Die intraoperative hypertherme intraperitoneale Chemotherapie als Therapieoption beim Ovarialkarzinom - Entwicklungen der letzten Jahre

Zusammenfassung

Der peritoneale Befall ist eine der größten therapeutischen Herausforderungen beim Ovarialkarzinom. Die komplette chirurgische Resektion der Tumorreste spielt dabei eine entscheidende Rolle für die Prognose der Patientinnen. Der chirurgische Teil des Konzeptes beinhaltet die parietale und viszerale Peritonektomie, oft in Form einer multiviszeralen Resektion. Die Kombination der Chirurgie mit der hyperthermen intraperitonealen Chemotherapie (HIPEC) hat bei gastrointestinalen Malignomen mit Peritonealkarzinose für ausgewählte Patienten die Prognose erheblich verbessert. Analog dazu wurden beim Ovarialkarzinom mit Peritonealkarzinose Daten von über 300 Patientinnen, die multimodal behandelt wurden, über die letzten vier Jahre publiziert. Die Kollektive sind relativ klein und inhomogen, die Patientinnen zum Teil unterschiedlich behandelt worden. Es konnte jedoch die technische Durchführbarkeit mit einer niedrigen Letalität und vertretbaren Morbidität in Zentren nachgewiesen werden. Die intraoperative HIPEC ergänzt das therapeutische Konzept für ausgewählte Patientinnen, jedoch ersetzt sie nicht die adjuvante systemische Chemotherapie. Prospektiv randomisierte Phase-III-Studien sollen klären, welchen Stellenwert die HIPEC in dem vorgestellten Konzept einnimmt. Ein gemeinsames Studienprotokoll der Deutschen Gesellschaft für Viszeralchirurgie/Arbeitsgruppe Chirurgische Onkologie zusammen mit der Arbeitsgruppe Gynäkologische Onkologie/Ovar wäre daher hilfreich.

Abstract

Peritoneal metastases represent a therapeutic challenge in the treatment of ovarian cancer. Macroscopically complete surgical cytoreduction is decisive for the patient's prognosis. The surgical part of the treatment includes a parietal and visceral peritonectomy, often carried out as a multivisceral resection. Its combination with intraperitoneal hyperthermic chemotherapy (HIPEC) has been found to significantly improve the prognosis of selected patients with gastrointestinal malignancies and peritoneal carcinomatosis. In the last four years several reports have been published on the use of a similar treatment in women with ovarian cancer, and more than 300 patients with ovarian cancer and peritoneal carcinomatosis were treated using this multimodal combination. However, the patient collectives were rather small and inhomogeneous and not all of the patients were treated according to the same protocol. Nevertheless, the technical feasibility of this method with low mortality and acceptable morbidity rates was demonstrated for patients treated in different centers. Intraoperative HIPEC enriches the presented concept but does not replace systemic or long-term intraperitoneal chemotherapy. Prospective, randomized phase III trials need to be designed, in order to define the exact role of HIPEC for this treatment concept. A protocol, combining proposals of the German Society of Visceral Surgery/Surgical Oncology Group and the Gynecology Oncology Group, would be therefore helpful.

