Current oncology reports
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For nearly 40 years, the medical treatment of colorectal cancer had been limited to the fluoropyrimidines until the recent development of irinotecan (CPT-11). In the past decade, a new agent has appeared, oxaliplatin. This third-generation platinum compound has synergistic activity with 5-fluorouracil and is non-cross-resistant with 5-fluorouracil, CPT-11, and other platinum agents. ⋯ Nevertheless, the US Food and Drug Administration recently denied approval for oxaliplatin as first-line treatment of colorectal cancer because of a lack of clear-cut survival advantage in clinical trials. Additional clinical trials in patients with colorectal cancer are ongoing in the United States and will test the activity of oxaliplatin in the metastatic and adjuvant setting. These studies will define the role for what appears to be a very useful and important agent.
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Current oncology reports · Sep 2000
ReviewCytotoxic chemotherapy: advances in delivery, pharmacology, and testing.
Adjuvant treatment of malignant gliomas, the most common types of primary brain tumors, with intravenous (iv) chemotherapy has not significantly improved survival for patients with these forms of cancer. A major factor in the failure of iv chemotherapy is the blood-brain barrier (BBB), a physiologic impediment to the delivery of cytotoxic chemotherapeutic drugs to the central nervous system (CNS). Intra-arterial and intrathecal infusion, blood-brain barrier disruption, high-dose chemotherapy, intratumoral administration, and convection-enhanced delivery are methods developed to overcome the BBB. ⋯ New methods for assessment of drug delivery to the brain tumor will assume increasing importance in the study of new cytotoxic chemotherapeutic drugs for these types of cancer. Pharmacokinetic studies are critical components of these clinical trials and allow assessment of drug delivery to the CNS and brain tumor. Additionally, pharmacokinetic studies will remain an important component of early clinical trials, particularly for identifying significant drug interactions involving the various supporting medications that are typically used in this patient population.
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Intermittent androgen deprivation is a controversial approach to management of prostate cancer. Preclinical models have demonstrated delay in time to prostate-specific antigen (PSA) progression in athymic mice bearing LNCaP tumors and a delay in time to androgen independence in androgen-dependent Shionogi carcinoma tumors in castrated animals exposed to intermittent androgen. Phase II clinical trials have demonstrated improved sexual function and quality of life in men discontinuing androgen deprivation. ⋯ Current ongoing phase III clinical trials of intermittent versus continuous androgen deprivation in men with metastatic disease or recurrent disease after localized therapy will assess the comparative impact on quality of life and survival. Final analyses of these critical trials will define the ultimate role of this approach in prostate cancer. In the interim, intermittent androgen deprivation should be considered an experimental approach.
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Control of malignant pain and related symptoms is paramount to clinical success in caring for cancer patients. To achieve the best quality of life for patients and families, oncologists and palliative care clinicians must work together to understand problems related to psychologic, social, and spiritual pain. ⋯ We discuss clinical experience with several classes of drugs that are currently used to treat cancer pain: 1) nonsteroidal anti-inflammatory drugs (NSAIDs), with emphasis on cyclooxygenase-2 (COX-2) inhibitors; 2) opioid analgesics, with specific emphasis on methadone and its newly recognized value in cancer pain; 3) ketamine, an antagonist at N-methyl d-aspartate (NMDA) receptors; and 4) bisphosphonates, used for pain resulting from bone metastases. New concepts that compare molecular actions of morphine at excitatory opioid receptors, and methadone at non-opioid receptor systems, are presented to underscore the importance of balancing central nervous system excitatory (anti-analgesic) versus inhibitory (analgesic) influences.
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Most terminally ill patients experience symptoms that require treatment as death approaches. The most common symptoms are pain (5% to 51%), dyspnea (28%), oral and respiratory secretions (25%), nausea and vomiting (10% to 14%), confusion (10%), myoclonus (12%), and bowel and bladder problems (over 20%). ⋯ Types of drugs that are important in symptom control include opioids, co-analgesics, anxiolytics, and anticholinergics. To be effective, these medications must be readily available for use and often need to be given by a non-oral route.