Effects of rucaparib: A Synthesis of Findings from 22 Studies

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Original Abstract of the Article

Major findings

Rucaparib is a PARP inhibitor used to treat recurrent ovarian cancer, especially in patients with BRCA1/2 gene mutations. 15 、 13 、 9 、 17 、 1 、 7 、 3 、 6 、 12 、 21 、 5 、 20 、 8 、 16 、 4 、 11 、 19 、 14 、 22 、 10 、 2 These studies show that rucaparib can be effective in treating recurrent ovarian cancer. 15 Rucaparib has shown to be more effective than other PARP inhibitors in patients with BRCA mutations. 12 In patients with BRCA1/2 mutations, RAD51C, RAD51D mutations, and high-level BRCA1 promoter methylation, rucaparib may be effective. 2 Rucaparib may have phototoxicity, and skin reactions should be carefully monitored. 13 Rucaparib can cause various side effects, including digestive, blood, and kidney effects. 9 、 11 、 14 Dosage adjustments may be necessary for patients with impaired liver function. 17 、 5 Rucaparib may interact with other drugs, and adjustments to their dosages may be needed. 1 、 8 Rucaparib may cause muscle damage, structural abnormalities, and decreased physical activity, but these side effects can potentially be improved by restoring muscle structure. 21 Rucaparib has not been shown to improve muscle weight, fiber size, or limb muscle strength. 21 Rucaparib can cause side effects such as fatigue and nausea in many patients, but these side effects are manageable. 1 Rucaparib may prolong survival compared to other treatments. 12 Rucaparib may be safer than other PARP inhibitors. 9 、 12 Rucaparib is a promising drug for treating recurrent ovarian cancer and can potentially prolong survival in many patients. However, rucaparib carries a risk of side effects and should be used under the guidance of a qualified physician.

Benefits and risks

Benefit summary

Rucaparib can potentially prolong survival in recurrent ovarian cancer patients and may be more effective than other PARP inhibitors. 12 Rucaparib may be effective in patients with BRCA1/2 mutations, RAD51C, RAD51D mutations, and high-level BRCA1 promoter methylation. 2 Additionally, rucaparib may be safer compared to other PARP inhibitors. 9 、 12

Risk summary

Rucaparib may have phototoxicity, and skin reactions should be carefully monitored. 13 It can cause various side effects, including digestive, blood, and kidney effects. 9 、 11 、 14 Dosage adjustments may be necessary for patients with impaired liver function. 17 、 5 Rucaparib may interact with other drugs, and adjustments to their dosages may be needed. 1 、 8

Comparison between studies

Commonalities between studies

Many studies demonstrate that rucaparib is effective in treating recurrent ovarian cancer and can potentially prolong survival in many patients. 15 、 12 Many studies also indicate that rucaparib carries a risk of side effects. 9 、 11 、 14 、 1 、 8 These studies suggest that rucaparib is a promising drug for treating recurrent ovarian cancer, but further research is needed.

Differences between studies

Several studies have demonstrated that rucaparib is more effective than other PARP inhibitors in patients with BRCA mutations. 12 Some studies have shown that rucaparib can cause muscle damage, structural abnormalities, and decreased physical activity. 21 However, these side effects can potentially be improved by restoring muscle structure. 21 The results of these studies suggest that further research is necessary to understand the effectiveness and safety of rucaparib.

Consistency and contradictions in results

Rucaparib has been shown to be effective in treating recurrent ovarian cancer and can potentially prolong survival in many patients. 15 、 12 However, rucaparib also carries a risk of side effects. 9 、 11 、 14 The results of these studies suggest that rucaparib is a promising drug for treating recurrent ovarian cancer, but further research is needed.