Schlüsselwörter

hypertherm - intraperitoneale Chemotherapie - Ovarialkarzinom

Key words

hyperthermic - intraperitoneal chemotherapy - ovarian cancer

Literatur

• 1 Fader A N, Rose P G. Role of surgery in ovarian carcinoma.  J Clin Oncol. 2007;  20 2873-2883
• 2 Eisenkop S M, Friedmann R L, Wang H J. Complete cytoreductive surgery is feasible and maximizes survival in patients with advanced epithelial ovarian cancer: a prospective study.  Gynecol Oncol. 1998;  69 103-108
• 3 Bristow R E, Tomacruz R S, Armstrong D K, Trimble E L, Montz F J. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis.  J Clin Oncol. 2002;  20 1248-1259
• 4 Chi D S, McCaughty K, Diaz J P, Huh J, Schwabenbauer S, Hummer A J, Venkatraman E S, Aghajanian C, Sonoda Y, Abu-Rustum N R, Barakat R R. Guidelines and selection criteria for secondary cytoreductive surgery in patients with recurrent, platinum-sensitive epithelial ovarian carcinoma.  Cancer. 2006;  106 1933-1939
• 5 Harter P, du Bois A. The role of surgery in ovarian cancer with spezial emphasis on cytoreductive surgery for recurrence.  Curr Opin Oncol. 2005;  17 505-514
• 6 Eisenkop S M, Friedman R L, Spirtos N M. The role of secondary cytoreductive surgery in the treatment of patients with recurrent epithelial ovarian carcinoma.  Cancer. 2000;  88 144-153
• 7 Scarabelli C, Gallo A, Carbone A. Secondary cytoreductive surgery for patients with recurrent epithelial ovarian carcinoma.  Gynecol Oncol. 2001;  83 504-512
• 8 Harter P, du Bois A, Hahmann M. et al . Surgery in recurrent ovarian cancer: the Arbeitgemeinschaft Gynaekologische Onkologie DESKTOP OVAR trial.  Ann Surg Oncol. 2006;  13 1702-1710
• 9 Sugarbaker P H. Peritonectomy procedures.  Ann Surg. 1995;  221 29-42
• 10 Eisenhauer E L, Abu-Rustum N R, Sonoda Y. et al . The addition of extensive upper abdominal surgery to achieve optimal cytoreduction improves survival in patients with stages IIIC - IV epithelial ovarian cancer.  Gynecol Oncol. 2006;  103 480-490
• 11 Rao G, Crispens M, Rotheberg M L. Intraperitoneal chemotherapy for ovarian cancer.  J Clin Oncol. 2007;  25 2867-2872
• 12 Dahl O, Dalene R, Schem B C. et al . Status of clinical hyperthermia.  Acta Oncol. 1999;  38 863-873
• 13 Vaart P JM, Vange N, Zoetmulder F AN, Goethem A R, Tellingen O, ten Bokkel Huinink W, Hettinga J VE, Lemstra W, Meijer C, Dam W A, Uges D RA, Konings A WT, Vries E GE, Kampinge H H. Mechanism of hyperthermic potentiation of cisplatin action in cisplatin-sensitive and ‐resistant tumor cells.  Br J Cancer. 1997;  75 1735-1743
• 14 Jähne J, Piso P, Schmoll E, Haulitschek-Hauss R, Sterzenbach H, Paul H, Pichlmayr R. Intraoperative (hypertherme) intraperitoneale Chemotherapie - Überlegungen und Aspekte zum sicheren intra- und postoperativen Umgang mit Zytostatika.  Langenbecks Arch Chir. 1997;  382 8-14
• 15 Sugarbaker P H, Mora J T, Carmignani P. et al . Update on chemotherapeutic agents utilized for perioperative intraperitoneal chemotherapy.  Oncologist. 2005;  10 112-122
• 16 Piso P, Bektas H, Werner U. et al . Improved prognosis following peritonectomy procedures and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from appendiceal carcinoma.  Eur J Surg Oncol. 2001;  27 286-290
• 17 Iesalnieks I, Kullmann F, Dahlke M, Ghali N, Agha A, von Breitenbuch P, Schoelmerich J, Schlitt H J, Piso P. Surgical management of patients with peritoneal carcinomatosis of gastrointestinal origin.  Z Gastroenterol. 2006;  44 1237-1245
• 18 Glehen O, Kwiatkowski F, Sugarbaker P H. et al . Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study.  J Clin Oncol. 2004;  22 3284-3292
• 19 Verwaal V, van Ruth S, de Bree E. et al . Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer.  J Clin Oncol. 2003;  21 3737-3743
• 20 Esquivel J, Sticca R, Sugarbaker P. et al . Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: a consensus statement.  Ann Surg Oncol. 2007;  14 128-133
