Skip to main content

Advertisement

SpringerLink
Log in

Dose-finding study of hepatic arterial infusion of irinotecan-based treatment in patients with advanced cancers metastatic to the liver

  • PHASE I STUDIES
  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Summary

Background Liver metastases are associated with a poor prognosis. We investigated the use of hepatic arterial infusion (HAI) of irinotecan combination therapy in patients with liver metastases. Patients and methods Patients with histologically confirmed advanced cancer with liver metastases that was refractory to standard therapy were eligible. A standard “3 + 3” phase I study design was used to determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD). Three cohorts were evaluated: HAI of irinotecan with systemic intravenous (IV) (a) bevacizumab, (b) oxaliplatin and bevacizumab, or (c) bevacizumab and cetuximab. Results From October 2009 through December 2013, 98 patients with various tumor types were enrolled (median age, 62 years, range, 34-85; and median number of prior therapies, 4, range, 1–11). In cohorts A and C, dose escalation continued until the highest dose level—considered the MTD—was reached. In cohort B, dose escalation continued until dose level 3, and dose level 2 was considered the MTD. Rates of grade 3/4 adverse events were as follows: diarrhea, 8 %; fatigue, 4 %; neutropenia, 4 %; thrombocytopenia, 2 %; and skin rash, 2 %. Seventy-seven patients were evaluable for response. Partial response was noted in 5 (6.5 %) patients (neuroendocrine cancer, n = 2; CRC, n = 2; NSCLC, n = 1); and stable disease ≥ 6 months in 17 (22.1 %) patients (CRC, n = 13; breast, n = 1; neuroendocrine, n = 1; NSCLC, n = 1; pancreatic, n = 1). Conclusions HAI irinotecan in combination with bevacizumab; oxaliplatin plus bevacizumab; or cetuximab plus bevacizumab was safe and may be a treatment option for selected patients with advanced cancer and liver involvement.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig 1

Similar content being viewed by others

References

  1. Wheler J, Tsimberidou AM, Hong D, Naing A, Jackson T, Liu S, Feng L, Kurzrock R (2009) Survival of patients in a Phase 1 Clinic: the M. D. Anderson Cancer Center experience. Cancer 115(5):1091–1099

    Article  PubMed  Google Scholar 

  2. Kelly H, Goldberg RM (2005) Systemic therapy for metastatic colorectal cancer: current options, current evidence. J Clin Oncol : Off J Am Soc Clin Oncol 23(20):4553–4560

    Article  CAS  Google Scholar 

  3. Kelly RJ, Kemeny NE, Leonard GD (2005) Current strategies using hepatic arterial infusion chemotherapy for the treatment of colorectal cancer. Clin Colorectal Cancer 5(3):166–174

    Article  PubMed  Google Scholar 

  4. Kanat O, Gewirtz A, Kemeny N (2012) What is the potential role of hepatic arterial infusion chemo-therapy in the current armamentorium against colorectal cancer. J Gastrointest Oncol 3(2):130–138

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Fraschini G, Charnsangavej C, Carrasco CH, Buzdar AU, Jabboury KW, Hortobagyi GN (1988) Percutaneous hepatic arterial infusion of cisplatin-vinblastine for refractory breast carcinoma metastatic to the liver. Am J Clin Oncol 11(1):34–38

    Article  CAS  PubMed  Google Scholar 

  6. Kohnoe S, Endo K, Yamamoto M, Ikeda Y, Toh Y, Baba H, Tajima T, Okamura T (2002) Protracted hepatic arterial infusion with low-dose cisplatin plus 5-fluorouracil for unresectable liver metastases from colorectal cancer. Surgery 131(1 Suppl):S128–S134

    Article  PubMed  Google Scholar 

  7. Fiorentini G, Rossi S, Dentico P, Meucci F, Bonechi F, Bernardeschi P, Cantore M, Guadagni S, De Simone M (2004) Oxaliplatin hepatic arterial infusion chemotherapy for hepatic metastases from colorectal cancer: a phase I-II clinical study. Anticancer Res 24(3b):2093–2096

    CAS  PubMed  Google Scholar 

  8. Mancuso A, Giuliani R, Accettura C, Palma M, D’Auria G, Cecere F, Paoluzzi L, Bezzi M, Massidda B, Cortesi E (2003) Hepatic arterial continuous infusion (HACI) of oxaliplatin in patients with unresectable liver metastases from colorectal cancer. Anticancer Res 23(2C):1917–1922

