Hot Topics in Ovarian Cancer

Intraperitoneal delivery of chemotherapy in ovarian cancer has been shown to be effective in front-line treatment. Three large, randomized studies investigating the intraperitoneal delivery of cisplatin, carboplatin or paclitaxel in combination with intravenous delivery have shown a survival advantage for patients treated with intraperitoneal chemotherapy.

Hyperthermia, on its own, is tumoricidal. Studies of hyperthermia in combination with chemotherapy have demonstrated increased DNA cross-linking and increased DNA adduct formation. Furthermore, cisplatin has been shown to penetrate more deeply into tumor implants when delivered intraperitoneally with hyperthermia.

The possible synergy between hyperthermia and chemotherapy agents has sparked clinical trials utilizing this combination in many disease types, such as gastric cancer, malignant mesothelioma, appendix cancer, and colorectal cancer, showing promising results.

Ovarian carcinoma is a logical target for directed intraperitoneal therapy in combination with heat and there are reports of clinical studies looking at hyperthermic intraperitoneal chemotherapy following surgical debulking in this disease, however, they are few and contain relatively small numbers of patients. We have also started using this treatment program here at the Johns Hopkins Medical Institutions for recurrent ovarian cancer with favorable results.

To find out more about this program and to see if you qualify as a candidate for this procedure, email us at: ovariancancercenter@jhmi.edu.

Here is recent literature with regards to HIPEC:

Hyperthermic intraperitoneal chemotherapy in conjunction with surgery for the treatment of recurrent ovarian carcinoma.

Division of Gynecologic Oncology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA. cwhelm@uoflobgyn.com

OBJECTIVES: To review experience of secondary surgical cytoreduction (SSC) with hyperthermic intraperitoneal chemotherapy (IPHC). METHODS: Eligible patients with ovarian cancer in whom pre-operative evaluation indicated that there was a good possibility that disease could be resected to < or = 5 mm underwent surgery followed by intraperitoneal perfusion of cisplatin (100 mg/m2) or mitomycin C (30-40 mg total dose) heated to 41-43 degrees C (105.8-109.4 degrees F) for 90 min. Data for analysis were extracted from retrospective chart review. RESULTS: Eighteen patients underwent surgery and IPHC between 9/02 and 3/05. Characteristics were median age 64 (37-77) years, mean prior laparotomies 1.4 (0-3), mean chemotherapy regimens 3.2 (0-7), mean time from initial therapy to IPHC 30.6 (1-88) months. Original histology: papillary serous 12, poorly differentiated adenocarcinoma 1, serous low malignant potential 2, mucinous 1 and mixed subtypes 2. 13 had recurrent disease and 5 had persistent disease following front-line therapy. 15 received cisplatin and 3 mitomycin C. The mean duration of surgery was 9.8 (5-16) h. The maximum dimension of residual lesions at the end of surgery prior to IPHC was nil (n=11), < or = 2 mm (n=4), < or = 5 mm (n=2) and < or = 10 mm (n=1). Mean time to return of bowel function was 7 (5-20) days and mean time to hospital discharge 11.5 (5-49) days. All patients developed CTEP grade 1 or 2 metabolic or hematologic toxicities. CTEP grade 3 or 4 metabolic toxicity occurred in 72% and a hematologic toxicity in 28%.There was one peri-operative death due to pulmonary embolus. Median progression-free interval was 10 months and median overall survival was 31 months. Improved outcome was significantly related to the size of residual disease prior to IPHC and postoperative chemotherapy. CONCLUSIONS: IPHC is a relatively well-tolerated procedure with the majority of the morbidity being related to associated surgery. When combined with SSC it has the potential to extend quality life in some patients with recurrent ovarian cancer and warrants continued research. Randomized studies are needed earlier in the course of the disease.

