toremifene and Lung-Neoplasms

To investigate the activity and clinical efficacy of toremifene plus mitomycin, vindesin and cisplatin regimen (MVP) in non-small cell lung cancer (NSCLC).. A549 cells were seeded into 96 wells at the concentration of 10 x 10(4)cells/well and exposed to different agents. Seventy-two hours later, the cytotoxicity of the agents were evaluated with the method of MTT. The clinical trial included 63 patients with chemtherapy-naive NSCLC and 30 patients who had received chemotherapy (Pre-treatment arm). The chemotherapy-naive patients were randomly divided into the toremifene-treatment arm and the control arm. Each patient was given MVP chemotherapy. Five days before the chemotherapy, those in the toremifene-treatment group and pre-treatment arm started toremifene 420 mg daily orally for 7 days. The response was evaluated after two cycles of chemotherapy and toxic side effects and the survival of the patients were followed up.. Toremifene decreased the IC(50) of chemotherapeutic agents and increased their cytotoxicity. In the clinical trial, the response rate and median survival were 47% and 11 months in the toremifene-treatment arm and 32% and 9 months in the control arm, respectively. The difference between the two arms was not significant. The response rate and median survival were 17% and 7 months in the pre-treatment arm, respectively. The toxicity among the three groups was not significantly different.. Toremifene can improve the cytotoxicity of cisplatin, mitomycin and vindesin. Toremifene plus MVP regimen is safe and effective in the treatment of NSCLC.

Topics: Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cell Division; Cisplatin; Female; Follow-Up Studies; Humans; Inhibitory Concentration 50; Lung Neoplasms; Male; Middle Aged; Mitomycins; Survival Rate; Toremifene; Tumor Cells, Cultured; Vindesine

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.. 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.. 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.. 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.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Female; Genes, fos; Humans; Lung Neoplasms; Male; Middle Aged; Protein Kinase C; Toremifene

The triphenylethylenes tamoxifen and toremifene have been reported to enhance the cytotoxicity of cisplatin by inhibition of protein kinase C (PKC) signal transduction pathways. However, the concentrations of tamoxifen and toremifene required for chemosensitization in preclinical models are generally > or =5 microM, at least tenfold higher than plasma levels observed in patients receiving these agents as antiestrogenic therapy. As part of a translational phase II trial investigating the efficacy and potential molecular mechanism of high-dose toremifene as a cisplatin modulator in metastatic non-small-cell lung cancer, plasma concentrations of toremifene and its active metabolite N-desmethyltoremifene were measured to determine whether targeted levels could be achieved clinically.. Treatment consisted of toremifene, 600 mg orally on days 1-7, and cisplatin, 50 mg/m2 intravenously on days 4 and 11, repeated every 28 days. Toremifene and N-desmethyltoremifene were measured by reverse-phase HPLC assay on days 4 and 11 prior to cisplatin infusion.. In the initial 14 patients, the mean total plasma concentrations of toremifene plus its N-desmethyl metabolite on days 4 and 11 were 14.04 (+/- 8.6) microM and 9.8 (+/- 4.4) microM, respectively. Variability in concentrations achieved did not correlate with renal or hepatic function, gender, or body surface area. Levels of N-desmethyltoremifene were higher on day 11 relative to toremifene concentrations.. We conclude that plasma levels achieved compare favorably with the levels required for cisplatin chemosensitization and PKC modulation in vitro. Targeted toremifene levels can be achieved clinically with 600 mg orally daily in combination with cisplatin and are well tolerated.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Toremifene

