A retrospective study comparing the efficacy of dose-dense chemotherapy, intraperitoneal chemotherapy and dose-dense chemotherapy with hyperthermic intraperitoneal chemotherapy in the treatment of advanced stage ovarian carcinoma

Published:November 09, 2019DOI:



      Hyperthermic intraperitoneal chemotherapy (HIPEC), intraperitoneal chemotherapy (IP) and dose-dense (DD) chemotherapy have been employed with varying success in the treatment of advanced stage ovarian carcinoma. Despite the clinical benefits associated with these specific forms of chemotherapy administration, they have not been comparatively analyzed, vis-à-vis their efficacy.

      Study design

      Advanced stage ovarian cancer patients who were treated with platinum/taxane chemotherapy via a DD regimen (n = 100), IP approach (n = 81) or a DD regimen in conjunction with HIPEC (n = 64) were retrospectively evaluated. The clinical variables of interest were patient age, body mass index, surgery and pathology data, chemotherapy regimen, inclusion of maintenance therapy, and progression free/overall survival.


      Progression free survival (PFS) was significantly more pronounced in the HIPEC (34.9 months) and IP (34.0 months) patients, compared to the DD group (27.6 months) (P = 0.005). A cox-proportional hazards regression model indicated that there was a decreased risk of disease progression accorded to the patients who were treated with IP chemo or HIPEC and DD chemotherapy (HR, 0.43; 95 % CI: 0.21–0.88; P = 0.022) and the subjects who underwent optimal cytoreductive surgery (HR, 2.42; 95 % CI: 1.22–4.80; P = 0.011). Positive BRCA status (HR, 0.434; 95 % CI: 1.59–3.44; P = 0.001) and number of chemotherapy regimens (HR, 1.36; 95 % CI: 1.159–1.61; P = 0.001) were significantly correlated with improved OS although we did not discern a survival benefit associated with any of the chemotherapy treatments (P = 0.136).


      We observed PFS advantages conferred to the ovarian cancer patients treated with HIPEC and IP chemotherapy compared to DD chemotherapy. However, an overall survival advantage related to the chemotherapy regimens was not borne out, possibly due to the retrospective nature of the study or differing time periods wherein the specific patient cohorts underwent treatment.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


