Phase I study of anti--epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer.

PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of a chimeric anti-epidermal growth factor receptor monoclonal antibody, cetuximab, in combination with radiation therapy (RT) in patients with advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: We treated 16 patients in five successive treatment schedules. A standard dose escalation procedure was used; three patients entered onto the study at each dose level of cetuximab received conventional RT (70 Gy, 2 Gy/d), and the final three patients received hyperfractionated RT (76.8 Gy, 1.2 Gy bid). Cetuximab was delivered as a loading dose of 100 to 500 mg/m(2), followed by weekly infusions of 100 to 250 mg/m(2) for 7 to 8 weeks. Circulating levels of cetuximab during therapy were determined using a biomolecular interaction analysis core instrument. Human antichimeric antibody response was evaluated with a double-antigen radiometric assay. The recommended phase II/III dose was defined as the optimal cetuximab dose level based on the pharmacologic parameters and adverse events. RESULTS: The most commonly reported adverse events were fever, asthenia, transaminase elevation, nausea, and skin toxicities (grade 1 to 2 in most patients). Skin toxicity outside of the RT field was not strictly dose-dependent; however, grade 2 or higher events were observed in patients treated with higher dose regimens. There was one grade 4 allergic reaction. Most acute adverse effects were associated with RT (xerostomia, mucositis, and local skin toxicity). No antibodies against cetuximab were detected. All patients achieved an objective response (13 complete and two partial remissions). CONCLUSION: Cetuximab can be safely administered with RT. The recommended dose for phase II/III studies is a loading dose of 400 to 500 mg/m(2) and a maintenance weekly dose of 250 mg/m(2).

Effects of pelvic rotation and needle angle on pubic arch interference during transperineal prostate implants.

PURPOSE: Pubic arch interference due to an enlarged prostate gland or a narrow pubic arch is often a limiting factor in adequate prostate coverage during transperineal brachytherapy. The purpose of this study was to evaluate the effects of both pelvic rotation and needle angles on pubic arch interference using CT-based 3-D information. METHODS AND MATERIALS: Seven patients had CT imaging in both supine and lithotomy positions and 3-D treatment planning was performed with three needle angles (20 downward, 0, 20 upward). The pubic arch interference was then measured and comparisons were made for each needle trajectory and pelvic position. RESULTS: Increasing pelvic rotation from supine to lithotomy position shows less pubic arch interference. Directing the needle tip upward shows less pubic arch interference in both supine and lithotomy positions when compared to needle tips directed downward. CONCLUSIONS: Both pelvic position and needle angles are important factors influencing pubic arch interference. Preplanning CT-based 3-D information may assist for individualized treatment planning in patients with a significant bony interference, thus avoiding pubic arch interference during implantation.

Primary lymphoma of the breast: breast mass as an initial symptom.

Seven patients with lymphoma presenting as a breast mass are described. Four of them fulfilled the criteria for primary lymphoma of the breast, and three had evidence of secondary lymphoma of the breast. Two patients were diagnosed with stage IAE disease, and both did well with local treatment with or without chemotherapy. Two patients were diagnosed with stage IIAE disease; both had distant failure without systemic chemotherapy. Although local treatment is curative in a subset of stage IAE disease, combination chemotherapy followed by local radiation is a safer approach. For stage IIAE disease, combination chemotherapy and local radiation therapy should be considered.