Faculty Collaboration Database

Dose-finding study of hepatic arterial infusion of irinotecan-based treatment in patients with advanced cancers metastatic to the liver. Invest New Drugs 2015 Aug;33(4):911-20

Date

05/21/2015

Pubmed ID

25990659

Pubmed Central ID

PMC4492845

DOI

10.1007/s10637-015-0251-5

Scopus ID

2-s2.0-84944441702 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

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.

Author List

Said R, Kurzrock R, Naing A, Hong DS, Fu S, Piha-Paul SA, Wheler JJ, Janku F, Kee BK, Bidyasar S, Lim J, Wallace M, Tsimberidou AM

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Phytogenic
Antineoplastic Combined Chemotherapy Protocols
Bevacizumab
Camptothecin
Cetuximab
Female
Hepatic Artery
Humans
Infusions, Intra-Arterial
Infusions, Intravenous
Liver Neoplasms
Male
Maximum Tolerated Dose
Middle Aged
Organoplatinum Compounds