benefit ratio of staging procedures and treatment and the influence of these strategies on the quality of life in the elderly.
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PMID:Prognosis and management strategies of lymphatic neoplasias in the elderly. II. Hodgkin's disease. 966 14

Doxorubicin is one of the most effective anticancer drug, but its usefulness is limited by the risk of developing cardiomyopathy, cardiac dysfunction and ventricular arrhythmias. Dexrazoxane is used to protect against doxorubicin cardiotoxicity. It is uncertain whether the dexrazoxane-mediated cardioprotective effect will be reflected in electrophysiological properties of the heart. The aim of the present study was to evaluate the occurrence of frequency-domain signal-averaged electrocardiographic (SAECG) abnormalities of the QRS complex and the initial ST segment in patients treated with and without dexrazoxane. Thirty children and young adults 2 months - 15 years after completion of doxorubicin-containing therapy for Hodgkin's disease were evaluated with SAECG. Patients from group I (n = 13) received combined therapy with doxorubicin and dexrazoxane (DOX/DZX), patients from group II (n = 17) received doxorubicin without dexrazoxane (DOX). Using fast Fourier transformation within the QRS complex and the initial ST segment, area ratio (AR) values 40-100/0-40 Hz were calculated. Significant differences in these frequency parameters in the QRS complex between DOX/DZX group and DOX group (19.45+/-12.72 vs 46.18+/-43.06; p = 0.03) might indicate protective effect of dexrazoxane on electrophysiological myocardial properties.
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PMID:Signal-averaged electrocardiography in survivors of Hodgkin's disease treated with and without dexrazoxane. 1132 39

Anthracyclines have been in clinical practice since the 1960s and represent one of the most commonly used classes of anticancer drugs. Doxorubicin (adriamycin) is one of the first anthracyclines in clinical use, has a broad anti-tumor spectrum, and has been used against hematopoietic malignancies such as lymphoma, myeloma and leukemia, and solid tumors such as breast cancer, ovarian cancer and sarcomas. There are two chemotherapeutic regimens containing doxorubicin that have been established as the state of the art therapy against malignant lymphomas. One is ABVD therapy for Hodgkin's lymphoma, and the other is CHOP therapy for aggressive non-Hodgkin's lymphoma (NHL). In these regimens as well as the regimen for breast cancer, doxorubicin is delivered by bolus intravenous infusion for 30 minutes to one hour. The use of continuous infusion schedules of doxorubicin for 72 to 96 hours has been reported to reduce the incidence of cardiac toxicity somewhat, providing a pharmacokinetic basis for the hypothesis that high peak concentrations are associated with an increased incidence of cardiotoxicity. VAD regimen for myeloma, and EPOCH regimen for relapsed aggressive NHL have been reported and used. However, this approach is not widespread because of concern over compromising antitumor efficacy, unpredictable toxicities, and logistical issues. Continuous infusion schedules of doxorubicin might be reevaluated for the clinical benefit especially for patients with breast cancer treated by trastuzumab and doxorubicin, because trastuzumab was reported to enhance cardiac toxicity.
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PMID:[Adriamycin (doxorubicin)]. 1168 Dec 38

A 49 year-old Indian housewife was diagnosed with Hodgkin's disease in 1995. She was given combination chemotherapy comprising Chlorambucil, Vincristine, Procarbazine and Prednisolone. Unfortunately she defaulted after two courses of chemotherapy. One year later, she developed progressive right knee swelling and pain, associated with loss of appetite, loss of weight, intermittent fever, night sweats and pruritus. The right knee swelling measured 15 cm x 20 cm and was warm and tender. A plain radiograph of the right knee revealed osteolytic lesions at the distal end of the right femur and the proximal ends of the right tibia and fibula, associated with gross periosteal reaction and soft tissue swelling. Apart from left cervical lymphoadenopathy, examination of other systems was unremarkable. Pelvic bone marrow biopsy was inconclusive. An open biopsy of the lower end of the right femur was consistent with Hodgkin's disease. She was given salvage combination therapy comprising Chlorambucil, Vincristine, Procarbazine, Prednisolone, Doxorubicin, Bleomycin and Vinblastine. She tolerated the treatment well and responded with significant reduction in the swelling and pain of the right knee. Unfortunately, she again defaulted treatment after 2 courses of chemotherapy. This case illustrates an unusual presentation of Hodgkin's disease in relapse.
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PMID:Relapsed Hodgkin's disease presenting as a right knee swelling. 1455 40


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