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Neoadjuvant chemotherapy followed by interval cytoreductive surgery in patients with unresectable, advanced stage epithelial ovarian cancer: a single centre experience

  • Gynecologic Oncology
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Abstract

Background

Recent data has shown that the use of neoadjuvant chemotherapy (NAC) significantly reduces tumor burden before optimal cytoreductive surgery (CS) and is associated with an improved overall survival (OS). The aim of our study was to evaluate response to treatment and survival of patients with advanced epithelial ovarian cancer (EOC) who received NAC followed by interval cytoreductive surgery (ICS).

Methods

Fifty-two patients with advanced EOC treated with NAC followed by ICS were retrospectively analyzed. Response to NAC, progression-free survival (PFS), and OS were evaluated. By using univariate and multivariate analyses, the predicted survival rates by the factors were analyzed.

Results

Median age of patients at diagnosis were 62 years (range 33–77). The serous cell type was the most common histology (98%). The majority of patients (94%) received a combination therapy of paclitaxel and carboplatin. A median of four cycles of NAC was administered. At the end of NAC, the clinical complete response (CR) with normal clinical examination and normal serum CA 125 level was achieved in 40 patients (77%). Moreover, a radiological CR and a radiological partial response were obtained in 35 patients (67%) and in 16 patients (31%), respectively. ICS was considered standard in 45 (86%) patients. Optimal cytoreduction could be achieved in 43 of 52 patients (83%). After ICS, pathological CR was established in 15 of 52 patients (29%). At the median follow-up of 25 months (range 9–102), 2-year PFS and OS were 31 and 90%, respectively. The median PFS time was 13.3 months (SE 1.1, 95% CI 11–15) and the median OS time was 47.5 months (SE 5.8, 95% CI 36.1–59). The univariate analysis showed that optimal or suboptimal cytoreduction and perioperative blood transfusion were important prognostic factors on OS for patients who received NAC. Patients treated with optimal cytoreduction had significantly better median OS (52.5 months, 95% CI 45–60) than patients who underwent suboptimal cytoreduction (24.2 months, 95% CI 11.3–37) (P = 0.001). Furthermore, the cytoreduction type (optimal vs. suboptimal), surgical procedure (standard vs. non-standard), and perioperative blood transfusion were independent prognostic factors of OS by multivariate analysis (χ 2 = 9.28, P = 0.002, HR 0.28, 95% CI 0.003–0.37; χ 2 = 4.44, P = 0.035, HR 0.15, 95% CI 0.026–0.87; χ 2 = 9.24, P = 0.002, HR 0.75, 95% CI 0.014–0.79, respectively).

Conclusions

This study demonstrates that NAC is associated with improved OS for patients with advanced EOC who received NAC followed by ICS. Additionally, our results showed that cytoreduction type, surgical procedure, and perioperative blood transfusion were independent prognostic indicators of OS for patients with advanced EOC who received NAC. Thereafter, NAC may be an alternative treatment to primary cytoreduction.

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References

  1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics, 2007. CA Cancer J Clin 57:43–66

    Article  PubMed  Google Scholar 

  2. Cannistra SA (2004) Cancer of the ovary. N Engl J Med 351:2519–2529

    Article  CAS  PubMed  Google Scholar 

  3. Karlan BY, Markman MA, Eifel PJ (2005) Ovarian cancer, peritoneal carcinoma and fallopian tube carcinoma. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology, 7th edn edn. Williams and Wilkins, Lippincott, pp 1364–1397

    Google Scholar 

  4. Yeole BB, Kumar AV, Kurkure A, Sunny L (2004) Population-based survival from cancers of breast, cervix and ovary in women in Mumbai, India. Asian Pac J Cancer Prev 5:308–315

    PubMed  Google Scholar 

  5. Holschneider CH, Berek JS (2000) Ovarian cancer: epidemiology, biology, and prognostic factors. Semin Surg Oncol 19:3–10

    Article  CAS  PubMed  Google Scholar 

  6. Beard CM, Hartmann LC, Atkinson EJ, O’Brien PC, Malkasian GD, Keeney GL, Melton LJ III (2000) The epidemiology of ovarian cancer: a population-based study in Olmsted County, Minnesota, 1935–1991. Ann Epidemiol 10:14–23

    Article  CAS  PubMed  Google Scholar 

  7. Hoskins WJ, McGuire WP, Brady MF, Homesley HD, Creasman WT, Berman M, Ball H, Berek JS (1994) The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma. Am J Obstet Gynecol 170:974–979

