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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Which strategy is more promising to improve the outcome of primary conventional chemotherapy in advanced Hodgkin's disease (HD): a moderate dose escalation or treatment intensification by shortening cycles? The answer generally depends on two factors: the tumour growth velocity and the chemosensitivity of the tumour. A simple mathematical model of tumour growth and chemotherapy effects was developed to quantify this dependency. The model allows to estimate the distribution of latency times (i.e., the time a tumour requires to grow from one cell to clinical detection) and the distribution of chemosensitivity in a patient population on the base of clinical data on tumour control and treatment given. The model was fitted to the data of 705 stage IIIB/IV HD patients of the German Hodgkin's Lymphoma Study Group (GHSG). The model reveals considerable heterogeneity in chemosensitivity and a significantly positive slope of the dose-response relationship at the standard treatment dose level. The model can be used to simulate the effect of various treatment escalation and intensification strategies. On the basis of such simulations we predict only small benefits (about 3% in 5-year tumour control rates) with shortening cycle intervals from 4 to 3 weeks. In contrast, we predict that a moderate dose escalation by 30% of a standard chemotherapy will lead to a potential benefit in the order of 10% in tumour control at 5 years. The presently ongoing HD9 trial of the GHSG is designed to demonstrate this effect.
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PMID:Rationale for dose escalation of first line conventional chemotherapy in advanced Hodgkin's disease. German Hodgkin's Lymphoma Study Group. 883 18

The BEACOPP chemotherapy regimen for advanced Hodgkin's disease employs a rearranged schedule permitting a shortened three-week cycle. With haematological growth factor support, the dosages of cyclophosphamide, etoposide and adriamycin could be moderately escalated. The 3-armed multicentre HD9 trial (recruitment 1993-1998; 1300 patients randomised) aimed to compare BEACOPP with the standard COPP/ABVD chemotherapy and to detect and measure the gain in efficacy, if any, due to moderate dose escalation of BEACOPP. Eight cycles were given, followed by local irradiation. The most recent interim analysis, with 689 evaluable patients, circa 40% of all expected events and a median observation time of 27 months, showed significant differences in progression rate (P) and in two-year freedom from treatment failure (F) between the treatment arms, with escalated BEACOPP (P = 2%, F = 89%) better than baseline BEACOPP (P = 9%, F = 81%) better than COPP/ABVD (P = 13%, F = 72%). Survival was not significantly different. Acute toxicity was more severe due to dose escalation, but remained manageable. These preliminary results suggest that BEACOPP improves efficacy. Moderate dose escalation is feasible with G-CSF support and appears likely to make a worthwhile improvement in the cure rate. The results must await confirmation (or otherwise) by the final analysis including all randomised patients and sufficiently mature data.
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PMID:BEACOPP: a new regimen for advanced Hodgkin's disease. German Hodgkin's Lymphoma Study Group. 992 40

In this article we summarize the theoretical arguments which led us in the German Hodgkin's Disease Study Group to introduce the BEACOPP-regimen and to initiate a large randomised trial to investigate the role of moderate dose escalation in the treatment of advanced stage Hodgkin's disease. Although some indications for a role of dose were available in the early 1990s no prospective randomised trial had been undertaken. In order to obtain an impression of the shape of the essential dose response characteristic we developed a novel statistical model that could be used to analyse a set of data in which dose variations had occurred. The model took tumour growth and chemotherapy effects into account. The model could be applied to clinical data on tumour control and treatment given in a patient population. The model was fitted to the data of 706 patients which had received COPP/ABVD-like regimens. It revealed considerable heterogeneity in chemosensitivity and a positive slope of the doseresponse relationship. The model was used to simulate the effect of various treatment strategies with dose escalation and schedule changes. On the basis of such simulations we predicted that shortening cycle intervals from 4 to 3 weeks should lead to small benefits (about 3% in five-year tumour control rates). In contrast, we predicted that a moderate average dose escalation by 30% of a standard chemotherapy would lead to a potential benefit in the order of 10%-15% in tumour control at five years. Subsequently we searched for a treatment scheme that would permit such a dose escalation. The BEACOPP-scheme was invented to allow the three major myelotoxic substances (cyclophsphamide, adriamycin and etoposide) to be given in the beginning of a cycle. These three substances were then subject to dose escalation in a dose finding trial. G-CSF was introduced to compensate for the myelotoxic effects. The dose level found feasible for a large multicentre setting turned out to be in the required magnitude. The HD9 trial of the GHSG was then initiated to examine whether the predicted dose response curve really exists.
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PMID:Model based development of the BEACOPP regimen for advanced stage Hodgkin's disease. German Hodgkin's Lymphoma Study Group. 992 41

