Longitudinal changes in serum HGF, IL-6, IL-8, and VEGF were detected with treatment response, relapse, or complications in individual patients and were associated with survival, with HGF showing the strongest relationship with survival. HGF, IL-6, IL-8, and VEGF merit investigation as markers of response, survival, and recurrence in larger prospective studies.

This study evaluated the safety and efficacy of a single administration of a recombinant adenovirus encoding human aquaporin-1 (AdhAQP1) to the parotid glands of adult rhesus monkeys. In anticipation of possible clinical use of this virus to correct irradiation damage to salivary glands, AdhAQP1 was administered (at either 2 ϫ 10 9 or 1 ϫ 10 8 plaque-forming units/gland) intraductally to irradiated glands and to their contralateral nonirradiated glands. Radiation (single dose, 10 Gy) significantly reduced salivary flow in exposed glands. Virus administration resulted in gene transfer to irradiated and nonirradiated glands and was without untoward local (salivary) or systemic (sera chemistry, complete blood count) effects in all animals. However, the effect of AdhAQP1 administration varied and did not result in a consistent positive effect on salivary flow rates for all animals under these experimental conditions. We conclude that a single adenoviral-mediated gene transfer to primate salivary glands is well-tolerated, although its functional utility in enhancing fluid secretion from irradiated parotid glands is inconsistent.

Purpose-To report the long-term outcomes and toxicity of a regimen of infusional paclitaxel delivered concurrently with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). 1995 and 1999, 35 patients with non-metastatic stage III or IV SCCHN were treated with 3 cycles of paclitaxel as a 120-hour continuous infusion beginning days 1, 21, and 42 concurrent with radiation. The initial 16 patients received 105 mg/m 2 /cycle, and the subsequent 19 patients received 120 mg/m 2 /cycle. External beam radiation was delivered to 70.2-72 Gy in 5 fractions per week. Patients were followed to evaluate disease outcomes and the late toxicity of this regimen. Methods-BetweenResults-Median follow-up for all patients is 56.5 months. The median survival was 56.5 months and the median time to local recurrence was not reached. Fifteen patients (43%) developed hypothyroidism. Eleven of the 33 patients who underwent percutaneous endoscopic gastrostomy tube (PEG) placement were PEG-dependent until death or last follow-up. Five patients (14%) required a tracheostomy until death, while 3 patients (9%) suffered from severe esophageal stricture. *corresponding author: 10 CRC, B2-3500, NCI, NIH, Bethesda, MD 20892, (301) 496-5457, E-mail: citrind@mail.nih.gov. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conflict of Interest:The authors report no conflicts of interest.This work was presented in part at the American Society of Therapeutic Radiology and Oncology in 2007. All evaluated long term survivors exhibited salivary hypofunction. Fibrosis in the radiation field occurred in 24 patients (69%). NIH Public AccessConclusion-Concurrent chemo-radiation therapy with a 120-hour infusion of paclitaxel provides long-term local control and survival in patients with SCCHN.Xerostomia, hypothyroidism, esophageal and pharyngeal complications, and subcutaneous fibrosis were common long-term toxicities; however, the vast majority of toxicities were grade 1 or 2.

Background: Otologic structures are often con· tained within head and neck cancer radiation treatment ports. The dosimetry to otologic structures has not been routinely analyzed and radiation treatment planning does not currently attempt to specifically avoid the inner ear structures when dosimetry is calculated. Recent studies demonstrate that up to 30o/ o of patients experie~e sensorineural hearing loss on multimodality tlierapy with cisplatin and radiation. Methods: In the current case series, radiation dosimetry to otologic structures was calculated from computed tomogram treatment plans on patients. Fifteen nasopharyngeal, oral cavity, oropharyngeal, and hypopharyngeal cancer patients were analyzed. Results: Between 8% and 102% of the total dose is delivered to the petrous bone/cochlea, with 4of15 patients getting more than 50% of the dose to at least one cochlea. The mastoid air cells received between 3% and 75% of the total dose, with higher doses being delivered to pa· tients with bulky high neck metastases or nasopharyngeal tumors. The eustachian tubes received between 2% and 102% of the total dose, with 10 of 15 patients receiving more than 50o/o of the dose to this anatomic site. Conclusion: We conclude that the cochlea and eustachian tubes receive significant radiation during treatment, particularly in nasopharyngeal cancer patients. Careful design of radiation treatment ports may allow for the reduction of radiation to hearing structures.

Paclitaxel administered as a 120-hour continuous infusion in combination with radiotherapy is a feasible and promising treatment for patients with advanced HNSCC.

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IP dFdC was well tolerated, and no significant toxicities were noted. The rapid decrease in peritoneal dFdC concentrations and low concentrations of IP dFdU imply almost total absorption of IP-administered dFdC. Little, if any, dFdC could be detected in plasma, but the steady-state plasma dFdU concentrations also imply absorption and inactivation of virtually all IP-administered dFdC. These findings are consistent with the known high CL(tb) and low incidence of local toxicity of dFdC and argue for its further evaluation as a drug for IP therapy.

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