    CAS  PubMed  Google Scholar 

  8. Hoskins WJ, Bundy BN, Thigpen JT, Omura GA (1992) The influence of cytoreductive surgery on recurrence-free interval and survival in small-volume stage III epithelial ovarian cancer: a Gynecologic Oncology Group study. Gynecol Oncol 47:159–166

    Article  CAS  PubMed  Google Scholar 

  9. Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ (2002) Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol 20:1248–1259

    Article  PubMed  Google Scholar 

  10. Tangjitgamol S, Manusirivithaya S, Laopaiboon M, Lumbiganon P (2009) Interval debulking surgery for advanced epithelial ovarian cancer: a Cochrane systematic review. Gynecol Oncol 112:257–264

    Article  PubMed  Google Scholar 

  11. Ansquer Y, Leblanc E, Clough K, Morice P, Dauplat J, Mathevet P, Lhommé C, Scherer C, Tigaud JD, Benchaib M, Fourme E, Castaigne D, Querleu D, Dargent D (2001) Neoadjuvant chemotherapy for unresectable ovarian carcinoma: a French multicenter study. Cancer 91:2329–2334

    Article  CAS  PubMed  Google Scholar 

  12. van der Burg ME (2001) Advanced ovarian cancer. Curr Treat Options Oncol 2:109–118

    Article  PubMed  Google Scholar 

  13. Fioretti P, Gadducci A, Del Bravo B, Prato B (1990) The potential of primary cytoreductive surgery in patients with FIGO stages III and IV ovarian carcinoma. Eur J Gynaecol Oncol 11:175–179

    CAS  PubMed  Google Scholar 

  14. Mazzeo F, Berlière M, Kerger J, Squifflet J, Duck L, D’Hondt V, Humblet Y, Donnez J, Machiels JP (2003) Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy in patients with primarily unresectable, advanced-stage ovarian cancer. Gynecol Oncol 90:163–169

    Article  CAS  PubMed  Google Scholar 

  15. Chan YM, Ng TY, Ngan HY, Wong LC (2003) Quality of life in women treated with neoadjuvant chemotherapy for advanced ovarian cancer: a prospective longitudinal study. Gynecol Oncol 88:9–16

    Article  CAS  PubMed  Google Scholar 

  16. Giannopoulos T, Butler-Manuel S, Taylor A, Ngeh N, Thomas H (2006) Clinical outcomes of neoadjuvant chemotherapy and primary debulking surgery in advanced ovarian carcinoma. Eur J Gynaecol Oncol 27:25–28

    CAS  PubMed  Google Scholar 

  17. Lawton FG, Redman CW, Luesley DM, Chan KK, Blackledge G (1989) Neoadjuvant (cytoreductive) chemotherapy combined with intervention debulking surgery in advanced, unresected epithelial ovarian cancer. Obstet Gynecol 73:61–65

    CAS  PubMed  Google Scholar 

  18. Jacob JH, Gershenson DM, Morris M, Copeland LJ, Burke TW, Wharton JT (1991) Neoadjuvant chemotherapy and interval debulking for advanced epithelial ovarian cancer. Gynecol Oncol 42:146–150

    Article  CAS  PubMed  Google Scholar 

  19. Hou JY, Kelly MG, Yu H, McAlpine JN, Azodi M, Rutherford TJ, Schwartz PE (2007) Neoadjuvant chemotherapy lessens surgical morbidity in advanced ovarian cancer and leads to improved survival in stage IV disease. Gynecol Oncol 105:211–217

    Article  CAS  PubMed  Google Scholar 

  20. Pectasides D, Farmakis D, Koumarianou A (2005) The role of neoadjuvant chemotherapy in the treatment of advanced ovarian cancer. Oncology 68:64–70

    Article  CAS  PubMed  Google Scholar 

  21. Kuhn W, Rutke S, Späthe K, Schmalfeldt B, Florack G, von Hundelshausen B, Pachyn D, Ulm K, Graeff H (2001) Neoadjuvant chemotherapy followed by tumor debulking prolongs survival for patients with poor prognosis in International Federation of Gynecology and Obstetrics Stage IIIC ovarian carcinoma. Cancer 92:2585–2591

    Article  CAS  PubMed  Google Scholar 

  22. Surwit E, Childers J, Atlas I, Nour M, Hatch K, Hallum A, Alberts D (1996) Neoadjuvant chemotherapy for advanced ovarian cancer. Int J Gynecol Cancer 6:356–366

    Article  Google Scholar 

  23. Loizzi V, Cormio G, Resta L, Rossi CA, Di Gilio AR, Cuccovillo A, Selvaggi L (2005) Neoadjuvant chemotherapy in advanced ovarian cancer: a case–control study. Int J Gynecol Cancer 15:217–223