• 21 Yan T D, Haveric N, Carmignani C P, Chang D, Sugarbaker P H. Abdominal computed tomography scans in the selection of patients with malignant peritoneal mesothelioma for comprehensive treatment with cytoreductive surgery and perioperative intraperitoneal chemotherapy.  Cancer. 2005;  103 839-849
• 22 Jaquet P, Sugarbaker P H. Clinical research methodologies on diagnosis and staging of patients with peritoneal carcinomatosis.  Cancer Treat Res. 1986;  82 359-374
• 23 Stephens A D, Alderman R, Chang D. et al . Morbidity and mortality analysis of 200 treatments with cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy using the coliseum technique.  Ann Surg Oncol. 1999;  6 790-796
• 24 Glehen O, Osinsky D, Cotte E. et al . Intraperitoneal chemohyperthermia using a closed abdominal procedure and cytoreductive surgery for the treatment of peritoneal carcinomatosis: morbidity and mortality analysis of 216 consecutive procedures.  Ann Surg Oncol. 2003;  10 863-869
• 25 Kusamura S, Younan R, Baratti D. et al . Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion: analysis of morbidity and mortality in 209 peritoneal surface malignancies treated with closed abdomen technique.  Cancer. 2006;  106 1144-1153
• 26 Armstrong D K, Bundy B, Wenzel L, Huang H Q, Baergen R, Lele S, Copeland L J, Walker J L, Burger R A. Gynecologic Oncology Group (2006) Intraperitoneal cisplatin and paclitaxel in ovarian cancer.  N Engl J Med. 2006;  354 34-43
• 27 Gore M, du Bois A, Vergote I. Intraperitoneal chemotherapy in ovarian cancer remains experimental.  J Clin Oncol. 2006;  24 4528-4530
• 28 Ryu K S, Kim J H, Ko H S, Kim J W, Ahn W S, Park Y G, Kim S J, Lee J M. Effects of intraperitoneal hyperthermic chemotherapy in ovarian cancer.  Gynecol Oncol. 2004;  94 325-332
• 29 Zanon C, Clara R, Chiappino I, Bortolini M, Cornaglia S, Simone P, Bruno F, De Riu L, Airoldi M, Pedani F. Cytoreductive surgery and intraperitoneal chemohyperthermia for recurrent peritoneal carcinomatosis from ovarian cancer.  World J Surg. 2004;  28 1040-1045
• 30 Look M, Chang D, Sugarbaker P H. Long-term results of cytoreductive surgery for advanced and recurrent epithelial ovarian cancers and papillary serous carcinoma of the peritoneum.  Int J Gynecol Cancer. 2004;  14 35-41
• 31 Piso P, Dahlke M H, Loss M, Schlitt H J. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from ovarian cancer.  World J Surg Oncol. 2004;  2 21
• 32 Reichmann T, Cracchiolo B, Sama J. et al . Cytoreductive surgery and intraoperative chemoperfusion for advanced ovarian cancer.  J Surg Oncol. 2005;  90 51-58
• 33 Gori J, Castano R, Toziano M, Habich D, Staringer J, De Quiros D G, Felci N. Intraperitoneal hyperthermic chemotherapy in ovarian cancer.  Int J Gynecol Cancer. 2005;  15 233-239
• 34 Rufian S, Munoz-Casares F C, Briceno J, Diaz C J, Rubio M J, Ortega R, Ciria R, Morillo M, Aranda E, Muntane J, Pera C. Radical surgery-peritonectomy and intraoperative intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis in recurrent or primary ovarian cancer.  J Surg Oncol. 2006;  94 316-324
• 35 Raspagliesi F, Kusamura S, Campos Torres J C, de Souza G A, Ditto A, Zanaboni F, Younan R, Baratti D, Mariani L, Laterza B, Deraco M. Cytoreduction combined with intraperitoneal hyperthermic perfusion chemotherapy in advanced/recurrent ovarian cancer patients: The experience of National Cancer Institute of Milan.  Eur J Surg Oncol. 2006;  32 671-675
• 36 Helm C W, Randall-Whitis L, Martin R S. et al . Hyperthermic intraperitoneal chemotherapy in conjuction with surgery for the treatment of recurrent ovarian carcinoma.  Gynecol Oncol. 2007; 
• 37 Cotte E, Glehen O, Mohamed F. et al . Cytoreductive surgery and intraperitoneal chemohyperthermia for chemoresistant and recurrent advanced epithelial ovarian cancer: prospective study of 81 patients.  World J Surg. 2007; 

1 geteilte Erstautorschaft