Summary Non-communicable diseases, including cancer, are overtaking infectious disease as the leading health-care threat in middle-income and low-income countries. Latin American and Caribbean ...countries are struggling to respond to increasing morbidity and death from advanced disease. Health ministries and health-care systems in these countries face many challenges caring for patients with advanced cancer: inadequate funding; inequitable distribution of resources and services; inadequate numbers, training, and distribution of health-care personnel and equipment; lack of adequate care for many populations based on socioeconomic, geographic, ethnic, and other factors; and current systems geared toward the needs of wealthy, urban minorities at a cost to the entire population. This burgeoning cancer problem threatens to cause widespread suffering and economic peril to the countries of Latin America. Prompt and deliberate actions must be taken to avoid this scenario. Increasing efforts towards prevention of cancer and avoidance of advanced, stage IV disease will reduce suffering and mortality and will make overall cancer care more affordable. We hope the findings of our Commission and our recommendations will inspire Latin American stakeholders to redouble their efforts to address this increasing cancer burden and to prevent it from worsening and threatening their societies.
Trastuzumab (herceptin) for early-stage breast cancer Ismael, Gustavo; Rosa, Daniela Dornelles; de Azambuja, Evandro ...
Hematology/oncology clinics of North America,
04/2007, Letnik:
21, Številka:
2
Journal Article
Recenzirano
Breast cancer patients who have HER2 gene amplification and, consequently, protein overexpression, generally show an aggressive course with short disease-free and overall survivals. Trastuzumab, a ...humanized monoclonal antibody against the extracellular domain of HER2 protein, has been shown to benefit patients who have HER2-positive metastatic breast cancer, and recently, the results of five adjuvant trials involving more than 13,000 women have been released. Here, the authors summarize the main results and outline the differences among these trials, which have demonstrated an important role of trastuzumab in the treatment of women who have HER2-overexpressing/amplified early breast cancer.
Summary Background A subcutaneous formulation of trastuzumab has been developed, offering potential improvements in patient convenience and resource use compared with the standard intravenous ...infusion of the drug. We compared the pharmacokinetic profile, efficacy, and safety of the subcutaneous and intravenous formulations in patients with HER2-positive early breast cancer. Methods The HannaH study was a phase 3, randomised, international, open-label, trial in the (neo)adjuvant setting. Patients with HER2-positive, operable, locally advanced or inflammatory breast cancer were randomly assigned to eight cycles of neoadjuvant chemotherapy administered concurrently with trastuzumab every 3 weeks either intravenously (8 mg/kg loading dose, 6 mg/kg maintenance dose) or subcutaneously (fixed dose of 600 mg); 1:1 ratio. Chemotherapy consisted of four cycles of docetaxel (75 mg/m2 ) followed by four cycles of fluorouracil (500 mg/m2 ), epirubicin (75 mg/m2 ), and cyclophosphamide (500 mg/m2 ), every 3 weeks. After surgery, patients continued trastuzumab to complete 1 year of treatment. Coprimary endpoints were serum trough concentration (Ctrough ) at pre-dose cycle 8 before surgery (non-inferiority margin for the ratio between groups of 0·80) and pathological complete response (pCR; non-inferiority margin for the difference between groups of −12·5%), analysed in the per-protocol population. This study is registered with ClinicalTrials.gov , number NCT00950300. Findings 299 patients were randomly assigned to receive intravenous trastuzumab and 297 to receive subcutaneous trastuzumab. The geometric mean presurgery Ctrough was 51·8 μg/mL (coefficient of variation 52·5%) in the intravenous group and 69·0 μg/mL (55·8%) in the subcutaneous group. The geometric mean ratio of Ctrough subcutaneous to Ctrough intravenous was 1·33 (90% CI 1·24–1·44). 107 (40·7%) of 263 patients in the intravenous group and 118 (45·4%) of 260 in the subcutaneous group achieved a pCR. The difference between groups in pCR was 4·7% (95% CI −4·0 to 13·4). Thus subcutaneous trastuzumab was non-inferior to intravenous trastuzumab for both coprimary endpoints. The incidence of grade 3–5 adverse events was similar between groups. The most common of these adverse events were neutropenia (99 33·2% of 298 patients in the intravenous group vs 86 29·0% of 297 in the subcutaneous group), leucopenia (17 5·7% vs 12 4·0%), and febrile neutropenia (10 3·4% vs 17 5·7%). However, more patients had serious adverse events in the subcutaneous group (62 21% of 297 patients) than in the intravenous group (37 12% of 298); the difference was mainly attributable to infections and infestations (24 8·1% in the subcutaneous group vs 13 4·4% in the intravenous group). Four adverse events led to death (one in the intravenous group and three in the subcutaneous group), all of which occurred during the neoadjuvant phase. Of these, two—both in the subcutaneous group—were deemed to be treatment related. Interpretation Subcutaneous trastuzumab, administered over about 5 min, has a pharmacokinetic profile and efficacy non-inferior to standard intravenous administration, with a similar safety profile to intravenous trastuzumab, and therefore offers a valid treatment alternative. Funding F Hoffmann-La Roche.