In this pharmacokinetics study, concentrations of toremifene (TOR), a new antiestrogen, were measured after a 7-day oral treatment in serum, lung, and tumor tissue to determine the optimal dose of TOR for the modulation of clinical multidrug resistance in patients with lung cancer. Target levels of the antiestrogen were based on previous in vitro studies. Altogether, 18 patients with operable lung tumors were studied. TOR was given in an open, nonrandomized, phase I study at three different dose levels. The medication consisted of oral TOR given for 7 days at either 240, 480, or 600 mg/day before surgical removal of the tumor. At least five patients were scheduled to be included at each dose level, with all five receiving the full course of therapy before escalation of the dose. Blood samples for serum TOR concentration measurements were taken on days 0 and 7. Specimens of tumor and normal lung tissue of approximately 0.5 g were taken on day 7. The concentrations of TOR and its metabolites were determined in serum, lung, and tumor tissue at different dose levels. Altogether, 12 evaluable patients completed the scheduled treatment. The concentrations measured in serum, lung, and tumor tissue increased along with the dose used, such that the highest TOR values were achieved at 600 mg/day, with mean values being 4.9 mumol/l, 175.0 mumol/g, and 122.7 mumol/g, respectively. The concentrations of TOR and its metabolite N-demethyltoremifene were highest in lung tissue, but the values measured in tumor specimens were also well above the respective concentrations detected in serum samples. The TOR doses of 240 and 480 mg/day were well tolerated. One patient in the group treated at 600 mg/day had to discontinue the treatment because of headache and nausea. TOR given at doses ranging from 480 to 600 mg/day for 7 days will produce serum, lung, and tumor concentrations of the parent drug and its metabolites that have been shown to reverse multidrug resistance of cancer cells in vitro. As the 480-mg/day dose of TOR produced tumor concentrations high enough to reverse multidrug resistance without producing adverse drug reactions, the dose recommended for the foreseen clinical trials in the reversal of multidrug resistance would be 480 mg/day for 7 days.

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Drug Resistance, Multiple; Humans; Lung Neoplasms; Middle Aged; Toremifene

The efficacy and safety of toremifene-ifosfamide as a first-line chemotherapy in non-small cell lung cancer were assessed. Sixteen patients were treated with oral toremifene (420 mg on days 1-4 and 240 mg on day 5) followed by ifosfamide infusion 5 g/m2 on day 5 every 3 weeks 1-6 times. Toremifene at the doses used did not enhance the effect or toxicity of ifosfamide in previously untreated non-small cell lung cancer patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Drug Administration Schedule; Drug Resistance, Multiple; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Toremifene; Treatment Outcome

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.

Topics: Aged; Antineoplastic Agents; Bone Neoplasms; Breast Neoplasms; Estrogen Antagonists; Female; Humans; Latvia; Lung Neoplasms; Menopause; Middle Aged; Remission Induction; Tamoxifen; Toremifene; USSR

A 67-year-old woman underwent total mastectomy, postoperative radiation therapy, and adjuvant hormonal therapy more than 9 years 4 months previously. There were no symptoms of recurrence for 3.5 years after completing adjuvant hormonal therapy. A hard mass appeared on the front chest wall and was diagnosed as recurrence of breast cancer histopathologically. A computed tomography (CT) scan revealed multiple metastases in the left side of the chest wall, in the left Level Ⅱ axillary lymph nodes, and in the left lung. The patient was prescribed high-dose tremifene (HD-TOR 120 mg/day). After less than 4 months, she presented with general fatigue and yellow skin, and was admitted with grade 4 hyperbilirubinemia and grade 3 hepatic dysfunction (AST and ALT). CT and magnetic resonance imaging (MRI) showed no abnormal findings in the liver or biliary tract. Drug-induced liver injury (DILI) caused by HD-TOR was suspected and this therapy was discontinued. The liver dysfunction showed a tendency to improve with conservative treatment and the patient was discharged on the 10th day of illness. She had almost recovered after 5.5 months. A liver biopsy, a drug-lymphocyte stimulation test, and other detailed examinations were not performed, but we judged this case to be one of liver failure caused by HD-TOR-induced DILI.

Topics: Aged; Antineoplastic Agents, Hormonal; Biopsy; Breast Neoplasms; Female; Humans; Liver Failure; Lung Neoplasms; Lymphatic Metastasis; Toremifene

