¹Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242-1009, USA

²Schering-Plough Research Institute, Kenilworth, New Jersey, USA

³University of Freiburg, Freiburg, Germany

⁴University of Ulm, Ulm, Germany

⁵University of California, Los Angeles, California, USA

Correspondence to: Dr Richard E Buller, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, 200 Hawkins Drive ¾ #4630 JCP, Iowa City, IA 52242-1009, USA. E-mail: richard-buller@uiowa.edu

^†Presented in part at the 9th International Conference on Gene Therapy of Cancer, San Diego, CA December 7-9, 2000.

Objective: We have previously reported the safety, efficient gene transfer, and favorable CA125 responses of individuals with recurrent ovarian cancer treated by p53 gene replacement with the adenoviral vector SCH 58500. The purpose of the present investigation was to evaluate the long-term follow-up of these heavily pretreated patients subsequent to SCH 58500 dosing. Methods: Patients (n=36) were treated with either single-dose SCH 58500 in the phase I study or with multiple doses (MD) of SCH 58500 over multiple cycles in combination of platinum-based chemotherapy in the phase I/II portion of the study. Five patients were initially treated in the single-dose group and re-enrolled in the MD group. The MD group was evaluated both without the re-enrolled patients as MD1 (n=19), and as MD2 (n=24), which included them. Patients who were only treated on the single-dose arm were designated as SD (n=12). Most patients received additional chemotherapy at the discretion of their physicians on completion of the trial. The current analysis is a retrospective sequential cohort survival analysis. Results: The first patient was treated in March 1997 and the last patient completed SCH 58500 in September 1998. There was no difference in age at diagnosis, Karnofsky performance status, interval between diagnosis to SCH 58500, prior cycles or regimen of chemotherapy, platinum-free interval, percent platinum refractory patients, pretreatment CA125, or largest tumor volume between groups. Both MD groups had a slightly longer chemotherapy-free interval before SCH 58500 than the SD group. Median survival of individuals who received MD SCH 58500 with chemotherapy was 12-13.0 months, compared to only 5 months for those treated with SD SCH 58500. There are 10 long-term survivors more than 20 months after MD treatment for recurrent disease compared to only 2 long-term survivors after SD SCH 58500. Conclusion: The 12- to 13.0-month median survival in a heavily pretreated population with recurrent ovarian cancer compares favorably to the 16-month median survival for individuals treated with paclitaxel at the time of initial recurrence of this disease and is more than double the 5-month survival seen with palliative radiotherapy or paclitaxel failure. These data suggest that further study of SCH58500 is clearly indicated. Cancer Gene Therapy (2002) 9, 567-572 doi:10.1038/sj.cgt.7700473

p53; gene therapy; ovarian cancer survival; adenovirus