Phase Ia/Ib trial of bispecific antibody MDX-210 in patients with advanced breast or ovarian cancer that overexpresses the proto-oncogene HER-2/neu.

PURPOSE: MDX-210 is a bispecific antibody that binds simultaneously to type I Fc receptors for immunoglobulin G (IgG) (Fc gamma RI) and to the HER-2/neu oncogene protein product. MDX-210 effectively directs Fc gamma RI-positive effector cells such as monocytes and macrophages to phagocytose or kill tumor cells that overexpress HER-2/neu. The goals of this phase Ia/Ib trial were to determine the maximum-tolerated dose (MTD) and/or the optimal biologic dose (OBD) of MDX-210. PATIENTS AND METHODS: Patients with advanced breast or ovarian cancer that overexpressed HER-2/neu were eligible for treatment. Cohorts of three patients received a single intravenous (IV) infusion of MDX-210 at increasing dose levels from 0.35 to 10.0 mg/m2. RESULTS: Treatment was well tolerated, with most patients experiencing transient grade 1 to 2 fevers, malaise, and hypotension only. Two patients experienced transient grade 3 hypotension at 10.0 mg/m2. Transient monocytopenia and lymphopenia developed at 1 to 2 hours, but no other hematologic changes were observed. Doses of MDX-210 > or = 3.5 mg/m2 saturated > or = 80% of monocyte Fc gamma RI and produced peak plasma concentrations > or = 1 microgram/mL, which is greater than the concentration for optimal monocyte/macrophage activation in vitro. Elevated plasma levels of the monocyte products tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and neopterin were observed with maximal levels at doses > or = 7.0 mg/m2. Localization of MDX-210 in tumor tissue was demonstrated in two patients. One partial and one mixed tumor response were observed among 10 assessable patients. CONCLUSION: MDX-210 is immunologically active at well-tolerated doses. The MTD and OBD is 7 to 10 mg/m2.

Capecitabine: nursing implications of a new oral chemotherapeutic agent.

PURPOSE/OBJECTIVES: To describe the new oral chemotherapeutic agent capecitabine (Xeloda, Roche Laboratories Inc., Nutley, NJ) and key concepts driving its development and to delineate the nursing impact of patient-administered, home-based chemotherapies. DATA SOURCES: Published papers, investigational materials, package inserts, and clinical experience. DATA SYNTHESIS: Capecitabine recently was approved to treat metastatic breast cancer refractory to paclitaxel and anthracycline-containing regimens. Efficacy has been demonstrated. However, although the current regimen is well-tolerated, > or = 40% of patients require dose modification because of grade 2 or greater toxicity, usually hand-foot syndrome or gastrointestinal symptoms. CONCLUSIONS: Capecitabine frees nurses from infusion-related workload, allowing and demanding a new type and level of patient education. Such education emphasizes compliance with the treatment plan and prevention, timely recognition, and management of toxicities. These practice changes also challenge nurses to advocate for reimbursement of educational practices. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses will play more of a central role as use of patient-administered, home-based therapies increases. Nurses must enhance their patient-education and telephone symptom-management skills and help to secure reimbursement for such activities.