-
[show abstract]
[hide abstract]
ABSTRACT: Rituximab is an important and well established component in the treatment of many patients with B-cell non-Hodgkin lymphoma. In this paper we review recent clinical trials investigating the addition of rituximab to standard chemotherapy regimens for treatment of patients with diffuse large B cell lymphoma and follicular lymphoma. This report focuses upon treatment efficacy, quality of life, and safety of rituximab or rituximab-containing regimens. More uniquely, we review economic aspects of lymphoma treatments, including the cost of standard chemotherapy regimens with or without rituximab, cost effectiveness of rituximab in both induction and maintenance treatment, and lymphoma's impacts on patient's productivity and their caregivers. We conclude that adding rituximab to standard chemotherapy treatment for patients with B-cell non-Hodgkin lymphoma is safe and cost-effective in numerous settings during both induction and maintenance therapies. Despite extensive review of the literature, many important questions have yet to be answered in the rituximab era and these represent important directions for future study.
ClinicoEconomics and Outcomes Research 01/2010; 2:37-45.
-
[show abstract]
[hide abstract]
ABSTRACT: Infusion-related reactions during administration of monoclonal antibody therapy are often mild and unlikely to recur with subsequent treatment. If patients experience another severe reaction upon reattempting treatment, future treatments with the same agent are typically not pursued. It is unclear whether different monoclonal antibodies that bind the same tumor cell or antigen are likely to induce similar infusion reactions. Here, we report the case of a patient with repeated severe infusion reactions with rituximab who subsequently safely received treatment with iodine-131 tositumomab and discuss the relevant literature.
The Oncologist 04/2007; 12(3):338-40. · 3.91 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: COX-2 inhibitors, such as celecoxib, and ubiquitin-proteasome pathway inhibitors, such as bortezomib, can down-regulate NF-kappaB, a transcription factor implicated in tumor growth. The objective of this study was to determine the maximum tolerated dose and dose-limiting toxicities of bortezomib in combination with celecoxib in patients with advanced solid tumors.
Patients received escalating doses of bortezomib either on a weekly schedule (days 1, 8, 15, 22, and 29 repeated every 42 days) or on a twice-weekly administration schedule (days 1, 4, 8, and 11 repeated every 21 days), in combination with escalating doses of celecoxib twice daily throughout the study period from 200 mg to 400 mg twice daily.
No dose-limiting toxicity was observed during the study period. Two patients had stable disease lasting for four and five months each, and sixteen patients developed progressive disease.
The combination of bortezomib and celecoxib was well tolerated, without dose limiting toxicities observed throughout the dosing ranges tested, and will be studied further at the highest dose levels investigated.
NCT00290680.
BMC Cancer 02/2007; 7:221. · 3.01 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Rasburicase is currently approved at a dosage of 0.15-0.2 mg/kg once/day for 5 days in pediatric patients with cancer to lower plasma uric acid concentrations and manage tumor lysis syndrome (TLS). Information on rasburicase dosing in adults is limited, with some data on using rasburicase as a single dose instead of multiple daily doses. Therefore, we evaluated the efficacy of a single dose of rasburicase for preventing or managing TLS in adults. We collected retrospective data for 11 adults with hematologic malignancies who received a single 6-mg dose of rasburicase. All patients received intravenous hydration with urinary alkalinization and allopurinol; however, due to adverse reactions, two patients received short courses of allopurinol. Only patients at high risk for TLS (e.g., large tumor burden, increasing uric acid concentration) or those with TLS received rasburicase. The single dose of rasburicase 6 mg resulted in a median 0.0773-mg/kg dose (range 0.0232-0.1361 mg/kg). The single 6-mg dose rapidly lowered uric acid concentrations in 10 of the 11 patients. The median uric acid concentration of 11.7 mg/dl (range 7.4-17.4 mg/dl) declined to 2.0 mg/dl (range 0.5-15.4 mg/dl) within a day after rasburicase administration (p=0.022). In these 10 patients, uric acid concentrations remained low despite subsequent chemotherapy, and none required additional rasburicase doses. The only patient who did not respond to the single 6-mg rasburicase dose was a morbidly obese man (259 kg, body mass index 87 kg/m2) who subsequently responded to an additional dose of rasburicase 12 mg. These results warrant further investigation of a single 6-mg dose of rasburicase in adults with TLS or at high-risk for developing TLS.
Pharmacotherapy 07/2006; 26(6):806-12. · 2.90 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Transcriptional silencing of tumor suppressor genes, associated with DNA methylation, is a common epigenetic event in hematologic malignancies. Although DNA hypermethylation of CpG islands is well described in acute leukemias and myelodysplastic syndromes, much less is known of the specific methylation changes that commonly occur in follicular B cell lymphomas. Earlier methylation studies of follicular lymphoma involved only cell lines; however there is a growing literature of methylation changes in primary human FL samples. Published studies of primary follicular lymphoma specimens have demonstrated that: androgen receptor, SHP1, and death-associated protein kinase genes are commonly methylated. By contrast, the cyclin dependent kinase inhibitors p15, p16, and p57 are uncommon epigenetic events in follicular lymphoma. Methylation of cyclin dependent kinase inhibitors is more common in high grade lymphomas, and may be an important step in the progression and transformation of follicular lymphoma. Further methylation studies in follicular lymphoma should investigate the prognostic and therapeutic significance of these epigenetic changes and investigate methylation of other genes. Finally, reactivation of methylated tumor suppressor genes through the use of hypomethylating agents is a promising and novel approach to the treatment of indolent and transformed follicular lymphomas.
Molecular Cancer 02/2006; 5:44. · 3.99 Impact Factor
