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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cooperative, phase II single-arm trial was conducted at two large tertiary referral cancer centers to evaluate the antineoplastic activity and toxicities of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with advanced esophageal cancer. The drug was given at a dose of 250 mg/m2 as a 24-hour continuous infusion. Repeat courses were given at 21-day intervals. De-escalation was based primarily on myelosuppression. All patients received recombinant human granulocyte colony-stimulating factor to minimize the risk of neutropenic fever. The primary goal of the study was tumor response. In the trial, which is ongoing, 42 patients have been assessed to date. Adenocarcinoma was the predominant histology in 30 patients, while epidermoid cancer was seen in 13 patients. Paclitaxel was identified as an active agent. Thirty percent of patients with adenocarcinoma and 25% of the smaller group with epidermoid carcinoma have had partial remissions. Complete remissions have not been seen to date. The median duration of response was 9 weeks. The major toxicity was myelosuppression; 11 patients required admission for neutropenic fever on 13 different occasions. Paclitaxel is an active drug in the treatment of esophageal cancer. Currently, there does not appear to be a difference in response on the basis of histologic subtype. Further studies with paclitaxel in combination with other drugs (eg, cisplatin and 5-fluorouracil), on different treatment schedules, and as part of multimodality therapy are indicated.
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PMID:A phase II trial of paclitaxel (Taxol) in advanced esophageal cancer: preliminary report. 752 58

Paclitaxel is a plant product isolated from the bark of the Western yew (Taxus brevifolia) that promotes the formation and stabilization of microtubules. This leads to growth arrest in the G2/M phase of the cell cycle. Paclitaxel has demonstrated significant antineoplastic activity in different tumor types, most notably in ovarian and breast carcinoma. In two Phase II trials (Eastern Cooperative Oncology Group [ECOG]/M.D. Anderson) in patients with previously untreated Stage IIIB-IV non-small cell lung cancer (NSCLC), response rates of 21% and 24% were reported. We are performing a Phase II trial investigating the efficacy of paclitaxel in patients with inoperable Stage IIIB-IV NSCLC. Forty-three patients were treated, 31 males and 12 females, with a median age of 59 years (range, 29-75), ECOG performance status 0-2, Stage IIIB 30%, Stage IV 70%. Patients were treated every 3 weeks with 225 mg/m2 as a 3-h infusion with standard premedication. Preliminary efficacy results from 37 patients include partial remissions in eight (21.6%) patients, no change in 22 (59.5%) and disease progression in seven (19%) patients. Eight patients are still receiving therapy. The hematologic toxicities (n = 43) were mild, and no World Health Organization (WHO) Grade 4 neutropenia was observed. Nonhematologic toxicities were Grade 1/2 polyneuropathy in 97.6%, Grade 1-3 myalgia/arthralgia in 76%, and Grade 1-3 nausea/vomiting in 18.6% of the patients. In conclusion, paclitaxel is an active single agent in this patient population. Mild hematologic toxicities were observed in the 3-h infusion setting (compared with 24-h infusion) and therapy was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II study with paclitaxel for the treatment of advanced inoperable non-small cell lung cancer. 755 41

We present a case report of a 56 year old female suffering from recurrence of simultaneous endometrial and ovarian carcinomas, confined to distant neck and axillary lymph nodes. Resistance of the tumor to conventional chemotherapy and radiotherapy was followed by experimental Paclitaxel treatment which led to complete regression of all metastatic foci.
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PMID:Extra-pelvic metastasis of endometrioid carcinoma; resistance to chemo-radiation therapy--response to paclitaxel treatment. Case report. 755 81

