Seminars in Oncology
Volume 33, Supplement 12 , Pages 1-2, December 2006

Introduction

  • David S. Alberts (Guest Editor)

      Affiliations

    • Corresponding Author InformationAddress reprint requests to David S. Alberts, MD, Arizona Cancer Center, 1515 N. Campbell Ave, Tucson, AZ 85274, USA

Arizona Cancer Center, University of Arizona, Tucson, AZ

Article Outline

 

Ovarian cancer has the highest mortality of all cancers of the female reproductive system. This, in part, is because of a lack of early symptoms and proven ovarian cancer screening tests. As a result, ovarian cancer is often diagnosed at an advanced stage, after the cancer has spread beyond the ovary.1 According to cancer statistics published in 2006,2 ovarian cancer accounts for approximately 3% of all cancers in women and is the fifth leading cause of cancer-related death among women in the United States.

The standard therapy regimen for advanced ovarian cancer patients includes surgery followed by a platinum-taxane combination chemotherapy infusion every 3 weeks for six cycles.3 The goal of the initial cytoreductive surgery is to debulk the tumor to the maximum extent possible. Typically, the surgery consists of laparotomy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy. The initial surgery plays a vital role in the therapy regimen because the residual disease after surgery (measured by its largest diameter) is a strong prognostic factor for survival.4 For almost a decade, intravenous combination chemotherapy regimens with cisplatin and paclitaxel have been the standard postoperative treatment for advanced ovarian cancer patients.5 Frequently, such aggressive treatments are associated with increased normal tissue toxicity.3 The clinical impact of such treatment toxicities is profound. Toxicities often interfere with the completion of the treatment schedule, resulting in poor outcomes. There have been several advances in cytoreductive surgery6 and chemotherapy (eg, introduction of carboplatin, topotecan)4, 5 to treat women with advanced ovarian cancer; however, the long-term cure rate is in the range of 20%. The ideal cancer treatment would increase survival and decrease recurrence, while preserving quality of life and causing minimal toxic effects on normal cells.

As early as 1978, direct instillation of chemotherapy into the peritoneal cavity was proposed by Dedrick et al.7 This study clearly showed the pharmacologic advantage of prolonged drug exposure, whereby the tumor is continuously bathing in the drug. With this prolonged exposure, the drug strips away cancer cells layer by layer with each cycle of intraperitoneal (IP) chemotherapy, termed as the “onion-skinning effect.” Phase I8, 9 and II10, 11 data support this approach. More recently, three phase III randomized trials12, 13, 14 have revolutionized this field of chemotherapy delivery. All three trials showed a significant overall survival benefit for patients receiving IP therapy. The magnitude of improvement shown by these trials led to a National Cancer Institute Clinical Announcement15 declaring that the IP route of chemotherapy administration in combination with an intravenous regimen should be given strong consideration for the treatment of women with advanced ovarian cancer because of its improved survival and short-lived and manageable toxicity profile.

In this supplement to Seminars in Oncology, the first article by Dr. Markman discusses the most recent randomized phase III trials, namely SWOG 8501, GOG 104,12 GOG 114,14 and GOG 172.13 These studies evaluated the performance of IP chemotherapy administration. One of the challenges with the IP regimen is the complications associated with the catheter used for chemotherapy administration.16 Additionally, as with many aggressive treatment regimens, IP therapy has associated treatment-related toxicities. Some of these toxicities are treatment-limiting and need special attention. In the second article, Dr. David S. Alberts and Ardie Delforge, RN, discuss clinical approaches to maximize the delivery of IP therapy while minimizing complications. Ways to mitigate drug toxicities with the use of cytoprotectants such as amifostine and prevent infection with the use of agents such as pegfilgrastim are discussed in detail. One of the key steps in propagating the IP therapy regimen as a standard of care for patients with advanced ovarian cancer would be to maintain the overall efficacy of the regimen while improving IP tolerability. To this end, in the final article, Dr. Muggia discusses the role of newer anticancer drugs with less toxicity and their potential in IP therapy regimens. The concluding remarks by Dr. Trimble focus on the role of the National Cancer Institute in disseminating information to the clinical community on the appropriate and effective ways of using IP chemotherapy to improve therapy outcomes in ovarian cancer.

