nach oben

Erschienen in:

01.02.2009 | Hepatobiliary and Pancreatic Tumors

A Phase I Study of Hyperthermic Isolated Hepatic Perfusion with Oxaliplatin in the Treatment of Unresectable Liver Metastases from Colorectal Cancer

verfasst von: Herbert J. Zeh III, MD, Charles K. Brown, MD, PhD, Matthew P. Holtzman, MD, Merrill J. Egorin, MD, Julianne L. Holleran, BS, Douglas M. Potter, PhD, David L. Bartlett, MD

Erschienen in: Annals of Surgical Oncology | Ausgabe 2/2009

Einloggen, um Zugang zu erhalten

Abstract

Isolated hepatic perfusion (IHP) is a proven approach for regional delivery of chemotherapy in patients with unresectable primary and metastatic tumors of the liver. Most trials of IHP have utilized melphalan as the active drug in the perfusate. We performed a phase I trial to evaluate the efficacy, safety, and maximum tolerated dose (MTD) of oxaliplatin delivered by hyperthermic isolated hepatic perfusion. A phase I dose-escalation trial of hyperthermic IHP with oxaliplatin in patients with unresectable metastatic colorectal cancer scheduled to undergo placement of a hepatic arterial infusion (HAI) pump was carried out. Thirteen patients were enrolled between November 2003 and September 2006. Dose-limiting veno-occlusive disease was observed at 60 mg/m². At the MTD of 40 mg/m² only minor transient liver dysfunction was observed. Ultrafilterable platinum area under the curve and maximum concentration delivered by IHP increased nonlinearly with dose as did platinum concentrations in liver biopsies obtained at the end of the 60 min IHP. Seventy-seven percent of patients had a >50% decrease in serum carcinoembryonic antigen (CEA) after IHP. The overall response rate to the combined IHP and HAI therapy was 66%. One patient had a durable complete response (>4 years). We conclude that hyperthermic IHP with oxaliplatin was safe and feasible at a dose of 40 mg/m². The ability to obtain complete vascular isolation with open IHP was confirmed. The response rate in this small phase I study was encouraging.

American Cancer Society. Facts and figures 2007. Atlanta, GA; 2007.

Lahr CJ, Soong SJ, Cloud G, Smith JW, Urist MM, Balch CM. A multifactorial analysis of prognostic factors in patients with liver metastases from colorectal carcinoma. J Clin Oncol. 1983;1(11):720–6.PubMed

Rougier P, Milan C, Lazorthes F, Fourtanier G, Partensky C, Baumel H, et al. Prospective study of prognostic factors in patients with unresected hepatic metastases from colorectal cancer. Br J Surg. 1995;82:1397–400.PubMedCrossRef

Choti MA, Bulkley GB. Management of hepatic metastases. Liver Transplant Surg. 1999;5:65–80.CrossRef

Manfredi S, Lepage C, Hatem C, Coatmeur O, Faivre J, Bouvier AM. Epidemiology and management of liver metastases from colorectal cancer. Ann Surg. 2006;244(2):254–9.PubMedCrossRef

Kato T, Yasui K, Hirai T, Kanemitsu Y, Mori T, Sugihara K, et al. Therapeutic results for hepatic metastasis of colorectal cancer with special reference to effectiveness of hepatectomy: analysis of prognostic factors for 763 cases recorded at 18 institutions. Dis Colon Rectum. 2003;46(10 Suppl):S22–31.PubMed

Ercolani G, Grazi GL, Ravaioli M, Cescon M, Gardini A, Varotti G, et al. Liver resection for multiple colorectal metastases: influence of parenchymal involvement and total tumor volume, vs number or location on long-term survival. Arch Surg. 2002;137(10):1187–92.PubMedCrossRef

Choti MA, Sitzmann JV, Tiburi MF, Sumetchotimetha W, Rangsin R, Schulick RD, et al. Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg. 2002;235(6):759–66.PubMedCrossRef

Nesbitt C, Glendinning RJ, Byrne C, Poston GJ. Factors that influence treatment strategies in advanced colorectal cancer. Eur J Surg Oncol. 2007;33(Suppl 2):S88–94.PubMed

10.