Paclitaxel, an anti-mitotic anti-cancer agent, is active against solid tumors. The inhibition of depolymerization and promotion of microtubular assembly are essential for the anti-tumor activity of paclitaxel. Microtubule-associated proteins (MAPs) co-polymerize with tubulin and play some roles in microtubular dynamics. We examined the effect of paclitaxel on the interaction between tubulin and MAPs. Human lung-cancer cells, PC-14, were synchronized to G1/S border by the thymidine-double-block technique. After release from exposure to thymidine, the cells were treated briefly with 2 nM paclitaxel and the levels of alpha and beta tubulins and MAPs were examined after various times. Immunoblot analysis of paclitaxel-treated cells showed no changes in the overall expression of alpha and beta tubulins, microtubule-associated protein 2 (MAP2) or MAPs in comparison with controls. The samples were immunoprecipitated with anti-alpha- and anti-beta-tubulin antibodies and reblotted with an anti-MAP2 antibody, which showed that the amount of co-immuno-precipitated MAP2 in the synchronized cells, were increased by the brief paclitaxel treatment. These results suggest that paclitaxel treatment enhances the interaction between alpha and beta tubulins and MAP2. Since the phosphorylation state of MAP2 regulates the affinity of MAP2 for tubulins, and mitogen-activated protein (MAP) kinase is considered to be one of the kinases responsible for MAP2 phosphorylation, the effect of paclitaxel treatment on the MAP-kinase activity of synchronized PC-14 cells was examined. Two bands with molecular masses of 42 and 44 kDa were detected by an "intra-gel" MAP-kinase assay using myelin basic protein as the substrate. Paclitaxel treatment inhibited the MAP-kinase activity of PC-14 cells and inhibition was maximal at the G2/M phase of the cell cycle. Similar, concentration-dependent inhibition by paclitaxel of cellular MAP kinase of human synchronized small-cell lung carcinoma, H69, was observed. No inhibition of the MAP kinase of the paclitaxel-resistant sub-line H69/Txl by paclitaxel was observed, suggesting that some change of the MAP-kinase cascade had occurred in these cells. No direct inhibition of MAP-kinase activity by paclitaxel was observed in the cell-free assay (in vitro), suggesting that paclitaxel did not inhibit MAP kinase directly. Since it has been speculated that p34cdc2 kinase is also a kinase that phosphorylates MAP2, the effect of paclitaxel treatment on the p34cdc2-kinase activity of synchronized PC-14 and PC-9 cells was examined. Paclitaxel inhibited p34cdc2-kinase activation at the G2/M phase. These results suggest that paclitaxel inhibited MAP kinase and p34cdc2 kinase in vivo indirectly. These actions of paclitaxel may be responsible for the increased affinity between MAP2 and tubulins that it induces.
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PMID:Enhanced interaction between tubulin and microtubule-associated protein 2 via inhibition of MAP kinase and CDC2 kinase by paclitaxel. 759 Dec 86

We reported previously (L. Milas et al., Cancer Res., 54: 3506-3510, 1994) that paclitaxel greatly enhances the response of a murine mammary carcinoma to subsequent irradiation and hypothesized that the enhanced radioresponse was mediated by tumor cell reoxygenation caused by treatment with paclitaxel. Because paclitaxel induced massive tumor cell destruction by apoptosis, it was reasoned that as apoptotic cells were removed from the tumor more hypoxic cells would have access to oxygen, be reoxygenated, and, thus, become more sensitive to radiation. The present study tested this hypothesis by assessing the effect of 60 or 40 mg/kg paclitaxel on radioresponse of an 8-mm MCA-4 tumor irradiated under air-breathing or hypoxic conditions 9, 24, 48, or 72 h after paclitaxel administration. If the hypothesis was correct, paclitaxel would enhance tumor radioresponse more under air breathing than under hypoxic conditions, and the enhancement would increase as the time between paclitaxel administration and tumor irradiation increased within a few days after paclitaxel treatment but only when radiation was given under air-breathing conditions. The effect of the treatments was determined by tumor growth delay and the radiation dose required to control 50% of the tumors (TCD50). Paclitaxel greatly enhanced tumor radioresponse under air-breathing (and not hypoxic) conditions, increasing tumor growth delay, and reducing TCD50. These effects increased as the time interval between paclitaxel administration and tumor irradiation increased within the observation period of 72 h after paclitaxel treatment. The enhancement factors for tumor growth delay ranged from 1.19 at 9 h to 1.86 at 48 h and for TCD50, from 1.16 at 9 h to 1.47 at 72 h after paclitaxel. Direct measurements of tumor pO2 showed a median value in untreated tumors of 6.2 mmHg, which increased to 10.5 mmHg at 24 h and to 31.2 mmHg at 48 h after paclitaxel administration. Overall, these results show that paclitaxel is a potent enhancer of tumor radioresponse and that its effect is mediated by reoxygenation of hypoxic tumor cells.
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PMID:Role of reoxygenation in induction of enhancement of tumor radioresponse by paclitaxel. 762 65

