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Toxicity and Outcomes Associated with Surgical Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Patients with Sarcomatosis

  • Bone and Soft Tissue Sarcomas
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Treatment of peritoneal recurrence following surgical resection of intra-abdominal sarcomas presents a significant challenge to clinicians. Historically, treatment with systemic chemotherapy has been ineffective and surgical resection alone has not been durable. We prospectively evaluated the feasibility of cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin (CDDP) alone or in combination with mitoxantrone (MITOX) for the treatment of sarcomatosis.

Methods

Two phase I trials of HIPEC were conducted (1998–2003). Eligible patients with evidence of sarcomatosis underwent cytoreductive surgery followed by HIPEC. In the first trial, CDDP dosing was established as 90 mg/m2 with a perfusate time of 90 minutes and temperature of 41°C. In the second trial, MITOX (20 mg/m2) was instilled following perfusion with CDDP. Toxicity, efficacy, and quality of life (QOL) were evaluated.

Results

A total of 28 patients were enrolled in the two trials. We noted a higher overall toxicity score and complication rate with combination CDDP/MITOX versus CDDP alone and shorter overall survival duration (5.5 months vs 16.9 months, respectively). In addition, local recurrence rates were similar in both groups (CDDP 79% vs CDDP/MITOX 68%). As expected, QOL scores at 6–8 weeks following HIPEC were 15–25% lower than the baseline scores; however, they returned to baseline at 3–6 months.

Conclusions

Although the HIPEC technique is feasible for patients with sarcomatosis, it is associated with significant toxicity and limited clinical benefit. Combination CDDP/MITOX failed to demonstrate any benefit over CDDP alone; moreover, there was an increase in toxicity.

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References

  1. Ross JA, Severson RK, Davis S, Brooks JJ. Trends in the incidence of soft tissue sarcomas in the United States from 1973 through 1987. Cancer 1993;72(2):486–90

    Article  PubMed  CAS  Google Scholar 

  2. Toro JR, Travis LB, Wu HJ, et al. Incidence patterns of soft tissue sarcomas, regardless of primary site, in the surveillance, epidemiology and end results program, 1978–2001: An analysis of 26,758 cases. Int J Cancer 2006;119(12):2922–30

    Article  PubMed  CAS  Google Scholar 

  3. Cancer Facts and Figures 2006. American Cancer Society 2006

  4. Ferrario T, Karakousis CP. Retroperitoneal sarcomas: grade and survival. Arch Surg 2003; 138(3):248–51

    Article  PubMed  Google Scholar 

  5. Jaques DP, Coit DG, Casper ES, Brennan MF. Hepatic metastases from soft-tissue sarcoma. Ann Surg 1995; 221(4):392–7

    Article  PubMed  CAS  Google Scholar 

  6. Ng EH, Pollock RE, Munsell MF, et al. Prognostic factors influencing survival in gastrointestinal leiomyosarcomas. Implications for surgical management and staging. Ann Surg 1992; 215(1):68–77

    Article  PubMed  CAS  Google Scholar 

  7. Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Sarcoma Meta-analysis Collaboration. Lancet 1997; 350(9092):1647–54

    Article  Google Scholar 

  8. Jaques DP, Coit DG, Hajdu SI, Brennan MF. Management of primary and recurrent soft-tissue sarcoma of the retroperitoneum. Ann Surg 1990; 212(1):51–9

    Article  PubMed  CAS  Google Scholar 

  9. Mendenhall WM, Zlotecki RA, Hochwald SN, et al. Retroperitoneal soft tissue sarcoma. Cancer 2005; 104(4):669–75

    Article  PubMed  Google Scholar 

  10. Bilimoria MM, Holtz DJ, Mirza NQ, et al. Tumor volume as a prognostic factor for sarcomatosis. Cancer 2002; 94(9):2441–6

    Article  PubMed  Google Scholar 

  11. Farma JM, Pingpank JF, Libutti SK, et al. Limited survival in patients with carcinomatosis from foregut malignancies after cytoreduction and continuous hyperthermic peritoneal perfusion. J Gastrointest Surg 2005; 9(9):1346–53

