Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prolactin (PRL) constitutes a growth factor for breast cancer cell proliferation and abnormally elevated blood concentrations of PRL are associated with poor prognosis and reduced efficacy of antitumor therapies in metastatic breast carcinoma. It has already been demonstrated that low-dose bromocriptine, an antiprolactinemic long-acting dopaminergic drug, normalizes PRL blood concentrations in metastatic breast cancer patients with abnormally elevated PRL levels. In addition, previous clinical studies have already demonstrated a lower efficacy of chemotherapy with taxotere in metastatic breast cancer, with persistent hyperprolactinemia. We planned a controlled clinical study to evaluate the influence of a concomitant administration of the antiprolactinemic drug bromocriptine on the efficacy of chemotherapy with taxotere, in metastatic breast cancer patients progressing after chemotherapeutic combinations containing anthracyclines. The study included 30 randomized consecutive patients treated with taxotere alone or taxotere plus bromocriptine. Taxotere was given I.V. at 100 mg/m2 every 21 days for 3 cycles. Bromocriptine was given orally at 2.5 mg/day every day until the end of the chemotherapeutic treatment. Bromocriptine therapy induced a significant decline in PRL mean blood concentrations compared to patients treated by chemotherapy alone. No complete response was obtained. A partial response (PR) occurred in 5 out of 14 (36%) patients treated with taxotere plus bromocriptine and in only 2 out of 16 (13%) patients treated with taxotere alone. Moreover, a stable disease (SD) was obtained in 5 out of 16 patients treated with taxotere alone and in 7 out of 14 patients concomitantly treated with bromocriptine. Therefore, the percent of non-progressive disease (PR + SD) achieved in patients treated with taxotere plus bromocriptine was significantly higher with respect to that found in patients treated with taxotere alone (12 out of 14 vs 7 out of 16, p < 0.025). This preliminary clinical study would suggest that the inhibition of PRL secretion by antiprolactinemic drugs such as bromocriptine may enhance the efficacy of chemotherapy for metastatic breast cancer.
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PMID:A clinical study of taxotere versus taxotere plus the antiprolactinemic agent bromocriptine in metastatic breast cancer pretreated with anthracyclines. 1216 12

Taxanes are effective in the treatment of metastatic breast cancer. Docetaxel has been shown to be more potent than paclitaxel in inducing bcl-2 phosphorylation and apoptosis and is clinically active in some paclitaxel-resistant breast tumors. HER-2/neu overexpression has been shown to correlate with resistance to hormonal therapy as well as chemotherapy. Using a HER-2/neu transfected MCF-7 human breast cancer cell line, we investigated the role of HER-2/neu overexpression on resistance to paclitaxel and docetaxel treatment. A control vector transfected MCF-7 human breast cancer cell line (MCF/neo) and a HER-2/neu transfected MCF-7 line (MCF/18) were treated with various concentrations of docetaxel or paclitaxel. Cell number was assessed using the MTT tetrazolium dye assay. In the control vector transfected MCF/neo cell line, paclitaxel and docetaxel gave similar dose-dependent growth inhibition ( p = 0.175). In HER-2/neu transfected MCF/18 cells, docetaxel treatment resulted in a dose-dependent inhibition similar to that seen in MCF/neo cells. Paclitaxel, however, gave significantly less growth inhibition than docetaxel in the HER-2/neu overexpressing MCF/18 cells (p = 0.0003). These data suggest that HER-2/neu overexpression may contribute to paclitaxel resistance. In contrast, the cytotoxic effects of docetaxel in these breast carcinoma cells are not affected by HER-2/neu expression. Therefore, docetaxel may be the preferred taxane therapy in HER-2/neu overexpressing breast tumors.
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PMID:Decreased response to paclitaxel versus docetaxel in HER-2/neu transfected human breast cancer cells. 1257 25