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is an attractive agent to combine with radiation for non-small cell lung cancer. We have been conducting clinical trials of weekly paclitaxel and concurrent radiation therapy. In a phase I study in non-small cell lung cancer, we determined the maximum tolerated dose of paclitaxel to be 60 mg/m2/wk with radiation. Patients received paclitaxel 60 mg/m2/wk as a 3-hour infusion for 6 weeks with radiation to the primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor (20 Gy). From March 1994 to February 1995, 33 patients have been entered by the Clinical Oncology Group of Rhode Island. The overall response rate (complete plus partial responses) of 25 evaluable patients as of March 1995 was 84%, with a confidence interval of 68 to 96. The major toxicity was esophagitis. Twenty percent of patients had grade 4 esophagitis. Only 8% of patients had grade 3 neutropenia. Combined-modality therapy with paclitaxel and radiation is a promising treatment for locally advanced non-small cell lung cancer with a high response rate and acceptable toxicity.
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PMID:Preliminary analysis of a phase II study of weekly paclitaxel and concurrent radiation therapy for locally advanced non-small cell lung cancer. 764 29

A case of peritoneal papillary serous carcinoma which developed after total abdominal hysterectomy and bilateral salpingo-oophorectomy for a benign condition is presented. The patient was treated with platinum-based chemotherapy to which she initially responded, but then the tumor progressed. High dose paclitaxel (250 mg/m2) was given. The patient tolerated this treatment well, achieving a rapid partial response with good palliation of symptoms. Paclitaxel should be considered for patients with a platinum resistant peritoneal papillary serous carcinoma.
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PMID:Peritoneal papillary serous carcinoma: response to Taxol in platinum resistant disease. 766 64

Paclitaxel is a novel chemotherapeutic agent that arrests cells in the radiosensitive G2 and M phases of the cell cycle and as such may act as a specific cell cycle radiosensitizer. We recently reported that paclitexel induces mitotic arrest in the MCA-4 murine mammary carcinoma and enhances radio-response of this tumor. However, the greatest enhancement was observed not when radiation was given at the time of peak mitotic arrest, which was 9 h after paclitaxel administration, but when it was given 24 h after paclitaxel. This implied the involvement of other mechanisms in radiosensitization; we hypothesized that tumor reoxygenation was a likely mechanism based on the observed massive loss of mitotically arrested cells at 24 h. The present study shows that paclitaxel greatly enhanced MCA-4 tumor radioresponse when radiation was given under air-breathing conditions (DMF = 1.74), but not when it was performed under hypoxic conditions. This observation supports the hypothesis of tumor reoxygenation as a mechanism of enhancement of tumor radioresponse. That reoxygenation occurred in tumors treated with paclitaxel 24 h earlier was confirmed by direct measurements of pO2 values, using the Eppendorf pO2 histograph. Median pO2 values increased from 6.2 mmHg in untreated tumors to 10.0 mmHg in tumors treated with paclitaxel. These observations emphasize the importance of timing of paclitaxel administration in relation to radiation treatment.
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PMID:Tumor reoxygenation as a mechanism of taxol-induced enhancement of tumor radioresponse. 777 32

Major improvements in survival from ovarian cancer will likely result from a combined effort in prevention, diagnosis, screening, and treatment. Oral contraceptives can decrease the risk of ovarian cancer in women with a family history of the disease. Screening currently is not routinely recommended and awaits further refinements in tumor markers and image techniques. Surgery and chemotherapy have been the cornerstones of treatment for most patients with ovarian cancer. Paclitaxel plus a platinum compound has now become a new standard chemotherapy regimen. However, numerous clinical questions need to be explored in prospectively randomized trials to determine how best to use this agent. Basic research in ovarian cancer will likely lead to the novel therapeutic targets and completely new approaches.
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PMID:Research directions in epithelial ovarian cancer. 783 3

The plasma disposition of paclitaxel in rabbits (7 mg/kg, 1 h i.v. inf.) was biphasic with half-lives of 0.36 and 6.36 h, and AUC was 9.46 micrograms.hr/ml. K12 value was larger than K21 and V2 was larger than V1, suggesting that paclitaxel had a favorable distribution profile in tissues. In S 180 bearing male ICR mice (30 mg/kg, i.v. bolus), the biphasic plasma disposition was also observed. The half-lives and AUC were 0.25 h, 2.23 h and 117.93 micrograms.hr/ml. Paclitaxel distributed widely in plasma rather than blood cells. The biliary level of paclitaxel in the enlarged gallbladder of ICR mice was markedly high, about 10-fold higher than the urinary level and 100-fold higher than the plasma level. The bioavailability with oral administration to ICR mice was poor. AUC(oral)/AUC(i.v.) ratio in the bile, liver, tumor and plasma was 18.91, 6.71, 0.83 and 0.45%, respectively.
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PMID:[Pharmacokinetics of paclitaxel in experimental animals. Part 1. Blood level]. 790 91


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