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. 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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Markman M, Hakes T, Reichman B et al. Ifosfamide and mesna in previously treated advanced epithelial ovarian cancer: activity in platinum-resistant disease J Clin Oncol 1992 10: 243–248
Tenbokkel Huinink W, Gore M, Carmichael J et al. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer J Clin Oncol 1997 15: 2183–2193
Israel VP, Garcia AA, Roman L et al. Phase II study of liposomal doxorubicin in advanced gynecologic cancers Gynecol Oncol 2000 78: 143–147
Thigpen JT, Blessing JA, Ball H et al. Phase II trial of paclitaxel in patients with progressive ovarian carcinoma after platinum-based chemotherapy: a gynecologic oncology group study J Clin Oncol 1994 12: 1748–1753
Aunoble B, Sanches R, Didier E et al. Major oncogenes and tumor suppressor genes involved in epithelial ovarian cancer Int J Oncol 2000 16: 567–576
Lynch HT, Casey MJ, Lynch J et al. Genetics and ovarian carcinoma Semin Oncol 1998 25: 265–280
Griffiths CT . Surgical resection of tumor bulk in the primary treatment of ovarian carcinoma Natl Cancer Inst Monogr 1975 42: 101–104
Hoskins WJ, Rubin SC, Dulaney E et al. Influence of secondary cytoreduction at the time of second-look laparotomy on the survival of patients with epithelial ovarian carcinoma Gynecol Oncol 1989 34: 365–372
Hoskins WJ, McGuire WP, Brady MF et al. The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma Am J Obstet Gynecol 1994 170: 974–979
Jänicke F, Hölscher M, Juhn W et al. Radical surgical procedure improves survival time in patients with recurrent ovarian cancer Cancer 1992 70: 2129–2136
Sood AK, Sorosky J, Dolan M et al. Distant metastases in ovarian cancer: why do they occur? Clin Cancer Res 1999 5: 2485–2490
Geisler J, Geisler H . Brain metastases in epithelial ovarian carcinoma Gynecol Oncol 1995 57: 246–249
Shahin MS, Hughes JH, Sood AK et al. The prognostic significance of p53 tumor suppressor gene alterations in ovarian carcinoma Cancer 2000 89: 2006–2017
Buller RE, Runnebaum IB, Karlan B et al. A phase I/II trial of rAd/p53 (SCH 58500) gene replacement in recurrent ovarian cancer Cancer Gene Ther 2002 9: 553–566
Wills KN, Maneval DC, Menzel P et al. Development and characterization of recombinant adenoviruses encoding human p53 for gene therapy of cancer Hum Gene Ther 1994 5: 1079–1088
Markman M, Iseminger KA, Hatch KD et al. Tamoxifen in platinum-refractory ovarian cancer: a gynecologic oncology group ancillary report Gynecol Oncol 1996 62: 4–6
Gershenson DM, Kavanagh JJ, Copeland LJ et al. Re-treatment of patients with recurrent epithelial ovarian cancer with cisplatin-based chemotherapy Obstet Gynecol 1989 73: 798–802
Gore ME, Fryatt I, Wiltshaw E et al. Treatment of relapsed carcinoma of the ovary with cisplatin or carboplatin following initial treatment with these compounds Gynecol Oncol 1990 36: 207–211
van der Burg MEL, Hoff AM, van Lent M et al. Carboplatin and cyclophosphamide salvage therapy for ovarian cancer patients relapsing after cisplatin combination chemotherapy Eur J Cancer 1991 27: 250–253
Vergote I, Himmelman A, Frankendal B et al. Hexamethylmelamine as second-line therapy in platin-resistant ovarian cancer Gynecol Oncol 1992 47: 282–286
Rosen GF, Lurain JR, Newton M . Hexamethylmelamine in ovarian cancer after failure of cisplatin-based multiple-agent chemotherapy Gynecol Oncol 1987 27: 173–179
Markman M, Rothman R, Hakes T et al. Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin J Clin Oncol 1991 9: 389–393
Eisenhauer EA, Huinink WW ten Bokkel, Swenerton KD et al. European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: High-dose versus low-dose and long versus short infusion J Clin Oncol 1994 12: 2654–2666
Einzig AI, Wiernik PH, Sasloff J et al. Phase II study and long-term follow-up of patients treated with taxol for advanced ovarian adenocarcinoma J Clin Oncol 1992 10: 1748–1753
Corn BW, Lanciano RM, Boente M et al. Effective radiotherapeutic palliation after chemotherapy failure Cancer 1994 74: 2979–2983
Buller RE, Skilling JS, Sood AK et al. Field cancerization: why late “recurrent” ovarian cancer is not recurrent Am J Obstet Gynecol 1998 178: 641–649
Buller RE, Shahin M, Karlan B et al. Multidose intraperitoneal (IP) rad/p53 (SCH 58500) gene replacement combined with chemotherapy in heavily pretreated recurrent ovarian cancer is associated with prolonged survival Proc Am Soc Clin Oncol 2001 20: 262a
Author information
Authors and Affiliations
Corresponding author
Additional information
Presented in part at the 9th International Conference on Gene Therapy of Cancer, San Diego, CA December 7–9, 2000.
Rights and permissions
About this article
Cite this article
Buller, R., Shahin, M., Horowitz, J. et al. Long term follow-up of patients with recurrent ovarian cancer after Ad p53 gene replacement with SCH 58500. Cancer Gene Ther 9, 567–572 (2002). https://doi.org/10.1038/sj.cgt.7700473
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.cgt.7700473
Keywords
This article is cited by
-
Understanding and addressing barriers to successful adenovirus-based virotherapy for ovarian cancer
Cancer Gene Therapy (2021)
-
Genetik des Ovarialkarzinoms
Der Gynäkologe (2013)
-
Biological activities of a recombinant adenovirus p53 (SCH 58500) administered by hepatic arterial infusion in a Phase 1 colorectal cancer trial
Cancer Gene Therapy (2006)
-
Gene therapy for ovarian cancer
Current Oncology Reports (2006)
-
Cooperative effect of adenoviral p53 gene therapy and standard chemotherapy in ovarian cancer cells independent of the endogenous p53 status
Cancer Gene Therapy (2004)