IRCCS Fondazione Instituto Nazionale dei Tumori

Milano, Italy

IRCCS Fondazione Instituto Nazionale dei Tumori

Milano, Italy
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Sabatucci I.,IRCCS Fondazione Instituto Nazionale Dei Tumori | Lorusso D.,IRCCS Fondazione Instituto Nazionale Dei Tumori
Recenti Progressi in Medicina | Year: 2017

PARP inhibitors interfere with single-strand DNA damage repair determining a progression of the defect in double-stranded breaks. About 50% of high-grade serous ovarian cancer patients presents deficient pathways of homologous recombination, involved on double-strand DNA damage repair. The inability to repair double-strand damage determines cell death, a process defined "synthetic lethality". Among the PARP inhibitors family, niraparib is the first one approved by FDA for the treatment of ovarian cancer patients, regardless of the presence or absence of gBRCA mutations. The label was obtained thanks to data of phase III ENGOT-OV16/NOVA trial, reporting an increased progression-free survival with a good toxicity profile for the drug. Further clinical trials are ongoing to evaluate extended indications on the use of niraparib for the treatment of ovarian cancer.


Paoletti X.,Institute National du Cancer | Oba K.,Kyoto University | Burzykowski T.,Hasselt University | Michiels S.,Institute Gustave Roussy | And 34 more authors.
European Journal of Cancer | Year: 2010

Context Despite potentially curative resection of stomach cancer, 50% to 90% of patients die of disease relapse. Numerous randomized clinical trials (RCTs) have compared surgery alone with adjuvant chemotherapy, but definitive evidence is lacking. Objectives To perform an individual patient-level meta-analysis of all RCTs to quantify the potential benefit of chemotherapy after complete resection over surgery alone in terms of overall survival and disease-free survival, and to further study the role of regimens, including monochemotherapy; combined chemotherapy with fluorouracil derivatives, mitomycin C, and other therapies but no anthracyclines; combined chemotherapy with fluorouracil derivatives, mitomycin C, and anthracyclines; and other treatments. Data Sources Data from all RCTs comparing adjuvant chemotherapy with surgery alone in patients with resectable gastric cancer.Wesearched MEDLINE (up to 2009), the Cochrane Central Register of Controlled Trials, the National Institutes of Health trial registry, and published proceedings from major oncologic and gastrointestinal cancer meetings. Study Selection All RCTs closed to patient recruitment before 2004 were eligible. Trials testing radiotherapy; neoadjuvant, perioperative, or intraperitoneal chemotherapy; or immunotherapy were excluded. Thirty-one eligible trials (6390 patients) were identified. Data Extraction As of 2010, individual patient data were available from 17 trials (3838 patients representing60%of the targeted data) with amedianfollow-up exceeding7years. Results There were 1000 deaths among 1924 patients assigned to chemotherapy groups and 1067 deaths among 1857 patients assigned to surgery-only groups. Adjuvant chemotherapy was associated with a statistically significant benefit in terms of overall survival (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.76-0.90; P<.001) and disease-free survival (HR, 0.82; 95% CI, 0.75-0.90; P<.001). There was no significant heterogeneity for overall survival across RCTs (P=.52) or the 4 regimen groups (P=.13). Five-year overall survival increased from 49.6% to 55.3% with chemotherapy. Conclusion Among the RCTs included, postoperative adjuvant chemotherapy based on fluorouracil regimens was associated with reduced risk of death in gastric cancer compared with surgery alone. © 2010 American Medical Association.

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