Intraperitoneal Chemotherapy

News Release and Questions and Answers - posted 6:00 p.m., January 4, 2006

Ovarian cancer is one of several types of cancer that tends to spread along peritoneal surfaces within the abdominal cavity. All organs and surfaces within the abdomen and pelvis are covered by a single layer of cells called the peritoneum. The peritoneal covering is as if all the abdominal and pelvic organs (e.g. intestines, uterus etc) and the surrounding surfaces are covered in cellophane. In theory and in practice, IP chemotherapy is advantageous in the treatment of ovarian cancer for several reasons: 1) IP therapy brings the anti-cancer drug directly where the majority of remaining cancer cells are (on the peritoneal surfaces), 2) IP therapy allows for delivery of a relatively higher concentration of the chemotherapy drug (10 to 1000 times, depending on the individual drug) to the peritoneal surfaces than is achievable with conventional intravenous treatment, and 3) IP chemotherapy drugs are absorbed slowly from the peritoneal cavity, which provides for a longer time period of exposure of the cancer cells to the drug, making cancer cell-killing more effective.

The conceptual approach to treating ovarian cancer with chemotherapy agents delivered directly into the abdominal cavity (intra-peritoneal or “IP” chemotherapy) is not new. In fact, this type of therapy was pioneered over 50 years ago; however, toxicity of the drugs in use at the time prevented wide acceptance of this technique. Recently, newer chemotherapy agents, increased understanding of drug absorption, and better drug delivery technology have renewed interest in IP chemotherapy for ovarian cancer.

Over the past 10 years, 7 randomized prospective clinical trials have evaluated the use of IP chemotherapy for the initial treatment of advanced ovarian cancer (NCI Clinical Announcement). The most recent of these trials was conducted by the Gynecologic Oncology Group and reported by Dr. Deborah Armstrong and colleagues in the New England Journal of Medicine. This study, GOG protocol 172, included 415 women with advanced ovarian cancer who were randomly assigned to a standard chemotherapy treatment arm with intravenous cisplatin and paclitaxel or to the experimental treatment arm with IP cisplatin and palcitaxel delivered by both IP and intravenous routes. This important study showed conclusively that IP chemotherapy was associated with an increase in the median survival time of 17 months; the median survival time for the standard treatment arm was 50 months compared to 67 months for the IP therapy arm. Although the toxicity of IP therapy in this study was generally of short duration and manageable, patients treated with IP therapy were more likely to experience hematologic, metabolic, and neurologic complications compared to patients treated with standard therapy. Despite the higher risk of toxicity, the magnitude of the survival advantage associated with IP therapy indicates that this form of treatment should be strongly considered as initial treatment for women with newly diagnosed advanced ovarian cancer.

Who is the ideal candidate for IP chemotherapy?

An important limitation of IP therapy is that chemotherapy drug penetration into cancer cells is limited to no more than a few millimeters. This means that only those patients who are left with minimal residual disease after initial cytoreductive (or debulking) surgery are likely to derive the benefits of IP treatment. The ideal goal is for surgery to remove or destroy all visible cancer prior to beginning chemotherapy treatment. For this reason, women with suspected ovarian cancer should have their surgery performed by a qualified gynecologic oncologist experienced in ovarian cancer surgery.

Although IP chemotherapy is most effective against cancer cells in the peritoneal cavity, approximately 70% of the drug delivered into the abdomen is actually absorbed into the systemic circulation and travels throughout the entire body. For this reason, patients with cancer cell spread to abdominal or pelvic lymph nodes can still receive IP therapy, as long as they have only minimal residual disease after surgery. The effectiveness of IP chemotherapy for ovarian cancer that has spread beyond the abdominal cavity is not known. Consequently, when disease has spread to the lungs, for example, conventional treatment with intravenous chemotherapy is usually administered.

The Johns Hopkins Ovarian Cancer Center of Excellence team has extensive experience with intraperitoneal chemotherapy, including the preceding cytoreductive surgery, IP catheter placement via laparotomy or laparoscopy, and management of complications. An appointment with one of our experts to discuss intraperitoneal chemotherapy for ovarian cancer can be scheduled by telephone at 410-502-4245, by email at kgos@jhmi.edu, or by faxing a copy of our appointment request form to 410-614-8718.

Attention Caregivers!

We are pleased to offer a DVD on the administration and management of intraperitoneal chemotherapy!

Intraperitoneal Chemotherapy for Ovarian Cancer:

A Nursing Management Perspective

The DVD is available to health care providers who want to become more familiar with this promising treatment strategy.

This instructional tool features members of our own GYN Oncology team , including nurses, chemotherapy nurse specialists, and physicians who have been instrumental in the development of IP chemotherapy.

If you are interested in purchasing this DVD, please click on the following link:

http://www.customflix.com/Store/ShowEStore.jsp?id=212895