After 10 years we are still not clear whether dose escalation with stem cell transplantation is relevant for some patients with poor prognosis Hodgkin's disease in first remission. Some of the problems relating to the controversy relate to the fact that the definition of high risk Hodgkin's disease in terms of prognostic factors is only now in 1998 being delineated properly. It is also possible that some of the dose escalation in lymphoma has taken place without an adequate amount of conventional therapy beforehand. It may be possible that dose escalation should be added to an adequate amount of conventional chemotherapy not integrated in a conventional regimen thus shortening it. Newer studies from the German Hodgkin's Disease Study Group, i.e. HD9, may be suggesting that conventional chemotherapy is producing good results in poor prognosis patients and thus negating the need for dose escalation and stem cell transplantation.
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PMID:The case for and against high-dose therapy with stem cell rescue for early poor prognosis Hodgkin's disease in first remission. 992 43

Chemotherapy-treated patients with advanced Hodgkin's disease (HD) differ considerably in acute hematotoxicity. Hematotoxicity may be indicative of pharmacological and metabolic heterogeneity. We hypothesized that low hematotoxicity might correlate with reduced systemic dose and thus reduced disease control. A total of 266 patients with advanced HD treated with cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, and dacarbazine (COPP-ABVD) were analyzed (HD6 trial of the German Hodgkin's Lymphoma Study Group). The reported WHO grade of leukocytopenia was averaged over chemotherapy cycles given and weighted with the reciprocal dose intensity of the corresponding cycle. The low and high toxicity groups were defined in retrospect as having had an averaged WHO grade of leukocytopenia </=2.1 and >2.1, respectively. The independent impact of low hematological toxicity on freedom from treatment failure (FFTF) was assessed multivariately adjusting for the international prognostic score for advanced HD. The results were validated in two independent cohorts [181 patients treated with COPP-ABVD (HD9-trial) and 250 patients treated with COPP-ABV-ifosfamide, methotrexate, etoposide, and prednisone (IMEP) (HD6 trial)]. The 5-year FFTF rates were 68% for patients with high toxicity vs 47% for patients with low toxicity [multivariate relative risk (RR) 2.0, 95% confidence interval (CI) 1.4-3.0, p=0.0002]. Patients with low toxicity received significantly higher nominal dose ( p=0.02) and dose intensity ( p<0.0001). This finding was confirmed in both validation cohorts (multivariate RR 2.1, 95% CI 1.2-3.8, p=0.01 and RR 1.5, 95% CI 1.01-2.26, p=0.04, respectively). Patients with low hematotoxicity have significantly higher failure rates despite higher doses and dose intensity. Hematotoxicity is an independent prognostic factor for treatment outcome. This observation suggests a strategy of individualized dosing adapted to hematotoxicity.
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PMID:Low acute hematological toxicity during chemotherapy predicts reduced disease control in advanced Hodgkin's disease. 1506 67

In contrast to younger patients, the prognosis of elderly patients with advanced Hodgkin's disease (HD) has not improved substantially over the last 20 years. We thus carried out a prospectively randomized study (HD9(elderly)) to compare the BEACOPP regimen in this setting against standard COPP-ABVD. Between February 1993 and 1998, 75 patients aged 66-75 years with newly diagnosed HD in advanced stages were recruited into the HD9 trial as a separate stratum (HD9(elderly)). Patients were assigned to eight alternating cycles of COPP and ABVD or eight cycles of BEACOPP in baseline doses. Radiotherapy was given to initial bulky or residual disease. In total, 68 of 75 registered patients were assessable: 26 were treated with COPP-ABVD and 42 with BEACOPP baseline. There were no significant differences between COPP-ABVD and BEACOPP in terms of complete remission (76%), overall survival (50%) and freedom from treatment failure (FFTF) (46%) at 5 years. At a median follow-up of 80 months, a total of 37 patients died: 14/26 patients (54%) treated with COPP-ABVD and 23/42 patients (55%) with BEACOPP. Two patients (8%) treated with COPP-ABVD and nine patients (21%) treated with BEACOPP died of acute toxicity. Hodgkin-specific FFTF at 5 years was 55% after COPP-ABVD and 74% after BEACOPP (P=0.13). Thus, there are no differences in survival between these regimens in elderly patients.
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PMID:A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly). 1559 49

In 1992, the German Hodgkin Study Group (GHSG) developed the BEACOPP regimen for further improving the outcome of patients with advanced Hodgkin's lymphoma (HL). Since then, BEACOPP has been introduced in 3 different prospective randomized clinical trials of the GHSG to find an equilibrium between maximal efficacy and least toxicity with the BEACOPP principle for the treatment of advanced stage HL. In the HD9 trial of the GHSG, with 1,186 patients, after a median observation time of 7 years, the rates for FFTF are 85 percent and for overall survival 90 percent for dose-escalated BEACOPP, and for COPP/ABVD (C/ABVD comparable to ABVD) the rate for FFTF is 67 percent and for overall survival it is 79 percent. These superior BEACOPP results are obtained inspite of a higher rate of secondary AML/MDS in the escalated BEACOPP arm. The number of toxic deaths during treatment, however, was lower for escalated BEACOPP (1.6 percent) than for C/ABVD (1.8 percent). The majority of patients were treated in an outpatient setting, in a multicenter study with more than 400 centers, including 120 private doctors, located in Germany and 9 other European countries. To reduce acute and long-term toxicity, the GHSG started in the consecutive studies HD12 and HD15 for advanced stage HL to de-escalate BEACOPP by reducing the number of escalated BEACOPP cycles and by applying the baseline dose BEACOPP, a time dense regimen, called BEACOPP-14. The excellent results obtained with the BEACOPP principle challenge the seemingly global consensus that ABVD is the gold standard treatment strategy for advanced stage HL.
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PMID:Could BEACOPP be the new standard for the treatment of advanced Hodgkin's lymphoma? 1677 1