Kemeny N. Management of liver metastases from colorectal cancer. Oncology. 2006;20(10):1161–76, 1179.

11.

Wicherts DA, de Haas RJ, Adam R. Bringing unresectable liver disease to resection with curative intent. Eur J Surg Oncol. 2007;33(Suppl 2):S42–51.PubMed

12.

Chun YS, Vauthey JN. Extending the frontiers of resectability in advanced colorectal cancer. Eur J Surg Oncol. 2007;33(Suppl 2):S52–8.PubMed

13.

Bismuth H, Adam R, Lévi F, Farabos C, Waechter F, Castaing D. Resection of nonresectable liver metastases from colorectal cancer after neoadjuvant chemotherapy. Ann Surg. 1996;224(4):509–22.

14.

Abdalla EK, Adam R, Bilchik AJ, Jaeck D, Vauthey JN, Mahvi D. Improving resectability of hepatic colorectal metastases: expert consensus statement. Ann Surg Oncol. 2006;13(10):1271–80.PubMedCrossRef

15.

Alexander HR, Libutti SK, Bartlett DL, Puhlmann M, Fraker DL, Bachenheimer LC. A phase I-II study of isolated hepatic perfusion using melphalan with or without tumor necrosis factor for patients with ocular melanoma metastatic to liver. Clin Cancer Res. 2000;6(8):3062–70PubMed

16.

Alexander HR, Bartlett DL, Libutti SK. Isolated hepatic perfusion: A potentially effective treatment for patients with metastatic or primary cancers confined to the liver. Cancer J Sci Am. 1998;4:2–11.PubMed

17.

Alexander HR, Bartlett DL, Libutti SK, Fraker DL, Moser T, Rosenberg SA. Isolated hepatic perfusion with tumor necrosis factor and melphalan for unresectable cancers confined to the liver. J Clin Oncol. 1998;16:1479–89.PubMed

18.

Alexander HR, Bartlett DL, Fraker DL, Libutti SK, Moser T, Rosenberg SA. Results of a Phase II study of isolated hepatic perfusion (IHP) with tumor necrosis factor (TNF) and melphalan for unresectable primary or metastatic cancer confined to the liver. Proc Soc Surg Oncol. 1997;6:8. Ref Type: Abstract.

19.

Alexander HR Jr, Libutti SK, Pingpank JF, Bartlett DL, Helsabeck C, Beresneva T. Isolated hepatic perfusion for the treatment of patients with colorectal cancer liver metastases after irinotecan-based therapy. Ann Surg Oncol. 2005;12(2):138–44.PubMedCrossRef

20.

Bartlett DL, Libutti SK, Figg WD, Fraker DL, Alexander HR. Isolated hepatic perfusion for unresectable hepatic metastases from colorectal cancer. Surgery. 2001;129(2):176–87.PubMedCrossRef

21.

Bartlett DL, Alexander HR Jr. Isolated hepatic perfusion. In: Steele GD Jr, Phillips TL, Chabner BA, editors. Hepatobiliary cancer. Canada: B.C. Decker; 2001. p. 245–53.

22.

de Wilt JH, van EB, Verhoef C, Eggermont AM. Isolated hepatic perfusion: experimental evidence and clinical utility. Surg Clin North Am. 2004;84(2):627–41.PubMedCrossRef

23.

Lise M, Pilati P, Da PP, Mocellin S, Ori C, Casara D, et al. Hyperthermic isolated liver perfusion for unresectable liver cancers: pilot study. J Chemother. 2004;16(Suppl 5):37–9.PubMed

24.

