Anti-cancer drugs
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The current standard treatment for early stage (I-III) renal cell cancer (RCC) is surgery. While the prognosis of stage I tumors is excellent, stage II and particularly stage III have a high risk of relapse. The adjuvant treatment of patients with RCC remains an area of investigation, with patient selection being a key aspect. ⋯ In the metastatic RCC setting, recent advances in the molecular understanding of oncogenic pathways have led to the development of new therapeutic strategies with the use of targeted therapies in the adjuvant setting. Neoadjuvant treatment is another treatment modality currently being evaluated for patients with early disease and in patients with metastatic RCC with inoperable primary tumors. The questions that remain unanswered include activity of these agents in early stages of the disease, patient selection, optimal start time of the adjuvant treatment, and finally, the optimal length of treatment.
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Chemotherapy-induced peripheral neuropathy (CIPN) is a major drug-induced adverse reaction that becomes a dose-limiting toxicity. However, effective strategies for preventing or treating CIPN are lacking. Accordingly, this study aimed to statistically identify predictors for CIPN. ⋯ For oxaliplatin, the predictors for CIPN were a large number of chemotherapy cycles (OR, 3.089; CI, 1.598-5.972; P=0.0008) and no co-administration of non-steroidal anti-inflammatory drugs (OR, 0.393; CI, 0.197-0.785; P=0.0082). For vincristine, predictors for CIPN were a large number of chemotherapy cycles (OR, 6.015; CI, 1.880-19.248; P=0.0025) and co-administration of an analgesic adjuvant (OR, 3.907; CI, 1.383-11.031; P=0.0101). In conclusion, our study indicates that CIPN will be alleviated by the co-administration of dexamethasone with bortezomib and non-steroidal anti-inflammatory drugs with oxaliplatin.
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Case Reports
Successful dexrazoxane treatment of a potentially severe extravasation of concentrated doxorubicin.
Dexrazoxane is now authorized for the treatment of anthracycline extravasations. Several clinical cases of doxorubicin extravasation treated with dexrazoxane have been reported to date, but detailed cases have not been published. We report a case of a successful dexrazoxane treatment for a potentially severe extravasation of concentrated doxorubicin. ⋯ Dexrazoxane proved to be effective and moderately well tolerated. A dexrazoxane stock in oncological facilities could help to promptly handle emergencies like this. Anthracyclines can be administered using reduced occlusion infusion pumps, but it seems preferable to always administer a free-running infusion to minimize accidents like this one.
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Randomized Controlled Trial
A phase I dose-escalation study of edotecarin (J-107088) combined with infusional 5-fluorouracil and leucovorin in patients with advanced/metastatic solid tumors.
Edotecarin (J-107088), a novel inhibitor of topoisomerase I has an additive effect on colon cell lines (HCT-116) when combined with 5-fluorouracil (5-FU). We conducted a phase I study to determine the maximum tolerated dose and recommended a phase II dose of edotecarin in combination with infusional 5-FU/leucovorin (LV) in patients with advanced solid tumors. Patients and cohorts of three to six patients were sequentially enrolled at progressively higher dose levels of edotecarin administered as a 1-h intravenous (IV) infusion every 2 weeks. ⋯ One confirmed complete response in a patient with hepatocellular carcinoma and seven stable disease responses were achieved in the 14 treated patients. Pharmacokinetic analysis showed that edotecarin achieved and maintained apparent steady-state plasma concentrations during the IV administration in both the cycles. The administration of edotecarin in combination with infusional 5-FU/LV once every 14 days, even without the 5-FU bolus, did not permit adequate time for recovery from neutropenia.
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Meta Analysis
Sorafenib improves the survival of patients with advanced hepatocellular carcinoma: a meta-analysis of randomized trials.
There is no effective systemic therapy for patients with advanced hepatocellular carcinoma (HCC) except liver transplantation. Sorafenib, a multikinase inhibitor, has been shown to significantly increase overall survival (OS) in a randomized, placebo-controlled, phase III trial of patients with HCC (SHARP). The aim of this study was to evaluate the effectiveness of sorafenib for advanced HCC by carrying out a meta-analysis of randomized controlled trials that compared sorafenib-based therapy with other agent-based therapy. ⋯ Sorafenib-based chemotherapy was also associated with a 79% prolongation of TPP (HR = 0.58, 95% CI = 0.49-0.69, P<0.001), and a 37.3% increase in OS (HR = 0.66, 95% CI = 0.55-0.78, P<0.001). Despite significant increases in the frequencies of hand-foot syndrome and diarrhea in patients receiving sorafenib-containing chemotherapy, no significant difference in other toxic events was observed. This meta-analysis suggests that sorafenib-based chemotherapy is superior to placebo-based chemotherapy in terms of TPP and OS without increase in severe toxic effects.