Seminars in oncology
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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 · 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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Seminars in oncology · Aug 2003
ReviewAntisense strategies targeting protein kinase C: preclinical and clinical development.
Altered protein kinase C-alpha (PKC-alpha) expression has been implicated in tumor promotion and carcinogenesis. One potentially attractive therapeutic intervention may be the use of selective antisense oligonucleotides to inhibit production of PKC-alpha. ⋯ Data from phase I and II studies have led to ongoing randomized phase III trials in combination with either cisplatin and gemcitabine or carboplatin and paclitaxel. Studies in other tumor types will also investigate the benefit of combining LY900003 with conventional chemotherapy.