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 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent results demonstrate an emerging role for paclitaxel in patients with urothelial-tract cancer and in patients with testicular cancer. Yielding response rates in the range of 40-50% as a single agent, paclitaxel is one of the most active drugs in metastatic bladder cancer. Ongoing trials of paclitaxel combination chemotherapy with cisplatin or cisplatin and ifosfamide demonstrate substantial objective remission rates above 70% and, in addition, a high range of complete responses. Thus, paclitaxel appears to be an important drug when used as part of first-line combination chemotherapy for metastatic bladder cancer. Ongoing clinical trials focus on the combination of paclitaxel with cisplatin, ifosfamide, gemcytabine, and carboplatin. Furthermore, paclitaxel administration has been demonstrated to be easily applicable to patients with reduced renal function, requiring no dose reduction and producing no increase in toxicity. Future strategies will have to compare the most active paclitaxel combination regimen with first-line MVAC (methotrexate, vinblastine, adriamycin, cisplatin) chemotherapy. Finally, the role of paclitaxel combination regimens needs to be explored in the adjuvant and neoadjuvant setting in patients with bladder cancer. In testicular cancer, paclitaxel has initially been tested in patients with cisplatin-refractory disease. Among 4 consecutive trials involving a total of 83 patients a response rate of 26% has been observed using dose schedules varying from 3-h to 24-h infusions and doses ranging from 175 to 250 mg/m2. The major toxicities of paclitaxel include neutropenia, neurotoxicity, and fatigue syndrome. Currently, combinations of paclitaxel with cisplatin +/- ifosfamide are used as first- or second-line salvage therapy in patients with relapsed metastatic testicular cancer. The German Testicular Cancer Study Group uses a paclitaxel (Taxol, ifosfamide, cisplatin; TIP) combination regimen as salvage treatment. Following the TIP regimen and the application of granulocyte colony-stimulating factor (G-CSF), peripheral blood stem cells (PBSC) are harvested and the patients subsequently receive high-dose chemotherapy with PBSC rescue. Since only a few drugs have demonstrated substantial activity in cisplatin-refractory disease, paclitaxel will be used in early salvage strategies and, possibly, as first-line chemotherapy as a part of platinum-based combination regimens in patients with testicular cancer. Further trials confirming the important role of paclitaxel in this highly curable malignancy and a thorough investigation of its acute and long-term toxicity will be the future tasks.
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PMID:The role of paclitaxel in chemosensitive urological malignancies: current strategies in bladder cancer and testicular germ-cell tumors. 898 35

This phase I/II study investigated the efficacy and toxic effects of combination chemotherapy using paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), ifosfamide, and cisplatin (TIP) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Twelve patients were entered in the phase I part of the study, results of which were reported previously. Fifty-three patients were treated in the phase II part of the study with 175 mg/m2 paclitaxel in a 3-hour infusion on day 1; 1,000 mg/m2/d ifosfamide in a 2-hour infusion on days 1 to 3; and 60 mg/m2 cisplatin on day 1, repeated every 3 to 4 weeks. Thirty-five men and 18 women were treated; the median age was 55 years (range, 27 to 73 years). Sites of disease and types of previous therapy varied among the patients. Among those with recurrent disease, 30 had locoregional disease, four had locoregional disease with distant metastasis, and 17 had distant metastasis only. Two patients had distant metastatic disease (MI) at the time of diagnosis. Of the 53 patients entered, 52 were assessable for disease response and toxic effects. Complete response was achieved in nine (17%) of 52 patients and partial response in 21 (40%); five (10%) patients had stable disease and 17 (33%) had progressive disease. When response rate was analyzed by disease sites, patients with locoregional sites showed a 43% major response (complete and partial) rate, and those with distant metastatic sites demonstrated an 80% major response rate (P=.04). The median duration of disease response in all patients was 4.9 months at completion of the study. Among the nine patients with complete response, three had progressive disease and the median duration of response was 6.9 months (range, 4.9 to 17 months); six were still in remission at the time of this writing, with a median duration of response of 12.8 months (range, 6.3 to 18.8+ months). The median survival time was 8.8 months, and the 1- and 2-year survival rates were 40% and 21.9%, respectively. The median follow-up time of the study was 11.8 months. The major toxic effects included neutropenia, cumulative peripheral neuropathy, and fatigue. Mucositis was rare; grade 3 mucositis developed in only one patient. Other side effects included neutropenic fever in 14 patients, all of whom completely recovered after antibiotic treatment. Grade 3 orthostatic hypotension and grade 3 peripheral neuropathy developed in one patient; supportive care led to gradual recovery. No deaths were caused by toxic effects. In conclusion, these preliminary results indicate that the TIP chemotherapy regimen produced high rates of major responses in patients with recurrent or metastatic head and neck squamous cell carcinoma, and responses were durable. The median, 1-year, and 2-year survival times were particularly promising. The TIP regimen should be pursued further as an induction regimen for locally advanced head and neck cancer.
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PMID:Role of paclitaxel, ifosfamide, and cisplatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. 957 61