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Acta Oncologica (Stockholm, Sweden) 2003A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The... (Review)
Review
A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for non-Hodgkin's lymphoma (NHL) is based on data from seven randomized trials. Moreover, data from 17 prospective studies, 22 retrospective studies and 27 other articles were used. In total, 73 scientific articles are included, involving 13,305 patients. The results were compared with those of a similar overview from 1996 including 14,137 patients. The conclusions reached can be summarized as follows: Indolent lymphomas. Data indicate that one-third to one-half of patients with indolent lymphoma in stage I are cured by radiotherapy (follow-up more than 15 years). Addition of chemotherapy to radiotherapy does not indicate any improvement in overall outcome. Optimal radiation dose is not defined and extended field is not superior to involved field. Aggressive localized lymphomas. Data indicate that half of the patients in stage I are cured by radiotherapy alone. Although randomized and non-randomized studies favour combined modality treatment with chemotherapy followed by radiotherapy instead of radiotherapy or chemotherapy alone in localized disease, no firm conclusions can be drawn. Conflicting data have been published on the value of radiotherapy towards bulky disease and no firm conclusions can be drawn. Optimal dose for radiation alone or after chemotherapy has not been established. Total body irradiation (TBI). The value of TBI for treatment of NHL has not been proven. There is no proof that fractionated TBI in conjunction with high-dose chemotherapy is superior to chemotherapy regimens alone. Primary CNS lymphomas. Data show that radiotherapy induces a response of short duration and is associated with major neurotoxicity, especially in elderly patients. High-dose methotrexate therapy seems to lead to longer survival than radiotherapy alone. No randomized trials have been performed. There is fairly good support for primary chemotherapy including high-dose methotrexate followed by radiotherapy in patients below 60 years. To minimize the risk of neurotoxicity of combined modality treatment it has been proposed to use chemotherapy alone and delay radiotherapy for relapse, especially in patients above 60 years, or use it in chemotherapy-resistant disease. Optimal chemotherapy regimen is not defined and the role of radiotherapy remains to be determined. Head and neck lymphomas. There is some support for combined modality treatment with chemotherapy and radiotherapy for aggressive lymphomas in Waldeyer's ring with limited disease. There are sparse data supporting radiotherapy alone in localized indolent lymphomas in salivary glands. Radioimmunotherapy (RIT). Radioimmunotherapy is a new treatment modality with systemic radiation for patients with advanced NHL, where conventional external beam radiotherapy plays only a minor role. Several phase I and II studies with RIT have documented promising results. A variety of monoclonal antibodies, radionuclides and study designs with both myeloablative and non-myeloablative approach have resulted in high response rates in patients with recurrent or refractory NHL. One randomized clinical trial is published, showing superior therapy results with radiolabelled antibody compared with the corresponding unlabelled antibody.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Female; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Prognosis; Radiotherapy Dosage; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Risk Assessment; Survival Analysis; Sweden; Treatment Outcome
PubMed: 14596518
DOI: 10.1080/02841860310014435 -
The Lancet. Oncology May 2003We have done a systematic review of all randomised studies in myeloma, identified through a comprehensive search. Our aim was to investigate and critically examine the... (Review)
Review
We have done a systematic review of all randomised studies in myeloma, identified through a comprehensive search. Our aim was to investigate and critically examine the effects of various treatment modalities on outcome in patients with multiple myeloma and address 22 specific clinical questions in the management of this disease. As a result of our analysis we identified two therapeutic advances in the management of myeloma that, according to the evidence, are most important for improving outcome. These advances were: introduction of high dose chemotherapy, which appears to be superior to conventional chemotherapy, and the use of bisphosphonates, which decrease the probability of pathological vertebral fractures. However, the overall quality of the body of evidence for myeloma management was poor. Many trials were done with small sample sizes, and did not include reporting power analysis. The majority of studies had inadequate allocation concealment, and few were analysed according to intention to treat principle. We conclude that the quality of total evidence supporting treatment recommendations in myeloma is modest at best and has an ample scope for improvement.
Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Purging; Bone Marrow Transplantation; Boronic Acids; Bortezomib; Diphosphonates; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Multiple Myeloma; Neoplasm Staging; Pyrazines; Randomized Controlled Trials as Topic; Recombinant Proteins; Salvage Therapy; Survival Analysis; Time Factors; Transplantation Conditioning; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome
PubMed: 12732167
DOI: 10.1016/s1470-2045(03)01077-5 -
Bone Marrow Transplantation May 2002For children with AML in CR1, the major consolidation therapies are BMT, ABMT and intensive chemotherapy. The relative effectiveness of these strategies is still... (Meta-Analysis)
Meta-Analysis
For children with AML in CR1, the major consolidation therapies are BMT, ABMT and intensive chemotherapy. The relative effectiveness of these strategies is still debated. We conducted a systematic review and meta-analysis of trials to determine the effectiveness of BMT and ABMT in CR1 in paediatric AML. Eligible studies enrolled patients <21 years from 1985 to 2000 with AML in CR1. Two groups of studies were identified: (1) Those comparing the outcome of patients with and without a histocompatible family donor; and (2) Randomised controlled trials (RCT) comparing ABMT with non-myeloablative chemotherapy. The relative risk statistic was calculated for outcomes of interest in each trial. If there was no excessive heterogeneity between trials the results were pooled, and an overall relative risk and risk difference for treatment effect across trials were calculated. Results of the analysis showed that allocation to BMT reduced risk of relapse and improved disease-free and overall survival. For ABMT, heterogeneity of effect between RCTs prevented pooling of results. In conclusion, BMT from a histocompatible family donor improves patient outcome. Data are insufficient to determine whether this is true for all subgroups of AML, and whether ABMT is superior to non-myeloablative chemotherapy. An individual patient data meta-analysis is required to further evaluate the available data.
Topics: Adolescent; Adult; Bone Marrow Transplantation; Child; Disease-Free Survival; Humans; Leukemia, Myeloid, Acute; Risk Factors; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome
PubMed: 12058234
DOI: 10.1038/sj.bmt.1703528 -
Acta Oncologica (Stockholm, Sweden) 2001A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for... (Review)
Review
A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy in patients with acute myeloid leukaemia (AML) is based on 129 scientific articles: one meta-analysis, 51 randomised trials, 39 prospective and 18 retrospective studies, and 20 other articles. Altogether, 39,557 patients were included in these studies. The conclusions reached can be summarized into the following points: Standard induction therapy for patients with AML, consisting of daunorubicin and ara-C in conventional doses, results in a complete remission (CR) rate of 50-60% in an unselected population and a long-term survival of about 10-20%. The total doses of both ara-C and daunorubicin are of importance for remission duration and in some studies also for survival. High-dose ara-C in the induction therapy prolongs remission duration in randomised trials, but has not been proven to affect long-term survival. It also increases toxicity and is not generally recommended. Idarubicin, another anthracyclin, has been compared with daunorubicin in conjunction with ara-C, resulting in a higher CR rate, especially in younger patients. In a meta-analysis of the five-randomised trials performed, a slight survival advantage was also seen with idarubicin. Yet, there is inconclusive evidence to conclude that idarubicin is superior to daunorubicin, and further trials are needed. Mitoxantrone improves the outcome of induction therapy in comparison with daunorubicin in some randomised studies, but conclusive evidence is still lacking. The addition of etoposide to daunorubicin or mitoxantrone and ara-C has improved CR rates, but has not convincingly improved survival and secondary leukaemias may be induced. New induction treatment strategies are defined by identification of prognostic subgroups. A risk stratification of AML patients as to chromosomal aberrations might be of importance for the choice of therapy. Moreover, the speed and the morphological response to the first induction course are predictive for relapse. However, no prospective randomised studies are as yet published regarding risk-adapted induction therapy. Post-remission dose-intensive chemotherapy prolongs the duration of remission, seemingly most in patients < 60 years. However, the data in support of these conclusions are sparse. A convincing effect on survival has not been shown. Limited data indicate that post-remission maintenance therapy with long-term attenuated chemotherapy prolongs time to recurrence, without evidence for prolongation of survival. Allogeneic bone marrow transplantation is an established practice for consolidation in first remission for young patients with an HLA-matched sibling. It is however not known which patients will really benefit from transplantation as no truly randomised comparison of allogeneic vs autologous transplantation or conventionally-dosed chemotherapy has been performed. Patients with and without an HLA-identical sibling have been compared on the basis of intention-to-treat principles ('genetic randomisation'). The disease-free survival seems to be prolonged in the donor group, due to a lower relapse rate with allogeneic transplantation. A higher procedure-related mortality makes the effects on total survival uncertain. Randomised trials with autologous transplantation vs conventional consolidation show a lower relapse rate and a trend for an improved disease-free survival. In one study, in which an autograft was added to four courses of intensive therapy, there was also a late survival advantage. Thus, the role for intensified post-remission treatment in first complete remission with high-dose chemotherapy followed by allogeneic or autologous marrow or stem cell transplantation requires further studies. Moreover, studies with stratification of therapy according to predictors for prognosis in the individual patient are needed. Allogeneic stem cell transplantation after minimal or reduced myeloablative conditioning ('mini-transplantation' or non-myelo stem cell transplantation) induces a host-vs-graft tolerance and an immune graft-vs-leukaemia effect. This new concept of immunotherapy seems to have a low procedure-related mortality, but long-term effects are unknown and evaluation in controlled clinical studies is required. Patients with relapsed AML can only infrequently achieve long-term remissions with chemotherapy in conventional doses. trolled data indicate that allogeneic transplantation can be a curative treatment for these patients a
Topics: Acute Disease; Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Cytarabine; Daunorubicin; Disease-Free Survival; Etoposide; Humans; Leukemia, Myeloid; Middle Aged; Mitoxantrone; Neoplasms, Second Primary; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome
PubMed: 11441935
DOI: 10.1080/02841860151116321 -
Acta Oncologica (Stockholm, Sweden) 2001A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for... (Review)
Review
A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy for B-cell chronic lymphocytic leukaemia (B-CLL) is based on data from 20 randomised controlled trials and one meta-analysis. Moreover, data from 19 prospective studies, one retrospective study and four other articles were used. Totally 44 scientific articles are included, involving 11,289 patients. The conclusions reached can be summarized into the following points: Primary treatment of patients with symptomatic B-CLL is recommended to be an oral alkylating agent such as chlorambucil. This drug induces tumour remission and symptomatic relief in a majority of patients with progressive disease. Response may be long-lasting, but cure is not obtained. Optimum dose and schedule of administration of chlorambucil or other alkylating agents have not been defined. It is recommended to defer initial therapy until required by disease progression. Large randomised trials have demonstrated that early treatment with chlorambucil in a continuous or an intermittent schedule does not prolong survival in B-CLL patients with low tumour burden (Binet stage A). The addition of corticosteroids to alkylator regimens has not been proven to give any benefit. Combination chemotherapy as primary treatment has not shown any advantage compared with single drugs. Early inclusion of anthracyclines to the therapy does not convincingly add to the activity of alkylating agents. The purine analogues fludarabine and 2-chlorodeoxyadenosine are active in B-CLL. However, like other drugs, they do not appear to be curative. In randomised multicentre trials a benefit from fludarabine as primary therapy compared with polychemotherapy (CHOP or CAP) has been observed in terms of tolerance and treatment response but not yet in survival. No randomised studies have been performed to show whether one of the purine analogues should be preferred. At relapse after single drug treatment, retreatment with the same drug often induces new remissions. However, the proportion of patients responding declines each time chlorambucil or any other single agent is readministered. At progression on single alkylating agents, the purine analogues or various combinations, mostly CHOP, frequently induce tumour remissions. For patients with advanced B-CLL failing to respond to fludarabine or CHOP, the prognosis is poor. None of the salvage regimens reported has produced durable remissions. High-dose chemo-radiotherapy with stem cell transplantation has been evaluated for young patients with B-CLL. A long survival has been shown in some patients following allogeneic and autologous transplantation. However, the risk of transplantation-related mortality is still high with allo-transplants and relapse is common after auto-transplantation. A benefit of purging autologous stem cells has been proposed but evidence is lacking. Thus, transplantation remains experimental; more patients and a longer follow-up are needed to assess if cure can be achieved. In the future an individual risk-adapted therapy will be required. The clinical heterogeneity of the disease has pointed to the necessity of new predictors for prognosis evaluated in prospective trials.
Topics: Adolescent; Adult; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Child; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Disease Progression; Doxorubicin; Humans; Leukemia, B-Cell; Prednisolone; Prognosis; Recurrence; Risk Factors; Salvage Therapy; Vidarabine; Vincristine
PubMed: 11441934
DOI: 10.1080/02841860151116303