Centchroman—a non‐steroidal anti‐cancer agent for advanced breast cancer: Phase‐II study

Abstract

Treatment with Centchroman (3,4-trans-2,2-dimethyl-3-phenyl-4-p-(beta-pyrrolidinoethoxy) phenyl-7-methoxy chroman) has been evaluated in 4 male and 75 female patients with advanced breast cancer. The overall response rate, including both male and female cases, was 40.5%. Among the female patients, the overall response rate was 38.7%. The median duration of response was 6 months. One of the 4 male patients showed a complete response and 2 showed partial responses. The responses were more marked for bone, pulmonary, soft tissue, skin and lymph-node metastases than for liver metastases.

Nuclear Receptors and Their Selective Pharmacologic Modulators

“…Antimutagenic effects from treatment with ormeloxifene have also been described, as it reduces sister chromatid exchange and chromosome aberrations in female Swiss albino mice exposed to genotoxic compounds (Giri et al, 1999). A phase 2 trial revealed that ormeloxifene has efficacy in the treatment of advanced breast cancer (Misra et al, 1989).…”

Centchroman induces G0/G1 arrest and Caspase-dependent Apoptosis involving Mitochondrial Membrane Depolarization in MCF-7 and MDA MB-231 Human Breast Cancer Cells

“…Tamoxifen (TAM) widely used to treat metastatic, hormone responsive breast cancer (Clarke et al, 2001;Macgregor and Jordan, 1998;Shiau et al, 1998;Muss 1992) displays its cytoproliferative/-static/-toxic (Taylor et al, 1984;Perry et al, 1995a) effects in ER (Estrogen anti-estrogenic activity (Anand and Ray, 1977;World Health Organization, 1993;Central Drug Research Institute, 1994Kamboj et al, 1977) is one of the most extensively documented molecules for contraceptive purposes. However, it has also been reported to be accountable for 40.5% regression of lesions in phase III multicentric clinical trials in stage III/IV advanced breast cancer patients (Mishra et al, 1989;Central Drug Research Institute, 1995). Our previous studies have demonstrated the anti-neoplasticity of CC in ER+ve MCF-7 cells similar to TAM (Srivastava et al, 2004).…”

Effect of ormeloxifene on ovariectomy-induced bone resorption, osteoclast differentiation and apoptosis and TGF beta-3 expression

“…New synthetic, non-steroidal compounds, called the selective estrogen receptor (ER) modulators or SERMs, have recently been shown to possess ER agonistic or antagonistic selectivity depending on the target tissue [5]. Ormeloxifene is a member of type-1 class of non-steroidal SERMs in clinical use [6], which possesses desirable bone-protective [7][8][9][10] and lipid lowing activities [11] of estrogen and reported to prevent advanced breast cancer in both women and men [6,12,13] without side effects associated with conventional HRT/ERT. The precise mechanism by which ormeloxifene and other such SERMs exert tissue-specific estrogen agonist/antagonistic effect remains enigmatic.…”