Intraoperative Hyperthermic Intraperitoneal Chemotherapy With Ovarian Cancer

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

Sex

Female

Maximum age

75 Years

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

• RESULTLim MC, Kang S, Choi J, Song YJ, Park S, Seo SS, Park SY. Hyperthermic intraperitoneal chemotherapy after extensive cytoreductive surgery in patients with primary advanced epithelial ovarian cancer: interim analysis of a phase II study. Ann Surg Oncol. 2009 Apr;16(4):993-1000. doi: 10.1245/s10434-008-0299-y. Epub 2009 Jan 24. PMID 19169758
• DERIVEDKim JH, Chun SY, Lee DE, Woo YH, Chang SJ, Park SY, Chang YJ, Lim MC. Cost-effectiveness of hyperthermic intraperitoneal chemotherapy following interval cytoreductive surgery for stage III-IV ovarian cancer from a randomized controlled phase III trial in Korea (KOV-HIPEC-01). Gynecol Oncol. 2023 Mar;170:19-24. doi: 10.1016/j.ygyno.2022.12.021. Epub 2023 Jan 4. PMID 36608383
• DERIVEDKim JH, Lee DE, Lee Y, Ha HI, Chang YJ, Chang SJ, Park SY, Lim MC. Quality of life outcomes from the randomized trial of hyperthermic intraperitoneal chemotherapy following cytoreductive surgery for primary ovarian cancer (KOV-HIPEC-01). J Gynecol Oncol. 2022 Jul;33(4):e54. doi: 10.3802/jgo.2022.33.e54. Epub 2022 May 31. PMID 35712968
• DERIVEDLim MC, Chang SJ, Park B, Yoo HJ, Yoo CW, Nam BH, Park SY; HIPEC for Ovarian Cancer Collaborators. Survival After Hyperthermic Intraperitoneal Chemotherapy and Primary or Interval Cytoreductive Surgery in Ovarian Cancer: A Randomized Clinical Trial. JAMA Surg. 2022 May 1;157(5):374-383. doi: 10.1001/jamasurg.2022.0143. PMID 35262624