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Purpose A Phase l trial of intravesical recombinant adenovirus-mediated interferon-α2b gene therapy (rAd-IFNα) formulated with the excipient SCH Syn3 was conducted in patients with non-muscle invasive bladder cancer (NMIBC) who recurred after Bacillus Calmette-Guerin (BCG). The primary objective was to determine the safety of rAd-IFNα/Syn3; secondary endpoints were to demonstrate effective rAd-IFNα gene expression and preliminary evidence of clinical activity at three months. Patients and Methods Seventeen patients with recurrent NMIBC after BCG were enrolled. A single treatment of rAd-IFNα (3×109 to 3×1011 particles/mL) formulated with the excipient Syn3 was administered. Patient safety was evaluated for ≥12 weeks. Efficacy of gene transfer was determined by urine IFNα protein concentrations. Preliminary drug efficacy was determined at 3 months. Results Intravesical rAd-IFNα/Syn3 was well tolerated as no dose limiting toxicity (DLT) was encountered. Urgency was the most common adverse event and all were grade 1 or 2. rAd-IFNα DNA was not detected in the blood, however, transient low serum IFNα and Syn3 levels were measured. High and prolonged dose-related urine IFNα levels were achieved with the initial treatment. Of the 14 patients treated at doses ≥ 1010 particles/mL with detectable urine IFNα, 6 (43%) experienced a complete response at 3 months and 2 remained disease free at 29.0 and 39.2 months respectively. Conclusion Intravesical rAd-IFNα/Syn3 was well tolerated with no DLT encountered. Dose dependent urinary IFNα concentrations confirmed efficient gene transfer and expression. Intravesical rAd-IFNα/Syn3 demonstrated promising clinical activity in NMIBC recurring after BCG.

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Background The nose is particularly vulnerable to cutaneous malignancies, making it the most common location for presentation. Recurrence of these cutaneous lesions is not uncommon, often compromising the timing of nasal restoration. It is the purpose of this report to reexamine the safety of primary nasal reconstruction in selected patients. Methods Seventy‐one patients who underwent nasal reconstruction at The University of Texas M. D. Anderson Cancer Center between 1987 and 1995 were retrospectively reviewed. There were 35 men and 36 women with an average age of 60 years. All nasal reconstructions were performed for defects secondary to malignancies. Basal cell carcinoma was the most common lesion (n = 49), followed by squamous cell carcinoma (n = 10) and melanoma (n = 7), with five additional variable malignancies. The most common location of the cutaneous lesions was the nasal dorsum, and the forehead flap was the most common adjacent tissue used for reconstruction. Immediate reconstruction was performed for 42 of the basal cell carcinomas, 6 of the squamous cell carcinomas, 6 melanomas, and 3 other lesions. Delayed restoration was performed for 7 basal cell carcinomas, 4 squamous cell carcinomas, 1 melanoma, and 2 additional lesions. The average time between surgical extirpation and the start of nasal reconstruction was 8.2 months for basal cell carcinoma, 29 months for squamous cell carcinoma, and 10 months for melanoma. Results Twenty‐six recurrent lesions were identified at an average of 36 months after extirpation. Despite these numbers, only three recurred after nasal reconstruction at our institution. Follow‐up averaged 41 months, with none less than 1 year. Seventy patients are still alive with no evidence of disease. Conclusion Primary reconstruction is safe in selected patients. Surgical delay in reconstruction should be considered if margins are questionable, the pathology is determined to be aggressive, if there is perineural or deep bony invasion, or if postoperative radiotherapy is to be initiated. Nasal reconstruction ultimately is based upon a complex series of issues but can be performed with few complications in an effort to restore self‐image. © 1997 John Wiley & Sons, Inc. Head Neck 19: 182–187, 1997.

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