Hepatic arterial infusion with irinotecan in patients with liver metastases of colorectal cancer: results of an extended phase I study

Autor: R Hammerstingl, T J Vogl, S Zangos, Katrin Eichler, T Dufas, T Gruber-Rouh
Rok vydání: 2012
Předmět:
Oncology
Male
medicine.medical_specialty
Colorectal cancer
medicine.medical_treatment
Irinotecan
Gastroenterology
Drug Administration Schedule
Cohort Studies
Hepatic arterial infusion
hemic and lymphatic diseases
Internal medicine
Drug Discovery
medicine
Humans
Pharmacology (medical)
neoplasms
Survival analysis
Aged
Pharmacology
Chemotherapy
medicine.diagnostic_test
Dose-Response Relationship
Drug

business.industry
Liver Neoplasms
Magnetic resonance imaging
General Medicine
Middle Aged
medicine.disease
Antineoplastic Agents
Phytogenic

Magnetic Resonance Imaging
Survival Analysis
digestive system diseases
respiratory tract diseases
Clinical trial
Infectious Diseases
Tolerability
Injections
Intra-Arterial

Camptothecin
Female
business
Colorectal Neoplasms
Tomography
X-Ray Computed

therapeutics
medicine.drug
Agranulocytosis
Zdroj: Chemotherapy. 59(1)
ISSN: 1421-9794
Popis: Background: To define the maximum tolerated dose (MTD) tolerability and efficacy of intra-arterial chemotherapy with irinotecan in patients with liver metastases of colorectal carcinoma (CRC). Methods: Superselective intra-arterial irinotecan was applied on days 1, 14, 28 and 42. The initial dose was 140 mg/m2 with escalation in the subsequent patient group to 160 mg/m2. The final protocol toxicity evaluation was 260 mg/m2. Patients required histologically proven disease and adequate bone marrow, liver and renal function, no extrahepatic metastasis and a life expectancy >12 weeks. Results: Thirty-three patients were enrolled (median age 65, range 49-78 years). On dose level VI (240 mg/m2), 1 case of dose-limiting toxicity (DLT) (granulocytopenia) was observed, leading to an enlarged cohort of 6 patients. As no additional DLT was detected on this level, an escalation to level VII was performed. On the dose level of 260 mg/m2, irinotecan DLTs were observed, resulting in the termination of escalation and the declaration of dose level VI as MTD. Imaging follow-up with Response Evaluation Criteria in Solid Tumors (RECIST) criteria revealed a complete response in 1 patient, stable disease in 31 patients, and progressed disease in 1 patient. The median time to progression was 4.7 months, the median overall survival 15.6 months. Conclusion: The method of intra-arterial chemotherapy with irinotecan is well tolerated and shows promising local response rates in liver metastases of CRC.
Databáze: OpenAIRE