Treatment of breast cancer

Osteosarcoma is the most common malignant primary bone tumor in children and adolescents. Current optimal treatment for osteosarcoma consists of multi-agent chemotherapy and aggressive surgical resection of all sites of disease involvement. The current national and international cooperative trial for patients with newly diagnosed osteosarcoma builds upon the backbone of cisplatin, doxorubicin, and methotrexate. This protocol is designed to clarify whether (i) the addition of ifosfamide and etoposide to postoperative chemotherapy with cisplatin, doxorubicin, and methotrexate improves the event-free survival and overall survival for patients with resectable osteosarcoma and a poor histologic response to 10 weeks of preoperative chemotherapy; and (ii) the addition of pegylated interferon-α-2b as maintenance therapy after postoperative chemotherapy with cisplatin, doxorubicin, and methotrexate improves the event-free survival and overall survival for patients with resectable osteosarcoma and a good histologic response to 10 weeks of preoperative chemotherapy. However, the optimal treatment strategy (or strategies) for patients with relapsed or metastatic disease has yet to be defined. This remains one of the persistent challenges in the treatment of osteosarcoma. Recent therapeutic advances have focused on circumventing chemotherapy resistance mechanisms, incorporation of non-classical agents into upfront therapy, targeting of the tumor micro-environment, and investigating the role of novel delivery mechanisms. In patients with localized disease the 5-year survival rate is at least 70%; patients with metastatic or recurrent disease have <20% chance of long-term survival despite aggressive therapies. These figures have changed little in the past 2 decades. This review focuses on the current therapy for osteosarcoma, and highlights emerging strategies that will hopefully change the outlook for patients with this disease.

Therapy for osteosarcoma: where do we go from here?

Cancer of the stomach.

Although contemporary treatments cure more than 80% of children with acute lymphoblastic leukaemia (ALL), some patients require intensive treatment and many patients still develop serious acute and late complications owing to the side effects of the treatments. Furthermore, the survival rate for adults with ALL remains below 40%. Therefore, new treatment strategies are needed to improve not only the cure rate but also the quality of life of these patients. Here, we discuss emerging new treatments that might improve the clinical outcome of patients with ALL. These include new formulations of existing chemotherapeutic agents, new antimetabolites and nucleoside analogues, monoclonal antibodies against leukaemia-associated antigens, and molecular therapies that target genetic abnormalities of the leukaemic cells and their affected signalling pathways.

New therapeutic strategies for the treatment of acute lymphoblastic leukaemia

Complications of the COX-2 Inhibitors Parecoxib and Valdecoxib After Cardiac Surgery

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 capecitabin...

Management of hand-foot syndrome induced by capecitabine.

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.

Pemetrexed, a Novel Antifolate Therapeutic Alternative for Cancer Chemotherapy

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.

A review of clinical experience with paclitaxel extravasations.

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.

Brad L Stanford

Papers

Management of hand-foot syndrome induced by capecitabine.

Pemetrexed, a Novel Antifolate Therapeutic Alternative for Cancer Chemotherapy

A review of clinical experience with paclitaxel extravasations.

Bortezomib Treatment for Multiple Myeloma

Opioid pharmacotherapy in terminal disease.