Sequence-dependent synergy of the proteasome inhibitor bortezomib and cytarabine in mantle cell lymphoma

Weigert, Oliver; Pastore, Alessandro; Rieken, Malte; Lang, Nicola; Hiddemann, Wolfgang; Dreyling, Martin

doi:10.1038/sj.leu.2404511

Cited by 61 publications

(43 citation statements)

References 24 publications

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“…Because its response rate is still low, a rationally combinational therapy would be the next step. Similarly, Weigert et al 18 performed in vitro studies and showed a sequencedependent synergy between BTZ and cytarabine in MCL. Their data suggest that pretreatment with cytarabine followed by proteasome inhibition may be a preferred approach.…”

Section: Discussionmentioning

confidence: 87%

“…We chose the BRC combination based on the effects of its single-agent activity and potential synergistic effect with other agents. [18][19][20] RTX has been used in clinical trials in newly-diagnosed and relapsed or refractory MCL, with ORR of 37%. 21 At M. D. Anderson Cancer Center, our upfront therapy for MCL is R-HyperCVAD/R-Methotrexate-Cytarabine.…”

Section: Discussionmentioning

confidence: 99%

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Bortezomib is synergistic with rituximab and cyclophosphamide in inducing apoptosis of mantle cell lymphoma cells in vitro and in vivo

et al. 2007

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Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma with poor clinical outcome. Although front therapy induces a high rate of complete remission (CR), relapse is inevitable and new regimens are much needed for relapsed MCL. The proteasome inhibitor bortezomib (BTZ) induces apoptosis and sensitizes MCL cells to chemotherapy in relapsed MCL, but CR rates are low, with a short duration of response and severe toxicity. Here we evaluated whether BTZ is additive or synergistic with cyclophosphamide (CTX) and rituximab (RTX). Increasing doses of BTZ with a fixed dose of RTX and CTX (BRC regimen) resulted in markedly synergistic growth inhibition of MCL cells. BRC significantly enhanced apoptosis in MCL cell lines and primary tumor cells compared with singleagent treatment. Furthermore, western blotting analysis indicated that BRC induces apoptosis earlier via activation and cleavage of caspases-8, -9 and -3, and poly (ADP-ribose) polymerase, than single-agent treatment. The pan-caspase inhibitor completely blocked apoptosis induced by BRC. In vivo studies showed that BRC eradicated subcutaneous tumors in MCL-bearing SCID mice and significantly prolonged the longterm event-free survival in 70% of the mice. Hence, our study demonstrates that cytoreductive chemotherapy with both BTZ and anti-CD20 antibody may offer a better therapeutic modality for relapsed MCL.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Bortezomib is synergistic with rituximab and cyclophosphamide in inducing apoptosis of mantle cell lymphoma cells in vitro and in vivo

et al. 2007

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“…The experiments were performed in triplicate and independently repeated 2 or 3 times. As previously described (12), the effects of sequential combination treatment were analyzed according to the Chou and Talalay method by using XLfit software (ID Business Solutions Ltd.) and evaluated using a combination index (CI) interpreted as: <0.7, synergistic; 0.7-1.3, additive; >1.3, antagonistic (13)(14)(15).…”

Section: In Vitro Cell Proliferation-inhibition Assays Of Monotherapymentioning

confidence: 99%

Schedule-dependent antitumor activity of the combination with erlotinib and docetaxel in human non-small cell lung cancer cells with EGFR mutation, KRAS mutation or both wild-type EGFR and KRAS

Furugaki¹

2010

Oncol Rep

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Abstract. Erlotinib is used as a standard treatment for recurrent advanced non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations in NSCLC have been shown to be a predictive factor of erlotinib, although the relationship between K-ras oncogene (KRAS) mutations and erlotinib resistance is controversial. Recently, in vitro sequence-dependent interactions of erlotinib and docetaxel have been studied on as a novel therapeutic approach against NSCLC. The purpose of the present study was to determine the optimum novel regimen of erlotinib and docetaxel against NSCLC cells which have EGFR mutation (HCC827 cells), KRAS mutation (A549 cells) or both wild-type (NCI-H292 cells). First, we analyzed the effects of in vitro combination for cell proliferation-inhibition using a combination index. In all cell lines, docetaxel followed by erlotinib treatment showed nearly additive effects. On the other hand, erlotinib followed by docetaxel treatment showed remarkable antagonistic interactions. Second, we examined the effect of combinations on the in vitro apoptosis induction. Erlotinib followed by docetaxel treatment reduced apoptosis induction compared with docetaxel alone; in contrast, docetaxel followed by erlotinib treatment had no inhibitory effects on docetaxelinduced apoptosis in any of the cell lines. Finally, an in vivo tumor growth inhibition test was performed using xenograft models. Docetaxel followed by erlotinib administration resulted in significant tumor growth inhibition compared with erlotinib or docetaxel monotherapy in all models. In conclusion, we demonstrated that docetaxel followed by erlotinib therapy was a potentially optimum regimen against NSCLC regardless of the mutation status of EGFR and KRAS.

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“…23 Thus, bendamustine-containing combinations or molecular-targeted approaches that have shown high response rates among patients with relapsed mantle-cell lymphoma might be alternative induction regimens. 22,[24][25][26] Similarly, it may be attractive to combine the rituximab-based maintenance regimen with other drugs that have been shown to be active against mantle-cell lymphoma. However, physicians need to be aware of the potential interactions between the initial therapy and the maintenance regimen.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Older Patients with Mantle-Cell Lymphoma

Kluin‐Nelemans¹,

Hoster²,

Dreyling³

2012

N Engl J Med

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Sequence-dependent synergy of the proteasome inhibitor bortezomib and cytarabine in mantle cell lymphoma

Cited by 61 publications

References 24 publications

Bortezomib is synergistic with rituximab and cyclophosphamide in inducing apoptosis of mantle cell lymphoma cells in vitro and in vivo

Bortezomib is synergistic with rituximab and cyclophosphamide in inducing apoptosis of mantle cell lymphoma cells in vitro and in vivo

Schedule-dependent antitumor activity of the combination with erlotinib and docetaxel in human non-small cell lung cancer cells with EGFR mutation, KRAS mutation or both wild-type EGFR and KRAS

Treatment of Older Patients with Mantle-Cell Lymphoma

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