Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Taxotere (RP 56976, NSC 628503) is a new semisynthetic analog of taxol (NSC 125973) with promising antitumor activity in a variety of preclinical screening systems. Clinical responses after treatment with taxol have been observed in ovarian cancer, breast, lung cancer and melanoma. Both agents act through induction of microtubule polymerization. We have studied and compared the antiproliferative action of Taxotere and taxol against a variety of freshly explanted human tumor specimens using an in vitro soft agar cloning system. Final concentrations of 0.025-10 micrograms/ml were used for both agents in short-term (1 h) or continuous (14 days) incubations. Taxotere was studied using a 1 h incubation in a total of 167 tumor specimens of which 85 (51%) were evaluable. At 10 micrograms/ml, Taxotere inhibited 32 out of 78 (41%) specimens (colony formation less than or equal to 0.5 x control). Cytotoxicity of Taxotere was observed against breast, lung, ovarian, colorectal cancer and melanoma tumor colony forming units. For comparison, 227 specimens were exposed to taxol for 1 h. At 10 micrograms/ml, 32 out of 97 evaluable specimens (33%) were significantly inhibited. Cytotoxicity was observed against breast, lung, ovarian, colorectal cancer and melanoma tumor colony forming units. In head-to-head comparisons, 29 specimens were found more sensitive to Taxotere than taxol, while only 13 were more sensitive to taxol than to Taxotere. These data indicate that cross-resistance between the two agents is incomplete and that on a concentration basis Taxotere is more cytotoxic than taxol in the majority of human primary tumor specimens evaluated.
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PMID:Effects of Taxotere and taxol on in vitro colony formation of freshly explanted human tumor cells. 135 30

The in vitro activities of taxol and taxotere in comparison with cisplatin and doxorubicin were assessed in 30 primary tumor cultures from human breast cancers. Both taxanes were much more potent than cisplatin and doxorubicin. Taxotere was 3.1; 296, and 9.6-fold more cytotoxic than taxol, cisplatin, and doxorubicin respectively. The cytotoxic activity observed in our experiments confirms the potential clinical relevance of the two taxanes in the management of breast cancer.
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PMID:In vitro activity of taxol and taxotere in comparison with doxorubicin and cisplatin on primary cell cultures of human breast cancers. 774 61

The activity of Taxol and Taxotere was evaluated on three established cell lines and 19 primary cultures of human ovarian cancers and compared with that of cisplatin and doxorubicin. The cytotoxic activity of the different drugs was assessed with a clonogenic assay in cell lines and with a proliferative assay (based on [3H]thymidine [3H-dT] incorporation of cells grown in double-layer agarose for four days) in primary tumor cultures. The two assays run in parallel on the OVCA432 cell line provided similar ranking of activity for all the drugs. Taxotere was more cytotoxic than Taxol in two cell lines and showed the same degree of activity in one cell line. Moreover, the two drugs were more cytotoxic than cisplatin and doxorubicin in all cell lines. In primary cultures both Taxol and Taxotere were less active than cisplatin and doxorubicin. An activity by at least one of these two compounds was seen in 9 of 19 cases. Taxol was more frequently active than Taxotere and generally more potent. A direct relationship was observed between the proliferative activity of the tumor cell population and response to Taxol and/or Taxotere. In fact, cell lines that were highly sensitive to Taxol and Taxotere displayed 3H-dT labeling index (LI) values much higher than those observed in primary cultures (39% to 45% versus 0.2% to 12.6%). Again, primary cultures sensitive to Taxol and/or Taxotere were characterized by a median 3H-dT LI value about three times higher than that observed in resistant cultures (8.0% versus 2.6%).
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PMID:In vitro cytotoxic activity of Taxol and Taxotere on primary cultures and established cell lines of human ovarian cancer. 790 83