    Article  CAS  PubMed  Google Scholar 

  24. Morice P, Dubernard G, Rey A, Atallah D, Pautier P, Pomel C, Lhommé C, Duvillard P, Castaigne D (2003) Results of interval debulking surgery compared with primary debulking surgery in advanced stage ovarian cancer. J Am Coll Surg. 197:955–963

    Article  PubMed  Google Scholar 

  25. Lee SJ, Kim BG, Lee JW, Park CS, Lee JH, Bae DS (2006) Preliminary results of neoadjuvant chemotherapy with paclitaxel and cisplatin in patients with advanced epithelial ovarian cancer who are inadequate for optimum primary surgery. J Obstet Gynaecol Res 32:99–106

    Article  CAS  PubMed  Google Scholar 

  26. Kayikçioglu F, Köse MF, Boran N, Calişkan E, Tulunay G (2001) Neoadjuvant chemotherapy or primary surgery in advanced epithelial ovarian carcinoma. Int J Gynecol Cancer 11:466–470

    Article  PubMed  Google Scholar 

  27. Vergote I, De Wever I, Tjalma W, Van Gramberen M, Decloedt J, van Dam P (1998) Neoadjuvant chemotherapy or primary debulking surgery in advanced ovarian carcinoma: a retrospective analysis of 285 patients. Gynecol Oncol 71:431–436

    Article  CAS  PubMed  Google Scholar 

  28. van der Burg ME, van Lent M, Buyse M, Kobierska A, Colombo N, Favalli G, Lacave AJ, Nardi M, Renard J, Pecorelli S (1995) The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer. N Engl J Med. 332:629–634

    Article  PubMed  Google Scholar 

  29. Aletti GD, Dowdy SC, Podratz KC, Cliby WA (2007) Analysis of factors impacting operability in stage IV ovarian cancer: rationale use of a triage system. Gynecol Oncol 105:84–89

    Article  PubMed  Google Scholar 

  30. Fagotti A, Ferrandina G, Fanfani F, Garganese G, Vizzielli G, Carone V, Salerno MG, Scambia G (2008) Prospective validation of a laparoscopic predictive model for optimal cytoreduction in advanced ovarian carcinoma. Am J Obstet Gynecol. 199:642.e1–646.e1

    Article  Google Scholar 

  31. Chen SS, Bochner R (1985) Assessment of morbidity and mortality in primary cytoreductive surgery for advanced ovarian carcinoma. Gynecol Oncol 20:190–195

    Article  CAS  PubMed  Google Scholar 

  32. Sharma S, Driscoll D, Odunsi K, Venkatadri A, Lele S (2005) Safety and efficacy of cytoreductive surgery for epithelial ovarian cancer in elderly and high-risk surgical patients. Am J Obstet Gynecol 193:2077–2082

    Article  PubMed  Google Scholar 

  33. Chi DS, Franklin CC, Levine DA, Akselrod F, Sabbatini P, Jarnagin WR, DeMatteo R, Poynor EA, Abu-Rustum NR, Barakat RR (2004) Improved optimal cytoreduction rates for stages IIIC and IV epithelial ovarian, fallopian tube, and primary peritoneal cancer: a change in surgical approach. Gynecol Oncol 94:650–654

    Article  PubMed  Google Scholar 

  34. van der Burg ME, Coens C, van Lent M, Kobierska A, Colombo N, Favalli G (2005) The survival benefit of interval debulking surgery (IDS) in advanced ovarian cancer maintained during ten years; the EORTC GCG 55865 study. Int J Gynecol Cancer 15(Suppl 2):79

    Google Scholar 

  35. Redman CW, Warwick J, Luesley DM, Varma R, Lawton FG, Blackledge GR (1994) Intervention debulking surgery in advanced epithelial ovarian cancer. Br J Obstet Gynaecol 101:142–146

    CAS  PubMed  Google Scholar 

  36. Rose PG, Nerenstone S, Brady MF, Clarke-Pearson D, Olt G, Rubin SC, Moore DH, Small JM (2004) Gynecologic Oncology Group. Secondary surgical cytoreduction for advanced ovarian carcinoma. N Engl J Med 351:2489–2497

    Article  CAS  PubMed  Google Scholar 

  37. Fanfani F, Ferrandina G, Corrado G, Fagotti A, Zakut HV, Mancuso S, Scambia G (2003) Impact of interval debulking surgery on clinical outcome in primary unresectable FIGO stage IIIc ovarian cancer patients. Oncology 65:316–322

