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

AbstractBACKGROUND:
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.
AuthorsRabih Said, Razelle Kurzrock, Aung Naing, David S Hong, Siqing Fu, Sarina A Piha-Paul, Jennifer J Wheler, Filip Janku, Bryan K Kee, Savita Bidyasar, Joann Lim, Michael Wallace, Apostolia M Tsimberidou
JournalInvestigational new drugs (Invest New Drugs) Vol. 33 Issue 4 Pg. 911-20 (Aug 2015) ISSN: 1573-0646 [Electronic] United States
PMID25990659 (Publication Type: Clinical Trial, Phase I, Journal Article)
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Organoplatinum Compounds
  • Oxaliplatin
  • Bevacizumab
  • Irinotecan
  • Cetuximab
  • Camptothecin
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Phytogenic (administration & dosage, adverse effects, therapeutic use)
  • Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
  • Bevacizumab (administration & dosage, adverse effects, therapeutic use)
  • Camptothecin (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
  • Cetuximab (administration & dosage, adverse effects, therapeutic use)
  • Female
  • Hepatic Artery
  • Humans
  • Infusions, Intra-Arterial
  • Infusions, Intravenous
  • Irinotecan
  • Liver Neoplasms (drug therapy, secondary)
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Organoplatinum Compounds (administration & dosage, adverse effects, therapeutic use)
  • Oxaliplatin

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