Anti-cancer drugs
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Herceptin extends survival in human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer patients when administered with paclitaxel or anthracycline/cyclophosphamide (AC), and the combination with 3-weekly paclitaxel is the current standard first-line therapy. However, other combinations may be equally effective. This review provides information on recent and ongoing trials of new Herceptin combinations. ⋯ High response rates have been observed in these clinical trials, e.g. up to 80% in combination with vinorelbine. Furthermore, Herceptin in combination with weekly paclitaxel, docetaxel or vinorelbine was well tolerated: there was no significant cardiotoxicity or unexpected toxicity and the combination showed an adverse event profile similar to that seen with monotherapy with the cytotoxic agent. Thus, Herceptin produces additional clinical benefit when added to all the cytotoxic agents with which it has been examined, further demonstrating its potential for use in HER2-positive breast cancer patients.
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Docetaxel is an active single agent in both first- and second-line therapy of patients with advanced non-small cell lung cancer (NSCLC). Randomized trials versus best supportive care have documented an improvement in overall survival for docetaxel therapy in both settings. Docetaxel also produced a significant 1-year survival rate improvement when compared with vinorelbine or ifosfamide as second-line therapy. ⋯ However, the combination of docetaxel with gemcitabine was associated with significantly less grade III/IV neutropenia, diarrhea and nausea/vomiting. Three drug regimens combining docetaxel with, for example, gemcitabine and carboplatin or with ifosfamide and cisplatin, are producing very high response rates in phase II trials. Whether three-drug combinations including docetaxel will result in an improved outcome for patients with advanced NSCLC remains to be determined.
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Single-agent docetaxel induces a response in 21-42% of patients with recurrent squamous cell cancer of the head and neck (SCCHN). When used in combination with 5-fluorouracil (5-FU), response rates (RRs) of between 24 and 27% have been reported. In contrast, in combination with cisplatin, docetaxel has achieved a RR of 33% in previously treated patients and 86% in a subgroup of chemotherapy-naive advanced stage patients. ⋯ The rate of pathological complete response was also high. The toxicities with TPF therapy were similar to those seen with cisplatin/5-FU regimens without docetaxel. A phase III trial of this approach is currently being conducted.
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Anemia represents a common side effect of cancer chemotherapy, and results in diminished overall well-being as well as side effects such as dyspnea, fatigue and decreased appetite. Treatment options for chemotherapy-induced anemia are transfusion of red blood cells and s.c. erythropoietin. Although transfusion is generally well tolerated, patients usually experience fluctuating hemoglobin levels because of hesitancy to transfuse to normal hemoglobin levels. ⋯ The costs associated with the drug have limited its use. In addition, patient preferences for the two treatment options have not been investigated. Economic analyses, including consideration of the costs associated with medical care as well as the consequences, will be essential in evaluating the potential of transfusions and erythropoietin in treating the anemia associated with cancer chemotherapy.
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The goals of chemotherapy for recurrent/refractory ovarian cancer are the palliation of disease-related symptoms, and improvement of quality and quantity of life. Previous studies of palliative therapy in advanced ovarian cancer have focused on surrogate measures of patient benefit rather than evaluating palliative end-points such as quality of life and clinical benefit. The impact of palliative chemotherapy on survival, quality of life and cost in advanced ovarian cancer are unknown as there have been no studies comparing palliative treatment with best supportive care. ⋯ Although palliative therapy may be associated with high costs, even modest prolongation of survival can render such treatment cost-effective. The major cost saving associated with palliative therapy is from the reduced need for hospitalization towards the end of life. Future studies in recurrent/refractory ovarian cancer should focus on palliative end-points and include a comparison with best supportive care.