Abstract
Objectives
Hyperthermic intraperitoneal chemotherapy (HIPEC) is an intriguing method of delivery wherein the cytotoxic agent is continuously heated and circulated throughout the peritoneum in an attempt to bolster drug efficacy. Despite HIPEC’s potential, ascertaining the optimal dose without compromising patient tolerability remains indeterminate.
Methods
We retrospectively evaluated 52 advanced stage ovarian cancer patients who were treated with consolidation HIPEC with carboplatin at varying doses (e.g., AUC 6, 8 or 10) subsequent to optimal debulking surgery and the attainment of a clinical complete response to their primary chemotherapy regimen. The following patient and operative characteristics were abstracted: demographics, surgery and pathology data, chemotherapy regimen, intraoperative results, toxicity, postoperative complications, length of hospital stay and survival data.
Results
Twelve patients received HIPEC carboplatin at an AUC 6, 15 subjects were treated with carboplatin at an AUC 8 and 25 underwent carboplatin at an AUC 10. There were no intraoperative complications during the administration of HIPEC; mean estimated blood loss was 50 mL and length of hospital stay was 1.65 days. In the overall study population, 5 patients developed grade 3/4 anemia and 33 subjects exhibited grade ≤2 thrombocytopenia and neutropenia. Thirteen patients also developed grade ≤2 nausea on postoperative day 1, which was successfully addressed with anti-emetic therapy; there were no hospital readmissions.
Conclusions
The results from the current evaluation suggest that consolidation hyperthermic intraperitoneal chemotherapy with carboplatin is both feasible and reasonably tolerated, even at an AUC of 10. However, additional, randomized study of this procedure incorporating chemotherapy dose escalation with a more extensive patient population is warranted.
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References
Mulier S, Claes JP, Dierieck V et al (2012) Survival benefit of adding hyperthermic intraperitoneal chemotherapy (HIPEC) at the different time-points of treatment of ovarian cancer: review of evidence. Curr Pharm Des 18:3793–3803
Cotte E, Passot G, Gilly FN et al (2010) Selection of patients and staging of peritoneal surface malignancies. World J Gastrointest Oncol 2:31–35
Argenta PA, Sueblinvong T, Geller MA et al (2013) Hyperthermic intraperitoneal chemotherapy with carboplatin for optimally-cytoreduced, recurrent, platinum-sensitive ovarian carcinoma: a pilot study. Gynecol Oncol 129:81–85
Zhou M, Yu P, Qu X et al (2013) Phase III trials of standard chemotherapy with or without bevacizumab for ovarian cancer: a meta-analysis. PLoS One 8:e81858
Burger RA, Brady MF, Bookman MA et al (2011) Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365:2473–2483
Perren TJ, Swart AM, Pfisterer J et al (2011) A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365:2484–2496
Markman M, Liu PY, Wilczynski S et al (2003) Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial. J Clin Oncol 21:2460–2465
Armstrong DK, Bundy B, Wenzel L et al (2006) Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 354:34–43
van der Vange N, van Goethem AR, Zoetmulder FA (2000) Extensive cytoreductive surgery combined with intra-operative intraperitoneal perfusion with cisplatin under hyperthermic conditions (OVHIPEC) in patients with recurrent ovarian cancer: a feasibility pilot. Eur J Surg Oncol 26:663–668
Yoshida Y, Sasaki H, Kurokawa T et al (2005) Efficacy of intraperitoneal continuous hyperthermic chemotherapy as consolidation therapy in patients with advanced epithelial ovarian cancer: a long-term follow-up. Oncol Rep 13:121–125
Salle B, Gilly FN, Carry PY et al (1993) Intraperitoneal chemo-hyperthermia in the treatment of peritoneal carcinomatosis of ovarian origin. Initial cases, physiopathologic data. J Gynecol Obstet Biol Reprod 22:369–371
Francescutti V, Rivera L, Seshadri M et al (2013) The benefit of intraperitoneal chemotherapy for the treatment of colorectal carcinomatosis. Oncol Rep 30:35–42