Grover AC, Libutti SK, Pingpank JF, Helsabeck C, Beresnev T, Alexander HR Jr Isolated hepatic perfusion for the treatment of patients with advanced liver metastases from pancreatic and gastrointestinal neuroendocrine neoplasms. Surgery. 2004;136(6):1176–82.PubMedCrossRef

25.

Alexander HR, Libutti SK, Bartlett DL, Puhlmann M, Fraker DL, Bachenheimer LC. A Phase I-II study of isolated hepatic perfusion using melphalan with or without tumor necrosis factor for patients with ocular melanoma metastatic to liver. Clin Cancer Res. 2000;6:3062–70.PubMed

26.

Alexander HR Jr, Bartlett DL, Libutti SK. National Cancer Institute experience with regional therapy for unresectable primary and metastatic cancer of the liver or peritoneal cavity. In: Markman M, editor. Current clinical oncology: regional chemotherapy: clinical research and practice. Totowa, NJ: Humana; 2000. p. 127–50.

27.

Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. 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. 2002;92(3):205–16.

28.

Erkmen K, Egorin MJ, Reyno LM, Morgan R Jr, Doroshow JH. Effects of storage on the binding of carboplatin to plasma proteins. Cancer Chemother Pharmacol. 1995;35(3):254–6.PubMedCrossRef

29.

Zamboni WC, Gervais AC, Egorin MJ, Schellens JH, Hamburger DR, Delauter BJ, et al. Inter- and intratumoral disposition of platinum in solid tumors after administration of cisplatin. Clin Cancer Res. 2002;8(9):2992–9.PubMed

30.

Kho Y, Jansman FG, Prins NH, Neef C, Brouwers Jr Population pharmacokinetics of oxaliplatin (85 mg/m²) in combination with 5-fluorouracil in patients with advanced colorectal cancer. Ther Drug Monit. 2006;28(2):206–11.PubMedCrossRef

31.

Graham MA, Lockwood GF, Greenslade D, Brienza S, Bayssas M, Gamelin E. Clinical pharmacokinetics of oxaliplatin: a critical review. Clin Cancer Res. 2000;6(4):1205–18.PubMed

32.

Wasserman E, Cuvier C, Lokiec F, Goldwasser F, Kalla S, Mery-Mignard D, et al. Combination of oxaliplatin plus irinotecan in patients with gastrointestinal tumors: results of two independent phase I studies with pharmacokinetics. J Clin Oncol. 1999;17(6):1751–9.PubMed

33.

Cho HK, Lee ES, Lee JW, Park JK, Kang JH, Lee KS, et al. Clinical pharmacokinetics of oxaliplatin and 5-fluorouracil administered in combination with leucovorin in Korean patients with advanced colorectal cancer. J Cancer Res Clin Oncol. 2006;132(5):320–6.PubMedCrossRef

34.

Takimoto CH, Graham MA, Lockwood G, Ng CM, Goetz A, Greenslade D, et al. Oxaliplatin pharmacokinetics and pharmacodynamics in adult cancer patients with impaired renal function. Clin Cancer Res. 2007;13(16):4832–9.PubMedCrossRef

35.

Synold TW, Takimoto CH, Doroshow JH, Gandara D, Mani S, Remick SC, et al. Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: a National Cancer Institute Organ Dysfunction Working Group study. Clin Cancer Res. 2007;13(12):3660–6.PubMedCrossRef

36.

Kern W, Braess J, Bottger B, Kaufmann CC, Hiddemann W, Schleyer E. Oxaliplatin pharmacokinetics during a four-hour infusion. Clin Cancer Res. 1999;5(4):761–5.PubMed

37.

Massari C, Brienza S, Rotarski M, Gastiaburu J, Misset JL, Cupissol D, et al. Pharmacokinetics of oxaliplatin in patients with normal versus impaired renal function. Cancer Chemother Pharmacol. 2000;45(2):157–64.PubMedCrossRef

38.

