Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Toremifene”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 253 records · Page 14Linked to original sources
PubMed2002

[A case of metastatic breast cancer responding to weekly paclitaxel and high-dose toremifene administrated alternately].

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.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

[Combined effects of toremifene and paclitaxel on human breast cancer cell lines].

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.

Antineoplastic Agents, Phytogenic↗
PubMed1992

[Phase I study of NK 622 (toremifene citrate)].

A phase I study of NK 622 (toremifene citrate), a novel antiestrogen, was conducted in female patients with cancer. Patients received a single oral dosing or daily once oral dosing for five consecutive days. Any adverse effects were not experienced in the single dosing of 40 or 60 mg of NK 622. In the daily administration of 10, 20, 40, 60, 120, 240 and 480 mg/day, one of three patients who received 20 mg/day experienced grade 1 anorexia, three of four patients received 240 mg/day experienced adverse effects: Grade 1 leukopenia in one patient, Grade 1 general hot flush in one patient, and Grade 1 nausea, hot flush in the face and vertigo, Grade 2 anorexia, fatigue, dull headache and general hot flush in another one patient. These symptoms recovered to normal levels after treatment. Serum hormone levels were examined in postmenopausal patients, and a significant increase of the sex hormone binding globulin level was observed in the patients received 120 and 240 mg/day doses. Serum levels of NK 622 determined as free base (TOR) reached the peak levels in 2 to 4 hours after administration on the 1st and 5th day in daily treatment, while a metabolite N-demethyltoremifene (TOR-1) reached the peak level in 4 to 170 hours. Maximum serum levels and area under the concentration versus time curves of TOR and TOR-1 increased dose-dependently. These values also increased by repetition of the treatment. Half-lives of TOR and TOR-1 in serum ranged in 74.5 to 148.9 hours and 154.1 to 653.1 hours, respectively. From these results, it was concluded that safety and efficacy of NK 622 should be assessed by using 240 mg or less doses in clinical phase II studies where breast cancer patients received long term treatment with NK 622.

Administration, Oral↗
PubMed2004

Primary toremifene treatment for elderly postmenopausal women with breast cancer.

Among patients with breast cancer who consulted the Department of Radiology, Kochi Medical School to undergo breast-conservation treatment, toremifene (TOR) alone was administered to 7 postmenopausal women as initial treatment for reasons such as the patient's desire, advanced age, and concomitant disease. In 6 patients, breast-conserving surgery was performed 1-12 months after the start of the administration of TOR alone. A 90-year-old patient has been treated with TOR alone for 56 months, and is being followed up. Six of 7 patients showed 50% or greater reduction of tumors, including 1 in whom the administration of TOR alone for 5 months reduced the tumor from a clinical diagnosis of skin invasion (T4b) to T1c, allowing lumpectomy under local anesthesia. In one patient, there were no changes (reduction ratio: 14%). No progressive disease was detected in any patient. In this study, the administration of TOR alone markedly reduced tumors in patients with estrogen receptor (ER)-positive breast cancer, facilitating down-staging. Treatment with TOR alone may be a useful neoadjuvant therapy or single therapy in elderly patients.

Aged↗
PubMed2005

[A patient with metastatic breast cancer associated with retention of pleural effusion with no response to both CMF and exemestane, whose life was saved by high-dose toremifene].

The patient was a 70-year-old woman, who became aware of a mass in her right breast in 2001, but left it untreated. On March 10, 2003, she visited a nearby doctor with the chief complaint of dyspnea. Since a large painful mass was palpable in the right breast, advanced right breast cancer was suspected, and the patient was referred to our department. Examination revealed the presence of right axillary lymph node metastasis, left pleural effusion, and left atelectasis, and the patient was admitted to our hospital on an emergency basis. Two cycles of CMF were begun on April 2, but CT indicated NC to PD. Therefore, exemestane (EXE, 25 mg/day), was administered on May 13. While the size of the primary lesion was partially decreased, the tumor marker levels were increasing markedly. Administration of EXE was therefore discontinued, and toremifene (TOR, 120 mg/day), was begun. The systemic condition began to improve one month after the start of TOR administration. Two months later, the primary lesion had decreased in size. At after 9 months of TOR treatment, the size of the primary lesion and the tumor marker levels continued to decrease, and both the left pleural effusion and the left atelectasis disappeared.

Aged↗
PubMed2005

[Experience of high-dose toremifene treatment for postmenopausal women with metastatic breast cancer].