The purpose of this study was to evaluate the efficacy and safety of docetaxel as second-line chemotherapy for advanced non-small cell lung cancer (NSCLC). Thirty-four patients with advanced NSCLC received docetaxel 75 mg/m2 (1-h intravenous infusion) every 3 weeks, with corticosteroid premedication. Of 28 evaluable cases, 18 were adenocarcinoma, 3 squamous cell, 3 large cell and 4 undifferentiated carcinoma. There were 16 male and 12 female patients with a median age of 55 (37-73) years and their median Karnofsky performance status was 70 per cent (60-90%). Five cases (19.2%) had liver metastases, 3 (11.5%) brain metastases, 6 (23%) bone metastases, and 17 (65.3%) metastatic nodules in the lung. Seventeen cases (50%) had received cisplatin-based and 12 (12/34, 35.3%) paclitaxel plus carboplatin prior to entering the present study. Besides chemotherapy, seven cases had received prior thoracic irradiation and two whole brain irradiation. Two cases had prior surgery for malignant pleural effusion and one had thoracotomy for the resection of the primary tumor. The time from the last dose of chemotherapy to the start of this study was less than 6 months in 20 cases, 6-12 months in 9, 12-24 months in 3 and more than 24 months in 2 cases. One patient with initial small cell lung cancer had developed NSCLC before entering this study. Three out of 28 cases achieved partial response (10.7%) and 13 out of 28 achieved stable disease (46.5%). The median survival time was 23.8 weeks. Neutropenia, grade 3 and 4 occurred in 38.8 per cent of all cycles. Skin rashes, diarrhea, asthenia, alopecia, neuropathy and edema were common non-hematologic toxicities. Docetaxel should be considered as second line chemotherapy in advanced NSCLC when primary chemotherapy including cisplatin and/or paclitaxel had failed.
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PMID:Docetaxel as second-line chemotherapy for advanced non-small cell lung cancer. 1267 67

Docetaxel is considered to be active in untreated and previously treated patients with gastric carcinoma. In a multinational phase II trial (TAX 325), 158 untreated patients with advanced gastric cancer (99% without prior chemotherapy) were randomized to receive, every 3 weeks, either docetaxel 85 mg/m2 plus cisplatin 75 mg/m2 (TC) or docetaxel 75 mg/m2 plus cisplatin 75 mg/m2, plus a 5-day continuous infusion of 750 mg/m2 5-fluorouracil (FU; TCF). By intent-to-treat analysis, patients receiving TCF had a significantly higher response rate and longer time to progression. Overall survival in the two arms was not significantly different. Toxicity (particularly gastrointestinal toxicity) was greater with the TCF combination than in the TC arm, and there was a greater need for dose reduction. However, adverse events in both arms were manageable and there were no deaths associated with either regimen. Following these findings, a phase III trial comparing a control arm of cisplatin plus 5-FU against an experimental arm consisting of the TAX 325 phase II docetaxel/cisplatin/5-FU regimen is now in progress.
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PMID:Docetaxel in combination for advanced gastric cancer. 1277 85

In this study we describe and discuss the dichotomous effects of docetaxel trastuzumab (Herceptin)/docetaxel therapy on the angiogenic molecular profile in two patients with her-2 + chemo-resistant recurrent breast carcinoma. In the first case, an intensification of angiogenesis occurred following therapy, accompanied by an impressive increase of the cancer cell proliferation index. This tumor did not express HIF1 alpha and shared a HIF-independent VEGF overexpression, which remained unaffected by therapy. An intensified formation of thymidine phosphorylase (TP)-rich stroma, presumably a response to docetaxel, shows a TP-dependent angiogenic response. In the second patient, VEGF and HIF1 alpha were down-regulated in post-treatment biopsies and this was accompanied by a sharp reduction of the vascular density and of the cancer cell proliferation rate. In both cases, c-erbB-2 expression was abrogated by Herceptin. Taking into account that Herceptin down-regulates VEGF through reduction of HIF1 alpha synthesis, this clinical study provides evidence that an anti-angiogenic effect from Herceptin/Docetaxel therapy is expected only in tumors with HIF1 alpha-dependent VEGF overexpression. In contrast, HIF1 alpha-independent VEGF angiogenic activity cannot be abrogated by Herceptin. Docetaxel mediated up-regulation of TP in the tumoral stroma may, on the contrary, result in angiogenesis intersification and rapid tumor relapse. Such an effect should be of clinical importance since Herceptin/Docetaxel-based regimens are currently evaluated for the adjuvant therapy of her-2 + breast cancer patients. Studying the Herceptin-induced phenotypic changes of tumors could lead to the identification of specific molecular profiles that bring about diverging angiogenic responses. Adjustment of the chemotherapy regimen accordingly would prove of clinical importance.
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PMID:The effect of trastuzumab/docatexel combination on breast cancer angiogenesis: dichotomus effect predictable by the HIFI alpha/VEGF pre-treatment status? 1282 Apr 39

