A phase I dose escalation study of concurrent chemoradiotherapy in patients with unresectable hepatocellular carcinoma
- Conditions
- Neoplasms
- Registration Number
- KCT0002644
- Lead Sponsor
- Yonsei University Health System, Gangnam Severance Hospital
- Brief Summary
Concurrent intra-arterial chemotherapy and radiotherapy (iA-CCRT) can increase the response rate in hepatocellular carcinoma (HCC), but may cause a higher toxicity. We conducted this Phase I study to investigate the dose-limiting toxicity of iA-CCRT for HCC. In total, 52.5 Gy in 25 fractions was prescribed as planning target volume (PTV) 1 at dose level 1. The dose escalation was 0.2 Gy per fraction and up to 2.5 Gy, with 62.5 Gy at level 3. Concurrent intra-arterial 5-fluorouracil was administered during the first and fifth weeks of radiotherapy (RT). Toxicities were graded using the Common Toxicity Criteria for Adverse Events, version 4.0. Results: Seventeen patients with HCC were analyzed: four at dose level 1, 6 at level 2, and 7 at level 3. The mean irradiated dose administered to the uninvolved liver at each dose level was 21.3, 21.6, and 18.2 Gy, respectively. There was no grade =3 gastrointestinal toxicity; two patients experienced grade 3 hyperbilirubinemia. All patients had Child-Pugh class A disease, but 3 patients developed class B disease after iA-CCRT. During a median follow-up of 13 months, the median progression-free survival (PFS) and overall survival (OS) were 10 and 22 months, respectively. Patients treated at dose level 3 showed improved PFS and OS. Conclusions: Radiation dose escalation of iA-CCRT did not cause any significant toxicities in patients with advanced HCC. Further large-scale studies with long-term follow-up are needed to determine the efficacy and feasibility of higher doses of iA-CCRT.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 17
1. Unresectable primary liver cancer
2. Age = 20 years
3. Whole body performance (ECOG) 0-2
4. Liver cirrhosis has a Child-Pugh score of 5-7
5. Minimum volume of normal liver without tumor invasion> 800 cc
6. Minimal distance between target (PTV1) and organ at risk (eg. duodenum, stomach) = 0.5cm
7. Adequate renal function (creatinine <1.8 mg / dl or Ccr> 50 ml / min)
8. BM reserve (ANC =1500 / mm3, PLT =50000 / mm3, Hb> 9 g / dl)
9. A lesion that can be measured or evaluated on CT
10. Patients who are pregnant and who agree to contraception
1. Patients who fail to perform respiratory training for treatment design
2. Patients with a history of previous abdominal radiation therapy
3. Patients who can not receive consent before treatment
4. Patients who do not agree to contraception as a conceived patient
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Radiation-induced liver disease (RILD)
- Secondary Outcome Measures
Name Time Method Gastrointestinal tract toxicity at Grade 4 or higher