Toremifene (TOR), a selective estrogen receptor modulator (SERM), showed efficacy equivalent to Tamoxifen (TAM) in terms of the objective response rate, stable disease, time to progression and overall survival in patients with metastatic breast cancer (MBC). High-dose TOR is also effective for patients with TAM-resistant breast cancer. We tried to study retrospectively the efficacy and the safety of high-dose TOR treatment for patients with MBC in our hospital. Ten patients received TOR 120 mg daily. Most of the patients were treated with one or more endocrine agents before high-dose TOR. Objective response and clinical benefits were found in 3 patients (30%) and 7 patients (70%), respectively. Median time to progression and median overall survival were 9 months and 21.5 months, respectively. In our study,we found the efficacy for patients with hormone receptor negative, TAM resistance and aromatase inhibitor (AI)-resistance breast cancer. Adverse events induced by high-dose TOR treatment were tolerable. High-dose TOR may be one of the optional treatments for patients with MBC after TAM and AI treatment.

Aged↗
PubMed2007

[A patient with advanced breast cancer refractory to chemotherapy accompanied by carcinomatous pleurisy and multiple bone metastasis that responded to combination therapy with high-dose toremifene and docetaxel].

The patient was a 76-year-old woman, who found a mass in her left breast around summer of 2003 but ignored it. She visited our hospital in April 2004 because of dyspnea and low-back pain. As there was a mass accompanied by partial ulceration all over the left precordium and bilateral pleural effusion, she was admitted for further evaluation and treatment. The patient was judged to be almost in a life-threatening condition, and thus thoracentesis was performed to remove pleural fluid, and chemotherapy with FEC was also performed. In addition, the patient was placed on oral exemestane (EXE). After four courses of therapy with FEC were completed, the drug was changed to paclitaxel (PTX) and chemotherapy was continued for another 3 months. It was confirmed that the tumor size had been reduced markedly and that the volume of pleural effusion had not increased. The patient was in a state of remission for a short time, but subsequently the tumor size increased again and the tumor bled continually in small amounts. The chemotherapeutic drug was changed to capecitabine, while EXE, which had been continued, was withdrawn and oral administration of 120 mg/day of toremifene (TOR) was started. However, the tumor size was not reduced. TOR was continued, while capecitabine was changed to docetaxel (DOC). Then, the tumor size was reduced again, until the breast became almost flat after 3 months and the patient no longer bled from the tumor. The volume of pleural effusion did not increase, nor did the patient have any more dyspnea. At present, she has been in a state of remission and is living at home with a certain QOL.

Aged↗
PubMed1990

[The results of a comparative clinical study of the antiestrogenic preparations toremifene and tamoxifen in locally advanced and disseminated breast cancer].

A randomized clinical trial performed in 50 female patients with advanced breast cancer showed 60 mg/day and 240 mg/day toremifene and 40 mg/day tamoxifen to be nearly equally effective. Partial, with few exceptions, response lasting 5-31 months was observed in 35-50% of cases whereas another 35-50% of patients showed no change. Toxicity was low.

Aged↗
PubMed1993

[Phase II study of NK 622 (toremifene citrate) in advanced breast cancer, a multicentral cooperative dose finding study].

In order to determine the usual dose in the first line therapy and a high dose in the second or third line therapy, a dose finding study of a novel antiestrogen NK 622 (toremifene citrate) was performed in patients (pts) with advanced or recurrent breast cancer. NK 622 was orally administered daily once for more than 8 weeks. In pts without previous drug therapy or in pts with cancer relapse after adjuvant therapy, the response rates [(CR + PR)/total] were 24.1% (7/29), 13.8% (4/29), 20.0% (1/5) and 40.0% (2/5) at doses of 40, 60, 120 and 240 mg/day, respectively. A 40 mg/day dose showed an objective response only in postmenopausal pts with estrogen receptor (ER) positive or unknown cancer. At a dose of 60 mg/day, some of the responding cases were premenopausal pts or pts with ER(-) cancer. In pts with cancer relapse during adjuvant therapy or in those with previous therapy and/or radiation, response rates were 25.0% (2/8), 0% (0/4), 13.5% (5/37) and 10.3% (4/39) at doses of 40, 60, 120 and 240 mg/day, respectively. Response was more frequent in pts with ER (+) cancer than with ER (-) cancer. The response rates in pts with previous therapy including tamoxifen (TAM) except medroxyprogesterone (MPA) were 14.3% (4/28) at a 120 mg/day dose and 6.1% (2/33) at a 240 mg/day dose. In pts with previous therapy including TAM, MPA and other antitumor agents, the rate was 18.2% (2/11) at a 120 mg/day dose. Side effects such as elevation of GOT, GPT and serum Ca level, decrease of hemoglobin, anorexia, nausea/vomiting, fatigue, dizziness and hot flush were observed. These side effects were moderate in grade and reversible. Dose dependency of side effects was not clearly observed in grade and incidence. From these results, NK 622 is expected to be a safe drug with efficacy in first line therapy at a dose of 40 mg/day and in second or third line therapy at a dose of 120 mg/day.

