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Background: Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors such as veliparib are potent sensitizing agents and have been safely combined with DNA-damaging agents such as temozolomide. The sensitizing effects of PARP inhibitors are magnified when cells harbor DNA repair defects.Methods: A single-arm, open-label, phase 2 study was performed to investigate the disease control rate (DCR) after 2 cycles of veliparib plus temozolomide in patients with metastatic colorectal cancer (mCRC) refractory to all standard therapies. Fifty patients received temozolomide (150 mg/m2 /d) on days 1 to 5 and veliparib (40 mg twice daily) on days 1 to 7 of each 28-day cycle. Another 5 patients with mismatch repair-deficient (dMMR) tumors were also enrolled. Twenty additional patients were then treated with temozolomide at 200 mg/m2 /d. Archived tumor specimens were used for immunohistochemistry to assess mismatch repair, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), and O(6)-methylguanine-DNA methyltransferase (MGMT) protein expression levels.Results: The combination was well tolerated, although some patients required dose reductions for myelosuppression. The primary endpoint was successfully met with a DCR of 24% and 2 confirmed partial responses. The median progression-free survival was 1.8 months, and the median overall survival was 6.6 months. PTEN protein expression and MGMT protein expression were not predictors of DCR. There was also a suggestion of worse outcomes for patients with dMMR tumors.Conclusions: In this heavily pretreated mCRC population, a combination of veliparib and temozolomide was well tolerated with temozolomide doses up to 200 mg/m2 /d, and it was clinically active. PARP inhibitor-based therapy merits further exploration in patients with mCRC. Cancer 2018;124:2337-46. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objective To analyse survival in patients with clinically localised, surgically resectable micropapillary bladder cancer ( MPBC) undergoing radical cystectomy ( RC) with and without neoadjuvant chemotherapy ( NAC) and develop risk strata based on outcome data. Patients and Methods A review of our database identified 103 patients with surgically resectable (≤ cT4acN0 cM0) MPBC who underwent RC. Survival estimates were calculated using Kaplan-Meier method and compared using log-rank tests. Classification and regression tree ( CART) analysis was performed to identify risk groups for survival. Results For the entire cohort, estimated 5-year overall survival and disease-specific survival ( DSS) rates were 52% and 58%, respectively. CART analysis identified three risk subgroups: low-risk: cT1, no hydronephrosis; high-risk: ≥ cT2, no hydronephrosis; and highest-risk: cTany with tumour-associated hydronephrosis. The 5-year DSS for the low-, high-, and highest-risk groups were 92%, 51%, and 17%, respectively ( P < 0.001). Patients down-staged at RC < pT1 regardless of the use of NAC had the best survival (5-year DSS of 96% vs 45% for those not down-staged; P < 0.001), while those who were not down-staged despite NAC had 5-year DSS of only 17%. Conclusion In patients with surgically resectable MPBC, NAC appears to confer benefit to patients with muscle-invasive disease without hydronephrosis, while patients with cT1 disease can proceed to upfront RC. Patients with hydronephrosis do not appear to respond well to NAC and have poor prognosis regardless of treatment paradigm. However, further external validation studies are needed to support the proposed risk stratification before treatment recommendations can be made. [ABSTRACT FROM AUTHOR]