    Article  PubMed  Google Scholar 

  12. Glehen O, Mohamed F, Sugarbaker PH. Incomplete cytoreduction in 174 patients with peritoneal carcinomatosis from appendiceal malignancy. Ann Surg 2004; 240(2):278–85

    Article  PubMed  Google Scholar 

  13. Koppe MJ, Boerman OC, Oyen WJ, Bleichrodt RP. Peritoneal carcinomatosis of colorectal origin: incidence and current treatment strategies. Ann Surg 2006; 243(2):212–2

    Article  PubMed  Google Scholar 

  14. Kikuchi K, Yamagata S, Yoshizumi M, Watanabe R. [Evaluation of intraperitoneal perfusion of COPP in peritonitis carcinomatosis]. Gan No Rinsho 1965; 11(12):834–7

    PubMed  CAS  Google Scholar 

  15. Vernick JJ, Oates GD, Magell J, Fried C. The use of anticancer agents for control of tumor growth in the peritoneal cavity after seeding with an experimental tumor. J Surg Res 1964; 4:559–61

    PubMed  CAS  Google Scholar 

  16. Spratt JS, Adcock RA, Muskovin M, et al. Clinical delivery system for intraperitoneal hyperthermic chemotherapy. Cancer Res 1980; 40(2):256–60

    PubMed  CAS  Google Scholar 

  17. Chi DS, McCaughty K, Diaz JP, et al. Guidelines and selection criteria for secondary cytoreductive surgery in patients with recurrent, platinum-sensitive epithelial ovarian carcinoma. Cancer 2006; 106(9):1933–9

    Article  PubMed  Google Scholar 

  18. Deraco M, Baratti D, Inglese MG, et al. Peritonectomy and intraperitoneal hyperthermic perfusion (IPHP): a strategy that has confirmed its efficacy in patients with pseudomyxoma peritonei. Ann Surg Oncol 2004; 11(4):393–8

    Article  PubMed  Google Scholar 

  19. Mahteme H, Sugarbaker PH. Treatment of peritoneal carcinomatosis from adenocarcinoid of appendiceal origin. Br J Surg 2004; 91(9):1168–73

    Article  PubMed  CAS  Google Scholar 

  20. Stewart JHt, Shen P, Russell GB, et al. Appendiceal neoplasms with peritoneal dissemination: outcomes after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy. Ann Surg Oncol 2006; 13(5):624–4

    Article  PubMed  Google Scholar 

  21. Sugarbaker PH. Cytoreductive surgery and peri-operative intraperitoneal chemotherapy as a curative approach to pseudomyxoma peritonei syndrome. Eur J Surg Oncol 2001; 27(3):239–43

    Article  PubMed  CAS  Google Scholar 

  22. Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 2006; 354(1):34–43

    Article  PubMed  CAS  Google Scholar 

  23. Abu-Surrah AS, Kettunen M. Platinum group antitumor chemistry: design and development of new anticancer drugs complementary to cisplatin. Curr Med Chem 2006; 13(11):1337–57

    Article  PubMed  CAS  Google Scholar 

  24. Kokufu I, Kurokawa E, Akashi H, et al. [Hepatic metastases from jejunal leiomyosarcoma treated effectively by repeated transarterial embolization with carboplatin]. Gan To Kagaku Ryoho 1993; 20(1):141–3

    PubMed  CAS  Google Scholar 

  25. Mavligit GM, Zukiwski AA, Salem PA, et al. Regression of hepatic metastases from gastrointestinal leiomyosarcoma after hepatic arterial chemoembolization. Cancer 1991; 68(2):321–3

    Article  PubMed  CAS  Google Scholar 

  26. Deraco M, Nonaka D, Baratti D, et al. Prognostic analysis of clinicopathologic factors in 49 patients with diffuse malignant peritoneal mesothelioma treated with cytoreductive surgery and intraperitoneal hyperthermic perfusion. Ann Surg Oncol 2006; 13(2):229–37

