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Investigational New Drugs
Erschienen in: Investigational New Drugs 4/2015

01.08.2015 | PHASE I STUDIES

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

verfasst von: Rabih 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

Erschienen in: Investigational New Drugs | Ausgabe 4/2015

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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.
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Metadaten
Titel
Dose-finding study of hepatic arterial infusion of irinotecan-based treatment in patients with advanced cancers metastatic to the liver
verfasst von
Rabih 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
Publikationsdatum
01.08.2015
Verlag
Springer US
Erschienen in
Investigational New Drugs / Ausgabe 4/2015
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-015-0251-5

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