A phase II study of arsenic trioxide in patients with relapsed or refractory malignant lymphoma

Abstract

Limited data have been reported regarding the use of arsenic trioxide (ATO) in the treatment of patients with relapsed or refractory malignant lymphoma; therefore, the present phase II study evaluated the efficacy and toxicity of ATO in such patients. A total of 35 patients were treated with ATO (0.25 mg/kg) infused for 1 h daily, 5 days a week, for a 6-week cycle. Patients were evaluated for the efficacy and toxicity of this regimen. The primary outcome evaluated was the overall response rate (ORR), including the complete and partial response rates. The secondary outcomes evaluated were the overall survival (OS), progression-free survival (PFS), and toxicity. Tumor response data were obtained from all 35 enrolled patients. The ORR was 43%, including complete responses in four patients (11%) and partial responses in 11 patients (31%). The median duration of response was 16 weeks (range 11-23 weeks). The median OS was 79 weeks (range 14-171 weeks), and the median PFS was 55 weeks (range 14-135 weeks). Grade I or II hematological toxicities were the most commonly reported adverse events. The results of this study appear promising for the treatment of relapsed or refractory malignant lymphoma, with well-tolerated ATO toxicity.

The crosstalk between trace elements with DNA damage response, repair, and oxidative stress in cancer

“…This finding suggests that ATO may be clinically helpful in MCL . Meanwhile, ATO can be considered as a promising treatment for the patients with relapsed or refractory malignant lymphoma . It has been shown that ATO has antiproliferative and proapoptotic effects on pancreatic cancer cell lines .…”

“…74 Meanwhile, ATO can be considered as a promising treatment for the patients with relapsed or refractory malignant lymphoma. 73,74 It has been shown that ATO has antiproliferative and proapoptotic effects on pancreatic cancer cell lines. 75 Regardless of encouraging in vitro evidence, ATO has no activity in patients with pancreatic cancer refractory to gemcitabine.…”

“…67,69 In the meantime, several clinical trials have studied the efficacy and toxicity of ATO in various cancers. 69,70,72,73 For example, evaluating the safety and efficacy of ATO in metastatic melanoma patients with stage IV melanoma indicated that single-agent ATO is well tolerated in patients with metastatic melanoma. 69,71 Furthermore, single-agent ATO at the dose of 0.16 to 0.24 mg/kg/d was not active against advanced hepatocellular carcinoma.…”

“…The exact action of ATO is still unclear; however, it can modulate different processes including apoptosis, angiogenesis, and proliferation . In the meantime, several clinical trials have studied the efficacy and toxicity of ATO in various cancers . For example, evaluating the safety and efficacy of ATO in metastatic melanoma patients with stage IV melanoma indicated that single‐agent ATO is well tolerated in patients with metastatic melanoma .…”

Long-term control of refractory follicular lymphoma after treatment of secondary acute promyelocytic leukemia with arsenic trioxide (As2O3) and all-trans retinoic acid (ATRA)

“…To our knowledge, only a small number of studies have reported on the therapeutic activity of As 2 O 3 and ATRA in patients with FL, and none of these studies reported any responses that were as impressive as observed in our case. One phase II clinical trial of As 2 O 3 for lymphoid malignancies showed that 0 of 3 patients with FL had a response to arsenic therapy in the frontline disease setting [ 3 ], whereas another phase II trial with 35 patients with relapsed refractory lymphoma (7 with FL) showed an overall response rate of 43%, with a median duration of response of 16 weeks [ 4 ]. There is modest efficacy of arsenic in myeloma, myelodysplastic syndrome, mantle cell lymphoma, and Burkitt's lymphoma [ 5 6 7 ].…”