Pixuvri (pixantrone)

P=N/A, N=15, Active, not recruiting, IRCCS Azienda Ospedaliero-Universitaria di Bologna

These findings suggest that pixantrone may be a promising drug for ovarian cancer patients by targeting MCM2 in the clinic.

Pixantrone caused DNA damage and exhibited inhibitory effects on SCLC cells in vitro and in a patient-derived xenograft mouse model. These results indicated that SMARCAL1 functions as an oncogene in SCLC, and pixantrone as a SMARCAL1 inhibitor bears therapeutic potentials in this deadly disease.

HOIL-1 is critical in promoting sorafenib resistance and CSC properties of HCC through Notch1 signaling. Pixantrone targeting HOIL-1 restrains the sorafenib resistance and provides a potential therapeutic intervention for HCC.

P2, N=74, Active, not recruiting, The Lymphoma Academic Research Organisation | Recruiting --> Active, not recruiting

In this real-life experience, pixantrone demonstrated long-term efficacy in a cohort of R/R DLBCL cases who had previously received at least two prior regimens; many of whom had characteristics associated with poor prognosis.

"The research was funded by: Servier Laboratoires Introduction: The Nordic Lymphoma Group (NLG) performed a dose-finding/expansion trial evaluating pixantrone, etoposide, bendamustine and, in CD20+ lymphomas, rituximab (P[R]EBEN) in patients (pts) with relapsed diffuse large B-cell (DLBCL) or peripheral T-cell (PTCL) lymphomas. The P[R]EBEN regimen is feasible on an out-pt basis and shows encouraging response rates and DoR. In PTCL, we observed an overrepresentation of AML/MDS, possibly related to the use of etoposide in multiple treatment lines. Gene expression analysis identified signatures and single genes predictive of long-term response."

Pixantrone has insufficient activity in the second- and third-line MBC setting. It appears, however, to have limited cardiotoxicity. (ClinicalTrials.gov ID: NCT01086605).

Furthermore, they were found to have anticancer activity, exemplified by mitoxantrone and pixantrone, and many are well known redox-active compounds. Compound 4 enhanced the production of PARP and caspase-3. Moreover, it activated the conversion of LC3A/B-I to LC3A/B-II showing that also autophagy plays a role in its mechanism of action, and it caused the phosphorylation of p70 s6 kinase.

The P[R]EBEN regimen is a feasible out-patient based treatment, applicable in frail, heavily pre-treated aggressive lymphoma pts and shows encouraging CR rates and DoR, particularly in early responders.