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Gemcitabine/Paclitaxel as First-Line Treatment of Advanced Breast Cancer

Gemcitabine (Gemzar) and paclitaxel exhibit good activity and goodsafety profiles when used alone and together in the treatment of advancedbreast cancer. In a phase II trial, 45 patients with metastaticbreast cancer received gemcitabine at 1,200 mg/m2 on days 1 and 8 andpaclitaxel at 175 mg/m2 on day 1 every 21 days. Twenty-seven patients(60.0%) had prior adjuvant therapy. Objective response was observedin 30 patients (objective response rate 66.7%, 95% confidence interval[CI] = 52%–71%), including complete response in 10 (22.2%) and partialresponse in 20 (44.4%). Median duration of response was 18 months(95% CI = 11–26.7 months), median time to tumor progression for theentire population was 11 months (95% CI = 7.1–18.7 months), medianoverall survival was 19 months (95% CI = 17.3–21.7 months), and the1-year survival rate was 69%. Treatment was well tolerated, with grade3/4 toxicities being infrequent. Grade 3/4 leukopenia, neutropenia, andthrombocytopenia were each observed in six patients (13.3%). No patientwas discontinued from the study due to hematologic ornonhematologic toxicity. Thus, the gemcitabine/paclitaxel combinationshows promising activity and tolerability when used as first-line treatmentin advanced disease. The combination recently has been shownto be superior to paclitaxel alone as first-line treatment in anthracyclinepretreatedadvanced disease according to interim results of a phase IIItrial and it should be further evaluated in comparative trials in breastcancer.

Latest Article

Immunologic and Biologic Properties of the Primary Tumor During Prolonged Neoadjuvant Chemoimmunotherapy

Patients with locally advanced cancers have a poor prognosis when treated with radiotherapy and/or surgery alone. The appearance of distant metastases shortly after removal of the primary tumor indicates that micrometastases are already present at the time of diagnosis. We observed a favorable outcome in patients with locally advanced breast cancer treated with a prolonged regimen of neoadjuvant chemotherapy plus granulocyte-macrophage colony-stimulating factor (GM-CSF [Leukine]) compared with patients receiving fewer chemotherapy cycles prior to surgery and radiotherapy. These results can partly be explained by the dose-intensive regimen used, but biologic and immunologic processes inherent to the prolonged presence of the primary tumor and its draining lymph nodes might also contribute to the beneficial outcome. The effects of the prolonged presence of the primary tumor during chemotherapy and GM-CSF administration on the antitumor immune response, and more specifically the functional properties of dendritic cells and T cells, are currently being investigated in a multicenter randomized clinical trial comparing prolonged neoadjuvant chemotherapy plus cytokines with a conventional treatment schedule. Aside from investigations concerning the immune system, other biologic processes, such as tumor angiogenesis, are being investigated at the same time. [ONCOLOGY 16(Suppl 1):32-39, 2002]