Arjona-Sanchez A, Muñoz-Casares C, Ortega-Salas R et al (2014) Long-term survival with peritoneal mucinous carcinomatosis from intraductal mucinous papillary pancreatic carcinoma treated with complete cytoreduction and hyperthermic intraperitoneal chemotherapy. Int J Hyperthermia 30:408–411
Tabrizian P, Shrager B, Jibara G et al (2014) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis: outcomes from a single tertiary institution. J Gastrointest Surg 18:1024–1031
Ansaloni L, Agnoletti V, Amadori A et al (2012) Evaluation of extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced epithelial ovarian cancer. Int J Gynecol Cancer 22:778–785
Gori J, Castaño R, Toziano M et al (2005) Intraperitoneal hyperthermic chemotherapy in ovarian cancer. Int J Gynecol Cancer 15:233–239
Lim MC, Kang S, Choi J et al (2009) 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 16:993–1000
Lim SJ, Cormier JN, Feig BW et al (2007) Toxicity and outcomes associated with surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with sarcomatosis. Ann Surg Oncol 14:2309–2318
López-Basave HN, Morales-Vasquez F, Mendez-Herrera C et al (2014) Intensive care unit admission after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Is it necessary? J Oncol 2014:307317
Lentz SS, Miller BE, Kucera GL et al (2007) Intraperitoneal hyperthermic chemotherapy using carboplatin: a phase I analysis in ovarian carcinoma. Gynecol Oncol 106:207–210
Ryu KS, Kim JH, Ko HS et al (2004) Effects of intraperitoneal hyperthermic chemotherapy in ovarian cancer. Gynecol Oncol 94:325–332
Elias D, Gilly F, Boutitie F et al (2010) Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol 28:63–68
Bristow RE, Montz FJ, Lagasse LD et al (1999) Survival impact of surgical cytoreduction in stage IV epithelial ovarian cancer. Gynecol Oncol 72:278–287
Therasse P, Arbuck SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216
Rustin GJ, Marples M, Nelstrop AE (2001) Use of CA-125 to define progression of ovarian cancer in patients with persistently elevated levels. J Clin Oncol 19:4054–4057
NIH (2010) Common terminology criteria for adverse events (version 4.03). National Institute of Health, Washington
Rettenmaier MA, Abaid LN, Erwin MR et al (2009) A retrospective review of the GelPort system in single-port access pelvic surgery. J Minim Invasive Gynecol 16:743–747
Calvert AH, Newell DR, Gunbrell LA et al (1989) Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 7:1748–1756
Ozols RF, Bundy BN, Greer BE et al (2003) Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 21:3194–3200
McGuire WP, Hoskin WJ, Brady MF et al (1996) Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and IV EOC. N Engl J Med 334:1–6
Los G, van Vugt MJ, Pinedo HM (1994) Response of peritoneal solid tumours after intraperitoneal chemohyperthermia treatment with cisplatin or carboplatin. Br J Cancer 69:235–241
Brown JV 3rd, Micha JP, Rettenmaier MA et al (2010) A pilot study evaluating a novel regimen comprised of carboplatin, paclitaxel, and bevacizumab for advanced-stage ovarian carcinoma. Int J Gynecol Cancer 20:1132–1136
Miyagi Y, Fujiwara K, Kigawa J et al (2005) Intraperitoneal carboplatin infusion may be a pharmacologically more reasonable route than intravenous administration as a systemic chemotherapy. A comparative pharmacokinetic analysis of platinum using a new mathematical model after intraperitoneal vs. intravenous infusion of carboplatin—a Sankai Gynecology Study Group (SGSG) study. Gynecol Oncol 99:591–596
Acknowledgments
This study was supported by a grant from the Nancy Yeary Women’s Cancer Research Foundation.
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The authors deny any conflicts of interest associated with this manuscript.
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Rettenmaier, M.A., Mendivil, A.A., Abaid, L.N. et al. The feasibility of administering varying high-dose consolidation hyperthermic intraperitoneal chemotherapy with carboplatin in the treatment of ovarian carcinoma. Arch Gynecol Obstet 291, 1381–1386 (2015). https://doi.org/10.1007/s00404-014-3590-0
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DOI: https://doi.org/10.1007/s00404-014-3590-0