Final report of a phase I study of veliparib (ABT-888) in combination with low-dose fractionated whole abdominal radiation therapy (LDFWAR) in patients with advanced solid malignancies and peritoneal carcinomatosis with a dose escalation in ovarian and fallopian tube cancers.

Reiss, Kim A.; Herman, Joseph M.; Zahurak, Marianna; Fyles, Anthony; Milosevic, Michael; Scardina, Angela; Joffe, Caitlin; Petito, Emily; Hacker-Prietz, Amy; Chen, Alice; Temkin, Sarah M.; Horiba, Naomi; Kinders, Robert J.; Wang, Lihua; Stayner, Lee‐Anne; Azad, Nilofer S.

doi:10.1200/jco.2016.34.15_suppl.2584

Cited by 12 publications

(13 citation statements)

References 15 publications

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“…For talazoparib in particular this has been noted in several pre-clinical studies [14,[23][24][25]37], as well as clinical trials demonstrating tolerability and efficacy in a variety of sites as described above [26][27][28]. One study has shown tolerability of combined PARP-inhibition (veliparib) when combined with low-dose fractionated whole abdominal radiation in patients with peritoneal carcinomatosis in ovarian and fallopian cancer patients [38]. In a phase I study of olaparib concurrent with cetuximab and radiotherapy for locally advanced head and neck cancer, the maximally tolerated dose was identified to be 50 mg twice daily, though the recommended phase II dose was deemed to be 25 mg by mouth twice daily [30].…”

Section: Discussionmentioning

confidence: 90%

Phase I study of the PARP inhibitor talazoparib with radiation therapy for locally recurrent gynecologic cancers

Lakomy

Urbauer

Westin

et al. 2020

Clinical and Translational Radiation Oncology

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Section: Discussionmentioning

confidence: 90%

Phase I study of the PARP inhibitor talazoparib with radiation therapy for locally recurrent gynecologic cancers

Lakomy

Urbauer

Westin

et al. 2020

Clinical and Translational Radiation Oncology

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“…Unlike the promising preclinical evidence, the veliparib-LDFWAR combination was not that advantageous in terms of the ADR and QoL. 22 Findings by Tadaaki Nishikawa Et al revealed that veliparib monotherapy showed manageable tolerability and safety profiles and a favourable pharmacokinetic profile at a twice-daily dose of 400 mg. The most frequent treatment-emergent adverse events were GI related and included nausea and vomiting (93.8% each), decreased appetite (62.5%), abdominal pain, diarrhea, and malaise (31.3% each).Out of the 16 patients enrolled, dose-limiting toxicities were observed for one patient at the 400 mg dose and the pharmacokinetic profile was consistent with that reported for the Western population.…”

Section: Ovarian Cancermentioning

confidence: 97%

Veliparib for the treatment of solid malignancies

George¹,

Thomas²,

Davice³

et al. 2022

J Oncol Pharm Pract

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Objective Veliparib is a poly adenosine diphosphate ribose polymerase (PARP) −1 and −2 inhibitor with chemo-sensitizing and anticancer activities that has shown promising results in early-phase trials. The aim of this comprehensive review is to summarise the profile of veliparib and to provide an overview of its early clinical investigations. Data Sources Details of all the completed trials evaluating the profile of veliparib were identified from ClinicalTrials.gov with the relevant keywords. Furthermore, databases such as Google Scholar and PubMed were searched using the National Clinical Trial (NCT) number to retrieve publications of results not listed in the trial registry. Data Summary A total of 25 completed clinical trials indicating the use of veliparib in solid malignancies were identified. The results showed that veliparib is well tolerated, both as a single agent and in combination with standard chemotherapy doses. Being a broad-spectrum potentiator of DNA-damaging agents and radiation, it has shown to improve the clinical outcomes, particularly in solid tumors like ovarian cancer, breast cancer and lung cancer. Conclusions The results from clinical trials indicate that veliparib can be an excellent therapeutic strategy for BRCA mutation associated cancers and tumors bearing deficiencies in the HR pathway as well. Further studies establishing the dosing, sequence of therapy, extended use and compatibility with various anti-cancer drugs are warranted to define its exact role in cancer therapy.

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“…It has been also investigated as a radiosensitizer in peritoneal carcinomatosis, in a small phase I trial which included only 4 patients with ovarian cancer. The combination was tolerable, while only one gBRCA mutated patient with platinum sensitive disease achieved a response (109). Recently, results of VELIA trial, which tested the addition of veliparib to the standard neoadjuvant therapy and its continuation as maintenance therapy, were announced (90).…”

Section: Combination With Chemotherapymentioning

confidence: 99%

The evolving role of PARP inhibitors in advanced ovarian cancer

Levva

Skolariki

Sogka

et al. 2021

Forum of Clinical Oncology

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The field of ovarian cancer has been revolutionized with the use of poly (ADP-ribose) polymerase (PARP) inhibitors, which present greater inhibition effect in epithelial subtype due to high rates of homologous recombination deficiency. PARP inhibition exploits this cancer pitfall by disrupting DNA repair, leading to genomic instability and apoptosis. Three PARP inhibitors (olaparib, niraparib, and rucaparib) are now approved for use in women with epithelial ovarian cancer, while others are under development. Among women with BRCA1/2 mutations, maintenance PARP therapy has led to a nearly fourfold prolongation of PFS, while those without BRCA1/2 mutations experience an approximately twofold increase in PFS. Differences in trial design, patient selection and primary analysis population affect the conclusions on PARP inhibitors. Limited OS data have been published and there is also limited experience regarding long-term safety. With regard to toxicity profile, there are no differences in serious adverse events between the experimental and control groups. However, combining adverse event data from maintenance phases, a trend towards more events in the experimental group, compared with controls, has been shown. The mechanisms of PARP-inhibitor resistance include restoration of HR through reversion mutations in HR genes, leading to resumed HR function. Other mechanisms that sustain sufficient DNA repair are discussed as well. PARP inhibitors play a pivotal role in the management of ovarian cancer, affecting the future treatment choices. Defining exactly which patients will benefit from them is a challenge and the need for HRD testing to define ‘BRCA-ness’ will add additional costs to treatment.

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Final report of a phase I study of veliparib (ABT-888) in combination with low-dose fractionated whole abdominal radiation therapy (LDFWAR) in patients with advanced solid malignancies and peritoneal carcinomatosis with a dose escalation in ovarian and fallopian tube cancers.

Cited by 12 publications

References 15 publications

Phase I study of the PARP inhibitor talazoparib with radiation therapy for locally recurrent gynecologic cancers

Phase I study of the PARP inhibitor talazoparib with radiation therapy for locally recurrent gynecologic cancers

Veliparib for the treatment of solid malignancies

The evolving role of PARP inhibitors in advanced ovarian cancer

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