Background: Anthracycline-based regimens have a limited role in patients with metastatic breast cancer due to cumulative cardiotoxicity and their common use in adjuvant chemotherapy. New nonanthracycline regimens are, therefore, needed for metastatic disease. Single-agent carboplatin is active in patients with previously untreated metastatic breast cancer, producing response rates of 20%-35%. Preclinical studies have demonstrated synergistic antitumor efficacy of carboplatin and trastuzumab in HER2(+) models.
Methods: Phase II and III clinical trial data of combination therapy with carboplatin (Paraplatin; Bristol-Myers Squibb; Princeton, NJ), a taxane, and/or trastuzumab (Herceptin; Genentech, Inc.; South San Francisco, CA) in metastatic breast cancer were identified from multiple sources, including: A) clinical trial data published in peer-reviewed journals within the last 5 years; B) preliminary clinical trial data from abstracts recently presented at national meetings; and C) phase III protocols currently evaluating carboplatin-based combination regimens.
Results: In several phase II studies, combination carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb) therapy was active and reasonably well tolerated in the first-line treatment of metastatic breast cancer, producing objective response rates of 53%-62%-substantially higher rates than those seen in other phase II trials of either drug alone. Similar phase II data for carboplatin with docetaxel (Taxotere; Aventis; Bridgewater, NJ) have been reported, and recent phase III data suggest that adding carboplatin to a paclitaxel/trastuzumab regimen produces superior efficacy than paclitaxel/trastuzumab alone for patients with HER2(+) metastatic disease. Drug scheduling plays an important role in the therapeutic ratio of this combination treatment.
Conclusions: Incorporation of carboplatin as a standard agent in first-line treatment of metastatic breast cancer has support from several recent studies. Preliminary results of combination carboplatin/taxane therapy with trastuzumab in metastatic disease are encouraging, and other carboplatin combinations are also being investigated in other phase II and III trials in patients selected based on the HER2 status of their cancer. Results are eagerly awaited.