    CAS  PubMed  Google Scholar 

  9. Kern W, Beckert B, Lang N, Stemmler J, Beykirch M, Stein J, Goecke E, Waggershauser T, Braess J, Schalhorn A et al (2001) 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 : Off J Eur Soc Med Oncol/ ESMO 12(5):599–603

    Article  CAS  Google Scholar 

  10. Lorenz M, Muller HH (2000) Randomized, multicenter trial of fluorouracil plus leucovorin administered either via hepatic arterial or intravenous infusion versus fluorodeoxyuridine administered via hepatic arterial infusion in patients with nonresectable liver metastases from colorectal carcinoma. J Clin Oncol : Off J Am Soc Clin Oncol 18(2):243–254

    CAS  Google Scholar 

  11. Kemeny N, Gonen M, Sullivan D, Schwartz L, Benedetti F, Saltz L, Stockman J, Fong Y, Jarnagin W, Bertino J et al (2001) Phase I study of hepatic arterial infusion of floxuridine and dexamethasone with systemic irinotecan for unresectable hepatic metastases from colorectal cancer. J Clin Oncol : Off J Am Soc Clin Oncol 19(10):2687–2695

    CAS  Google Scholar 

  12. Kemeny N, Jarnagin W, Gonen M, Stockman J, Blumgart L, Sperber D, Hummer A, Fong Y (2003) Phase I/II study of hepatic arterial therapy with floxuridine and dexamethasone in combination with intravenous irinotecan as adjuvant treatment after resection of hepatic metastases from colorectal cancer. J Clin Oncol : Off J Am Soc Clin Oncol 21(17):3303–3309

    Article  CAS  Google Scholar 

  13. Kerr DJ, Ledermann JA, McArdle CS, Buckels J, Neoptolemos J, Seymour M, Doughty J, Budden J, Taylor I (1995) Phase I clinical and pharmacokinetic study of leucovorin and infusional hepatic arterial fluorouracil. J Clin Oncol : Off J Am Soc Clin Oncol 13(12):2968–2972

    CAS  Google Scholar 

  14. Patt YZ, Hoque A, Lozano R, Pozdur R, Chase J, Carrasco H, Chuang V, Delpassand ES, Ellis L, Curley S et al (1997) Phase II trial of hepatic arterial infusion of fluorouracil and recombinant human interferon alfa-2b for liver metastases of colorectal cancer refractory to systemic fluorouracil and leucovorin. J Clin Oncol : Off J Am Soc Clin Oncol 15(4):1432–1438

    CAS  Google Scholar 

  15. Kemeny N, Huang Y, Cohen AM, Shi W, Conti JA, Brennan MF, Bertino JR, Turnbull AD, Sullivan D, Stockman J et al (1999) Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. N Engl J Med 341(27):2039–2048

    Article  CAS  PubMed  Google Scholar 

  16. Kemeny NE, Niedzwiecki D, Hollis DR, Lenz HJ, Warren RS, Naughton MJ, Weeks JC, Sigurdson ER, Herndon JE 2nd, Zhang C et al (2006) Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: a randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481). J Clin Oncol : Off J Am Soc Clin Oncol 24(9):1395–1403

    Article  CAS  Google Scholar 

  17. Mocellin S, Pilati P, Lise M, Nitti D (2007) Meta-analysis of hepatic arterial infusion for unresectable liver metastases from colorectal cancer: the end of an era? J Clin Oncol : Off J Am Soc Clin Oncol 25(35):5649–5654

    Article  Google Scholar 

  18. Barber FD, Mavligit G, Kurzrock R (2004) Hepatic arterial infusion chemotherapy for metastatic colorectal cancer: a concise overview. Cancer Treat Rev 30(5):425–436

    Article  CAS  PubMed  Google Scholar 

  19. Tsimberidou AM, Ye Y, Wheler J, Naing A, Hong D, Nwosu U, Hess KR, Wolff RA (2013) A phase I study of hepatic arterial infusion of nab-paclitaxel in combination with intravenous gemcitabine and bevacizumab for patients with advanced cancers and predominant liver metastases. Cancer Chemother Pharmacol 71(4):955–963

