title: Long term follow-up of patients with recurrent ovarian cancer after Ad p53 gene replacement with SCH 58500.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242-1009, USA. richard-buller@uiowa.edu
authors.forename: Richard E
authors.initials: RE
authors.lastname: Buller
authors.forename: Mark S
authors.initials: MS
authors.lastname: Shahin
authors.forename: Jo Ann
authors.initials: JA
authors.lastname: Horowitz
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Runnebaum
authors.forename: Vikas
authors.initials: V
authors.lastname: Mahavni
authors.forename: Stan
authors.initials: S
authors.lastname: Petrauskas
authors.forename: Rolf
authors.initials: R
authors.lastname: Kreienberg
authors.forename: Beth
authors.initials: B
authors.lastname: Karlan
authors.forename: Dennis
authors.initials: D
authors.lastname: Slamon
authors.forename: Mark
authors.initials: M
authors.lastname: Pegram
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D016190:Carboplatin / Q000627:therapeutic use; D015331:Cohort Studies; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016158:Genes, p53; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy*; D017239:Paclitaxel / Q000627:therapeutic use; D012008:Recurrence; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D016190:Carboplatin; D017239:Paclitaxel