The purpose of this study was to evaluate the efficacy and toxicity of docetaxel as single-agent neoadjuvant chemotherapy in locoregionally advanced cervical carcinoma. Between April 1998 and August 2000, 38 untreated patients with International Federation of Gynecology and Obstetrics stages IIB to IVA were entered onto this study. The median age was 44 years (range: 25-66 years). Stages: IIB 22 patients, IIIB 15 patients, and IVA 1 pt. Treatment consisted of docetaxel 100 mg/m2 IV infusion during 1 hour. Standard premedication with dexamethasone, diphenhydramine, and ranitidine was used. Cycles were repeated every 3 weeks for three courses, followed by radical surgery when it was judged appropriate, or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. 106 cycles of therapy were administered; all patients were evaluable for TX, whereas 35 were evaluable for response (3 patients refused further treatment after the first cycle of therapy). Complete response (CR): 1 patient (3%); partial response: 11 patients (31%), for an overall objective response rate of 34% (95% CI: 15-53%); no change (NC): 16 patients (46%); and progressive disease: 7 patients (20%). Six patients (17%) underwent surgery and a pathologic CR was confirmed in 1 of them. The median time to treatment failure and the median survival have not been reached yet. The limiting toxicity was leukopenia in 25 patients (69%) (G1-G2: 14 patients, G3: 10 patients, and G4: 1 patient). Neutropenia: 28 patients (78%) (G1-G2: 10 patients, G3: 8 and G4: 10). Myalgias: 17 patients (47%) (G1-G2: 15 patients and G3: 2 patients). Emesis: 21 patients (55%) (G1-G2: 19 patients and G3: 2 patients). Alopecia G3: 13 patients (36%); rash cutaneous 26 patients (68%) (G1-G2: 22 patients and G3: 4 patients). There were no hypersensitivity reactions or fluid-retention syndrome. The received dose intensity was 91% of that projected. Docetaxel is an active drug against advanced cervical carcinoma with moderate toxicity. Further evaluation in association with other agents is clearly justified.
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PMID:Docetaxel as neoadjuvant chemotherapy in patients with advanced cervical carcinoma. 1452 74

Taxol (paclitaxel) and Taxotere (docetaxel) are considered as two of the most important anti-cancer chemotherapy drugs. The cytotoxic action of these drugs has been linked to their ability to inhibit microtubule depolymerization, causing growth arrest and subsequent cell death. Studies by a number of laboratories have also linked suppression of mitogen activated protein kinase (MAPK) signaling to enhanced Taxol toxicity. The present study examined the interactions of the semi-synthetic taxane Taxotere with MEK1/2 inhibitors in epithelial tumor cells. Concurrent treatment of MDA-MB-231 mammary and DU145 prostate carcinoma cells with Taxotere and MEK1/2 inhibitor resulted in protection from the anti-proliferative effects of Taxotere in MTT assays. In contrast, in MCF-7 mammary cells, concurrent Taxotere and MEK1/2 inhibitor treatment weakly enhanced the anti-proliferative effects of the taxane. Sequential treatment of MDA-MB-231 and MCF-7 cells with Taxotere followed by MEK1/2 inhibitor also enhanced the anti-proliferative effects of the taxane in MTT assays. However, no enhancement was observed in DU145 or PC-3 cells. Colony formation assays, including isobologram analyses, provided a more definitive demonstration that MCF-7 and MDA-MB-231 cells were sensitized to the toxic effects of Taxotere by U0126. Similar data were observed using Laulimalide, which binds to tubulin at a different site to Taxotere. The enhancement in Taxotere anti-proliferative effects by U0126 correlated with increased cell killing, 48-72h after treatment of cells that was blocked by inhibition of caspase 9, but not caspase 8, function. This observation was associated with prolonged suppression of ERK1/2 and AKT activity, without alteration in either p38 or JNK1/2 activity. Collectively these findings demonstrate that sequential administration of Taxotere followed by MEK1/2 inhibition can lead to increased cell death and loss of reproductive capacity in some, but not all, human tumor cells.
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PMID:Sequence dependent exposure of mammary carcinoma cells to Taxotere and the MEK1/2 inhibitor U0126 causes enhanced cell killing in vitro. 1468 75