Administration, Oral↗
PubMed1993

[Efficacy and safety of high dose NK 622 (toremifene citrate) in tamoxifen failed patients with breast cancer].

Efficacy and safety of high dose administration of NK 622 (toremifene citrate) were studied in tamoxifen (TAM)--failed patients with breast cancer. The patients included in the study were the following failure cases in TAM therapy: unresponded cases in TAM therapy (TAM unresponded cases), temporary responded (CR, PR) but progressed cases in TAM therapy (TAM temporary responded cases), and those relapsing during TAM adjuvant therapy or within 6 months after the adjuvant therapy (TAM adjuvant failed cases). NK 622 of a 120 mg/day dose were orally given daily once at least for 8 weeks. The response rates in evaluable cases were 6.3% (1/16) in TAM unresponded cases, 11.1% (1/9) in TAM temporary responded cases, 15.4% (4/26) in TAM adjuvant failed cases, and 11.8% (6/51) in total cases including 1 CR and 5 PR cases. Long NC in which duration of NC maintained for more than 6 months was observed in 18.8% (3/16) of TAM unresponded cases, 22.2% (2/9) of TAM temporary responded cases, 11.5% (3/26) of TAM adjuvant failed cases, and 15.7% (8/51) of total cases. Rates of response and long NC were 14.3 and 19.0% in postmenopausal patients with estrogen receptor positive cancer, respectively. A median value of duration to the onset of response was 34 days (15-137). Median duration of response and long NC were 127 days (39-381) and 238.5 days (178-281), respectively. Adverse effects were experienced in 3 (5.1%) of 59 patients: nausea in 1, vertigo in 1 and increase of GOT, GPT, LDH and gamma-GTP in another 1. The side effects were moderate and reversible. From these results, NK 622 seems to become a safe and effective drug for TAM-failed patients with breast cancer by using a 120 mg/day dose.

Administration, Oral↗
PubMed1993

[Clinical evaluation of NK 622 (toremifene citrate) in advanced or recurrent breast cancer--a comparative study by a double blind method with tamoxifen].

Efficacy and safety of NK 622 (toremifene citrate) were compared with tamoxifen (TAM) by a double blind test in patients with advanced or recurrent breast cancer. NK 622 and TAM were given orally for 12 weeks or more at daily doses of 40 and 20 mg/body, respectively. Eligible cases in NK622 and TAM groups were both 57 patients. No significant difference was observed in patient characteristics between either group. Response rates were 26.3% (8 CR and 7 PR, 15/57) in the NK 622 group and 28.1% (3 CR and 13 PR, 16/57) in the TAM group. Median values of duration to onset of CR were 91 days in the NK 622 group and 169 days in the TAM group. The duration was significantly shorter with the NK 622 group. Median duration of efficacy in CR and PR cases was 155 days in the NK 622 group and 154.5 days in the TAM group. Adverse effects were encountered in 7 patients (12.3%) of each of the 2 groups. The side effects were fatigue, hot flush, WBC decrease, abnormal values in liver function tests, etc. in the NK 622 group and anorexia, nausea, eruption, feeling of warmth, sweating, dry mouth, dizziness, abnormal values in liver function tests, etc. in the TAM group. Administration was discontinued in one patient with eruption and another patient with abnormal values of liver function tests in the TAM group, while there was no such case in the NK 622 group. Including the discontinued cases, the side effects were moderate and reversible in both groups. The patients in whom a drug was determined as useful or more numbered 24/57 (42.1%) in the NK 622 group and 23/57 (40.4%) in the TAM group. There was not significant difference between the 2 groups in the above results except the duration to onset of CR. From these results, NK 622 is expected to show comparable efficacy, safety, and usefulness in patients undergoing TAM treatment for advanced or recurrent breast cancer.

