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Bruce D Cheson

Publications and source records attributed to Bruce D Cheson.

At least 19 recordsLinked to original sources
PubMed2006

Prolonged follow-up after initial therapy with 2-chlorodeoxyadenosine in patients with indolent non-Hodgkin lymphoma: results of Cancer and Leukemia Group B Study 9153.

BACKGROUND: The objective of this study was to determine the efficacy and toxicity of 2-chlorodeoxyadenosine (2-CdA) in patients with untreated, indolent non-Hodgkin lymphoma (NHL). METHODS: For this multicenter, single-arm, Phase II study, 44 patients with treatment-naive, stage III or IV, indolent NHL (International Working Formulation subtypes A, B, and C) were enrolled. Patients received 0.14 mg/kg per day of 2-CdA as a 2-hour bolus infusion for 5 consecutive days every 28 days until maximal response or a total of 6 cycles. RESULTS: Thirty-eight patients were eligible for response evaluation. The overall response rate was 100% (95% confidence interval [95% CI], 90.8-100%), and the complete response rate was 31.6% (95% CI, 17.5-48.7%). In the intent-to-treat population, the median failure-free survival was 2.0 years (95% CI, 1.3-3.4 years), and the overall survival rate was 7.0 years (95% CI, 4.3-9.4 years). Six patients had sustained remissions that lasted a median of 8.7 years (range, from 5.9 years to > or =11 years). Although 68% of patients experienced at least 1 grade 3 or 4 event, consisting primarily of myelosuppression, severe infections were rare, with only 8 grade 3 infections. Four late malignancies (prostate adenocarcinoma, ductal carcinoma in situ, and myelodysplasia) and 4 patients with large cell transformation were reported. CONCLUSIONS: 2-CdA is an active, well-tolerated therapy for patients with untreated, indolent NHL.

Adolescent↗
PubMed2006

The cancer and leukemia group B lymphoma committee.

The malignant lymphomas include at least 30 entities that are distinct with respect to histology, immunology, genetics, clinical features, and outcome following therapy. The clinical behavior of these diseases ranges from indolent but generally incurable to aggressive and frequently fatal yet potentially curable with appropriate chemotherapy or chemotherapy-antibody regimens. Over the past 50 years, the Cancer and Leukemia Group B (CALGB) Lymphoma Committee has conducted a series of clinical trials that have contributed to an improvement in outcome for patients with a number of the more common lymphoma subtypes. The World Health Organization has classified approximately 30 neoplastic diseases of the hematopoietic and lymphoid tissues (1). The Cancer and Leukemia Group B (CALGB) Lymphoma Committee highlight below clinical trials that have resulted in improved patient outcome for the more frequent lymphoma subtypes.

Biomedical Research↗
PubMed2006

Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia.

The myelodysplastic syndromes (MDSs) are heterogeneous with respect to clinical characteristics, pathologic features, and cytogenetic abnormalities. This heterogeneity is a challenge for evaluating response to treatment. Therapeutic trials in MDS have used various criteria to assess results, making cross-study comparisons problematic. In 2000, an International Working Group (IWG) proposed standardized response criteria for evaluating clinically significant responses in MDS. These criteria included measures of alteration in the natural history of disease, hematologic improvement, cytogenetic response, and improvement in health-related quality of life. The relevance of the response criteria has now been validated prospectively in MDS clinical trials, and they have gained acceptance in research studies and in clinical practice. Because limitations of the IWG criteria have surfaced, based on practical and reported experience, some modifications were warranted. In this report, we present recommendations for revisions of some of the initial criteria.

Humans↗
PubMed2006

Monoclonal antibody therapy for B-cell malignancies.

For decades, chemotherapy was the only available approach for patients with advanced lymphoid malignancies. Treatment paradigms were dramatically altered by the availability of novel and active targeted agents, particularly the monoclonal antibodies, alemtuzumab and rituximab. These agents are now playing an increasingly important role in the treatment of lymphoid malignancies. Alemtuzumab is being used earlier in the course of chronic lymphocytic leukemia in patients with a more intact immune system, when it is likely to have its greatest activity. The immunosuppressive properties of monoclonal antibodies are also being explored in the stem cell transplant setting, including in vivo purging and, with alemtuzumab, for the management of graft-versus-host disease. Rituximab has become ubiquitous in the treatment of most B-cell malignancies. Further research with this antibody is focused on optimizing its use and determining its role in each of the relevant disease states. In addition, newer antibodies are in development for treating chronic lymphocytic leukemia and other B-cell malignancies. New treatment regimens, including combinations of monoclonal antibodies, could enhance complete response rates and prolong progression-free survival, perhaps eventually improving our ability to cure patients with lymphoid malignancies.

Alemtuzumab↗
PubMed2006

Sequential doxorubicin and topotecan in relapsed/refractory aggressive non-Hodgkin's lymphoma: results of CALGB 59906.

Topoisomerase enzymes are critical components of genomic replication and function to minimize torsional stress on DNA. Sequential administration of a topoisomerase II inhibitor followed by a topoisomerase I inhibitor is potentially synergistic due to increased target enzyme levels. Patients with relapsed or refractory aggressive non-Hodgkin's lymphomas (NHL) were eligible for this phase II study of doxorubicin 25 mg/m2 intravenous (IV) on day 1 and topotecan 1.75 mg/m2/day IV on days 3 - 5, every 21 days. The trial objectives included the overall response rate, progression-free survival, and toxicity. Twenty-six patients were enrolled and 25 patients are assessable for toxicity and response. The median age was 58 (range 23 - 74) years. The patients had received a median of two (range one to five) prior regimens, including five patients with a prior stem cell transplant. Five patients (20%, 95% confidence interval 0.07, 0.42) responded with two (8%) complete remissions and three (12%) partial remissions; an additional four (16%) patients had stable disease. Both patients achieving a complete remission had Burkitt's lymphoma. There were no treatment-related deaths. In conclusion, the combination of doxorubicin and topotecan is well tolerated and has modest activity in relapsed/refractory NHL, with occasional patients having a prolonged remission. The activity in Burkitt's lymphoma should be investigated further.