A late phase II clinical study of RP56976 (docetaxel) was conducted in patients with advanced/recurrent gastric cancer as a multicenter cooperative trial. Docetaxel was administered intravenously at a dose of 60 mg/m2 every 3-4 weeks. Of the 76 patients enrolled, 66 patients were eligible and 59 patients were evaluable for response. One patient showed complete response (CR), 13 patients partial response (PR), 1 patient minor response (MR), 19 patients no change (NC) and 25 patients had progressive disease (PD). The overall response rate in 59 evaluable patients was 23.7% (95% CI = 13.6-36.6%). The primary tumor showed a 4.3% (1/23) response, while the metastatic lesions in the abdomen, pelvic mass, lung, liver, and lymph nodes showed response rates of 62.5% (5/8), 33.3% (1/3), 33.3% (1/3), 14.8% (4/27), and 13.9% (5/26), respectively. About hematological toxicity, severe (Grade 3 or more) leukopenia was observed in 36 patients (56.3%) and neutropenia in 52 patients (81.3%). Other major toxicity (Grade 3 or more) included nausea/vomiting in 11 patients (17.2%), anorexia in 9 patients (14.1%), fatigue in 5 patients (7.8%), and alopecia in 7 patients (10.9%), all which were tolerable. The results show that docetaxel is an effective anticancer agent for advanced/recurrent gastric cancer.
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PMID:[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent gastric cancer: a Japanese Cooperative Study Group trial (group A)]. 979 14

A late phase II clinical study of RP56976 (docetaxel) in patients with advanced or recurrent gastric cancer was performed to evaluate the anti-tumor activity and clinical toxicity as a multicenter cooperative trial. Docetaxel was administered intravenously at a dose of 60 mg/m2 every 3-4 weeks. Of 72 patients enrolled, 63 patients were eligible and 59 patients were evaluable for response. The anti-tumor effects obtained complete response (CR) in one patient partial response (PR) in 13, minor response (MR) in 3, no change (NC) in 20, and progressing disease (PD) in 22 patients. The overall response rate in 59 patients was 23.7% (14/59). For 14 CR or PR cases, a response appeared 10 to 107 days (median 33.5 days) and 1 to 8 (median 2) times of dosing after the initial administration. The response rate was 9.5% in the primary tumor, 31.3% livers, 50.0% abdominal tumor, and 24.1% lymph nodes, respectively. The major adverse reactions were gastrointestinal symptoms including nausea/vomiting, anorexia, fatigue, alopecia and fever. Leukocytopenia and neutrocytopenia were also observed with a high incidence, but they recovered after 8 days from the nadir. The results show that docetaxel is an effective anti-tumor agent for advanced or recurrent gastric cancer. It is necessary to conduct another clinical trial by concomitant administration with other anti-tumor agents.
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PMID:[A late phase II clinical study of RP56976 (docetaxel) in patients with advanced or recurrent gastric cancer: a cooperative study group trial (group B)]. 1009 45

We report a case history of a patient treated with single agent docetaxel (100 mg/mq every three weeks) for a metastatic salivary gland carcinoma. After surgical treatment of primary tumor, this patient underwent two subsequent resections for local relapses. However, lung and liver metastases developed which were unsuccessfully treated with carboplatin + doxorubicin, and bleomycin. Salvage therapy with docetaxel induced a significant regression (> 50%) of both liver and lung metastases. Docetaxel seems to be active in metastatic salivary gland carcinoma, and a multicentric phase II trial is now ongoing to better evaluate its activity in this disease.
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PMID:[Docetaxel in the treatment of metastatic carcinoma of the salivary glands: report of a case]. 1036 47

Docetaxel is an excellent agent with a high antitumor effect for advanced/recurrent head and neck cancer. A 67-year-old male with advanced hypopharyngeal cancer (T3N2bM1: Stage IV) underwent two courses of superselective intra-arterial infusion of docetaxel and intravenous administration of CDDP and 5-FU. Using a coaxial technique, a microcatheter was placed in the feeding artery. Using imaging techniques docetaxel (60 mg/body and 30 mg/body) was infused into the vessels. During chemotherapy the patient received concomitant radiotherapy (50 Gy). MRI after chemoradiation showed a complete response for the primary tumor and a partial response for the neck metastasis. Grade 4 leukopenia and neutropenia and grade 3 pharyngitis/esophagitis were observed during chemoradiotherapy, but these adverse effects abated immediately and were not critical. We conclude that this superselective intra-arterial infusion of docetaxel will be useful and safe for head and neck cancer.
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PMID:[A case of advanced hypopharyngeal carcinoma successfully treated with superselective intra-arterial infusion of docetaxel]. 1186 43

