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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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.