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  • 1
    ISSN: 1569-8041
    Keywords: chemotherapy ; edatrexate ; paclitaxel ; synergism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The antifolate edatrexate and the microtubule-stabilizing agent paclitaxel have both demonstrated single-agent activity in lung and breast cancer. In vitro, the sequential combination of edatrexate followed by paclitaxel produced synergistic antitumor effects. This trial was designed to find the maximum tolerated doses of edatrexate and paclitaxel when given every two weeks utilizing this sequential schedule. Patients and methods: Thirty-four patients with solid tumors received edatrexate intravenously on days 1 and 15 and paclitaxel intravenously as a three-hour infusion on days 2 and 16 of each 28-day cycle. Edatrexate was escalated from 40 to 120 mg/m2 and the paclitaxel dose fixed at 135 mg/m2. When the maximum-tolerated dose was not reached, edatrexate was fixed at 120 mg/m2 and paclitaxel escalated to 175 and 210 mg/m2. Results: All 34 patients were assessable. The maximum tolerated doses were 120 mg/m2 of edatrexate and 210 mg/m2 of paclitaxel. Grade 3 myalgia, peripheral neuropathy, leukopenia, and an infusion-related reaction occurred. Eight patients with non-small-cell lung cancer and one with bladder cancer achieved major objective responses. Conclusions: The recommended phase II doses are 120 mg/m2 of edatrexate days 1 and 15 and 175 mg/m2 of paclitaxel as a three-hour infusion days 2 and 16 of a 28 day cycle. These results warrant phase II trials of the combination leading to phase III studies comparing the two drugs to a single agent to confirm the preclinical evidence of synergy.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1569-8041
    Keywords: lung cancer ; radiotherapy ; Taxotere
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Docetaxel is one of the most active single agents for the treatment of non-small-cell lung cancer. Given the preclinical indications for synergy and the lack of cross-resistance with other active agents in this disease, clinical trials of docetaxel combinations have been undertaken. Phase I and II clinical trials of docetaxel in combination with cisplatin, carboplatin, gemcitabine, vinorelbine, or thoracic radiation for patients with non-small-cell lung cancer were reviewed. The endpoint for phase I trials was to define the phase II doses for the docetaxel combinations where overall response rates, median and one year survival were the endpoints. Five phase I–II studies of docetaxel and cisplatin have reported response rates ranging from 21% to 48%. Median survival times ranged from 8 to 13 months, and one-year survivals from 32% to 58%. Combining docetaxel with vinorelbine resulted in a 37% response rate and a median survival of 9.4 months. Docetaxel in combination with gemcitabine produced a response rate of 53%. The adverse events of these combinations were manageable. Responses have also been reported in studies of docetaxel administered with carboplatin or thoracic radiation therapy. Combinations of docetaxel with platinum, vinorelbine, gemcitabine, and radiation were active in non-small-cell lung cancer with acceptable adverse effects. Phase III trials are currently in progress to further define the role of docetaxel combinations in the first-line treatment of this disease.
    Type of Medium: Electronic Resource
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