a controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer.

ONYX-015 is an adenovirus with the E1B 55-kDa gene deleted, engineered to selectively replicate in and lyse p53-deficient cancer cells while sparing normal cells. Although ONYX-015 and chemotherapy have demonstrated anti-tumoral activity in patients with recurrent head and neck cancer, disease recurs rapidly with either therapy alone. We undertook a phase II trial of a combination of intratumoral ONYX-015 injection with cisplatin and 5-fluorouracil in patients with recurrent squamous cell cancer of the head and neck. There were substantial objective responses, including a high proportion of complete responses. By 6 months, none of the responding tumors had progressed, whereas all non-injected tumors treated with chemotherapy alone had progressed. The toxic effects that occurred were acceptable. Tumor biopsies obtained after treatment showed tumor-selective viral replication and necrosis induction.

Adenovirus-Mediated Wild-Type p53 Gene Transfer into Head and Neck Cancers.

Mutation of the p53 tumor-suppressor gene is recognized as one of the most common genetic alterations in human malignancy to date (1). Approximately 60% of human tumors are thought to possess mutation at the p53 locus. Transient overexpression of the wild-type p53 gene in various malignancies has been considered a potential molecular intervention strategy (2 -7). This strategy is based on the role that wild-type p53 plays as a tumor-suppressor gene and inducer of cell-cycle arrest and apoptosis (1 ,8-11).

Adenovirus-mediated wild-type p53 gene transfer as a surgical adjuvant in advanced head and neck cancers.

A high incidence of locoregional failure contributes to the poor overall survival rate of around 50% for patients with squamous cell carcinoma of the head and neck (SCCHN). In vitro and in vivo preclinical work with adenovirus-mediated wild-type p53 gene transfer using the recombinant p53 adenovirus (Ad-p53) has shown its promise as a novel intervention strategy for SCCHN. These data have translated into Phase I and Phase II studies of Ad-p53 gene transfer in patients with advanced, locoregionally recurrent SCCHN. The safety and overall patient tolerance of Ad-p53 has been demonstrated. Of 15 resectable but historically noncurable patients in the surgical arm of a Phase I study, 4 patients (27%) remain free of disease, with a median follow-up time of 18.25 months. Surgical and gene transfer-related morbidities were minimal. These results provide preliminary support for the use of Ad-p53 gene transfer as a surgical adjuvant in patients with advanced SCCHN. The implications of our findings for the management of SCCHN in general are discussed.

Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma.

PURPOSE: Standard therapies of head and neck squamous cell carcinoma (HNSCC) often cause profound morbidity and have not significantly improved survival over the last 30 years. Preclinical studies showed that adenoviral vector delivery of the wild-type p53 gene reduced tumor growth in mouse xenograft models. Our purpose was to ascertain the safety and therapeutic potential of adenoviral (Ad)-p53 in advanced HNSCC. PATIENTS AND METHODS: Patients with incurable recurrent local or regionally metastatic HNSCC received multiple intratumoral injections of Ad-p53, either with or without tumor resection. Patients were monitored for adverse events and antiadenoviral antibodies, tumors were monitored for response and p53 expression, and body fluids were analyzed for Ad-p53. RESULTS: Tumors of 33 patients were injected with doses of up to 1 x 10(11) plaque-forming units (pfu). No dose-limiting toxicity or serious adverse events were noted. p53 expression was detected in tumor biopsies despite antibody responses after Ad-p53 injections. Clinical efficacy could be evaluated in 17 patients with nonresectable tumors: two patients showed objective tumor regressions of greater than 50%, six patients showed stable disease for up to 3.5 months, and nine patients showed progressive disease. One resectable patient was considered a complete pathologic response. Ad-p53 was detected in blood and urine in a dose-dependent fashion, and in sputum. CONCLUSION: Patients were safely injected intratumorally with Ad-p53. Objective antitumor activity was detected in several patients. The infectious Ad-p53 in body fluids was asymptomatic, and suggests that systemic or regional treatment may be tolerable. These results suggest the further investigation of Ad-p53 as a therapeutic agent for patients with HNSCC.

Prevention of central venous catheter-related infections by using maximal sterile barrier precautions during insertion.

OBJECTIVE: In many hospitals, the only sterile precautions used during the insertion of a nontunneled central venous catheter are sterile gloves and small sterile drapes. We investigated whether the use of maximal sterile barrier (consisting of mask, cap, sterile gloves, gown, and large drape) would lower the risk of acquiring catheter-related infections. DESIGN: Prospective randomized trial. SETTING: A 500-bed cancer referral center. METHODS: We randomized patients to have their nontunneled central catheter inserted under maximal sterile barrier precautions or control precautions (sterile gloves and small drape only). All patients were followed for 3 months postinsertion or until the catheter was removed, whichever came first. Catheter-related infections were diagnosed by quantitative catheter cultures and/or simultaneous quantitative blood cultures. RESULTS: The 176 patients whose catheters were inserted by using maximal sterile barrier precautions were comparable to the 167 control patients in underlying disease, degree of immuno-suppression, therapeutic interventions, and catheter risk factors for infections (duration and site of catheterization, number of catheter lumen, catheter insertion difficulty, reason for catheter removal). There were a total of four catheter infections in the test group and 12 in the control group (P = 0.03, chi-square test). The catheter-related septicemia rate was 6.3 times higher in the control group (P = 0.06, Fisher's exact test). Most (67%) of the catheter infections in the control group occurred during the first 2 months after insertion, whereas 25% of the catheter infections in the maximal sterile precautions group occurred during the same period (P < 0.01, Fisher's exact test). Cost-benefit analysis showed the use of such precautions to be highly cost-effective. CONCLUSION: Maximal sterile barrier precautions during the insertion of nontunneled catheters reduce the risk of catheter infection. This practice is cost-effective and is consistent with the practice of universal precautions during an invasive procedure.

Vascular access devices--management of common complications.

Developments in vascular access technology, along with advances in therapy, have created specific challenges for the intravenous nurse caring for patients with indwelling vascular access devices. The nurse clinician must be aware of clinical and technical complications that may occur, as well as the nursing management of those complications.