Cautions regarding real-life applications

Rucaparib is effective in treating recurrent ovarian cancer and can potentially prolong survival in many patients. 15 、 12 However, rucaparib carries a risk of side effects and should be used under the guidance of a qualified physician. 9 、 11 、 14 When using rucaparib, it is crucial to consult with your doctor and choose the treatment method suitable for your physical condition. 15 、 13 、 9 、 17 、 1 、 7 、 3 、 6 、 12 、 21 、 5 、 20 、 8 、 16 、 4 、 11 、 19 、 14 、 22 、 10 、 2

Limitations of current research

While there are many studies on rucaparib, they have limitations. For example, many studies have been conducted with small sample sizes. 15 、 13 、 9 、 17 、 1 、 7 、 3 、 6 、 12 、 21 、 5 、 20 、 8 、 16 、 4 、 11 、 19 、 14 、 22 、 10 、 2 Also, many studies are conducted on specific patient populations, making it uncertain whether the results can be applied to other patient groups. 15 、 13 、 9 、 17 、 1 、 7 、 3 、 6 、 12 、 21 、 5 、 20 、 8 、 16 、 4 、 11 、 19 、 14 、 22 、 10 、 2 Further research is needed to assess the effectiveness and safety of rucaparib.

Directions for future research

Further research on rucaparib is needed. In particular, research is required to investigate the long-term effectiveness and safety of rucaparib and its effects when used in combination with other treatments. 12 Studies using larger sample sizes are also necessary to evaluate the effectiveness and safety of rucaparib. 15 、 13 、 9 、 17 、 1 、 7 、 3 、 6 、 12 、 21 、 5 、 20 、 8 、 16 、 4 、 11 、 19 、 14 、 22 、 10 、 2 It is also necessary to compare the effectiveness and safety of rucaparib to other PARP inhibitors. 12

Conclusion

Rucaparib is effective in treating recurrent ovarian cancer and can potentially prolong survival in many patients. 15 、 12 However, rucaparib carries a risk of side effects and should be used under the guidance of a qualified physician. 9 、 11 、 14 When using rucaparib, it is crucial to consult with your doctor and choose the treatment method suitable for your physical condition. 15 、 13 、 9 、 17 、 1 、 7 、 3 、 6 、 12 、 21 、 5 、 20 、 8 、 16 、 4 、 11 、 19 、 14 、 22 、 10 、 2

Literature analysis of 22 papers
Positive Content
17
Neutral Content
4
Negative Content
1
Article Type
0
1
2
5
21
1.

Clinical Pharmacokinetics and Pharmacodynamics of Rucaparib.

Author: LiaoMingxiang, BeltmanJeri, GiordanoHeidi, HardingThomas C, MaloneyLara, SimmonsAndrew D, XiaoJim J

Ovarian cancer treatment
Prostate cancer treatment
Fatigue
Nausea
QTc prolongation
Torsades de pointes

Rucaparib is a PARP inhibitor used to treat recurrent ovarian cancer and metastatic castration-resistant prostate cancer. It is taken orally twice a day and has a manageable safety profile, with the most common side effects being fatigue and nausea. Rucaparib is moderately bioavailable and can be taken with or without food. It is metabolized and excreted by the kidneys and liver.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

2.

Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2).

Author: SwisherElizabeth M, KwanTanya T, OzaAmit M, TinkerAnna V, Ray-CoquardIsabelle, OakninAna, ColemanRobert L, AghajanianCarol, KonecnyGottfried E, O'MalleyDavid M, LearyAlexandra, ProvencherDiane, WelchStephen, ChenLee-May, Wahner HendricksonAndrea E, MaLing, GhatagePrafull, KristeleitRebecca S, DorigoOliver, MusaferAshan, KaufmannScott H, ElvinJulia A, LinDouglas I, ChambersSetsuko K, DominyErin, VoLan-Thanh, GobleSandra, MaloneyLara, GiordanoHeidi, HardingThomas, DobrovicAlexander, ScottClare L, LinKevin K, McNeishIain A

Predicts response to rucaparib
Platinum resistance

Rucaparib, a PARP inhibitor, showed promising efficacy in patients with relapsed high-grade ovarian carcinoma who had previously received platinum-based chemotherapy. Mutations in RAD51C, RAD51D, and high-level BRCA1 promoter methylation were associated with response to rucaparib. BRCA1 methylation loss might be a key factor in developing resistance to platinum and PARP inhibitors. This study suggests that rucaparib may be an effective treatment option for patients with relapsed ovarian cancer who have certain genetic markers.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

5.

Dose Adjustment of Poly (ADP‑Ribose) Polymerase Inhibitors in Patients with Hepatic or Renal Impairment.

