Back to Search
Start Over
Phase II study of sirolimus in treatment-naive patients with advanced hepatocellular carcinoma
- Source :
- Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 44(7)
- Publication Year :
- 2011
-
Abstract
- Background Rapalogs are emerging as promising targeted anticancer drugs. Activation of the PI3K/Akt/mTOR pathway has been observed in 15–50% of hepatocellular carcinomas. Methods In this phase II study, patients with advanced hepatocellular carcinoma and underlying cirrhosis received sirolimus (20 mg/week for 1 month then 30 mg/week). Tumour response was assessed every 8 weeks. The primary endpoint was the objective tumour response rate according to the Response Evaluation Criteria in Solid Tumours criteria. Secondary endpoints included the objective response according to the modified Response Evaluation Criteria in Solid Tumours criteria, safety, and pharmacokinetic parameters. Results Twenty-five patients received sirolimus for a median of 20.6 weeks. Two patients had an objective response (8%, 95CI: 0.98–26.03), including one complete response, and 8 patients had stable disease. There were 2 cases of grade 5 toxicity (infections) and 5 cases of grade 3 toxicity. The main grade 1/2 toxicity was mild transient fatigue (76%). Median time to radiological progression and overall survival were 15.3 weeks (range: 8.2–173.9) and 26.4 weeks (range: 8.2–173.9) respectively. Use of the modified Response Evaluation Criteria in Solid Tumours criteria did not identify any further responders. Conclusion These data suggest that first-line sirolimus shows antitumoural efficacy in advanced hepatocellular carcinoma. Larger trials with Child A patients are needed.
- Subjects :
- Adult
Liver Cirrhosis
Male
Mucositis
medicine.medical_specialty
Cirrhosis
Carcinoma, Hepatocellular
Phases of clinical research
Kaplan-Meier Estimate
Infections
Gastroenterology
Multimodal Imaging
Therapy naive
Pharmacokinetics
Internal medicine
Acne Vulgaris
medicine
Clinical endpoint
Humans
Fatigue
Aged
Sirolimus
Hepatology
business.industry
TOR Serine-Threonine Kinases
Liver Neoplasms
Middle Aged
medicine.disease
Surgery
Epistaxis
Treatment Outcome
Hepatocellular carcinoma
Positron-Emission Tomography
Toxicity
Disease Progression
Female
business
Tomography, X-Ray Computed
Immunosuppressive Agents
medicine.drug
Subjects
Details
- ISSN :
- 18783562
- Volume :
- 44
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
- Accession number :
- edsair.doi.dedup.....60adad15d436e49ac98fd8c12c4ecb2f