Management of hand-foot syndrome induced by capecitabine.

INTRODUCTION: Capecitabine (Xeloda) is a systemic prodrug of 5-fluorouracil (5-FU), which is administered in an oral formulation. Hand-foot syndrome (HFS) has proven to be a chronic dose-limiting toxicity of capecitabine, leading to significant morbidity in patients receiving this agent. The purpose of this review is to define the pathophysiology, risk factors, incidence and management of capecitabine-induced HFS. METHODS: Literature for this review article was collected from the following databases: PubMed, CINAHL, and the proceedings of the American Society of Clinical Oncology (ASCO) confined to the years 1995-2006. The following key terms were used in the search: hand-foot syndrome, palmar-plantar erythrodysesthesia, capecitabine, Xeloda, colorectal cancer, and metastatic breast cancer. RESULTS: HFS associated with capecitabine is a serious dose-limiting toxicity. Incidence of grade 3/4 toxicity is of extreme significance, and introduces the need for dose reductions and/or interruptions in capecitabine therapy. Drug-related therapies studied include topical emollients and creams, systemic and topical corticosteroids, nicotine patch, vitamin E, pyridoxine, and COX-2 inhibitors. However, due to the lack of randomized, controlled trials with these therapies, the current mainstay of treatment for the management of this toxicity is interruption of therapy and, if necessary, dose reduction. CONCLUSION: Treatment interruption or dose reduction remain the only methods shown to effectively manage HFS, but supportive measures to reduce pain and discomfort and prevent secondary infection are very important. Many other prophylactic and treatment strategies have been investigated, with pyridoxine and COX-2 inhibitors being the most promising in case reports and retrospective studies; therefore, prospective, randomized, controlled trials are needed to prove their efficacy.

Pemetrexed, a novel antifolate therapeutic alternative for cancer chemotherapy.

Pemetrexed is a newly approved antifolate agent for the treatment of malignant pleural mesothelioma (MPM) and metastatic non-small cell lung cancer (NSCLC). We performed a PubMed/MEDLINE database search to identify relevant literature from January 1966-April 2005. Bibliographies from identified references were searched as well, as were abstracts from the 2004 and 2005 proceedings of the American Society of Clinical Oncology. We discuss the pharmacology of pemetrexed, describing its mechanism of action and comparing it with methotrexate. The pharmacokinetics and pharmacodynamics of pemetrexed are described to provide a better understanding of the properties of this drug. Therapeutic uses are assessed, beginning with the approved indications of MPM and NSCLC. However, pemetrexed has been studied in numerous phase II trials for other types of solid malignancies, and completed trials are reviewed. Data on adverse effects and drug interactions are also provided. Finally, dosing and administration are reviewed, including appropriate premedication. Premedication, including administration of steroids and vitamin supplements, has been shown to decrease the frequency and severity of pemetrexed toxicities. Pemetrexed should be used as a standard of care for unresectable MPM and recurrent metastatic NSCLC.

Bortezomib treatment for multiple myeloma.

OBJECTIVE: To review the pharmacology, pharmacokinetics, and place of bortezomib in the therapy of multiple myeloma (MM). DATA SOURCES: A MEDLINE search was conducted (1985-May 2003). Meeting abstracts, bibliographies from identified articles, and the package insert were also used. Search terms were bortezomib, multiple myeloma, Velcade, PS-341, LDP-341, MLNM341, and proteasome inhibitor. STUDY SELECTION AND DATA EXTRACTION: All published information relevant to the clinical activity of bortezomib in MM was considered. All human clinical studies, with an emphasis on Phase II trials, were selected. DATA SYNTHESIS: Current therapy for MM yields significant, although temporary, responses. Bortezomib is a novel anticancer agent with significant activity in relapsed and refractory MM. CONCLUSIONS: Although the clinical trial data are incomplete, bortezomib offers a novel therapeutic modality for patients with MM who would otherwise have few options.

A review of clinical experience with paclitaxel extravasations.

Paclitaxel is a novel anti-neoplastic with a wide spectrum of activity in various malignant tumors. Extravasation of chemotherapy drugs is a widely feared adverse event in oncology patients. A Medline search between 1966 and October 2002 was conducted to identify case reports related to paclitaxel extravasation, as well as a bibliography screening of identified papers. The goal of this work is to summarize the available reports of paclitaxel extravasation and assess its vesicant potential. Additionally, management strategies for extravasation events due to paclitaxel are assessed.

Implementation and results of a test dose program with taxanes.

PURPOSE: A pilot taxane test-dose policy was developed and implemented to determine whether the severity of patient hypersensitivity reaction and drug waste would be reduced. PATIENTS AND METHODS: Data from 206 eligible cancer patients undergoing first-dose taxane chemotherapy were analyzed. The severity of hypersensitivity reactions before and after the implementation of taxane test dose was graded (scale 1-4) and analyzed for statistical differences between groups. Average drug wastage was calculated before and after program initiation. RESULTS: Twenty-two of 206 patients (10.7%) experienced a hypersensitivity reaction. The mean hypersensitivity reaction severity for reacting patients who did not receive a test dose (N = 12) was 3.3, and for those who were given a test dose (N = 10), it was 1.5. Only one of five patients who experienced a hypersensitivity reaction that required hospitalization was from the test-dose group. The value of drug alone wasted before test-dose utilization was about $1794 per reacting patient, and the use of taxane test doses saved approximately $1784 per reacting individual. This represented more than a $178 savings for every patient receiving a taxane for the first time. These figures do not include resuscitation, hospital, and other subsequent other costs associated with morbidity. CONCLUSIONS: Implementation of a taxane test-dose policy significantly reduced hypersensitivity reaction severity, drug wastage, and hospitalizations.