A Randomized, Open-Label Phase II Trial of Volasertib as Monotherapy and in Combination With Standard-Dose Pemetrexed Compared With Pemetrexed Monotherapy in Second-Line Treatment for Non–Small-Cell Lung Cancer

Ellis, Peter; Leighl, Natasha B.; Hirsh, Vera; Reaume, M. Neil; Blais, Normand; Wierzbicki, Rafal; Sadrolhefazi, Behbood; Gu, Yu; Liú, Dan; Pilz, Korinna; Chu, Quincy S.

doi:10.1016/j.cllc.2015.05.010

Cited by 47 publications

(33 citation statements)

References 27 publications

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“…In addition, the combination schedule did not demonstrate superior clinical efficacy compared with pemetrexed monotherapy. The response rate in patients treated with the combination (21.3%) was double of that in patients treated with pemetrexed monotherapy (10.6%), but no significant difference in PFS was observed between both treatment arms (3.3 months for combination vs. 5.3 months for pemetrexed monotherapy) …”

Section: Clinical Trials With Volasertibmentioning

confidence: 85%

“…The response rate in patients treated with the combination (21.3%) was double of that in patients treated with pemetrexed monotherapy (10.6%), but no significant difference in PFS was observed between both treatment arms (3.3 months for combination vs. 5.3 months for pemetrexed monotherapy). 95 Furthermore, a phase I/II study evaluated the effectiveness of the Plk1 inhibitor in combination with low-dose cytarabine (LDAC) in patients with AML ineligible for intensive induction therapy. In the phase I part of the trial, dose escalation was performed in patients with relapsed/refractory AML to determine MTD of volasertib combined with LDAC (32 patients) or as monotherapy (56 patients).…”

Section: Clinical Trials With Volasertib In Combination Therapiesmentioning

confidence: 99%

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Spotlight on Volasertib: Preclinical and Clinical Evaluation of a Promising Plk1 Inhibitor

Bossche

Lardon

Deschoolmeester

et al. 2016

Medicinal Research Reviews

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Considering the important side effects of conventional microtubule targeting agents, more and more research focuses on regulatory proteins for the development of mitosis-specific agents. Polo-like kinase 1 (Plk1), a master regulator of several cell cycle events, has arisen as an intriguing target in this research field. The observed overexpression of Plk1 in a broad range of human malignancies has given rise to the development of several potent and specific small molecule inhibitors targeting the kinase. In this review, we focus on volasertib (BI6727), the lead agent in category of Plk1 inhibitors at the moment. Numerous preclinical experiments have demonstrated that BI6727 is highly active across a variety of carcinoma cell lines, and the inhibitor has been reported to induce tumor regression in several xenograft models. Moreover, volasertib has shown clinical efficacy in multiple tumor types. As a result, Food and Drug Administration (FDA) has recently awarded volasertib the Breakthrough Therapy status after significant benefit was observed in acute myeloid leukemia (AML) patients treated with the Plk1 inhibitor. Here, we discuss both preclinical and clinical data available for volasertib administered as monotherapy or in combination with other anticancer therapies in a broad range of tumor types.

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Section: Clinical Trials With Volasertibmentioning

confidence: 85%

Section: Clinical Trials With Volasertib In Combination Therapiesmentioning

confidence: 99%

Spotlight on Volasertib: Preclinical and Clinical Evaluation of a Promising Plk1 Inhibitor

Bossche

Lardon

Deschoolmeester

et al. 2016

Medicinal Research Reviews

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“…The clinical benefit is currently being validated in a phase III trial (POLO-AML-2, see Supplementary Information S1 (table)). In contrast, several phase II clinical trials for patients with solid tumours showed disappointing results with lack of sufficient clinical activity 218–220 . Future clinical application will depend on identification of biomarkers that can predict clinical response.…”

Section: Targeting Of Other Cell Cycle Proteinsmentioning

confidence: 99%

Cell cycle proteins as promising targets in cancer therapy

2017

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Preface Cancer is characterized by uncontrolled proliferation resulting from aberrant activity of various cell cycle proteins; therefore, cell cycle regulators are considered attractive targets in cancer therapy. Intriguingly, animal models demonstrated that some of these proteins are not essential for proliferation of non-transformed cells and development of most tissues. In contrast, many cancers are uniquely dependent on these proteins and are hence selectively sensitive to their inhibition. After decades of research on the physiological functions of cell cycle proteins and their relevance for cancer, this knowledge recently translated into the first approved cancer therapeutic targeting of a direct regulator of the cell cycle. Here, we review the role of cell cycle proteins in cancer, the rationale for targeting them in cancer treatment and results of clinical trials, as well as future therapeutic potential of various inhibitors. We focus only on proteins that directly regulate cell cycle progression. Cyclin-dependent kinases with transcriptional functions, as well as PARP inhibitors, which are highly successful in targeting BRCA1/BRCA2-mutant tumours, are not covered by this review.

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“…A total of 26 clinical trials with Volasertib have been reported (reviewed in Van den bossche et al) either using it alone or in combination with other chemotherapeutic agents . In the most advanced trials, Volasertib has been assayed against AML (NCT01721876), nonsmall cell lung cancer (NSCLC; NCT00824408), ovarian cancer (NCT01121406), and urothelial cancer (NCT01023958) . With respect to the potential use of Volasertib against solid tumors several clinical trials have been completed (NCT01348347, NCT01145885, NCT00969761, among others), but still none have reached phase II.…”

Section: Clinical Trialsmentioning

confidence: 99%

Therapeutic potential of pteridine derivatives: A comprehensive review

Carmona‐Martínez

Ruiz–Alcaraz

Vera

et al. 2018

Medicinal Research Reviews

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Pteridines are aromatic compounds formed by fused pyrazine and pyrimidine rings. Many living organisms synthesize pteridines, where they act as pigments, enzymatic cofactors, or immune system activation molecules. This variety of biological functions has motivated the synthesis of a huge number of pteridine derivatives with the aim of studying their therapeutic potential. This review gathers the state‐of‐the‐art of pteridine derivatives, describing their biological activities and molecular targets. The antitumor activity of pteridine‐based compounds is one of the most studied and advanced therapeutic potentials, for which several molecular targets have been identified. Nevertheless, pteridines are also considered as very promising therapeutics for the treatment of chronic inflammation‐related diseases. On the other hand, many pteridine derivatives have been tested for antimicrobial activities but, although some of them resulted to be active in preliminary assays, a deeper research is needed in this area. Moreover, pteridines may be of use in the treatment of many other diseases, such as diabetes, osteoporosis, ischemia, or neurodegeneration, among others. Thus, the diversity of the biological activities shown by these compounds highlights the promising therapeutic use of pteridine derivatives. Indeed, methotrexate, pralatrexate, and triamterene are Food and Drug Administration approved pteridines, while many others are currently under study in clinical trials.

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A Randomized, Open-Label Phase II Trial of Volasertib as Monotherapy and in Combination With Standard-Dose Pemetrexed Compared With Pemetrexed Monotherapy in Second-Line Treatment for Non–Small-Cell Lung Cancer

Cited by 47 publications

References 27 publications

Spotlight on Volasertib: Preclinical and Clinical Evaluation of a Promising Plk1 Inhibitor

Spotlight on Volasertib: Preclinical and Clinical Evaluation of a Promising Plk1 Inhibitor

Cell cycle proteins as promising targets in cancer therapy

Therapeutic potential of pteridine derivatives: A comprehensive review

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