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Activity and safety of RAD001 (everolimus) in patients affected by biliary tract cancer progressing after prior chemotherapy: a phase II ITMO study
- Source :
- Annals of oncology : official journal of the European Society for Medical Oncology. 25(8)
- Publication Year :
- 2014
-
Abstract
- Background Biliary tract cancer (BTC) is a highly lethal disease for which the best available therapy remains undetermined. The mammalian target of rapamycin (mTOR) pathway is up-regulated in several cancers, including BTC, and preclinical evidence indicates that mTOR inhibition may be effective in the treatment of BTC. We sought to evaluate the activity and tolerability of the mTOR inhibitor RAD001—everolimus—in patients with BTC progressing after prior chemotherapy. Patients and methods This was an open-label, single-arm, phase II study (EUDRACT 2008-007152-94) conducted in eight sites in Italy. Patients with locally advanced, metastatic or recurrent BTC progressing despite previous chemotherapy received a daily oral dose of everolimus 10 mg administered continuously in 28-day cycles. The two primary end points were disease control rate (DCR) and objective response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival (OS) and time-to-progression (TTP). Results Thirty-nine patients were enrolled. The DCR was 44.7%, and the ORR was 5.1%. One patient showed a partial response at 2 months and one patient showed a complete response sustained up to 8 months. The median (95% confidence interval) PFS was 3.2 (1.8–4.0) months, and the median OS was 7.7 (5.5–13.2) months. The median TTP was 2.0 (1.7–3.7) months. Most common toxicities were asthenia (43.6%), thrombocytopenia (35.9%), pyrexia (30.8%) and erythema, mainly of mild-to-moderate severity. Two patients required dose reduction due to adverse events. Conclusion Everolimus demonstrated a favourable toxicity profile and encouraging anti-tumour activity. Further trials are needed to establish the role of everolimus in the treatment of BTC. EUDRACT 2008-007152-94.
- Subjects :
- Adult
Male
medicine.medical_specialty
Organoplatinum Compounds
medicine.medical_treatment
Phases of clinical research
Antineoplastic Agents
Pharmacology
Gastroenterology
Deoxycytidine
Disease-Free Survival
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
Everolimus
Adverse effect
Aged
Sirolimus
Chemotherapy
business.industry
Surrogate endpoint
Hematology
Middle Aged
Chemotherapy regimen
Survival Analysis
Biliary Tract Neoplasms
Oncology
Tolerability
Chemotherapy, Adjuvant
Disease Progression
Quality of Life
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 15698041
- Volume :
- 25
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Annals of oncology : official journal of the European Society for Medical Oncology
- Accession number :
- edsair.doi.dedup.....ca91294fcf4475018c41833f493cc4b5