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Tsimberidou AM, Leick MB, Lim J, Fu S, Wheler J, Piha-Paul SA, Hong D, Falchook GS, Naing A, Subbiah IM et al (2013) Dose-finding study of hepatic arterial infusion of oxaliplatin-based treatment in patients with advanced solid tumors metastatic to the liver. Cancer Chemother Pharmacol 71(2):389–397

    Article  CAS  PubMed  Google Scholar 

  21. Tsimberidou AM, Fu S, Ng C, Lim JA, Wen S, Hong D, Wheler J, Bedikian AY, Eng C, Wallace M et al (2010) A phase 1 study of hepatic arterial infusion of oxaliplatin in combination with systemic 5-fluorouracil, leucovorin, and bevacizumab in patients with advanced solid tumors metastatic to the liver. Cancer 116(17):4086–4094

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Tsimberidou AM, Moulder S, Fu S, Wen S, Naing A, Bedikian AY, Daring S, Uehara C, Ng C, Wallace M et al (2010) Phase I clinical trial of hepatic arterial infusion of cisplatin in combination with intravenous liposomal doxorubicin in patients with advanced cancer and dominant liver involvement. Cancer Chemother Pharmacol 66(6):1087–1093

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Tsimberidou AM, Letourneau K, Fu S, Hong D, Naing A, Wheler J, Uehara C, McRae SE, Wen S, Kurzrock R (2011) Phase I clinical trial of hepatic arterial infusion of paclitaxel in patients with advanced cancer and dominant liver involvement. Cancer Chemother Pharmacol 68(1):247–253

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. van Riel JM, van Groeningen CJ, Kedde MA, Gall H, Leisink JM, Gruia G, Pinedo HM, van der Vijgh WJ, Giaccone G (2002) Continuous administration of irinotecan by hepatic arterial infusion: a phase I and pharmacokinetic study. Clin Cancer Res : Off J Am Assoc Cancer Res 8(2):405–412

    Google Scholar 

  25. Fiorentini G, Lucchi SR, Giovanis P, Cantore M, Guadagni S, Papiani G (2001) Irinotecan hepatic arterial infusion chemotherapy for hepatic metastases from colorectal cancer: results of a phase I clinical study. Tumori 87(6):388–390

    CAS  PubMed  Google Scholar 

  26. van Riel JM, van Groeningen CJ, de Greve J, Gruia G, Pinedo HM, Giaccone G (2004) Continuous infusion of hepatic arterial irinotecan in pretreated patients with colorectal cancer metastatic to the liver. Ann Oncol : Off J Eur Soc Med Oncol/ ESMO 15(1):59–63

    Article  Google Scholar 

  27. Fiorentini G, Rossi S, Dentico P, Bernardeschi P, Calcinai A, Bonechi F, Cantore M, Guadagni S, De Simone M (2003) Irinotecan hepatic arterial infusion chemotherapy for hepatic metastases from colorectal cancer: a phase II clinical study. Tumori 89(4):382–384

    CAS  PubMed  Google Scholar 

  28. Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Pitot HC, Alberts SR (2004) A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol : Off J Am Soc Clin Oncol 22(1):23–30

    Article  CAS  Google Scholar 

  29. Saltz LB, Lenz HJ, Kindler HL, Hochster HS, Wadler S, Hoff PM, Kemeny NE, Hollywood EM, Gonen M, Quinones M et al (2007) Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 study. J Clin Oncol : Off J Am Soc Clin Oncol 25(29):4557–4561

    Article  CAS  Google Scholar 

  30. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335–2342

    Article  CAS  PubMed  Google Scholar 

  31. van der Pal HJ, van Dalen EC, van Delden E, van Dijk IW, Kok WE, Geskus RB, Sieswerda E, Oldenburger F, Koning CC, van Leeuwen FE et al (2012) High risk of symptomatic cardiac events in childhood cancer survivors. J Clin Oncol : Off J Am Soc Clin Oncol 30(13):1429–1437

    Article  Google Scholar 

  32. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, Van Oosterom AT, Christian MC (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92(3):205–216

    Article  CAS  PubMed  Google Scholar 

  33. Saliba F, Hagipantelli R, Misset JL, Bastian G, Vassal G, Bonnay M, Herait P, Cote C, Mahjoubi M, Mignard D et al (1998) Pathophysiology and therapy of irinotecan-induced delayed-onset diarrhea in patients with advanced colorectal cancer: a prospective assessment. J Clin Oncol : Off J Am Soc Clin Oncol 16(8):2745–2751

