Low‐dose weekly paclitaxel for recurrent or refractory aggressive non‐Hodgkin lymphoma

Abstract

BACKGROUND. Many patients with recurrent, intermediate or high-grade non-Hodgkin lymphoma (NHL) may not respond to or are not candidates for aggressive salvage chemotherapy. Effective, less toxic regimens are needed. Although highdose taxanes have not been reported to be very effective for the treatment of lymphoma, different delivery rates may allow for different mechanisms of action to be manifest and result in a different toxicity profile and response rate. The current study tested this hypothesis by using low-dose, weekly paclitaxel in patients with recurrent or refractory NHL. METHODS. Adults age Ͼ 18 years with refractory or recurrent, aggressive NHL who were not considered curable with standard high-dose therapy received paclitaxel at a dose of 80 mg/m 2 weekly for 5 weeks for 2 cycles. RESULTS. Thirty-four patients with refractory NHL and 4 patients with recurrent disease were treated. Approximately 45% of the patients had achieved a prior disease remission. The median number of prior regimens received was 3, 74% of the patients had an International Prognostic Index of Ն 3 at the time of study entry, and 29% had failed high-dose therapy with autologous hematopoietic support. Only one patient encountered severe toxicity (sepsis). Myelosuppression was reported to occur in approximately 20% of patients. A total of 10 patients (26%) achieved a complete disease response and 4 patients (11%) achieved a partial response. CONCLUSIONS. In the current study, low-dose, weekly paclitaxel therapy was found to provide a well tolerated and less toxic approach to the treatment of refractory NHL, with encouraging responses noted in heavily pretreated patients. However, evaluation in patients with an earlier stage of disease is warranted. Cancer 2004;

Aurora inhibitor MLN8237 in combination with docetaxel enhances apoptosis and anti-tumor activity in mantle cell lymphoma

“…Paclitaxel has been evaluated in relapsed/refractory B-NHL as continuous intravenous infusion over 3 h [200 mg/m2] [44], 24 h [175 mg/m2] [45], 96 h [140 mg/m2] [46] and 3 h [250 mg/m 2 ] [47] with response rates of 17% to 50% that were deemed modest. Lower dose infusions of 100 mg/m2 Q3W [48], 80 mg/m2 Q1W [49] and 90 mg/m2 Q1W [50] produced response rates of 23% to 42%. Together the data support the interpretation that taxol, as a single agent is not effective in B-NHL and therefore has not been incorporated into combination therapy [51].…”

Preclinical Evaluation of Gemcitabine Combination Regimens for Application in Acute Myeloid Leukemia

“…There is growing evidence of a microtubuleindependent mechanism of paclitaxel-induced apoptosis (reviewed in ref. 18), including a recent trial from our group (19) /well) were exposed to 3, 10, and 30 nmol/L paclitaxel for 24 hours, pooled together, and fixed with an ice-cold solution of 70% ethanol and distilled water. RNA was removed by incubation with 5 mg/mL of RNase A and DNA was stained with 5 mg/mL of propidium iodide.…”

Antiproliferative activity of RAD001 (everolimus) as a single agent and combined with other agents in mantle cell lymphoma

“…Low-dose administration of paclitaxel has been reported to be a well-tolerated, less toxic alternative for patients with aggressive NHL. 39 Like vincristine, paclitaxel interferes with proper cell division. However, while vincristine inhibits microtubule formation, paclitaxel binds microtubules, interfering with their depolymerization and disassembly of the mitotic spindle.…”