Author: ZhaoDehua, LongXiaoqing, WangJisheng

Improved efficacy
Reduced toxicity

This review focuses on the effects of hepatic and renal impairment on the pharmacokinetics (PK) of poly (ADP-ribose) polymerase (PARP) inhibitors. The review characterizes and summarizes the impact of hepatic and renal function on the PK of five PARP inhibitors, providing specific recommendations for clinicians prescribing these drugs in patients with hepatic or renal impairment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

6.

Rucaparib in recurrent ovarian cancer: real-world experience from the rucaparib early access programme in Spain - A GEICO study.

Author: YuberoAlfonso, BarquínAranzazu, EstévezPurificación, PajaresBella, SánchezLuisa, RechePiedad, AlarcónJesús, CalzasJulia, GabaLydia, FuentesJosé, SantaballaAna, SalvadorCarmen, MansoLuis, HerreroAna, TausÁlvaro, MárquezRaúl, MadaniJulia, MerinoMaría, MarquinaGloria, CasadoVictoria, ConstenlaManuel, GutiérrezMaría, DosilAlba, González-MartínAntonio

Ovarian cancer treatment

Rucaparib is a poly(ADP-ribose) polymerase inhibitor approved in Europe for maintenance therapy for recurrent platinum-sensitive ovarian cancer. The Rucaparib Access Programme (RAP) was designed to provide early access to rucaparib for this indication, as well as for patients with BRCA-mutated platinum-sensitive or platinum-resistant ovarian cancer.

Observational StudyResearch that observes and collects data on participants' behavior and outcomes in their natural state, without intervention.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

7.

Novel pharmacological effects of poly (ADP-ribose) polymerase inhibitor rucaparib on the lactate dehydrogenase pathway.

Author: NonomiyaYuma, NoguchiKohji, KatayamaKazuhiro, SugimotoYoshikazu

Ovarian cancer treatment

Rucaparib, a PARP inhibitor, suppressed lactate dehydrogenase (LDH)-mediated conversion of pyruvic acid to lactic acid in ovarian cancer cells, contributing to its pharmacological effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Safety profile of poly (ADP-ribose) polymerase (PARP) inhibitors in cancer: a network meta-analysis of randomized controlled trials.

Author: BaoShengnan, YueYuanping, HuaYijia, ZengTianyu, YangYiqi, YangFan, YanXueqi, SunChunxiao, YangMengzhu, FuZiyi, HuangXiang, LiJun, WuHao, LiWei, ZhaoYang, YinYongmei

Gastrointestinal toxicity
Hematological toxicity

Olaparib had the best safety profile among PARP inhibitors, with a lower risk of grade 3-5 adverse events compared to other PARP inhibitors, conventional therapy, and the combination of a PARP inhibitor with an angiogenesis inhibitor.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

10.

Incidence and risk of hypertension associated with PARP inhibitors in cancer patients: a systematic review and meta-analysis.

Author: ChenXiu, WenQinglian, KouLiqiu, XieXiaolu, LiJun, LiYaling

Hypertension
PARP inhibitor use

This meta-analysis analyzed the incidence and risk of hypertension associated with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors in cancer patients. Olaparib 200-600 mg/day (excluding olaparib plus cediranib regimen) may be the most suitable PARP inhibitor for cancer patients with a high risk of hypertension. Niraparib, olaparib 800 mg/day, and olaparib combined with cediranib may increase the risk of developing hypertension in cancer patients.

Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

11.

Practical guidance for the management of side effects during rucaparib therapy in a multidisciplinary UK setting.

Author: TookmanLaura, KrellJonathan, NkolobeBaleseng, BurleyLaura, McNeishIain A

Maintenance
Ovarian cancer treatment
Anemia
Fatigue
Liver enzyme elevations
Nausea
Vomiting

PARP inhibitors are a new type of cancer drug that is showing promise in the treatment of ovarian cancer. This paper discusses some of the real-world challenges and side effects of rucaparib, a PARP inhibitor. The authors provide guidance on how a multidisciplinary team can effectively manage these side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

13.

Evaluation of phototoxicity induced by the anticancer drug rucaparib.