    CAS  Google Scholar 

  34. Pozzo C, Barone C, Szanto J, Padi E, Peschel C, Bukki J, Gorbunova V, Valvere V, Zaluski J, Biakhov M et al (2004) Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study. Ann Oncol : Off J Eur Soc Med Oncol/ ESMO 15(12):1773–1781

    Article  CAS  Google Scholar 

  35. Conroy T, Paillot B, Francois E, Bugat R, Jacob JH, Stein U, Nasca S, Metges JP, Rixe O, Michel P et al (2005) Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer–a Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer study. J Clin Oncol : Off J Am Soc Clin Oncol 23(6):1228–1236

    Article  CAS  Google Scholar 

  36. Okusaka T, Ikeda M, Fukutomi A, Ioka T, Furuse J, Ohkawa S, Isayama H, Boku N (2014) Phase II study of FOLFIRINOX for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. Cancer Sci 105(10):1321–1326

    Article  CAS  PubMed  Google Scholar 

  37. Mathijssen RH, van Alphen RJ, Verweij J, Loos WJ, Nooter K, Stoter G, Sparreboom A (2001) Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin Cancer Res : Off J Am Assoc Cancer Res 7(8):2182–2194

    CAS  Google Scholar 

  38. Marsh S, Hoskins JM (2010) Irinotecan pharmacogenomics. Pharmacogenomics 11(7):1003–1010

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Canal P, Gay C, Dezeuze A, Douillard JY, Bugat R, Brunet R, Adenis A, Herait P, Lokiec F, Mathieu-Boue A (1996) Pharmacokinetics and pharmacodynamics of irinotecan during a phase II clinical trial in colorectal cancer. Pharmacology and Molecular Mechanisms Group of the European Organization for Research and Treatment of Cancer. J Clin Oncol : Off J Am Soc Clin Oncol 14(10):2688–2695

    CAS  Google Scholar 

  40. Abigerges D, Chabot GG, Armand JP, Herait P, Gouyette A, Gandia D (1995) Phase I and pharmacologic studies of the camptothecin analog irinotecan administered every 3 weeks in cancer patients. J Clin Oncol : Off J Am Soc Clin Oncol 13(1):210–221

    CAS  Google Scholar 

  41. Rowinsky EK, Grochow LB, Ettinger DS, Sartorius SE, Lubejko BG, Chen TL, Rock MK, Donehower RC (1994) Phase I and pharmacological study of the novel topoisomerase I inhibitor 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) administered as a ninety-minute infusion every 3 weeks. Cancer Res 54(2):427–436

    CAS  PubMed  Google Scholar 

  42. de Forni M, Bugat R, Chabot GG, Culine S, Extra JM, Gouyette A, Madelaine I, Marty ME, Mathieu-Boue A (1994) Phase I and pharmacokinetic study of the camptothecin derivative irinotecan, administered on a weekly schedule in cancer patients. Cancer Res 54(16):4347–4354

    PubMed  Google Scholar 

  43. Catimel G, Chabot GG, Guastalla JP, Dumortier A, Cote C, Engel C, Gouyette A, Mathieu-Boue A, Mahjoubi M, Clavel M (1995) Phase I and pharmacokinetic study of irinotecan (CPT-11) administered daily for three consecutive days every three weeks in patients with advanced solid tumors. Ann Oncol : Off J Eur Soc Med Oncol/ ESMO 6(2):133–140

    CAS  Google Scholar 

  44. Swen JJ, Nijenhuis M, de Boer A, Grandia L, Maitland-van der Zee AH, Mulder H, Rongen GA, van Schaik RH, Schalekamp T, Touw DJ et al (2011) Pharmacogenetics: from bench to byte–an update of guidelines. Clin Pharmacol Ther 89(5):662–673

    Article  CAS  PubMed  Google Scholar 

  45. Tsunedomi R, Hazama S, Fujita Y, Okayama N, Kanekiyo S, Inoue Y, Yoshino S, Yamasaki T, Suehiro Y, Oba K et al (2014) A novel system for predicting the toxicity of irinotecan based on statistical pattern recognition with UGT1A genotypes. Int J Oncol 45(4):1381–1390