    Article  PubMed  Google Scholar 

  27. Muller H, Nakchbandi V. Cytoreductive surgery plus intraperitoneal hyperthermic perfusion is an effective treatment for metastasized malignant mixed mesodermal tumours (MMMT)—report of six cases. Eur J Surg Oncol 2004; 30(5):573–7

    Article  PubMed  CAS  Google Scholar 

  28. Glehen O, Kwiatkowski F, Sugarbaker PH, 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(16):3284–92

    Article  PubMed  CAS  Google Scholar 

  29. Dietel M, Arps H, Gerding D, et al. Effectiveness of mitoxantrone on the proliferation of cell cultures derived from malignant mesenchymal tumors of human origin. J Cancer Res Clin Oncol 1988; 114(2):197–203

    Article  PubMed  CAS  Google Scholar 

  30. Smith IE. Mitoxantrone (novantrone): a review of experimental and early clinical studies. Cancer Treat Rev 1983; 10(2):103–15

    Article  PubMed  CAS  Google Scholar 

  31. Ehninger G, Schuler U, Proksch B, et al. Pharmacokinetics and metabolism of mitoxantrone. A review. Clin Pharmacokinet 1990; 18(5):365–80

    PubMed  CAS  Google Scholar 

  32. Schopman EM, Van Bree C, Bakker PJ, et al. Hyperthermia-enhanced effectiveness of mitoxantrone in an experimental rat tumour. Int J Hyperthermia 1996; 12(2):241–54

    PubMed  CAS  Google Scholar 

  33. Wiedemann G, Mella O, Roszinski S, et al. Hyperthermia enhances mitoxantrone cytotoxicity on human breast carcinoma and sarcoma xenografts in nude mice. Int J Radiat Oncol Biol Phys 1992; 24(4):669–73

    PubMed  CAS  Google Scholar 

  34. Eilber FC, Rosen G, Forscher C, et al. Recurrent gastrointestinal stromal sarcomas. Surg Oncol 2000; 9(2):71–5

    Article  PubMed  CAS  Google Scholar 

  35. Eilber FC, Rosen G, Forscher C, et al. Surgical resection and intraperitoneal chemotherapy for recurrent abdominal sarcomas. Ann Surg Oncol 1999; 6(7):645–50

    Article  PubMed  CAS  Google Scholar 

  36. Common Toxicity Criteria. Washington D.C.: National Cancer Institute, 1999

  37. Ware JE Jr., Sherbourne CD. The MOS 36-item short-form health survey (SF−36). I. Conceptual framework and item selection. Med Care 1992; 30(6):473–83

    Article  PubMed  Google Scholar 

  38. Cella DF, Tulsky DS, Gray G, et al. The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J Clin Oncol 1993; 11(3):570–9

    PubMed  CAS  Google Scholar 

  39. Berthet B, Sugarbaker TA, Chang D, Sugarbaker PH. Quantitative methodologies for selection of patients with recurrent abdominopelvic sarcoma for treatment. Eur J Cancer 1999; 35(3):413–9

    Article  PubMed  CAS  Google Scholar 

  40. Bonvalot S, Cavalcanti A, Le Pechoux C, et al. Randomized trial of cytoreduction followed by intraperitoneal chemotherapy versus cytoreduction alone in patients with peritoneal sarcomatosis. Eur J Surg Oncol 2005; 31(8):917–23

    Article  PubMed  CAS  Google Scholar 

  41. Rossi CR, Deraco M, De Simone M, et al. Hyperthermic intraperitoneal intraoperative chemotherapy after cytoreductive surgery for the treatment of abdominal sarcomatosis: clinical outcome and prognostic factors in 60 consecutive patients. Cancer 2004; 100(9):1943–50

