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Intraperitoneal (IP) chemotherapy refers to chemotherapy that is delivered directly into the pelvis/abdominal area, in contrast to intravenous (IV) chemotherapy that is delivered via a vein. The idea behind IP chemotherapy is that direct delivery of the chemotherapy to the area of cancer, such as the ovaries will increase the actual active doses to the cancer cells. The use of IP chemotherapy is often regional, is mainly used in patients with stage III ovarian cancer, and is available in fewer than 50% of clinical practices.1-6

IP chemotherapy involves additional technical skills and special training compared to standard IV chemotherapy. Researchers from the Dana-Farber Cancer Institute evaluated the rate of IP chemotherapy use in 6 National Comprehensive Cancer Network institutions. The study included 823 women who were diagnosed with ovarian cancer between 2003 and 2012. Use of IP plus IV chemotherapy (IP/IV) increased from 0% to 33% between 2003-2006. Its use further increased to 50% from 2007-2008, but “plateaued thereafter.”

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Is IP Therapy Effective?

Chemotherapy administered directly into the peritoneal (abdominal) cavity in addition to intravenous chemotherapy has been reported to improve survival by nearly 1.5 years for patients with stage III ovarian cancer.

Patients with stage III ovarian cancer are considered to have advanced disease, as their cancer has spread from the ovaries. Standard treatment involves the surgical removal of as much cancer as possible with surgery, as well as systemic treatment with chemotherapy and a PARP inhibitor in appropriate individuals.

Researchers affiliated with the Gynecologic Oncology Group (GOG) reported the results of a phase III trial directly comparing intravenous chemotherapy plus IP chemotherapy to intravenous chemotherapy alone in patients with stage III ovarian cancer. This trial included 415 patients, all of whom had no cancerous masses greater than 1.0 cm in diameter following surgery to remove as much cancer as possible. Following surgery, patients were treated with either intravenous paclitaxel (Taxol®) plus cisplatin (Platinol®) only, or intravenous paclitaxel plus IP paclitaxel/cisplatin.

Patients treated with the addition of IP chemotherapy had significantly improved outcomes:

  • Median duration of progression-free survival was 18 months in patients treated with intravenous chemotherapy only, compared with 24 months for IP chemotherapy.
  • Median duration of survival was improved by approximately 16 months in patients treated with IP chemotherapy (49 months for patients treated with intravenous chemotherapy only, versus 66 months for those treated with IP chemotherapy).
  • During treatment, patients who received IP chemotherapy had a greater incidence of serious side effects (pain, fatigue, low blood cell levels, gastrointestinal side effects, metabolic side effects, neurologic side effects) and had a reduced quality of life. However, one year after treatment, quality of life was similar between the two groups of patients.

The researchers concluded that the addition of IP chemotherapy to intravenous chemotherapy significantly improves progression-free survival and overall survival in patients with stage III ovarian cancer. Women with ovarian cancer should speak with their physician prior to surgery to determine if they may be eligible for IP therapy, as surgery may have to be tailored to allow benefit of this treatment approach. Patients may also wish to speak with their physician regarding the individual risks and benefits of a clinical trial further evaluating different doses or treatment regimens for IP chemotherapy.2

What is Hyperthermic IP Chemotherapy?

Intraperitoneal administration of hyperthermic chemotherapy may improve survival among patients with Stage III ovarian cancer. Hyperthermic chemotherapy refers to chemotherapy that is heated before it is infused. It is thought that hyperthermic chemotherapy may provide greater anticancer activity than standard chemotherapy. Intraperitoneal hyperthermic chemotherapy (IPHC), an investigative approach, refers to heated chemotherapy that is administered directly into the abdomen.

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Researchers from South Korea reviewed clinical data involving IPHC among women with advanced ovarian cancer. This data included 96 patients who underwent initial surgery and chemotherapy. All patients then underwent a second surgery and IPHC. Twenty-two patients were treated with IPHC that included the chemotherapy agent paclitaxel; 45 patients were treated with IPHC that included the chemotherapy agent carboplatin; and 29 patients (control group) received standard therapy (no IPHC).