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

Combination chemotherapy with docetaxel (T), cisplatin (P), fluorouracil (5-FU) and leucovorin has been reported to have major activity against squamous cell carcinoma of the head and neck (SCCHN) administered as a 4-day (TPFL4) or 5-day (TPFL5) regimen. The purpose of this study was to evaluate the efficacy and toxicity of a modified TPFL regimen (m-TPFL) for locally advanced SCCHN, consisting of a modified dosage with docetaxel, cisplatin, 5-FU and l-leucovorin (l-LV) designed for Japanese patients. Organ preservation of the primary tumor site was also assessed. Thirty-four Japanese patients with locally advanced SCCHN were eligible. Docetaxel was administered as a 1-h i.v. infusion at 48 mg/m2 on day 1; cisplatin, 24 mg/m2/day; 5-FU, 560 mg/m2/day and l-LV, 125 mg/body/day were delivered on days 1-4 by continuous i.v. infusion. This regimen was administered every 28 days. Patients who achieved a complete response (CR) after induction chemotherapy underwent radiation therapy alone. Ninety-one cycles were administered. The main hematological toxicity was neutropenia, classified as grade III or IV in 18.7% of cycles. The most common non-hematologic toxicities included anorexia, stomatitis and alopecia. The clinical overall response rate to m-TPFL was 88.2%, with 58.8% CRs and 29.4% partial responses. After definitive locoregional therapy, 25 of 34 patients were disease-free with preserved primary tumor site anatomy. Overall and progression-free survival rates at the 2-year follow-up are 92.8 and 75.3%, respectively. Our m-TPFL regimen designed for Japanese patients yielded excellent response rates with an acceptable toxicity profile in good-performance-status patients.
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PMID:Induction chemotherapy with docetaxel, cisplatin, fluorouracil and l-leucovorin for locally advanced head and neck cancers: a modified regimen for Japanese patients. 1459 74

Docetaxel has demonstrated activity as a radiosensitizer in numerous preclinical studies, probably due to its role as a cell cycle synchronizer for the G2/M radiosensitive phase of the cell cycle. We conducted a phase I trial to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of docetaxel with concurrent thoracic radiation therapy (TRT) to patients with unresectable stage III non small-cell lung cancer (NSCLC). Fifteen patients were entered into this study. Docetaxel was administered as a 1-hour intravenous (I.V.) infusion, repeated every week for 6 weeks with starting dose of 20 mg/m2. Doses were escalated in 10 mg/m2 increments in successive cohorts of three new patients, if tolerated. Unacceptable toxicity was defined as grade = 3 nonhematologic or hematologic toxicity according to Eastern Cooperative Oncology Group (ECOG) toxicity criteria. TRT was administered to the primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor (20 Gy). At the first dose level (20 mg/m2/week), one patient developed grade 4 hyperglycemia and accrual was expanded to five patients. At the second level (30 mg/m2/week), two out of six patients developed grade 3 esophagitis. At the third level (40 mg/m2/week), two out of four patients developed grade 3 esophagitis and one patient developed grade 3 pulmonary toxicity. The weekly docetaxel MTD with concurrent radiation therapy (RT) was found to be 30 mg/m2. The DLT was esophagitis and pulmonary toxicity. Other toxicities encountered included skin reaction, nausea and vomiting, as well as diarrhea. Additionally, there were no treatment-related mortalities or late-occurring toxicities. Esophagitis was the principal DLT of concurrent weekly docetaxel and thoracic radiation in the outpatient setting. The MTD of concurrent weekly docetaxel with TRT is 30 mg/m2 weekly for 6 weeks. This study is still open to accrual with weekly docetaxel and TRT in locally advanced NSCLC patients.
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PMID:A phase I trial of outpatient weekly docetaxel and concurrent radiation therapy for stage III unresectable non small-cell lung cancer: a Vanderbilt Cancer Center Affiliate Network (VCCAN) Trial. 1472 40


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