Raymond E, Chaney SG, Taamma A, Cvitkovic E. Oxaliplatin: a review of preclinical and clinical studies. Ann Oncol. 1998;9(10):1053–71.PubMedCrossRef

39.

Kern W, Beckert B, Lang N, Stemmler J, Beykirch M, Stein J, et al. Phase I and pharmacokinetic study of hepatic arterial infusion with oxaliplatin in combination with folinic acid and 5-fluorouracil in patients with hepatic metastases from colorectal cancer. Ann Oncol. 2001;12(5):599–603.PubMedCrossRef

40.

Fiorentini G, Rossi S, Dentico P, Meucci F, Bonechi F, Bernardeschi P, et al. Oxaliplatin hepatic arterial infusion chemotherapy for hepatic metastases from colorectal cancer: a phase I–II clinical study. Anticancer Res. 2004;24(3b):2093–6.PubMed

41.

Guthoff I, Lotspeich E, Fester C, Wallin I, Schatz M, Ehrsson H, et al. Hepatic artery infusion using oxaliplatin in combination with 5-fluorouracil, folinic acid and mitomycin C: oxaliplatin pharmacokinetics and feasibility. Anticancer Res. 2003;23(6):5203–8.PubMed

42.

Mancuso A, Giuliani R, Accettura C, Palma M, D’Auria G, Cecere F, et al. Hepatic arterial continuous infusion (HACI) of oxaliplatin in patients with unresectable liver metastases from colorectal cancer. Anticancer Res. 2003;23(2C):1917–22.PubMed

43.

Meyer L, Hildebrandt B, Riess H. 5-fluorouracil, folinic acid and oxaliplatin administered via hepatic arterial infusion as regional second-line therapy for advanced colorectal cancer. Oncology. 2003;64(4):473–4.PubMedCrossRef

44.

Rietbroek RC, van de Vaart PJ, Haveman J, Blommaert FA, Geerdink A, Bakker PJ, et al. Hyperthermia enhances the cytotoxicity and platinum-DNA adduct formation of lobaplatin and oxaliplatin in cultured SW 1573 cells. J Cancer Res Clin Oncol. 1997;123(1):6–12.PubMedCrossRef

45.

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

46.

van Iersel LB, Verlaan MR, Vahrmeijer AL, van Persijn van Meerten EL, Tijl FG, Sparidans RW, et al. Hepatic artery infusion of high-dose melphalan at reduced flow during isolated hepatic perfusion for the treatment of colorectal metastases confined to the liver: a clinical and pharmacologic evaluation. Eur J Surg Oncol. 2007;33(7):874–81.

47.

Mocellin S, Pilati P, Da PP, Forlin M, Corazzina S, Rossi CR, et al. Correlation between melphalan pharmacokinetics and hepatic toxicity following hyperthermic isolated liver perfusion for unresectable metastatic disease. Ann Surg Oncol. 2007;14(2):802–9.PubMedCrossRef

48.

Yoshizumi T, Gondolesi GE, Bodian CA, Jeon H, Schwartz ME, Fishbein TM, et al. A simple new formula to assess liver weight. Transplant Proc. 2003;35(4):1415–20.PubMedCrossRef

49.

Vauthey JN, Abdalla EK, Doherty DA, Gertsch P, Fenstermacher MJ, Loyer EM, et al. Body surface area and body weight predict total liver volume in Western adults. Liver Transpl. 2002;8(3):233–40.PubMedCrossRef

50.

Takimoto CH, Remick SC, Sharma S, Mani S, Ramanathan RK, Doroshow JH, et al. Administration of oxaliplatin to patients with renal dysfunction: a preliminary report of the national cancer institute organ dysfunction working group. Semin Oncol. 2003;30(15):20–5.PubMedCrossRef

51.