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References 

  1. National Cancer Institute: NCI Clinical Announcement on Intraperitoneal Therapy for Ovarian Cancer. Available at: http://www.cancer.gov/clinicaltrials/developments/IPchemo-digest (accessed Dec 6, 2006)
  2. Jemal A, Siegel R, Ward E, et al. Cancer statistics 2006. CA Cancer J Clin. 2006;56:106–130
  3. Ozols RF, Bundy BN, Greer BE, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage II ovarian cancer: A Gynecologic Oncology Group study. J Clin Oncol. 2003;21:3194–3200
  4. Bristow RE, Tomacruz RS, Armstrong DK, et al. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: A meta-analysis. J Clin Oncol. 2002;20:1248–1259
  5. McGuire WP, Hoskins WJ, Brady MF, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III & IV ovarian cancer. N Engl J Med. 1996;334:1–6
  6. Theodoridis TD, Bontis JN. Laparoscopy and oncology: Where do we stand today?. Ann N Y Acad Sci. 2003;997:282–291
  7. Dedrick R, Myers C, Bungay P, et al. Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep. 1978;62:1–11
  8. Litterst CL, Torres IJ, Arnold S, et al. Absorption of antineoplastic drugs following large-volume ip administration of rats. Cancer Treat Rep. 1982;66:147–155
  9. Los G, Verdegaal EM, Mutsaers PH, et al. Penetration of carboplatin and cisplatin into rat peritoneal tumor nodules after intraperitoneal chemotherapy. Cancer Chemother Pharmacol. 1991;28:159–165
  10. Markman M, Brady MF, Spirtos NM, et al. Phase II trial of intraperitoneal paclitaxel in carcinoma of the ovary, tube, and peritoneum: A Gynecologic Oncology Group Study. J Clin Oncol. 1998;16:2620–2624
  11. Markman M, Reichman B, Hakes T, et al. Responses to second-line cisplatin-based intraperitoneal therapy in ovarian cancer: Influence of a prior response to intravenous cisplatin. J Clin Oncol. 1991;9:1801–1805
  12. Alberts DS, Liu PY, Hannigan EV, et al. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med. 1996;335:1950–1955
  13. Armstrong DK, Bundy B, Wenzel L, et al. Phase III randomized trial of intravenous cisplatin and paclitaxel versus an intensive regimen of intravenous paclitaxel, intraperitoneal cisplatin and intraperitoneal paclitaxel in stage III ovarian cancer: A Gynecologic Oncology Group Study. N Engl J Med. 2006;354:34–43
  14. Markman M, Bundy BN, Alberts DS, et al. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: An intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001;19:1001–1007
  15. National Cancer Institute. NCI Clinical Announcement. Intraperitoneal Chemotherapy for Ovarian Cancer. Available at: http://ctep.cancer.gov/highlights/clin_annc_010506.pdf (accessed July 7, 2006)
  16. Walker JL, Armstrong DK, Huang HQ, et al. Intraperitoneal catheter outcomes in a phase III trial of intravenous versus intraperitoneal chemotherapy in optimal stage III ovarian and primary peritoneal cancer (A Gynecologic Oncology Group study). Gynecol Oncol. 2006;100:27–32

 This activity is supported by an unrestricted educational grant from MedImmune Oncology, Inc, a subsidiary of MedImmune, Inc.

 Dr Alberts has received grant and research support from and serves on the speakers bureau for MedImmune, Inc. He is also a paid consultant for Amgen Inc.

PII: S0093-7754(06)00427-1

doi:10.1053/j.seminoncol.2006.11.005

Seminars in Oncology
Volume 33, Supplement 12 , Pages 1-2, December 2006

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