        • Siegel R.L.
        • Miller K.D.
        • Jemal A.
        Cancer statistics, 2018.
        CA Cancer J Clin. 2018; 68: 7-30
        • Timmermans M.
        • Sonke G.S.
        • Van de Vijver K.K.
        • van der Aa M.A.
        • Kruitwagen R.F.P.M.
        No improvement in long-term survival for epithelial ovarian cancer patients: a population-based study between 1989 and 2014 in the Netherlands.
        Eur J Cancer. 2018; 88: 31-37
        • Katsumata N.
        • Yasuda M.
        • Takahashi F.
        • et al.
        Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial.
        Lancet. 2009; 374: 1331-1338
        • Abaid L.N.
        • Micha J.P.
        • Rettenmaier M.A.
        • Brown J.V.
        • Mendivil A.A.
        • Lopez K.L.
        • et al.
        A phase II study of modified dose-dense paclitaxel and every 4-week carboplatin for the treatment of advanced-stage primary epithelial ovarian, fallopian tube, or peritoneal carcinoma.
        Cancer Chemother Pharmacol. 2013; 72: 101-107
        • Mendivil A.A.
        • Rettenmaier M.A.
        • Abaid L.N.
        • Brown 3rd, J.V.
        • Mori K.M.
        • Lopez K.
        • et al.
        Consolidation hyperthermic intraperitoneal chemotherapy for the treatment of advanced stage ovarian carcinoma: a 3 year experience.
        Cancer Chemother Pharmacol. 2017; 80: 405-410
        • Armstrong D.K.
        • Bundy B.
        • Wenzel L.
        • Huang H.Q.
        • Baergen R.
        • et al.
        Intraperitoneal cisplatin and paclitaxel in ovarian cancer.
        N Engl J Med. 2006; 354: 34-43
        • Havrilesky L.J.
        • Alvarez Secord A.
        • Ehrisman J.A.
        • Berchuck A.
        • Valea F.A.
        • Lee P.S.
        • et al.
        Patient preferences in advanced or recurrent ovarian cancer.
        Cancer. 2014; 120: 3651-3659
        • Chua T.C.
        • Robertson G.
        • Liauw W.
        • Farrell R.
        • Yan T.D.
        • Morris D.L.
        Intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery in ovarian cancer peritoneal carcinomatosis: systematic review of current results.
        J Cancer Res Clin Oncol. 2009; 135: 1637-1645
        • Calvert A.H.
        • Newell D.R.
        • Gunbrell L.A.
        • et al.
        Carboplatin dosage: prospective evaluation of a simple formula based on renal function.
        J Clin Oncol. 1989; 7: 1748-1756
        • Chi D.S.
        • Eisenhauer E.L.
        • Lang J.
        • et al.
        What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma (EOC)?.
        Gynecol Oncol. 2006; 103: 559-564
        • National Institutes of Health
        • National Cancer Institute
        CTCAE: common terminology criteria for adverse events, version 4.03.
        • Natarajan L.
        • Pu M.
        • Parker B.A.
        • Thomson C.A.
        • Caan B.J.
        • Flatt S.W.
        • et al.
        Time-varying effects of prognostic factors associated with disease-free survival in breast cancer.
        Am J Epidemiol. 2009; 169: 1463-1470
        • Landrum L.M.
        • Java J.
        • Mathews C.A.
        • Lanneau Jr., G.S.
        • Copeland L.J.
        • Armstrong D.K.
        • et al.
        Prognostic factors for stage III epithelial ovarian cancer treated with intraperitoneal chemotherapy: a Gynecologic Oncology Group study.
        Gynecol Oncol. 2013; 130: 12-18
        • Markman M.
        • Bundy B.N.
        • Alberts D.S.
        • Fowler J.M.
        • Clark-Pearson D.L.
        • Carson L.F.
        • et al.
        Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group.
        J Clin Oncol. 2001; 19: 1001-1007
        • Ba M.
        • Long H.
        • Zhang X.
        • Tang Y.
        • Wu Y.
        • Wang S.
        • et al.
        Hyperthermic intraperitoneal perfusion chemotherapy and cytoreductive surgery for controlling malignant ascites from ovarian Cancer.
        Int J Gynecol Cancer. 2016; 26: 1571-1579
        • Yoshihama T.
        • Nomura H.
        • Iwasa N.
        • Kataoka F.
        • Hashimoto S.
        • Nanki Y.
        • et al.
        Efficacy and safety of dose-dense paclitaxel plus carboplatin as neoadjuvant chemotherapy for advanced ovarian, fallopian tube or peritoneal cancer.
        Jpn J Clin Oncol. 2017; 47: 1019-1023
        • Oskay-Ozcelik G.
        • Chekerov R.
        • Sommer H.
        • et al.
        Sequential chemotherapy with carboplatin followed by weekly paclitaxel in advanced ovarian cancer: results of a multicenter phase II study of the northeastern German society of gynecological oncology.
        Gynecol Oncol. 2010; 116: 317-322
        • Fujiwara K.
        • Sakuragi N.
        • Suzuki S.
        • Yoshida N.
        • Maehata K.
        • Nishiya M.
        • et al.
        First-line intraperitoneal carboplatin-based chemotherapy for 165 patients with epithelial ovarian carcinoma: results of long-term follow-up.
        Gynecol Oncol. 2003; 90: 637-643
        • van Driel W.J.
        • Koole S.N.
        • Sikorska K.
        • Schagen van Leeuwen J.H.
        • Schreuder H.W.R.
        • Hermans R.H.M.
        • et al.
        Hyperthermic intraperitoneal chemotherapy in ovarian cancer.
        N Engl J Med. 2018; 378: 230-240
        • Dann R.B.
        • DeLoia J.A.
        • Timms K.M.
        • Zorn K.K.
        • Potter J.
        • Flake 2nd, D.D.
        • et al.
        BRCA1/2 mutations and expression: response to platinum chemotherapy in patients with advanced stage epithelial ovarian cancer.
        Gynecol Oncol. 2012; 125: 677-682
        • Tan D.S.
        • Rothermundt C.
        • Thomas K.
        • Bancroft E.
        • Eeles R.
        • Shanley S.
        • et al.
        “BRCAness” syndrome in ovarian cancer: a case-control study describing the clinical features and outcome of patients with epithelial ovarian cancer associated with BRCA1 and BRCA2 mutations.
        J Clin Oncol. 2008; 26: 5530-5536
        • Bailey C.H.
        • Jameson G.
        • Sima C.
        • et al.
        Progression-free survival decreases with each subsequent therapy in patients presenting for phase I clinical trials.
        J Cancer. 2012; 3: 7-13
        • Eng K.H.
        • Hanlon B.M.
        • Bradley W.H.
        • Szender J.B.
        Prognostic factors modifying the treatment-free interval in recurrent ovarian cancer.
        Gynecol Oncol. 2015; 139: 228-235
        • Sioulas V.D.
        • Schiavone M.B.
        • Kadouri D.
        • Zivanovic O.
        • Roche K.L.
        • O’Cearbhaill R.
        • et al.
        Optimal primary management of bulky stage IIIC ovarian, fallopian tube and peritoneal carcinoma: Are the only options complete gross resection at primary debulking surgery or neoadjuvant chemotherapy?.
        Gynecol Oncol. 2017; 145: 15-20