Int J Fertil Womens Med. 2004 Nov-Dec;49(6):278-80.
Toremifene, a new agent for treatment of mastalgia: an open study.
Hamed H, Kotheri A, Beechey-Newman N, Fentiman IS.
Department of Academic Oncology, Breast Unit, Guy's and St Thomas' Hospital Trust, London, UK.

OBJECTIVE: Endocrine agents have been widely used in the treatment of mastalgia. Toremifene is an agent that predominantly has antiestrogenic properties with minimal estrogenic activities. This study was aimed at investigating this drug in the treatment of mastalgia and to evaluate its tolerability and efficacy. METHODS: Seventeen premenopuasal women with a mean age of 37.7 years complaining of moderate to severe mastalgia received toremifene 60 mg daily. The treatment period was 12 weeks. 70% of patients had cyclical and 30% had noncyclical mastalgia. RESULTS: All women with cyclical mastalgia responded to toremifene compared with only 75% of those with non-cyclical mastalgia. Four patients withdrew from the study after 4 weeks because of side effects, accounting for 23.5% of patients in the study. CONCLUSION: This small study has shown that toremifene is an effective agent in the treatment of mastalgia, but a high incidence of side effects makes it ineligible as an agent of choice for treatment of mastalgia.

Gan To Kagaku Ryoho. 2003 May;30(5):669-75
Combined effects of toremifene and paclitaxel on human breast cancer cell lines.
Maruyama S, Kuroiwa S, Saimoto A, Nishikawa K.
Research and Development Division, Nippon Kayaku Co., Ltd.

Effects of toremifene (TOR) in combination with paclitaxel (TXL) on various human breast cancer cell lines were evaluated. TOR and TXL exhibited additive effects on estrogen receptor (ER)-positive cancer cell lines, MCF-7 and T-47D, and a sub-additive effect on a tamoxifen (TAM)-resistant line, T-47D/TAM. To all three ER-negative cancer cell lines, the combined treatment also showed additive effects on MDA-MB-134VI, MDA-MB-231 and MDA-MB-453. Furthermore, a synergistic effect was observed on a multi-drug resistant (MDR) line, Adr. This synergistic effect was more potent in the combination with TOR than that with TAM. The combined treatment increased intracellular TXL, and the accumulation by TOR was 1.5-fold that by TAM. Consequently, the ratio of G2M arrested cells was higher, with statistical significance, in the TOR combination than in the TAM combination. In addition, these synergistic effects in MDR cells were also observed in the combination of TXL with major clinical active metabolites, N-desmethyl-TOR (TOR-1) and 4-hydroxy-TOR (TOR-2). These results suggest that the combination therapy of TOR and TXL might be an effective clinical treatment for breast cancer patients.

Gan To Kagaku Ryoho. 2002 Nov;29(11):1963-6
A case of metastatic breast cancer responding to weekly paclitaxel and high-dose toremifene administrated alternately].
Article in Japanese
Murakami H, Noda S, Okamura Y, Sakakibara T, Ishikawa T, Nakamura H, Yaguchi T, Harada A.
Dept. of Surgery, Kainan Hospital.

A 64-year-old woman underwent muscle-preserving mastectomy for breast cancer in April 1999. She developed multiple lung metastases 3 months later. The metastases partially responded to 10 cycles of CAF (cyclophosphamide, adriamycin, 5-fluorouracil). However, her lung metastases worsened again 7 months later and CAF was not effective (progressive disease). We therefore began administration of low-dose paclitaxel (80 mg/m2/week) and high-dose toremifene (120 mg/day) alternately in April 2001. This alternative therapy brought a marked decrease in the lung metastases. After 4 cycles of this treatment, lung metastatic findings had disappeared from her chest X-ray. This alternative therapy is potentially effective against metastatic breast cancer.

Cancer Chemother Pharmacol 2001 Jul;48(1):22-8
Activity of high-dose toremifene plus cisplatin in platinum-treated non-small-cell lung cancer: a phase II California Cancer Consortium Trial.
Lara PN Jr, Gandara DR, Longmate J, Gumerlock PH, Lau DH, Edelman MJ, Gandour-Edwards R, Mack PC, Israel V, Raschko J, Frankel P, Perez EA, Lenz HJ, Doroshow JH.
Division of Hematology-Oncology, University of California Davis Cancer Center, Sacramento 95817, USA.

PURPOSE: Although cisplatin is an important agent in non-small-cell lung cancer (NSCLC), de novo resistance is common and acquired resistance emerges rapidly during therapy. Proposed mediators of platinum resistance include the protein kinase C (PKC) signal transduction pathway and associated c-FOS overexpression. While estrogen administration has been reported to upregulate PKC and c-FOS _expression, the triphenylethylenes tamoxifen and toremifene potentiate platinum cytotoxicity by inhibition of PKC. Downregulation of c-FOS _expression has been reported to result from PKC inhibition. In view of these findings, we hypothesized that toremifene would reverse platinum resistance and that this interaction would be influenced by tumor estrogen receptor (ER) status. MATERIALS AND METHODS: A phase II trial of high-dose toremifene (600 mg orally daily on days 1-7) plus cisplatin (50 mg/m2 intravenously on days 4 and 11) every 28 days in NSCLC patients was conducted. A group of 30 patients with metastatic NSCLC who had been previously treated with platinum-based therapy were enrolled. RESULTS: All of the 30 patients were assessable for toxicity and 28 for tumor response. Therapy was well tolerated with minimal hematologic and non-hematologic toxicity. Common toxicity criteria grade 3 hematologic toxicity was seen in only three patients. Five patients achieved a partial response for an overall response rate of 18% (95% CI 6-37). Median overall survival was 8.1 months (95% CI 5.4-17). To assess PKC, ER, and c-Fos _expression by immunohistochemistry, 12 informative pretreatment patient tumor specimens were obtained. Four patient tumor specimens were positive for one or both PKC isoforms (alpha and epsilon) while c-Fos was overexpressed in three. None of the responding patient tumors exhibited c-FOS or PKC-epsilon overexpression. ER _expression was found to be infrequent (8%), contrasting with previous reports in this tumor type. CONCLUSION: While this phase II study indicates that high-dose toremifene plus cisplatin is feasible, active, and well tolerated in NSCLC patients previously treated with platinum compounds, the mechanism of action remains unclear. Further study of this regimen is warranted.

Drug information

Toremifene citrate belongs to the general group of drugs known as anti-hormones. It is used to treat advanced breast cancer, and may be used with other medicines to treat other cancers.
Toremifene citrate blocks estrogen. The cancer cells which depend on estrogen to divide, stop growing and die.

Caution! Before starting to take this medicine, it is vital that you should consult your doctor! Do not use it on your own initiative, without medical advice.
Also, you should read carefully important health information about this drug given here:

www.nlm.nih.gov

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FARESTON
Generic name: Toremifene

Breast cancer

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60 mg	30 tab	USD 78.00
60 mg	100 tab	USD 221.00