    Article  PubMed  Google Scholar 

  42. Rossi CR, Foletto M, Mocellin S, et al. Hyperthermic intraoperative intraperitoneal chemotherapy with cisplatin and doxorubicin in patients who undergo cytoreductive surgery for peritoneal carcinomatosis and sarcomatosis: phase I study. Cancer 2002; 94(2):492–9

    Article  PubMed  CAS  Google Scholar 

  43. Elias D, Bonnay M, Puizillou JM, et al. Heated intra-operative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis: pharmacokinetics and tissue distribution. Ann Oncol 2002; 13(2):267–72

    Article  PubMed  CAS  Google Scholar 

  44. Rossi CR, Mocellin S, Pilati P, et al. Pharmacokinetics of intraperitoneal cisplatin and doxorubicin. Surg Oncol Clin N Am 2003; 12(3):781–94

    Article  PubMed  Google Scholar 

  45. Koukourakis MI. Amifostine in clinical oncology: current use and future applications. Anticancer Drugs 2002; 13(3):181–209

    Article  PubMed  CAS  Google Scholar 

  46. Rufian S, Munoz-Casares FC, Briceno J, et al. Radical surgery-peritonectomy and intraoperative intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis in recurrent or primary ovarian cancer. J Surg Oncol 2006; 94(4):316–24

    Article  PubMed  Google Scholar 

  47. 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(8):863–9

    Article  PubMed  CAS  Google Scholar 

  48. Glehen O, Schreiber V, Cotte E, et al. Cytoreductive surgery and intraperitoneal chemohyperthermia for peritoneal carcinomatosis arising from gastric cancer. Arch Surg 2004; 139(1):20–26

    Article  PubMed  CAS  Google Scholar 

  49. Shen P, Levine EA, Hall J, et al. Factors predicting survival after intraperitoneal hyperthermic chemotherapy with mitomycin C after cytoreductive surgery for patients with peritoneal carcinomatosis. Arch Surg 2003; 138(1):26–33

    Article  PubMed  CAS  Google Scholar 

  50. Sugarbaker PH. Intraperitoneal chemotherapy and cytoreductive surgery for the prevention and treatment of peritoneal carcinomatosis and sarcomatosis. Semin Surg Oncol 1998; 14(3):254–61

    Article  PubMed  CAS  Google Scholar 

  51. van der Vange N, van Goethem AR, Zoetmulder FA, et al. 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 2000; 26(7):663–8

    Article  PubMed  Google Scholar 

  52. McQuellon RP, Loggie BW, Fleming RA, et al. Quality of life after intraperitoneal hyperthermic chemotherapy (IPHC) for peritoneal carcinomatosis. Eur J Surg Oncol 2001; 27(1):65–73

    Article  PubMed  CAS  Google Scholar 

  53. McQuellon RP, Loggie BW, Lehman AB, et al. Long-term survivorship and quality of life after cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis. Ann Surg Oncol 2003; 10(2):155–62

    Article  PubMed  Google Scholar 

  54. Mudan SS, Conlon KC, Woodruff JM, et al. Salvage surgery for patients with recurrent gastrointestinal sarcoma: prognostic factors to guide patient selection. Cancer 2000; 88(1):66–74

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

We thank Dawn Chalaire of the M. D. Anderson Department of Scientific Publications for editing this manuscript.

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Authors and Affiliations

  1. Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Sherry J. Lim, Janice N. Cormier, Barry W. Feig, Paul F. Mansfield, Janet R. Griffin, Peter W. T. Pisters, Raphael E. Pollock & Kelly K. Hunt

  2. Department of Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Robert S. Benjamin

  3. Division of Pharmacy, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Judy L. Chase

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  1. Sherry J. Lim
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Correspondence to Kelly K. Hunt.

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Lim, S.J., Cormier, J.N., Feig, B.W. et al. Toxicity and Outcomes Associated with Surgical Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Patients with Sarcomatosis. Ann Surg Oncol 14, 2309–2318 (2007). https://doi.org/10.1245/s10434-007-9463-z

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  • DOI: https://doi.org/10.1245/s10434-007-9463-z

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