In 1992, the German Hodgkin Study Group (GHSG) developed the BEACOPP regimen for further improving the outcome of patients with advanced Hodgkin's lymphoma (HL). Since then, BEACOPP has been introduced in 3 different prospective randomized clinical trials of the GHSG to find an equilibrium between maximal efficacy and least toxicity with the BEACOPP principle for the treatment of advanced stage HL. In the HD9 trial of the GHSG, with 1,186 patients, after a median observation time (mot) of 7 years, the rates for freedom from treatment failure (FFTF) are 85 percent, and for overall survival (OS) 90 percent for dose-escalated BEACOPP, and for COPP/ABVD (C/ABVD comparable to ABVD) the rate for FFTF is 67 percent, and for OS it is 79 percent. These superior BEACOPP results are obtained inspite of a higher rate of secondary AML/MDS in the esc. BEACOPP arm. The number of toxic deaths during treatment, however, was lower for esc. BEACOPP (1.6 percent) than for C/ABVD (1.8 percent). The majority of patients were treated in outpatient setting, in a multicenter study with more than 400 centers, including 120 private doctors, in Germany and 9 other European countries. The reduce acute and longterm toxicity, the GHSG started in the consecutive studies HD12 and HD15 for advanced stage HL to de-escalate BEACOPP by reducing the number of escalated BEACOPP cycles and by applying the baseline-dose BEACOPP, a time-dense regimen, called BEACOPP-14. The excellent results obtained with the BEACOPP principle challenge the seemingly global consensus that ABVD is the gold standard treatment strategy for advanced stage HL.
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PMID:Could BEACOPP be the new standard for the treatment of advanced Hodgkin's lymphoma (HL)? 1711 82

Hodgkin Lymphoma (HL) has become one of the most curable cancers, even in adulthood, through continuous improvement of therapeutic options and their verification by large multicenter trials. Today more than 95% of patients with HL in early stages and in advanced stages 85-90% can be cured. Nevertheless, these good results are threatened by treatment associated toxicities such as infertility, cardiopulmonary toxicity and secondary malignancies. It is therefore the aim of future trial generations both to maintain the excellent treatment results and to minimize late effects. In 1964 for the first time deVita et al. described the MOPP polychempotherapy for patients with advanced HL which led to cure rates in more than 50%. Around ten years later Bonadonna et al. established the non cross resistant alternative regime to MOPP, ABVD which nowadays is accepted as "gold standard" for the treatment of advanced HL. MOPP and/or ABVD and furthermore the alternating MOPP/ABVD or the MOPP/ABV hybrid with and without the help of consolidative radiation resulted in around 70% long term survival rates, 30-40% of patients experienced tumor progression or relapses within 5 years. This led the German Hodgkin Study Group (GHSG) [Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D, et al. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med 2003; 348: 2386-95] to improve the efficacy of COPP/ABVD by time- and dose-intensification, omission of Velban and Dacarbazin and adding Etoposide resulting in the BEACOPP principle. From the initial pilot studies in 1992 three trial generations, HD9, HD12, HD15, have now established this principle as one of the most effective chemotherapy regimen in advanced HL. We certainly hope that it will not last another 20 years to establish the BEACOPP regimen as an attractive curative treatment option for at least the high risk cohorts of HL.
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PMID:Will BEACOPP be the standard for high risk Hodgkin lymphoma patients in advanced stages? 1771 96

Current therapy for Hodgkin disease is aimed at high cure rates and optimal survivorship. Although intensified chemotherapy with the escalated BEACOPP regimen resulted in higher rates of cure and survival compared with COPP/ABVD in the high-profile HD9 randomized controlled trial (RCT), this regimen has not been universally adopted by patients and physicians due to the attendant increased risks of early and late complications. Appropriately, questions emerge as to whether the results of this trial should be interpreted as establishing the superiority of BEACOPP over the current standard ABVD therapy, and whether clinical or biologic prognostic factors can better select patients for more intensive treatment. The widespread availability and high predictive accuracy of functional imaging with PET scans has led to promising, preliminary studies assessing early response to therapy with this diagnostic tool. In this review, the characteristics and outcomes of patients treated with ABVD in RCT will be made and compared with COPP/ABVD in HD9; clinical and biologic prognostic factors will be discussed, including PET imaging; and newer strategies targeted at minimizing treatment complications while maximizing cure rates will be discussed. Although enthusiasm for PET imaging is great, the challenges for using this diagnostic tool for risk-adapted therapies are substantial. Importantly, physicians and patients should be aware of these challenges, support the RCT that seek to address them, and carefully weigh risks and benefits for individual patients.
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PMID:Risk, cure and complications in advanced hodgkin disease. 1802 30


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