Author: Mateos-PujanteAlejandro, JiménezMaría Consuelo, AndreuInmaculada

Breast and ovarian tumor treatment
Photosensitivity

Rucaparib (RCP) is a potent selective inhibitor of both PARP-1 and PARP-2 enzymes that induces synthetic lethality in cancer cells. RCP is potentially phototoxic. The phototoxicity is attributed to both proteins and genomic DNA.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

BRCAness, Homologous Recombination Deficiencies, and Synthetic Lethality.

Author: MuraiJunko, PommierYves

Cancer treatment

BRCAness, a concept describing tumors with deficiencies in homologous recombination repair (HRR), can be identified through genomic profiling. This review explores how BRCAness can be used to select appropriate therapies, including PARP inhibitors, topoisomerase I inhibitors, and platinum derivatives.

EditorialAn article in which the editor or publisher expresses their opinion or perspective on a particular topic or issue. Its purpose is to convey a specific message or idea to the reader.
Research Support, N.I.H., IntramuralFunding provided by the NIH for research projects within the NIH.
CommentA short article/note that provides an opinion/perspective/interpretation on a published paper/topic.

Language : English

17.

Pharmacokinetics and safety of rucaparib in patients with advanced solid tumors and hepatic impairment.

Author: GrechkoNikolay, SkarbovaViera, Tomaszewska-KiecanaMonika, RamlauRodryg, CentkowskiPiotr, DrewYvette, DziadziuszkoRafal, ZemanovaMilada, BeltmanJeri, NashEileen, HabeckJenn, LiaoMingxiang, XiaoJim

Rucaparib, a poly(ADP-ribose) polymerase inhibitor, is approved for treating recurrent ovarian and metastatic castration-resistant prostate cancer. However, limited data exists on its use in patients with hepatic dysfunction. This study examines whether liver impairment impacts the pharmacokinetics, safety, and tolerability of rucaparib in patients with advanced solid tumors.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

A phase II trial of bevacizumab and rucaparib in recurrent carcinoma of the cervix or endometrium.

Author: JacksonC G, MooreK N, CantrellL, EricksonB K, DuskaL R, RichardsonD L, LandrumL M, HolmanL L, WalkerJ L, MannelR S, MoxleyK M, QueimadoL, CohoonA, DingK, DockeryL E

ARID1A mutation response
Limited efficacy
Toxicity similar

This study investigated the efficacy and tolerability of bevacizumab combined with rucaparib in patients with recurrent cervical or endometrial cancer. The combination did not demonstrate significant improvement in anti-tumor activity overall, but patients with ARID1A mutations showed a higher response rate and progression-free survival.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

19.

Utilization of Poly(ADP-Ribose) Polymerase Inhibitors in Ovarian Cancer: A Retrospective Cohort Study of US Healthcare Claims Data.

Author: ArendRebecca C, O'MalleyDavid M, BanerjeeSusana, McLaurinKimmie, DavidsonRichard, LongGráinne H

Cardiovascular events
Dose decrease
Increased medical cost
Treatment gap

Niraparib had a higher risk of experiencing a chemotherapy-induced emesis (CEI) compared to olaparib or rucaparib. Olaparib had higher persistence and adherence rates than niraparib or rucaparib. Niraparib and rucaparib had higher healthcare resource utilization (HCRU) and costs than olaparib.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Observational StudyResearch that observes and collects data on participants' behavior and outcomes in their natural state, without intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

20.

The Molecular Mechanisms of Actions, Effects, and Clinical Implications of PARP Inhibitors in Epithelial Ovarian Cancers: A Systematic Review.

Author: LauChien-Hui, SeowKok-Min, ChenKuo-Hu

Apoptosis induction
Drug resistance combat
Ovarian cancer treatment
Drug resistance
PGCCs

This review article discusses the use of poly (ADP-ribose) polymerase (PARP) inhibitors in the treatment of ovarian cancer. Ovarian cancer is a deadly gynecologic malignancy. The researchers found that PARP inhibitors are effective in treating ovarian cancers that have mutations in BRCA1 or BRCA2, genes involved in DNA repair. They also found that PARP inhibitors face challenges such as drug resistance and the emergence of polyploidy giant cancer cells.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

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