Current opinion in oncology
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Strictly speaking, multidrug resistance (MDR) describes the experimental observation of cross resistance to various structurally unrelated cytotoxic agents in laboratory models of cancer. These drugs have in common their origin as natural products, and in 1985 the basis of this MDR was established as the over-expression of a membrane glycoprotein, called P-glycoprotein (Pgp), which acts as a drug efflux pump actively depleting intracellular drug concentrations in resistant tumour cells. Since then, MDR has arguably taken on a second meaning, i.e. 'misunderstood drug resistance', through the understandable, but mistaken assumption by many scientists and some clinicians that the clinical observation in cancer patients treated with chemotherapy of resistance to a wide range of cytotoxic drugs (either as a primary or acquired property) inevitably involves the same mechanism. ⋯ The most recent studies have used more potent modulating agents, such as the cyclosporin analogue, PSC833. Interpretation of data from these trials is complicated by pharmacokinetic interactions between the target cytotoxic drug and the modulating agent. Randomized trials are now underway in a number of tumour types; thus a clearer picture of the clinical relevance of MDR should emerge over the next few years.
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Both paclitaxel and docetaxel have shown activity when used as a single agent in patients with squamous cell carcinoma of the head and neck (SCCHN). Combinations of both drugs with platinum derivatives and antimetabolites have been tested in patient populations with encouraging results, but some have exhibited considerable toxicity. ⋯ Other agents such as vinorelbine, ifosfamide, thymetaq, trimetrexate, gemcitabine and topotecan showed variable activity in patients with SCCHN, but their role is still questionable. Following the optimistic view on the role of chemoradiation, combinations of paclitaxel (with or without carboplatin) with radiotherapy were studied, and the results seem feasible and promising.
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Chemotherapy was considered the standard for treatment of neuroendocrine tumors during the 1970s and 1980s. During the 1980s both interferon alfa and somatostatin analogue therapies were developed and significantly improved the clinical management of malignant neuroendocrine tumors. Surgery remains the cornerstone of treatment and should always be considered in patients with neuroendocrine tumors, even if a cure is not possible. ⋯ These treatments can be supplemented by liver embolizations and chemoembolization to reduce the masses in the liver. When these treatments fail, tumor-targeted irradiation can be attempted, such as 131I-MIBG (metaiodobenzylguanidine) and 90Y DOTA (1,4,7,10-tetraazacyclododecane-N,N(I),N(II),N(III)-tetraacetic acid)-octreotide. The treatment of neuroendocrine gut and pancreatic tumors necessitates a multimodal approach, and more effective medical treatment is being developed.
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In the past few years a combination of a 5-HT3 receptor antagonist plus dexamethasone has been shown to be the most efficacious antiemetic prophylaxis of acute emesis induced by cisplatin and moderately emetogenic chemotherapy. In the prevention of cisplatin-induced delayed emesis oral metoclopramide or ondansetron, both combined with dexamethasone, offer similar antiemetic protection. ⋯ On the other hand, a recent observational study suggested that patients presenting acute vomiting or acute moderate-severe nausea, having a high incidence of delayed emesis, should always receive antiemetic prophylaxis. Instead, patients obtaining complete protection from acute emesis may not require any antiemetic prophylaxis.
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Renal cell carcinoma remains a major challenge for urologic oncologists. Over the past year, progress has been made in understanding the molecular biology of this disease and in describing new prognostic factors for outcome following nephrectomy. ⋯ No new active chemotherapeutic agents have been identified. Prospective randomized trials suggest that autologous tumor cell vaccines as currently used offer little therapeutic benefit.