Adult↗
PubMed2006

Radioimmunotherapy of non-Hodgkin's lymphomas.

The availability of active monoclonal antibodies has altered the treatment paradigms for patients with non-Hodgkin's lymphomas (NHL). Nevertheless, some patients do not respond, while almost all of the others eventually relapse and require additional treatment. Thus, more effective alternatives are needed. Radioimmunotherapy (RIT) is an attractive option because of the inherent radiosensitivity of most NHL. Yttrium-90 ibritumomab tiuxetan and iodine-131 tositumomab are the first two radioimmunoconjugates currently available for clinical use. These agents appear comparably active in patients with follicular and low-grade NHL after failure following chemotherapy and/or rituximab. Activity has also been demonstrated against other histologies, including diffuse large B-cell NHL, mantle cell NHL, and transformed NHL. Toxicities primarily include myelosuppression, with a potential risk of treatment-associated myelodysplastic syndrome and acute myelogenous leukemia. Current clinical trials are attempting to optimize the use of these agents by evaluating them earlier in the course of the disease, and sequenced with a variety of chemotherapy regimens. Hopefully, the rational development of RIT will lead to a prolongation of survival for patients with NHL.

Animals↗
PubMed2006

Risky management.

Explore the source record for details and available documents.

Emotions↗
PubMed2005

The progress and promise of molecular imaging probes in oncologic drug development.

As addressed by the recent Food and Drug Administration Critical Path Initiative, tools are urgently needed to increase the speed, efficiency, and cost-effectiveness of drug development for cancer and other diseases. Molecular imaging probes developed based on recent scientific advances have great potential as oncologic drug development tools. Basic science studies using molecular imaging probes can help to identify and characterize disease-specific targets for oncologic drug therapy. Imaging end points, based on these disease-specific biomarkers, hold great promise to better define, stratify, and enrich study groups and to provide direct biological measures of response. Imaging-based biomarkers also have promise for speeding drug evaluation by supplementing or replacing preclinical and clinical pharmacokinetic and pharmacodynamic evaluations, including target interaction and modulation. Such analyses may be particularly valuable in early comparative studies among candidates designed to interact with the same molecular target. Finally, as response biomarkers, imaging end points that characterize tumor vitality, growth, or apoptosis can also serve as early surrogates of therapy success. This article outlines the scientific basis of oncology imaging probes and presents examples of probes that could facilitate progress. The current regulatory opportunities for new and existing probe development and testing are also reviewed, with a focus on recent Food and Drug Administration guidance to facilitate early clinical development of promising probes.

Antineoplastic Agents↗
PubMed2005

Monoclonal antibody therapy of chronic lymphocytic leukemia.

Cure of patients with chronic lymphocytic leukemia (CLL) has been an elusive goal. The recent availability of active monoclonal antibodies has rekindled enthusiasm for new and innovative therapeutic approaches. Alemtuzumab, induces responses in about a third of patients with relapsed or refractory CLL following therapy with fludarabine and an alkylating agent. Whereas, rituximab has limited activity in previously treated patients, response rates of 50-70% have been reported in those without prior therapy. Recent data on combinations with rituximab and chemotherapy have shown promise for improving patient outcome. Newer antibodies in development include the primatized monoclonal antibody lumiliximab (IDEC-152), directed against CD23. Other biological approaches include the use of antisense oligonucleotides, proapoptic small molecules, and vaccines directed against the malignant B cells. The rational development of combinations of these promising approaches may eliminate the need for chemotherapy, leading to safer and more effective approaches for patients with CLL.

Alemtuzumab↗
PubMed2005

Response assessment of aggressive non-Hodgkin's lymphoma by integrated International Workshop Criteria and fluorine-18-fluorodeoxyglucose positron emission tomography.

PURPOSE: To determine whether a response classification based on integration of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) into the International Workshop Criteria (IWC) provides a more accurate response assessment than IWC alone in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Fifty-four patients with aggressive NHL who underwent FDG-PET and computed tomography 1 to 16 weeks after four to eight cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone were assessed for complete response (CR), unconfirmed CR (CRu), partial response (PR), stable disease (SD), and progressive disease (PD) by the IWC and by integrated IWC and FDG-PET (IWC+PET). Progression-free survival (PFS) was also compared between IWC- and IWC+PET-assigned response designations. RESULTS: By IWC, 17 patients had a CR, seven had a CRu, 19 had a PR, nine had SD, and two had PD. In comparison, by IWC+PET, 35 patients had a CR, 12 had a PR, six had SD, one had PD, and zero had a CRu. In separate multivariate models, PFS was significantly shorter in patients with PR than in those with a CR using IWC (hazard ratio [HR], 8.9; P = .021) or IWC+PET (HR, 29.7; P = .0003). However, when the two classifications were included in the same multivariate model, only IWC+PET was a statistically significant independent predictor for PFS (P = .008 v P = .72 for IWC). In addition, when patients with a PR by IWC and a CR by IWC+PET were compared with those with a CR by IWC and a CR by IWC+PET, there was no significant difference in PFS (HR, 1.6; P = .72), indicating that IWC+PET identified a subset of IWC-PR patients with a more favorable prognosis. CONCLUSION: Compared with IWC, the IWC+PET-based assessment provides a more accurate response classification in patients with aggressive NHL.

Adult↗