Multidrug resistance protein could be a target for improving the efficacy of paclitaxel (PXL). Toremifene (TOR) may moderate P-gp-related drug resistance in vitro. Some P-gp moderators may change the pharmacokinetic parameters of PXL in vivo. A pharmacokinetic (PK) study in metastatic breast cancer patients (MBC) was conducted to determine the safety and efficacy of PXL and TOR.. Fifteen patients received 80 mg/m(2) PXL (i.v.) weekly and 120 mg/body TOR (p.o.) daily. For the pharmacokinetic study, PXL was administered on days 1, 8, 15, 32, and 39; TOR was given from day 18 to the end of study. On days 1, 8, 15, 18, 32, and 39, blood samples were collected from the patients who received either PXL alone or PXL + TOR, and these were analyzed by high-performance liquid chromatography.. Among the 15 patients enrolled in the study, one showed a partial response, and eight had a stable disease. TOR caused no specific adverse events that were greater than grade 3, and its toxicity profile in combination with PXL was similar to that of PXL monotherapy. The PK profile of PXL was similar with or without TOR. The PK parameters of PXL indicated no inter- or intra-patient variability in previously treated patients with MBC. No increased PXL toxicity was observed.. The PK profile of combined PXL and TOR was similar to that of PXL monotherapy. The addition of TOR to PXL in previously treated patients with MBC appears safe.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Bone Neoplasms; Breast Neoplasms; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Liver Neoplasms; Lung Neoplasms; Middle Aged; Neoplasm Staging; Paclitaxel; Prognosis; Survival Rate; Tissue Distribution; Toremifene; Treatment Outcome

Adenoid cystic carcinoma of the salivary gland (ACC-SG) is a slow-growing tumor that is refractory to most chemotherapeutic agents. Estrogen receptor (ER) antagonists provide a novel approach for recurrent disease.. We report two cases of ACC-SC in which Tamoxifen/Toremifene were used.. Both patients obtained long-term stability of disease with no associated toxicity.. Given the relatively unsuccessful treatments for ACC-SC and the low toxicity of ER antagonists, such therapy should be considered in these patients for its potential disease-stabilizing effects.

Topics: Adult; Antineoplastic Agents, Hormonal; Carcinoma, Adenoid Cystic; Combined Modality Therapy; Female; Humans; Lung Neoplasms; Neoplasm Recurrence, Local; Salivary Gland Neoplasms; Tamoxifen; Toremifene

High-dose toremifene therapy (120 mg/day) is useful for the recurrence of receptor-positive breast cancer. However, some reports show that combination therapy of high-dose toremifene and chemotherapy exhibits additive effects. Twelve patients were given oral chemotherapy (capecitabine, 5'-DFUR+CPA, S-1) with high-dose toremifene. The overall response rate was 41.7%, in addition to 58.3% with no change beyond three months. Adverse events were restricted to headache, stomatitis and nausea. Average time to progressive (TTP) was 5.8 months. It was shown that high-dose toremifene and oral chemotherapy were useful for breast cancer recurrence without severe side effects.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Cyclophosphamide; Deoxycytidine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Floxuridine; Fluorouracil; Humans; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Quality of Life; Skin Neoplasms; Tegafur; Toremifene

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.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Lung Neoplasms; Mastectomy, Modified Radical; Middle Aged; Paclitaxel; Remission Induction; Toremifene

To study the toxic effect of toremifene (TOR) and its synergistic effect with cisplatin (DDP) on human lung adenocarcinoma cell line A549.. The cytotoxic effects of these agents on human lung cancer cell line A549 were monitored by a tetrazolium-based colorimetric assay (MTT assay). The cell cycle and DNA content were detected by flow cytometer technic. p21 expression level was monitored by Western blot.. Toremifene inhibited the growth of A549 cell, with > or = 5 micromol/L significantly enhancing the chemosensitivity of cisplatin. TOR enhanced the antitumor activity of DDP at S, G(2) and M phases of cells. And p21 expression was increased after TOR and DDP had been given.. Toremifene (> or = 5 micromol/L) combined with cisplatin shows significant synergistic anti-tumor effect on A549 cells.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cell Division; Cisplatin; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Humans; Lung Neoplasms; Toremifene; Tumor Cells, Cultured

