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Ovarian Cancer

Stage III Ovarian Cancer

Patients diagnosed with stage III ovarian cancer have cancer that has spread from the ovaries and pelvic organs into the upper abdomen or lymph nodes. Currently, the standard treatment for stage III ovarian cancer consists of both surgery and systemic treatment with chemotherapy. Historically, less than 40% of patients experienced long-term survival following standard treatment for stage III ovarian cancer.  This was because it was difficult to completely remove the cancer with surgery and the available chemotherapy was unable to eradicate the remaining cancer.

Doctors are improving on these results by using a combined approach consisting of neoadjuvant therapy followed by surgery, adjuvant therapy, and maintenance therapy.

Neoadjuvant Therapy: refers to systemic chemotherapy that is given prior to surgery. Neoadjuvant therapy consisting of 3 cycles of chemotherapy prior to surgical cytoreduction reduces the side effects of surgery and leads to more optimal cancer debulking.2

Cytoreductive Surgery: also called debulking occurs following neoadjuvant therapy and the surgeon attempt to remove as much of the ovarian cancer as possible. Cytoreductive surgery is beneficial because it reduces the number of cancer cells that ultimately need to be destroyed by systemic therapy and therefore, decreases the likelihood of the cancer becoming resistant.

HIPEC: Intraperitoneal (IP) chemotherapy delivers chemotherapy directly into the abdominal cavity, where there is the greatest number of cancer cells. The chemotherapy is administered through a large catheter that is placed into the abdomen during the surgery to remove the cancer. This treatment appears to be most effective if surgery or other therapy has already reduced the size of any remaining cancer deposits to less than 1 cm, or about half an inch (this is sometimes referred to as “optimally debulked”). Among patients with stage III epithelial ovarian cancer, the addition of HIPEC to interval cytoreductive surgery delays cancer recurrence and prolongs overall survival compared to treatment with surgery alone. In a pivotal trial evaluating HIPEC median overall survival was 33.9 months for surgery compared to 45.7 months in the surgery-plus-HIPEC group.3

Adjuvant Therapy: All patients with stage III ovarian cancer are offered additional systemic chemotherapy treatment after surgery to eradicated remaining undetectable cancer that have spread outside the ovary and were not removed by surgery. Adjuvant chemotherapy is administered to decrease the risk of cancer recurrence following recovery from surgery because treatment with combination chemotherapy prolongs the duration of survival and prevents more recurrences of cancer compared to treatment with alone.1

Maintenance Therapy: Following the primary treatment of stage IV ovarian cancer with surgery and neoadjuvant and/or adjuvant chemotherapy additional treatment with “maintenance therapy” may also be recommended. Maintenance therapy is also systemic therapy administered with the goal to “maintain” a remission or prevent or delay the cancer’s return if the cancer is in remission after initial treatment. Some doctors believe the term “continuous therapy” is more appropriate since the cancer is essentially being treated on an ongoing basis. Maintenance therapy using Avastin and PARP inhibitor medications for 2 years has been shown to significantly decrease the risk of ovarian cancer recurrence in women who are in partial or complete remission after platinum-based chemotherapy.

PARP Inhibitors: The poly ADP-ribose polymerase (PARP) enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. PARP inhibitors are a new class of precision cancer medicines that contribute to cancer cell death and increased sensitivity to chemotherapy.  By blocking the PARP enzyme, DNA inside the cancerous cells is less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth.  Although all women appear to benefit from PARP treatment, individuals who test positive for BRCA and HRD appear to derive the greatest benefit.4,5,6

Next: Surgery for Ovarian Cancer

References


1 https://www.cancer.gov/types/ovarian/patient/ovarian-epithelial-treatment-pdq

2 Wright AA, et al. J Clin Oncol  2016; 34:3460-73

3 https://www.nejm.org/doi/full/10.1056/NEJMoa1708618

4 Shapira-Frommer R, Oza AM, Domchek SM, et al. A phase II open-label, multicenter study of single-agent rucaparib in the treatment of patients with relapsed ovarian cancer and a deleterious BRCA mutation. Journal of Clinical Oncology. 33, 2015 (supplement; abstract 5513).

5 Tesaro Inc., press release. Tesaro’s niraparib significantly improved progression-free survival for patients with ovarian cancer in both cohorts of the phase 3 NOVA trial. Available at: http://ir.tesarobio.com/releasedetail.cfm?ReleaseID=977524. Accessed July 6, 2016.

6 Moore KA, et al. N Engl J Med 2018; 379:2495-2505

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