Quality of Life Analyses in a Clinical Trial of DPPE (tesmilifene) Plus Doxorubicin Versus Doxorubicin in Patients with Advanced or Metastatic Breast Cancer: NCIC CTG Trial MA.19

Abstract

Different analyses yielded slightly different conclusions but, in general, the QOL analyses were concordant and showed that patients on DOX alone had fewer disease and treatment related adverse events and better QOL. Interestingly, the QOL response analysis also showed that aggressive premedication regimens appear to ameliorate potential negative effects of DPPE on emesis and nausea as measured by patient assessed QOL.

Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems

“…This suggests that the doxorubicin effect on Bcl‐2 expression is mediated by p53 pathways. Theoretically, this means the ratio of Bcl‐2/Bax must be altered as seen with doxorubicin treatment, allowing downstream activation of different caspases [45] . To achieve the required threshold in the Bcl‐2/Bax ratio the chemotherapy drug must be delivered at a higher concentration or incubated for a longer duration.…”

Ligands of the antiestrogen-binding site induce active cell death and autophagy in human breast cancer cells through the modulation of cholesterol metabolism

“…Despite a lack of a clear understanding of its mechanism of action at that time, tesmilifene was evaluated for the treatment of breast and prostate cancer with some encouraging results in phase II and III clinical trials. [6][7][8] However, a pivotal phase III trial was recently aborted because of the lack of a therapeutic outcome. This strongly reinforces the need to understand better the mechanism of action of drugs to optimize their clinical use.…”

“…This led us to identify the AEBS as a hetero-oligomeric complex composed of two subunits: the 3b-hydroxysterol-D 7 -reductase (DHCR7) and 3b-hydroxysterol-D 8 -D 7 -isomerase (D8D7I); these two enzymes are involved in post-lanosterol cholesterol biosynthesis. 2 Binding to the AEBS of ligands, such as PBPE or Tx, inhibits these enzymes and induces the accumulation of their sterol substrates in breast cancer cells, which leads to the doubling of the unesterified sterol content in cells.…”

Effects of endurance exercise and doxorubicin on skeletal muscle myogenic regulatory factor expression

“…Furthermore, exploring the in vivo effects of DOX as with the current study allows for analysis of different skeletal muscle types as it has been shown previously that DOX has a differential effect on skeletal muscle types 12 . Nonetheless, DOX treatment impairs skeletal muscle function © C I C E d i z i o n i I n t e r n a z i o n a l i in vivo 13 , and cancer patients receiving DOX experience debilitating fatigue 14 . Because this debilitating fatigue can compromise a cancer patient's quality of life, there is need to obtain a better understanding of how DOX affects skeletal muscle.…”