Oncology Ny
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Review
Docetaxel in combination with platinums in patients with advanced non-small-cell lung cancer.
Docetaxel (Taxotere) is a semisynthetic taxoid that possesses significant activity as a single agent in the treatment of patients with non-small-cell lung cancer. In previously untreated patients with non-small-cell lung cancer, 100 mg/m2 of docetaxel administered as an intravenous infusion over 1 hour once every 3 weeks produced response rates that ranged from 21% to 38% and median survivals of 25.2 to 47.0 weeks. In patients with advanced non-small-cell lung cancer who had previously failed cisplatin (Platinol)-based chemotherapy, docetaxel produced median response rates of 20% to 21% and median survival of 28 to 42 weeks. ⋯ Regarding docetaxel and carboplatin, results from phase I trials in patients with nonhematologic solid tumors indicate that this combination is well tolerated. The maximum tolerated dose of docetaxel in combination with carboplatin (target area under the time-concentration curve of 6 mg/mL.min) is 90 mg/m2 without granulocyte-colony stimulating factor (G-CSF) (filgrastim [Neupogen]) support and 100 mg/m2 with G-CSF support. The combination of docetaxel and carboplatin is presently being evaluated in a multicenter phase II study for patients with advanced non-small-cell lung cancer.
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Docetaxel (Taxotere) and doxorubicin (Adriamycin) have each demonstrated significant activity in metastatic breast cancer. Thus, the combination of docetaxel and doxorubicin has been evaluated in phase I trials to establish the dose-limiting toxicity, maximum tolerated dose, recommended dose for future phase II and III studies, and toxicity profile of the two agents used in combination. Results from phase I trials in patients with metastatic breast cancer indicate that the docetaxel/doxorubicin combination is well tolerated. ⋯ Febrile neutropenia complicated by grade 3 infection was the dose-limiting effect at the maximum tolerated dose. The response rate at this dose level was 90%. Based on the preliminary results of phase I studies, further phase II and III studies of a docetaxel/doxorubicin combination regimen are warranted.
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Multicenter Study Clinical Trial
Docetaxel as neoadjuvant chemotherapy in patients with stage III breast cancer.
Optimal management of locally advanced breast cancer (stage III) generally includes a combination of primary chemotherapy followed by surgery (if feasible), and local radiotherapy and adjuvant chemotherapy with or without hormonal therapy. An ongoing phase II study is being performed to evaluate the use of 4 cycles of 100 mg/m2 of docetaxel (Taxotere) administered as a 1-hour intravenous infusion once every 3 weeks followed by surgery, 4 cycles of standard-dose doxorubicin/cyclophosphamide (Cytoxan, Neosar) chemotherapy, and radiation, with and without tamoxifen (Nolvadex) in patients with locally advanced breast cancer. Preliminary results from 33 patients included in this phase II study are reported here. ⋯ One patient with a complete response was confirmed to have a complete pathologic response at the time of surgery. Febrile neutropenia was noted in 8 patients (24%) and in 8 of the 120 treatment cycles (7%) administered. Future trials aimed at increasing the number of pathologic complete responses in patients with stage III breast cancer may require the use of docetaxel in combination with other active agents or the use of dose-dense scheduling schemes.
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The results from preclinical studies using murine tumor models show that the combination of docetaxel (Taxotere) and fluorouracil (5-FU) is highly synergistic. Phase I studies in patients with advanced solid tumors indicate that 60 mg/m2 of docetaxel administered as a 1-hour intravenous infusion followed by a daily intravenous bolus of 300 mg/m2 of 5-FU on days 1 through 5 is the recommended dose for phase II studies. ⋯ Ongoing phase I/II and II studies are investigating the combination of docetaxel with continuous infusion of 5-FU in patients with metastatic breast cancer and with cisplatin (Platinol) and continuous infusion of 5-FU, with and without leucovorin, in patients with head and neck cancer. Preliminary results are encouraging and warrant further study.
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Clinical Trial Controlled Clinical Trial
Combination docetaxel/cyclophosphamide in patients with advanced solid tumors.
Preclinical studies show that docetaxel (Taxotere) and cyclophosphamide (Cytoxan, Neosar) are synergistic against MA 13/C mammary adenocarcinoma. Both agents are highly active as monotherapy in a number of tumors, including metastatic breast cancer. Therefore, we performed a phase I dose-finding study to determine the maximum tolerated dose of this combination regimen in patients with advanced solid tumors. ⋯ The recommended dose for phase II studies of cyclophosphamide/docetaxel is 700/75 mg/m2 in previously treated patients and 800/75 mg/m2 in previously untreated patients. G-CSF support did not allow for further dose escalation. Preliminary results from this phase I trial indicate that the combination of docetaxel and cyclophosphamide produced an objective response rate of 69% in 32 patients with metastatic breast cancer (including 3 patients who achieved complete responses).