Administration, Oral↗
PubMedDate not supplied

The effect of Toremifene on the expression of some genes in human mononuclear cells.

Toremifene exerts multiple and varied effects on the gene expression of human peripheral mononuclear cells. After short-term, in vitro exposure to therapeutical levels, distinct changes in P-glycoprotein, steroid receptors, p53 and Bcl-2 expression take place. In view of the increasing use of antiestrogens in cancer therapy and prevention, there is obvious merit in long-term in vivo studies to be conducted.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Effects of chronic administration of tamoxifen and toremifene on DNA adducts in rat liver, kidney, and uterus.

To assess the effects of chronic administration of tamoxifen (TAM) and toremifene (TOR) on genetic damage related to carcinogenesis, we measured DNA adduct formation by (32)P-postlabeling in liver, kidney, and uterus of Fischer rats given TAM or TOR in the diet for 18 months. TAM induced high levels of DNA adducts in the liver in a dose-dependent manner. The total adduct levels were 3000 +/- 870 and 6100 +/- 1500 adducts per 10(9) nucleotides for the 250- and 500-ppm groups, respectively. TOR induced a dose-dependent level of adducts that was lower than that observed for TAM. The total hepatic adduct level was 70 +/- 5, 130 +/- 20, and 70 +/- 20 for 250, 500, and 750 ppm TOR, respectively. Both TAM and TOR induced a low level of adducts in the kidney, and TOR significantly enhanced endogenous DNA adduct formation. The total adduct level was 480 +/- 140, 420 +/- 210, and 680 +/- 80 adducts per 10(9) nucleotides for control, 500 ppm TAM, and 500 ppm TOR, respectively. Although neither TAM nor TOR induced adducts in the uterus, TAM significantly enhanced endogenous DNA modifications in this tissue. The total uterine adduct level was 70 +/- 30, 130 +/- 50, and 70 +/- 20 for control, 500 ppm TAM, and 500 ppm TOR, respectively. These observations demonstrate a correlation between DNA adduct formation and carcinogenicity for these compounds. The effectiveness of TOR and TAM in increasing endogenous DNA adducts indicates that a mechanism other than direct DNA damage may also be involved in their carcinogenicity.

Animals↗
PubMed1998

[The in vitro combination-effect of toremifene with CAF (cyclophosphamide, adriamycin, 5-fluorouracil) on growth of various human mammary carcinomas].

Toremifene (TOR) is a new antiestrogenic agent, a triphenylethylene derivative that was developed as an alternative to tamoxifene (TAM). TOR has been observed to be more effective than TAM with milder toxicity at high doses. We examined the in vitro combination-effect of TOR with cyclophosphamide, adriamycin, 5-fluorouracil and three drug mixture (CAF) on the growth of various human mammary carcinomas. The combination shows a semi-additive or additive growth inhibitory effect on all estrogen positive cells used here except one cell line. In particular, the additive or synergic combination-effect was observed on TAM resistant cells. Furthermore, TOR exhibits a chemosensitizing activity in ADR-resistant cells by expressing P-glycoprotein coded by MDR-1 (multidrug resistance gene). The chemosensitizing activity is dose-dependent of TOR. As described above, the combination of TOR with CAF shows more than a semi-additive effect in this experiment. In conclusion, the addition of high-dose TOR to CAF therapy might be useful for advanced/recurrent breast cancer.

Antineoplastic Agents, Hormonal↗
PubMed1998

Intrinsic reactivity of tamoxifen and toremifene metabolites with DNA.

The antiestrogen tamoxifen is known to cause liver cancer in rats. This may be due to the formation of abundant DNA adducts in rat liver. A likely precursor to some of the tamoxifen adducts in rats is alpha-hydroxytamoxifen. It is not clear whether the rat data are relevant to human exposure. In the present study, we show that one of the major metabolites in humans reacts with double-stranded DNA in vitro in the absence of any metabolizing enzymes or activating chemicals. At least two distinct adduct spots resulting from 4-hydroxy-N-desmethyltamoxifen (metabolite Bx) were detected by 32P postlabeling and thin layer chromatography. The adduct level increases dramatically when metabolite Bx is irradiated with UV light to fuse into a phenanthrene ring system. 4-hydroxy-N-desmethyltoremifene, which differs from Bx by a single chlorine atom, forms fewer DNA adducts without irradiation but similar amounts after irradiation. These results suggest that the chlorine atom may interfere with drug-DNA interactions which facilitate adduct formation.

Antineoplastic Agents, Hormonal↗