• Effective oral chemotherapy for breast cancer: pillars of strength.

      Findlay, M; Von Minckwitz, G; Wardley, Andrew M; Faculty of Medical & Health Sciences, University of Auckland, Auckland, New Zealand. mp.findlay@auckland.ac.nz (2008-02)
      Traditionally, anticancer therapy has been dominated by intravenous drug therapy. However, oral agents provide an attractive approach to chemotherapy and use of oral treatments is increasing. We discuss the benefits and challenges of oral chemotherapy from the perspectives of patients, healthcare providers and healthcare funders. Important issues include patient preference, efficacy, compliance, bioavailability, reimbursement, use in special patient populations, financial and staff time savings and flexibility of dosing. We review data for traditional oral agents (e.g. cyclophosphamide, methotrexate), newer oral chemotherapies (e.g. capecitabine), oral formulations of traditionally intravenous agents (e.g. vinorelbine, idarubicin) and new biologic agents under evaluation in breast cancer (e.g. tyrosine kinase inhibitors). Lastly, we review studies of all-oral combination regimens. The wealth of data available and the increasing use of oral agents in breast cancer suggest that many of the concerns and perceptions about oral therapy, including efficacy and bioavailability, have been overcome, and that oral therapy will play a major role in breast cancer management in the future in both the metastatic and adjuvant settings.
    • A phase I dose-escalation and bioavailability study of oral and intravenous formulations of erlotinib (Tarceva, OSI-774) in patients with advanced solid tumors of epithelial origin.

      Ranson, Malcolm R; Shaw, H; Wolf, J; Hamilton, M; McCarthy, S; Dean, Emma J; Reid, A; Judson, I; Department of Medical Oncology, University of Manchester, Christie Hospital NHS Foundation Trust, Wilmslow Road, Withington, Manchester M20 4BX, UK. malcolm.ranson@manchester.ac.uk (2010-05)
      PURPOSE: An intravenous (IV) erlotinib formulation has not been characterized in cancer patients but may be useful in those with gastrointestinal abnormalities that impact on the ability to take oral medication. This study sought to determine the maximum tolerated dose (MTD) of erlotinib administered as a single 30-min infusion in patients with advanced solid tumors and absolute bioavailability of erlotinib tablets at matched doses. METHODS: This was a two-center, open label, Phase I, dose-escalation and bioavailability study of single dose IV and oral erlotinib. RESULTS: The highest escalated IV erlotinib dose achieved was 100 mg, with only mild adverse events reported. The MTD for IV erlotinib was not reached as a predetermined erlotinib plasma concentration cap of 4 microg/mL was exceeded in 3/6 patients. No dose-limiting toxicity was observed. Median bioavailability of erlotinib tablets was 76%. CONCLUSIONS: A 100 mg single IV dose of erlotinib, given as a 30-min infusion, was well tolerated with only minor adverse events and the high level of bioavailability of oral erlotinib was confirmed.
    • Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study.

      Kaufman, Bella; Mackey, John R; Clemens, Michael R; Bapsy, Poonamalle P; Vaid, Ashok; Wardley, Andrew M; Tjulandin, Sergei; Jahn, Michaela; Lehle, Michaela; Feyereislova, Andrea; et al. (2009-11-20)
      PURPOSE: TAnDEM is the first randomized phase III study to combine a hormonal agent and trastuzumab without chemotherapy as treatment for human epidermal growth factor receptor 2 (HER2)/hormone receptor-copositive metastatic breast cancer (MBC). PATIENTS AND METHODS: Postmenopausal women with HER2/hormone receptor-copositive MBC were randomly assigned to anastrozole (1 mg/d orally) with or without trastuzumab (4 mg/kg intravenous infusion on day 1, then 2 mg/kg every week) until progression. The primary end point was progression-free survival (PFS) in the intent-to-treat population. Results Overall, 103 patients received trastuzumab plus anastrozole; 104 received anastrozole alone. Patients in the trastuzumab plus anastrozole arm experienced significant improvements in PFS compared with patients receiving anastrozole alone (hazard ratio = 0.63; 95% CI, 0.47 to 0.84; median PFS, 4.8 v 2.4 months; log-rank P = .0016). In patients with centrally confirmed hormone receptor positivity (n = 150), median PFS was 5.6 and 3.8 months in the trastuzumab plus anastrozole and anastrozole alone arms, respectively (log-rank P = .006). Overall survival in the overall and centrally confirmed hormone receptor-positive populations showed no statistically significant treatment difference; however, 70% of patients in the anastrozole alone arm crossed over to receive trastuzumab after progression on anastrozole alone. Incidence of grade 3 and 4 adverse events was 23% and 5%, respectively, in the trastuzumab plus anastrozole arm, and 15% and 1%, respectively, in the anastrozole alone arm; one patient in the combination arm experienced New York Heart Association class II congestive heart failure. CONCLUSION: Trastuzumab plus anastrozole improves outcomes for patients with HER2/hormone receptor-copositive MBC compared with anastrozole alone, although adverse events and serious adverse events were more frequent with the combination.