A patient with lung and pleural metastases from breast cancer treated effectively with toremifene is reported. A 62-year-old woman underwent mastectomy for breast cancer, and had high levels of estrogen and progesterone receptor. After 2-years of adjuvant UFT therapy, lung and pleural metastases were seen on a chest x-ray. The patient received a high-dose of toremifene (120 mg/day). After five months with toremifene, a chest x-ray and CT scan showed the disappearance of lung and pleural metastases. No recurrence or metastases have been detected for twenty months to date. No serious side effects were noticed. High-dose toremifene might be an effective therapy for cases of postmenopausal metastatic breast cancer, with high levels of estrogen and progesterone receptor.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Female; Humans; Lung Neoplasms; Middle Aged; Pleural Neoplasms; Selective Estrogen Receptor Modulators; Toremifene

In this study, we demonstrated that toremifene citrate (TOR) inhibited the tube formation and migration of human umbilical vein endothelial cells (HUVEC) in vitro. Moreover, TOR suppressed angiogenesis in rabbit cornea and lung metastasis of human fibrosarcoma HT-1080 cells in nude mice. The antiangiogenic activity in vitro was apparent at the concentration of 5 microM which is clinically achievable by oral administration of 120 mg/kg of TOR. These results suggest that clinical treatment with 120 mg/day of TOR might be expected to exhibit antiangiogenesis and antimetastasis effects, in addition to inhibition of estrogen-dependent tumor cell growth.

Topics: Angiogenesis Inhibitors; Animals; Corneal Neovascularization; Estrogens; Fibrosarcoma; Humans; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Metastasis; Rabbits; Selective Estrogen Receptor Modulators; Toremifene

A 68-year-old woman complained of obstructive jaundice 9 years after a radical mastectomy. CT scan demonstrated multiple metastasis of the liver and two coin lesions of the right lung. The biliary tract was completely obstructed at the portal fissure. Multiple liver and lung metastasis of breast cancer were diagnosed because of high CA 15/3 serum levels and normal gastrointestinal study. Following unsuccessful treatment with tamoxifen (TAM), we used toremifene (TORE) and 5'-deoxy-5-fluorouridine (5'-DFUR) followed by percutaneous transhepatic cholangiodrainage (PTCD). The biliary tract was reopening and jaundice disappeared with improvement of the general condition. Then endocrine therapy with medroxy progesterone acetate and UFT and chemotherapy with CAF (Cyclophosphamide, Adriamycin, 5-FU) were begun. A partial response (PR) was obtained with the disappearance of liver metastasis and two coin lesions of the lung 5 months after the first treatment. The effect of chemo-endocrine combination therapy continued for 5 months. Survival time from recurrence was 13 months. In our case, PR was obtained by using chemo-endocrine combination therapy, although a poor prognosis has been reported in patients with obstructive jaundice caused by multiple liver metastasis of recurrent breast cancer.

Topics: Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cholestasis; Cyclophosphamide; Doxorubicin; Drainage; Female; Floxuridine; Fluorouracil; Humans; Liver Neoplasms; Lung Neoplasms; Mastectomy, Radical; Medroxyprogesterone Acetate; Tamoxifen; Tegafur; Toremifene; Uracil

Two cases of metastatic breast cancer are reported in which endocrine chemotherapy with Toremifene + 5'-DFUR proved markedly effective. Case 1: A 69-year-old female. After CAF therapy as a adjuvant chemotherapy, Tamoxifen and Tegafur had been administered. At the 5th postoperative year, multiple metastases to lung and a rise in the tumor marker were found. Since the patient was not desirous of intensive chemotherapy, administration of Toremifene 120 mg/day and 5'-DFUR 800 mg/day was initiated. The patient showed PR 9 months after and achieved CR 14 months later. Case 2: A 48-year-old female. CAF therapy for a total of 6 cycles was performed as adjuvant chemotherapy. The patient was administered Tamoxifen and followed. On bone scintigrams 3.5 years after surgery, an abnormal accumulation appeared in the left sternoclavicular joint, and an infiltrative tumor mass was formed in the skin of that region. Administration of Toremifene + 5'-DFUR was initiated. After 6 months, the infiltrative mass disappeared. These findings are suggestive of the effectiveness of this combined chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Female; Floxuridine; Humans; Lung Neoplasms; Middle Aged; Remission Induction; Toremifene