Docetaxel is one of the most active drugs in second-line therapy for non-small-cell-lung-carcinoma (NSCLC). The aim of this multicenter study was to evaluate the safety and efficacy of weekly low-dose docetaxel. Forty-two patients with advanced NSCLC pretreated with cisplatinum-based chemotherapy were enrolled. Docetaxel was administered at a dose of 25 mg/m(2) weekly for 12 consecutive weeks. A total of 386 doses were given with a median number of 10 doses per patient (range: 3-12). Treatment showed low incidence of hematologic toxicity and modest non-hematologic toxicity. An episode of grade 4 thrombocytopenia was reported but no episodes of grade 3 or 4 neutropenia. Most frequent non-hematologic toxicities were asthenia and alopecia. Response rate was 10.5% and median survival time (MST) was 12.8 weeks. Weekly treatment with 25 mg/m(2) docetaxel for 12 consecutive weeks appears to be a feasible and active regimen with mild toxicity in heavily pretreated NSCLC patients.
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PMID:Second line therapy with weekly low-dose docetaxel for pretreated non-small-cell lung carcinoma patients: a multicenter Italian phase II study. 1475 67

Raf-1 protein serine/threonine kinase plays an important role in cell proliferation and cell survival. We have previously described a novel cationic liposome-entrapped formulation of raf antisense oligodeoxyribonucleotide (LErafAON) and its use as a radiosensitizer. The aim of this study was to examine the effect of combination of LErafAON and a chemotherapeutic agent on growth of human prostate (PC-3) and pancreatic tumor xenografts in athymic mice (Aspc-1 and Colo 357). In PC-3 tumor-bearing mice, administration of a combination of LErafAON (i.v., 25 mg/kg/dose, x10/16) and cisplatin (i.v., 11.0 mg/kg/dose, x3), epirubicin (EPI) (i.v., 9.0 mg/kg/dose, x3) or mitoxantrone (MTO) (i.v., 2.5 mg/kg/dose, x3) led to enhanced tumor growth inhibition as compared with single agents (LErafAON+cisplatin versus cisplatin, p<0.0002, n=8; LErafAON+EPI versus EPI, p<0.0001, n=6; LErafAON+MTO versus MTO, p<0.05, n=5). In prostate or pancreatic tumor-bearing mice, combination of LErafAON (i.v., 25 mg/kg/dose, x10/13) with docetaxel (Taxotere) (i.v., 5, 7.5 or 10 mg/kg/dose, x2/4) led to tumor regression or enhanced growth inhibition as compared with single agents (PC-3: LErafAON+Taxotere versus Taxotere, p<0.02, n=7; Aspc-1: LErafAON+Taxotere versus Taxotere, p<0.03, n=5; Colo 357: LErafAON+Taxotere versus Taxotere, p<0.04, n=7). Combination of LErafAON (i.v., 25 mg/kg/dose, x10/13) with gemcitabine (i.v., 75 mg/kg/dose, x4/6) also caused a significant tumor growth inhibition in the two pancreatic carcinoma models studied (Aspc-1: LErafAON+gemcitabine versus gemcitabine, p<0.0001, n=7; Colo 357: LErafAON+gemcitabine versus gemcitabine, p<0.002, n =5). LErafAON treatment (i.v., 25 mg/kg/dose, x10) caused inhibition of Raf-1 protein expression in these tumor tissues (around 25-60%, n=4-7). Interestingly, Taxotere treatment per se also led to decreased steady state level of Raf-1 protein in PC-3 and Aspc-1 tumor tissues (i.v., 10 mg/kg/dose, x1 or 7.5 mg/kg/dose, x2; around 25-80%, n=2/6). Present studies demonstrate enhanced tumor growth inhibition or regression in response to a combination of a chemotherapeutic drug and LErafAON. These data provide a proof-of-principle for the clinical use of LErafAON in combination with chemotherapy for cancer treatment.
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PMID:Combination with liposome-entrapped, ends-modified raf antisense oligonucleotide (LErafAON) improves the anti-tumor efficacies of cisplatin, epirubicin, mitoxantrone, docetaxel and gemcitabine. 1501 58

Chemotherapy in head and neck carcinoma is used as palliative treatment but also as induction treatment or combined treatment with concurrent radiation therapy. Platinum and 5-fluorouracil are the most commonly used cytotoxic agents. Docetaxel is an active drug for treating head and neck carcinoma. For patients with recurrent or metastatic disease, docetaxel could be used either as a second line chemotherapy or a first line for patients who received previously platinum or 5FU. In combination with platinum and 5FU, used as induction chemotherapy the TPF regimen is a very active treatment with an overall response rate of 85 to 90% with a manageable acute toxicity rate. This approach is under investigation in terms of ability to obtain more larynx preservation compared to the standard approach with platinum and 5FU. Docetaxel is a radiosensitizer. Concurrent radiochemotherapy using docetaxel alone is feasible, Trials are needed to define the optimal regimen for combining radiation, platinum and docetaxel.
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PMID:[Docetaxel and squamous cell carcinoma of the head and neck]. 1504 56


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