Seminars in oncology
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Seminars in oncology · Oct 2000
ReviewCurrent and planned clinical trials with trastuzumab (Herceptin).
Trastuzumab (Herceptin; Genentech, Inc, So. San Francisco, CA) is a high-affinity, humanized anti-HER2 antibody that has shown benefit in the therapy of patients with metastatic HER2-overexpressing breast cancer. Results from initial clinical trials of trastuzumab as a single agent or in combination with chemotherapy established important guidelines for the therapy of HER2-positive tumors, but represent an early phase of clinical development. ⋯ Combination studies are not limited to cytotoxic agents, as laboratory and clinical data have demonstrated that HER2 overexpression results in resistance to hormonal therapy. Therefore, a series of studies combining hormonal treatments with trastuzumab is being considered. Finally, the integration of trastuzumab into the adjuvant and neoadjuvant settings will be studied by United States and European cooperative groups.
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Respiratory emergencies may originate from disease in the airways, thoracic vessels, and pulmonary parenchyma. Airway obstruction may be amenable to bronchoscopic therapies, including laser ablation photodynamic therapy (PDT) and stent placement. Asthma is common, but may be mimicked by endobronchial metastasis. ⋯ Parenchymal lung disease may result from infections, with neoplastic and iatrogenic etiologies. The incidence of Pneumocystis carinii pneumonia (PCP) is increasing among cancer patients, but it can be prevented by prophylaxis. Attempts to treat adult respiratory distress syndrome (ARDS) through modification of inflammatory mediators have been disappointing, and the prognosis remains poor.
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Glioblastoma multiforme and anaplastic astrocytoma are the most common primary central nervous system malignancies and are the major cause of morbidity/ mortality despite combined modality approaches. Temozolomide (TMZ), a novel, oral, second-generation alkylating agent, has demonstrated antitumor activity against a broad range of solid tumors and highly resistant malignancies, including high-grade glioma Temozolomide does not require hepatic metabolism for activation, rapidly penetrates the cerebrospinal fluid, and consistently demonstrates reproducible linear pharmacokinetics with approximately 100% oral bioavailability. In preliminary clinical studies, TMZ has demonstrated meaningful efficacy and an acceptable safety profile in the treatment of patients with malignant glioma. ⋯ These studies represent the largest evaluation of a single agent in patients with recurrent malignant gliomas and were rigorously controlled with strict, prospectively defined criteria for assessment of tumor response, central review of histology, and validated instruments to assess health-related quality of life. Temozolomide was effective in delaying disease progression and maintaining health-related quality of life. Temozolomide represents a promising new agent in the treatment of malignant glioma.
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Seminars in oncology · Jun 2000
ReviewChemotherapy for advanced ovarian cancer: overview of randomized trials.
Until the mid-1970s, standard therapy for ovarian carcinoma was a single alkylating agent. Subsequently, combination chemotherapy was shown to be superior to such therapy. During the 1980s, cisplatin-based combination chemotherapy became the standard chemotherapy regimen for advanced ovarian cancer; however, other classes of agents with documented activity against ovarian tumors appeared to be cross-resistant with platinum. ⋯ During the 1990s, the combination of platinum (cisplatin or carboplatin) plus paclitaxel rapidly evolved into front-line chemotherapy for advanced ovarian cancer. The series of randomized phase III studies that have compared the activity of platinum/paclitaxel with alternative regimens, including the previous standard combination of cisplatin/cyclophosphamide, support the combination of platinum/paclitaxel as the current standard chemotherapy for advanced ovarian cancer. Outstanding issues that stem from this phase III experience include the impact of nonprotocol salvage regimens on survival and the potential benefits of sequential single-agent regimens.