The current standard treatment for ovarian cancer, tubal cancer, and primary peritoneal cancer is maximal cytoreductive surgery followed by chemotherapy. Recent randomized trials of Gynecologic Oncology Group (GOG) revealed the survival gain in intraperitoneal chemotherapy compared to the intravenous chemotherapy after the optimal cytoreduction in ovarian cancer (GOG#104, GOG#114, GOG#172). Experts attributed such survival gain to the earlier cycles of intraperitoneal chemotherapy when adhesion was minimal from extensive cytoreductive procedures.

Hyperthermia has an anti-cancer activity itself. Especially, hyperthermia promotes chemotherapy to penetrate deeper into the cancer tissue. Therefore, the combination of intraperitoneal chemotherapy with hyperthermia theoretically could lead to higher response rate and better survival outcomes.

*HIPEC: hyperthermic intraperitoneal chemotherapy

There will be an interim analysis when 50% of patients are enrolled.

At the interim analysis, a statistical test will be performed. The nominal significance levels will be determined later. The exact nominal significance level will be determined based on the exact number of events at the time of the interim analysis. The Stopping boundaries will be calculated using an O'Brien-Fleming error spending function

If a patient is allocated to operation to remove ovarian cancer and metastatic disease in the abdomen, this trial could be considered. Before operation, laboratory test results, image result, patient's medical history, and baseline quality of life will be checked and reviewed.

When optimal cytoreduction (residual tumor<1cm) is attained, this HIPEC (hyperthermic intraperitoneal chemotherapy) could be considered. For the primary advanced epithelial ovarian cancer, HIPEC will be performed at random. For the recurrent ovarian cancer, HIPEC will be performed after completion of cytoreductive procedures. Usually, HIPEC takes one and half hours after cytoreductive surgery.

After cytoreductive surgery followed by HIPEC, adjuvant chemotherapy will be added. The cycle of chemotherapy will be determined according to the patients' clinical outcomes. The laboratory test results, image result, patient's medical history, and baseline quality of life will be checked after the operation, during chemotherapy, and after chemotherapy.

Cytoreduction: an operation to remove ovarian cancer and its metastatic disease

There will be an interim analysis when 50% of patients are enrolled.

At the interim analysis, a statistical test will be performed. The nominal significance levels will be determined later. The exact nominal significance level will be determined based on the exact number of events at the time of the interim analysis. The Stopping boundaries will be calculated using an O'Brien-Fleming error spending function

Inclusion Criteria:

1. Disease status Primary ovarian cancer, tubal cancer, and primary peritoneal cancer (Stage III or more)
2. Residual tumor < 1cm after completion of cytoreductive surgery
3. Age < 75 year
4. Expected survival > 3 months
5. Performance status: ECOG 0-1
6. Adequate bone marrow function Hb ≥8 g/dl (After correction in case of iron deficient anemia) WBC ≥ 3,000/mm3, Platelet ≥ 100,000/mm3
7. Adequate renal function Creatinine ≤ 1.5 mg/dl
8. Adequate hepatic function Bilirubin ≤ 1.5 mg/dl and AST and ALT ≤ 80 IU/L
9. Optimal cardiopulmonary function for surgery
10. Voluntary participation after getting written informed consent.

Exclusion Criteria:

1. Unresectable extraperitoneal metastasis (brain, bone, lung parenchyme, and supraclavicular lymph node)
2. Suboptimal debulking (residual tumor > 1cm)
3. Previous History of other malignancies (except excision of skin cancer, thyroid cancer)
4. Serious heart disease or renal failure
5. Serious cardiopulmonary insufficiency
6. Uncontrolled infection
7. Uncontrolled intercurrent disease
8. Psychogenic disorder
9. Patients who are suitable candidates by legally
10. Pregnant or breast-feeding patients
11. Patients who are unsuitable candidates by doctor's decision
12. MMMT
13. Cancer tissue is not confirmed during surgery after neo-adjuvant chemotherapy

Blinded to the participants