  • Among patients with Stage III ovarian cancer, survival at five years was nearly 85% for those treated with IPHC–paclitaxel; 63% for those treated with IPHC–carboplatin; and approximately 33% in the control group.
  • Progression-free survival at three years for patients with Stage III ovarian cancer was 56.3% in both IPHC groups and only 16.7% in the control group.4

Quality of Life Assessed for Intraperitoneal Chemotherapy in Ovarian Cancer

Intraperitoneal chemotherapy tends to have greater side effects during and immediately following treatment than intravenous chemotherapy. However, neurotoxicity (damage to the nervous system) was the only side effect that remained greater for an extended time among patients treated with IP chemotherapy.6

Intraperitoneal chemotherapy involves the administration of a chemotherapy drug directly into the abdominal cavity. Because ovarian cancer commonly spreads within the peritoneal cavity, researchers have speculated that more direct administration of chemotherapy to the sites of cancer may be more effective than intravenous (administration into the vein) treatment only. Although IP chemotherapy improves outcomes compared with intravenous chemotherapy for patients with Stage III ovarian cancer, associated side effects and impact on quality of life are still being evaluated.

Researchers have evaluated quality-of-life issues associated with IP chemotherapy among patients with Stage III ovarian cancer. This quality-of-life data was recorded in the Gynecologic Oncology Group (GOG 172) clinical trial in which patients were treated with either IPor intravenous chemotherapy including the agents Taxol® (paclitaxel) and Platinol® (cisplatin); the two treatment groups were directly compared. In this trial, both progression-free survival and overall survival were significantly improved among patients treated with IP chemotherapy.

The current study includes patient-reported quality-of-life assessments for IP and intravenous chemotherapy. Assessments were completed at the following intervals: prior to therapy, before the fourth cycle of chemotherapy, three to six months following chemotherapy, and 12 months following chemotherapy.

  • Patients treated with IP chemotherapy reported worse abdominal pain, health-related quality-of-life disruption, and neurotoxicity during treatment than patients treated with intravenous chemotherapy.
  • Twelve months following therapy, only neurotoxicity remained greater for patients treated with IP chemotherapy than for those treated with intravenous chemotherapy.
  • Quality of life was improved for both groups of patients over time.

The researchers concluded that IP chemotherapy is associated with significantly greater side effects during therapy than intravenous chemotherapy. However, it appears that neurotoxicity is the only side effect that remains significantly greater at 12 months following therapy for patients treated with IP chemotherapy.

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References

  1. Wright A, Cronin A, Milne D, et al. Use and effectiveness of intraperitoneal chemotherapy for treatment of ovarian cancer. Journal of Clinical Oncology. 2015; 33 (26): 2841-2847.
  2. Armstrong D, Bundy B, Wenzel L, et al. Intraperitoneal Cisplatin and Paclitaxel in Ovarian Cancer. New England Journal of Medicine. 2005; 354:34-43
  3. Muntz H, McGonigle K, Malpass T, et al. Phase II Study of Intraperitoneal Topotecan as Consolidation Chemotherapy in Ovarian and Primary Peritoneal Cancer. Proceedings from the 23rd annual Chemotherapy Foundation Symposium. November 2005. New York. Abstract #48.
  4. Bae J, Lee J, Ryu K, et al. Treatment of ovarian cancer with paclitaxel- or carboplatin-based intraperitoneal hyperthermic chemotherapy during secondary surgery. Gynecologic Oncology. 2007; 106: 193-200.
  5. Rothenberg M, Liu P, Braly P, et al. Combined peritoneal and intravenous chemotherapy for women with optimally debulked ovarian cancer: results from an Intergroup Phase II Trial. Journal of Clinical Oncology. 2003; 21: 1313-1319.
  6. Wenzel L, Huang H, Armstrong D, et al. Health-related quality of life during and after intraperitoneal versus intravenous chemotherapy for optimally debulked ovarian cancer: a Gynecologic Oncology Group study. Journal of Clinical Oncology. 2007; 25: 437-443.
  7. Elit L, Oliver TK, Covens A, et al. Intraperitoneal chemotherapy in the first-line treatment of women with Stage III epithelial ovarian cancer: a systematic review with meta-analysis. Cancer.2007;109:692-702.