Seminars in oncology
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Seminars in oncology · Jun 2000
ReviewTemozolomide in early stages of newly diagnosed malignant glioma and neoplastic meningitis.
Temozolomide is a novel, oral, second-generation alkylating agent. Preclinical and phase I/II studies have demonstrated its efficacy against newly diagnosed high-grade glioma and anaplastic astrocytoma. Its antineoplastic effect is accompanied by quality of life benefits in patients with these debilitating tumors. ⋯ Patients treated with temozolomide benefit from both its systemic and intracranial activity. Recently, intrathecal temozolomide has been shown to increase median survival in athymic rats bearing subarachnoid human malignant glioma xenografts. Its efficacy, convenient dosing, and predictable safety profile make it an ideal agent for future study of these difficult-to-treat central nervous system malignancies.
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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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Neurologic complications of cancer and its therapy are varied and common, but there are few true neurologic emergencies. However, when a neurologic emergency does occur, rapid diagnosis and treatment can preserve neurologic function and, in some circumstances, save a life. Epidural spinal cord compression, raised intracranial pressure (ICP), status epilepticus, and intracerebral hemorrhage (ICH) are the most common neurologic emergencies in the cancer patient. This chapter details the clinical features, possible etiologies, diagnostic tests, and treatment options for each of these complications.
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Seminars in oncology · Apr 2000
ReviewDocetaxel (Taxotere) in combination with anthracyclines in the treatment of breast cancer.
Considering the single-agent activity of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) and doxorubicin in breast cancer and their potential non-cross-resistance, several docetaxel/anthracycline-based combination chemotherapies were developed in phase I and II programs for metastatic breast cancer patients. The rationale for these combinations was also reinforced by the fact that docetaxel showed significant activity in phase III trials in patients previously exposed or having failed anthracycline chemotherapy. In a pivotal randomized phase III study of doxorubicin plus docetaxel versus doxorubicin plus cyclophosphamide as first-line chemotherapy for 429 patients with metastatic breast cancer, doxorubicin/docetaxel emerged as the more effective regimen. ⋯ However, there were no septic deaths among 213 patients receiving doxorubicin/ docetaxel. Extrahematologic toxicity appeared mild for both regimens and the combination docetaxel/doxorubicin did not increase the cardiac toxicity expected for an anthracycline-containing regimen. Docetaxel plus doxorubicin is the first regimen, involving a newly developed agent, proven superior to a standard anthracycline-containing combination in metastatic breast cancer and its potential is now being investigated in the adjuvant setting.
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Seminars in oncology · Apr 2000
ReviewDocetaxel (Taxotere) as a single agent and in combination chemotherapy for the treatment of patients with advanced non-small cell lung cancer.
Docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) has high and reproducible single-agent activity in non-small cell lung cancer, inducing responses in nearly one third of patients treated first-line. As a second-line treatment, docetaxel is the only agent so far shown in randomized trials to prolong survival when compared with either vinorelbine or ifosfamide or best supportive care. When docetaxel is given on a weekly rather than once every 3 week schedule, the risk of neutropenia is reduced while activity appears to be maintained. ⋯ A phase II study of 51 patients treated with the combination of 100 mg/m2 docetaxel and 900 mg/m2 gemcitabine reported a 13-month median survival. In a randomized phase II trial comparing docetaxel/gemcitabine with docetaxel/cisplatin, the two regimens had comparable efficacy and toxicity. Response rates of up to 50% have been reported using docetaxel in conjunction with vinorelbine.