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Neyns B, Van Nieuwenhove Y, Aerts M, Fontaine C, Vermeij J, Schallier D, Decoster L, De Mey J, Vandenbroucke F, Hoorens A et al (2006) Hepatic arterial infusion of oxaliplatin and L-folinic acid-modulated 5-fluorouracil for colorectal cancer liver metastases. Anticancer Res 26(1B):611–619

    CAS  PubMed  Google Scholar 

  47. Rathore R, Safran H, Soares G, Dubel G, McNulty B, Ahn S, Iannitti D, Kennedy T (2010) Phase I study of hepatic arterial infusion of oxaliplatin in advanced hepatocellular cancer: a brown university oncology group study. Am J Clin Oncol 33(1):43–46

    Article  CAS  PubMed  Google Scholar 

  48. Neyns B, Aerts M, Van Nieuwenhove Y, Fontaine C, De Coster L, Schallier D, Vanderauwera J, De Munck F, Vandenbroucke F, Everaert H et al (2008) Cetuximab with hepatic arterial infusion of chemotherapy for the treatment of colorectal cancer liver metastases. Anticancer Res 28(4C):2459–2467

    CAS  PubMed  Google Scholar 

  49. Fu S, Naing A, Moulder SL, Culotta KS, Madoff DC, Ng CS, Madden TL, Falchook GS, Hong DS, Kurzrock R (2011) Phase I trial of hepatic arterial infusion of nanoparticle albumin-bound paclitaxel: toxicity, pharmacokinetics, and activity. Mol Cancer Ther 10(7):1300–1307

    Article  CAS  PubMed  Google Scholar 

  50. Kemeny NE, Jarnagin WR, Capanu M, Fong Y, Gewirtz AN, Dematteo RP, D’Angelica MI (2011) Randomized phase II trial of adjuvant hepatic arterial infusion and systemic chemotherapy with or without bevacizumab in patients with resected hepatic metastases from colorectal cancer. J Clin Oncol : Off J Am Soc Clin Oncol 29(7):884–889

    Article  CAS  Google Scholar 

  51. Garcia SS, Atkins JT, Falchook GS, Tsimberidou AM, Hong DS, Trivedi MV, Kurzrock R (2013) Transient severe hyperbilirubinemia after hepatic arterial infusion of oxaliplatin in patients with liver metastases. Cancer Chemother Pharmacol 72(6):1265–1271

    Article  CAS  PubMed  Google Scholar 

  52. Kemeny N, Capanu M, D’Angelica M, Jarnagin W, Haviland D, Dematteo R, Fong Y (2009) Phase I trial of adjuvant hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone plus systemic oxaliplatin, 5-fluorouracil and leucovorin in patients with resected liver metastases from colorectal cancer. Ann Oncol : Off J Eur Soc Med Oncol/ ESMO 20(7):1236–1241

    Article  CAS  Google Scholar 

  53. Sorich J, Taubes B, Wagner A, Hochster H (2004) Oxaliplatin: practical guidelines for administration. Clin J Oncol Nurs 8(3):251–256

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported by the National Cancer Institute at the National Institutes of Health (P30 CA016672).

Author information

Authors and Affiliations

  1. Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    Rabih Said, Aung Naing, David S. Hong, Siqing Fu, Sarina A. Piha-Paul, Jennifer J. Wheler, Filip Janku, Joann Lim & Apostolia M. Tsimberidou

  2. Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA

    Rabih Said

  3. Department of Internal Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA

    Razelle Kurzrock

  4. Department of Gastrointestinal Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Bryan K. Kee

  5. Charlie Norwood VA Medical Center, 1 Freedom Way, 255, Augusta, GA, 30904, USA

    Savita Bidyasar

  6. Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Michael Wallace

Authors
  1. Rabih Said
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Razelle Kurzrock
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aung Naing
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David S. Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Siqing Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sarina A. Piha-Paul
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jennifer J. Wheler
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Filip Janku
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bryan K. Kee
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Savita Bidyasar
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Joann Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Michael Wallace
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Apostolia M. Tsimberidou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Apostolia M. Tsimberidou.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Said, R., Kurzrock, R., Naing, A. et al. Dose-finding study of hepatic arterial infusion of irinotecan-based treatment in patients with advanced cancers metastatic to the liver. Invest New Drugs 33, 911–920 (2015). https://doi.org/10.1007/s10637-015-0251-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10637-015-0251-5

Keywords

Search

Navigation