A 43-year-old female underwent muscle preserving mastectomy with 6 cycles of adjuvant CMF chemotherapy for breast cancer. She developed multiple lung metastases 16 months later. The metastases were refractory to 3 cycles of CAF administration, and worsened (PD). We therefore added high-dose toremifene to her treatment. This combination therapy brought a marked decrease in the lung metastases. After 9 cycles of CAF with high-dose toremifene therapy, lung metastatic findings had almost disappeared from her chest X-ray. Following this treatment, UFT and toremifene were orally administered for maintenance therapy. Thirty-two months later at present, no increase in these lesions has been observed. High-dose antiestrogen drugs have the potential to inhibit P-glycoprotein. The combination of high-dose toremifene with CAF is potentially effective against ADM-resistant breast cancer.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Doxorubicin; Drug Resistance, Neoplasm; Estrogen Antagonists; Female; Fluorouracil; Humans; Lung Neoplasms; Mastectomy; Toremifene

Two cases of recurrent breast cancer, for which combined therapy using toremifene and oral chemotherapeutic agents were effective, are reported. In case 1, high-dose toremifene (120 mg/day) and 5'-DFUR were administered to a forty-seven-year-old woman with lung metastasis of estrogen-receptor positive breast cancer, who had been previously treated with polychemotherapy and tamoxifen. A complete response was obtained after six months of treatment and this condition has remained for longer than one year. In case 2, a fifty-year-old woman developed liver and lung matastasis of breast cancer with increased tumor marker levels. Forty mg/day of toremifene and oral cyclophosphamide was started and transarterial embolization of the hepatic artery using lipiodol, adriamycin and mitomycin C was performed. Both hepatic and pulmonary metastasis disappeared, and the tumor maker level was normalized one month later. No regrowth of the tumors has been observed for more than six months. The chemosensitizing effect of toremifene might be responsible for the favorable effects on these matastases of breast cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Female; Floxuridine; Humans; Lung Neoplasms; Middle Aged; Mitomycin; Remission Induction; Tamoxifen; Toremifene

The ability of the anti-oestrogens tamoxifen, toremifene and their 4-hydroxy and N-desmethyl metabolites to modify doxorubicin (dox) toxicity to intrinsically resistant and multidrug resistant cell lines was compared, using human breast and lung cancer, and Chinese hamster ovary cell lines. The anti-oestrogens significantly enhanced dox toxicity to multidrug resistant, P-glycoprotein-positive cell lines, but did not affect toxicity to intrinsically resistant, P-glycoprotein-negative cells. Modification was observed at clinically achievable anti-oestrogen concentrations. Toremifene and tamoxifen would therefore appear to be good candidates for in vivo studies as MDR modulating agents in selected patients with P-glycoprotein-positive tumours.

Topics: Animals; Antibodies, Monoclonal; ATP Binding Cassette Transporter, Subfamily B, Member 1; Breast Neoplasms; Carrier Proteins; Cell Division; CHO Cells; Cricetinae; Doxorubicin; Drug Interactions; Drug Resistance; Drug Screening Assays, Antitumor; Epitopes; Estrogen Antagonists; Humans; Lung Neoplasms; Membrane Glycoproteins; Tamoxifen; Toremifene; Tumor Cells, Cultured

In this study we describe the effects of tamoxifen, toremifene and their 4-hydroxy and N-desmethyl metabolites on the toxicity of a range of drugs to human breast and lung cancer and to Chinese hamster ovary cell lines, determined using a tetrazolium-based semi-automated colorimetric assay. Vinblastine resistance was completely abolished in an mdr1-transfected lung cancer cell line (S1/1.1), indicating that P-glycoprotein-mediated multidrug resistance can be fully reversed by anti-oestrogens. A substantial (14- to 39-fold) enhancement of vinblastine toxicity to highly multidrug-resistant (MCF-7Adr) cells expressing P-glycoprotein was also observed in the presence of tamoxifen, toremifene and their metabolites, while m-amsacrine, cisplatin and melphalan toxicity was unaffected.

Topics: Amsacrine; Animals; Breast Neoplasms; Cell Survival; CHO Cells; Cisplatin; Cricetinae; Dose-Response Relationship, Drug; Drug Resistance; Humans; Lung Neoplasms; Melphalan; Tamoxifen; Toremifene; Tumor Cells, Cultured; Vinblastine