    Article  PubMed  Google Scholar 

  38. Onnis A, Marchetti M, Padovan P, Castellan L (1996) Neoadjuvant chemotherapy in advanced ovarian cancer. Eur J Gynaecol Oncol 17:393–396

    CAS  PubMed  Google Scholar 

  39. Vergote CG, Tropé F, Amant GB, Kristensen JE, Sardi T, Ehlen N, Johnson RHM, Verheijen MEL, van der Burg AJ, Lacave P, Benedetti Panici GG, Kenter A, Casado C, Mendiola C, Coens G, Stuart S, Pecorelli NS (2008) EORTC-GCG/NCIC-CTG randomized trial comparing primary debulking surgery with neoadjuvant chemotherapy in stage IIIC-IV ovarian, fallopian tube and peritoneal cancer. Plenary presentation at the 12th Biennial meeting International Gynecologic Cancer Society IGCS, Bangkok, Thailand October 25–28, 2008 (abs.)

  40. van der Burg ME, Vergote I (2003) Gynecological Cancer Group of the EORTC. The role of interval debulking surgery in ovarian cancer. Curr Oncol Rep 5:473–481

    Article  PubMed  Google Scholar 

  41. Voest EE, van Houwelingen JC, Neijt JP (1989) A meta-analysis of prognostic factors in advanced ovarian cancer with median survival and overall survival (measured with the log relative risk) as main objectives. Eur J Cancer Clin Oncol 25:711–720

    Article  CAS  PubMed  Google Scholar 

  42. Rafii A, Deval B, Geay JF, Chopin N, Paoletti X, Paraiso D, Pujade-Lauraine E (2007) Treatment of FIGO stage IV ovarian carcinoma: results of primary surgery or interval surgery after neoadjuvant chemotherapy: a retrospective study. Int J Gynecol Cancer. 17:777–783

    Article  CAS  PubMed  Google Scholar 

  43. Bristow RE, Montz FJ, Lagasse LD, Leuchter RS, Karlan BY (1999) Survival impact of surgical cytoreduction in stage IV epithelial ovarian cancer. Gynecol Oncol 72:278–287

    Article  CAS  PubMed  Google Scholar 

  44. Liu PC, Benjamin I, Morgan MA, King SA, Mikuta JJ, Rubin SC (1997) Effect of surgical debulking on survival in stage IV ovarian cancer. Gynecol Oncol 64:4–8

    Article  CAS  PubMed  Google Scholar 

  45. Pignata S, Scambia G, Savarese A, Breda E, Sorio R, Pisano C, Lorusso D, Cognetti F, Vernaglia Lombardi A, Gebbia V, Scollo P, Morabito A, Signoriello G, Perrone F (2009) Carboplatin and pegylated liposomal doxorubicin for advanced ovarian cancer: preliminary activity results of the MITO-2 phase III trial. Oncology 76:49–54

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was presented as a poster in the 12th Biennial Meeting International Gynecologic Cancer Society 2008. Bilici A, Salepci T, Oven B, Seker M, Salman T, Gumus M, Yaylaci M, Turan C, Unal O, Kars B. Neoadjuvant chemotherapy followed by surgical cytoreduction in advanced epithelial ovarian cancer: a single center experience. IGCS, 2008 (abstr 386).

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Authors and Affiliations

  1. Department of Medical Oncology, Dr. Lütfi Kırdar Kartal Education and Research Hospital, Istanbul, Turkey

    Ahmet Bilici, Taflan Salepci, Mahmut Gumus, Bala Basak Oven Ustaalioglu, Mesut Seker, Tarik Salman & Mustafa Yaylaci

  2. Department of Medical Oncology, Marmara University, Medical Faculty, Istanbul, Turkey

    Faysal Dane

  3. Department of Gynecology and Obstetrics, Dr. Lütfi Kırdar Kartal Education and Research Hospital, Istanbul, Turkey

    Cem Turan & Orhan Unal

  4. Menderes Mah, 23.sok, Çaglar Apt., No: 16, Daire: 1, Esenler, 34210, Istanbul, Turkey

    Ahmet Bilici

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  1. Ahmet Bilici
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Correspondence to Ahmet Bilici.

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Bilici, A., Salepci, T., Dane, F. et al. Neoadjuvant chemotherapy followed by interval cytoreductive surgery in patients with unresectable, advanced stage epithelial ovarian cancer: a single centre experience. Arch Gynecol Obstet 282, 417–425 (2010). https://doi.org/10.1007/s00404-009-1330-7

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