Taken overall these data suggest that there is no pharmacologic d

Taken overall these data suggest that there is no pharmacologic disadvantage

of the combination of PLD with bevacizumab. In platinum-sensitive ovarian cancer relapse bevacizumab has been associated with carboplatin/PLD regimen in another phase-II trial with promising results. Among the 54 patients enrolled, the ORR was 72.2% Inhibitors,research,lifescience,medical (95% CI: 58.4, 83.5), the median duration of response was 11.9 months, and median TTP was 13.9 months (95% CI: 11.4, 16.0). The safety profile was consistent with the known toxicities of these agents, making this association a potential treatment option for platinum-sensitive ovarian cancer patients [57]. PLD is also under investigation with Inhibitors,research,lifescience,medical other antiangiogenetic drugs. A phase-III ongoing trial (TRINOVA 2 study) compares PLD to PLD in association with AMG386, an angiopoietin inhibitor [59]. Panitumumab is a fully human monoclonal antibody specific to the epidermal growth factor receptor (EGFR). No previous studies have evaluated the effect of Inhibitors,research,lifescience,medical panitumumab in ovarian cancer (OC) based on KRAS mutation status. The main purpose of the PaLiDo study, a phase-II nonrandomized multicenter trial presented at ASCO 2012 [58], was to investigate the response rate in platinum-resistant, KRAS wild-type OC patients treated with PLD and panitumumab. Patients with relapsed and pretreated (no more than two lines) ovarian cancer

were treated with panitumumab (6mg/kg days 1 Inhibitors,research,lifescience,medical and 15) and with PLD (40mg/m² day 1) every 4 weeks. Progression-free and overall survival in the intention-to-treat population (N 543) was 2.7 months (2.5–3.2 months,

95% CI) and 8.1 months (5.6–11.7 months, 95% CI), respectively, with a considerable skin toxicity, grade 3 in about 40% of patients. Other phase-I trials evaluated PLD in combination with the mTOR inhibitor temsirolimus [60] and with the folate receptor ligand farletuzumab [86] (humanized monoclonal antibody that binds to folate receptor-α, a target which is largely absent in normal epithelium and overexpressed in EOC) showing VRT752271 feasibility Inhibitors,research,lifescience,medical and activity. Data regarding combinations are very preliminary, but, at least with antiangiogenetic drugs, the combination seems tolerable and active. Another field of development is that of the patients with BRCA mutation. BRCA1- or BRCA2-mutated ovarian cancer all patients are defective of the mechanisms of DNA repairing. This determines an improved chemosensitivity to some DNA-damaging agents [87]. PLD that leads to DNA damage by inhibiting topoisomerase II may prove to be more effective in these patients [88]. In a recent study from Kaye et al. [89], the PARP inhibitor olaparib was compared with PLD in BRCA-mutated patients. The study showed significant single-agent olaparib activity while PFS was not significantly improved compared to PLD.

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