Takimoto CH, Remick SC, Sharma S, Mani S, Ramanathan RK, Doroshow J, et al. Dose-escalating and pharmacological study of oxaliplatin in adult cancer patients with impaired renal function: a National Cancer Institute Organ Dysfunction Working Group Study. J Clin Oncol. 2003;21(14):2664–72.PubMedCrossRef

52.

Fakih MG, Padmanabhan A. CEA monitoring in colorectal cancer. What you should know. Oncology. 2006;20(6):579–87.PubMed

53.

Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007;25(13):1670–6.PubMedCrossRef

54.

Goldberg RM, Rothenberg ML, Van CE, Benson AB, III, Blanke CD, Diasio RB, et al. The continuum of care: a paradigm for the management of metastatic colorectal cancer. Oncologist. 2007;12(1):38–50.PubMedCrossRef

Titel: A Phase I Study of Hyperthermic Isolated Hepatic Perfusion with Oxaliplatin in the Treatment of Unresectable Liver Metastases from Colorectal Cancer
verfasst von: Herbert J. Zeh III, MD
Charles K. Brown, MD, PhD
Matthew P. Holtzman, MD
Merrill J. Egorin, MD
Julianne L. Holleran, BS
Douglas M. Potter, PhD
David L. Bartlett, MD
Publikationsdatum: 01.02.2009
Verlag: Springer-Verlag
Erschienen in: Annals of Surgical Oncology / Ausgabe 2/2009
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-008-0179-5

Neu im Fachgebiet Chirurgie

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

23.04.2024 Ablationstherapie Nachrichten

Nach der Katheterablation von Vorhofflimmern kommt es bei etwa einem Drittel der Patienten zu Rezidiven, meist binnen eines Jahres. Wie sich spätere Rückfälle auf die Erfolgschancen einer erneuten Ablation auswirken, haben Schweizer Kardiologen erforscht.

Hinter dieser Appendizitis steckte ein Erreger

23.04.2024 Appendizitis Nachrichten

Schmerzen im Unterbauch, aber sonst nicht viel, was auf eine Appendizitis hindeutete: Ein junger Mann hatte Glück, dass trotzdem eine Laparoskopie mit Appendektomie durchgeführt und der Wurmfortsatz histologisch untersucht wurde.

Mehr Schaden als Nutzen durch präoperatives Aussetzen von GLP-1-Agonisten?

23.04.2024 Operationsvorbereitung Nachrichten

Derzeit wird empfohlen, eine Therapie mit GLP-1-Rezeptoragonisten präoperativ zu unterbrechen. Eine neue Studie nährt jedoch Zweifel an der Notwendigkeit der Maßnahme.

Ureterstriktur: Innovative OP-Technik bewährt sich

19.04.2024 EAU 2024 Kongressbericht

Die Ureterstriktur ist eine relativ seltene Komplikation, trotzdem bedarf sie einer differenzierten Versorgung. In komplexen Fällen wird dies durch die roboterassistierte OP-Technik gewährleistet. Erste Resultate ermutigen.

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Aktuelle BDC Leitlinien-Webinare

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare

CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare

CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske

Dr. med. Benjamin Meyknecht

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare

CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2009

Positive Sentinel Lymph Nodes are a Negative Prognostic Factor for Survival in T1–2 Oral/Oropharyngeal Cancer: A Long-Term Study on 103 Patients

Sentinel-Lymph-Node-Based Management or Routine Axillary Clearance? One-Year Outcomes of Sentinel Node Biopsy Versus Axillary Clearance (SNAC): A Randomized Controlled Surgical Trial

Diffuse Malignant Peritoneal Mesothelioma: Failure Analysis Following Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Undertreatment of Tracheal Carcinoma: Multidisciplinary Audit of Epidemiologic Data

CD24 Expression Is a Novel Prognostic Factor in Esophageal Squamous Cell Carcinoma

Strong Impact of Micrometastatic Tumor Cell Load in Patients with Esophageal Carcinoma

Update Chirurgie