Seminars in oncology
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Seminars in oncology · Aug 2003
ReviewRecent experience with oxaliplatin or irinotecan combined with 5-fluorouracil and leucovorin in the treatment of colorectal cancer.
During the last decade, considerable progress has been made in the development of 5-fluorouracil/leucovorin (5-FU/LV) regimens that optimize antitumor efficacy while minimizing toxicity in the management of colorectal cancer. The use of continuous infusions allowed the administration of high doses of 5-FU and LV, leading to enhanced efficacy with acceptable toxicity. ⋯ Several studies have shown that combinations with irinotecan or oxaliplatin have improved response rates and survival over 5-FU/LV regimens alone in first-line therapy of advanced colorectal cancer. Other trials currently in progress attempt to identify whether these new chemotherapeutic regimens can improve survival in the adjuvant setting.
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Oxaliplatin has become an integral part of various chemotherapy protocols, and in advanced colorectal cancer in particular. While oxaliplatin has only mild hematologic and gastrointestinal side effects, its dose-limiting toxicity is a cumulative sensory neurotoxicity that resembles that of cisplatin with the important difference of a more rapid and complete reversibility. The reversibility of neurotoxicity has been assured in long-term follow-up of patients who have received adjuvant oxaliplatin-based chemotherapy. ⋯ Several neuromodulatory agents such as calcium-magnesium infusions, antiepileptic drugs like carbamazepine or gabapentin, amifostine, alpha-lipoic acid, and glutathione have shown promising activity in prophylaxis and treatment of oxaliplatin-induced neurotoxicity. However, larger confirmatory trials are still lacking so that, to date, no evidence-based recommendation can be given for the prophylaxis of oxaliplatin-induced neurotoxicity. The predictability of neurotoxicity associated with oxaliplatin-based therapy should allow patients and doctors to develop strategies to manage this side effect in view of the individual patient's clinical situation.
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Seminars in oncology · Jun 2003
ReviewPractical considerations in the use of oral fluoropyrimidines.
Since its synthesis over 40 years ago, several studies including patients with colorectal cancer have shown that prolonged exposure to 5-fluorouracil (5-FU) is associated with better antitumor activity and decreased toxicity. However, the use of continuous-infusion 5-FU is costly and is associated with the need for a catheter and infusion pump. ⋯ Two large randomized studies that included patients with metastatic colorectal cancer have shown superior response rates for capecitabine compared with bolus regimens of 5-FU with equal times to progression, overall survival, and duration of response. Because of its favorable toxicity profile and the efficacy shown in early trials, capecitabine is currently being investigated in the adjuvant setting and in combination with radiotherapy and with other chemotherapy agents.
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Seminars in oncology · Apr 2003
ReviewAntisense therapy directed to protein kinase C-alpha (Affinitak, LY900003/ISIS 3521): potential role in breast cancer.
As our understanding of the biology of cancer increases, the attempts to target specific molecules associated with the promotion of cancer are accelerating. One of the targets currently being studied as an important tumor-promoting factor is protein kinase C-alpha (PKC-alpha). ⋯ Although its single-agent activity in breast cancer is modest, its potential role may be in concert with traditional chemotherapy. This is a review of the pharmacology and current status of the clinical development of LY900003 and its potential role in treating patients with breast cancer.