External Beam Radiotherapy for Unresectable Hepatocellular Carcinoma. A Multicenter Phase I/II Trial.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically, cytologically, or radiologically confirmed hepatocellular carcinoma
- Clinical stage T2-4, N0-1, M0 (stage II, IIIA, IIIB, IIIC) OR unresectable T1,
N0-1, M0 (stage I) disease
- M1 disease allowed in phase I if at least 90% of the tumor load (volume) is
in the liver
- Measurable disease (at least one liver lesion that can be measured in at least one
dimension as ≥ 10 mm in multislice CT scan/MRI)
- Volumetry of liver tumor and residual liver tissue: residual liver volume (= total
liver volume - gross tumor volume) has to be ≥ 800 mL and ≥ 40% of total liver volume
- No operable disease (with curative intent or planned liver transplantation)
- No presence of clinical ascites
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- Cirrhosis Child-Pugh class A or B (Child-Pugh score of ≤ 9)
- Hemoglobin ≥ 100 g/L
- ANC ≥ 1,200/mm³
- Platelet count ≥ 50,000/mm³
- ALT and AST ≤ 7 times upper limit of normal (ULN)
- AP ≤ 10 times ULN
- Bilirubin ≤ 50 μmol/L
- INR ≤ 2
- Creatinine clearance ≥ 50 mL/min
- Functional left kidney (scintigraphy mandatory for phase I, phase II only if
indicated)
- Lipase ≤ 2 times ULN (phase I only)
- Able to tolerate proton-pump inhibitors or H2 antagonists during radiation therapy
- Not pregnant
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 4 months after
completion of study therapy
- No prior malignancy allowed, except for the following:
- Adequately treated cervical carcinoma in situ
- Adequately treated localized nonmelanoma skin cancer
- Any other malignancy from which patient has been disease-free for 5 years
- No presence of medically uncontrolled encephalopathy
- No myocardial infarction within the past 6 months
- No esophageal varices ≥ grade 3, with red signs, or bleeding within the past 3 months
- No symptoms of colitis, enteritis, esophagitis, fistula, gastritis, ileus, necrosis,
perforation, stricture, or ulcer
- No severe anorexia, constipation, dehydration, diarrhea, or vomiting
- No serious underlying medical condition that, in the opinion in the investigator,
would preclude study participation (e.g., active autoimmune disease or uncontrolled
diabetes)
- Portal vein thrombosis allowed
- No psychiatric disorder precluding understanding of information on study related
topics or giving informed consent
- No nutritional intake < 1500 calories per day (corrected)
- No weight loss ≥ 15 % within the past 3 months
PRIOR CONCURRENT THERAPY:
- At least 8 weeks since prior transarterial chemoembolization (TACE), radiofrequency
ablation, or radiotherapy (RT) unless progressive disease was documented after this
therapy
- At least 21 days since prior and no other concurrent treatment with experimental
drugs
- At least 21 days since prior and no other concurrent treatment on another clinical
trial
- At least 21 days since prior and no other concurrent anticancer therapy
- No prior RT to the abdomen or caudal chest
- Prior RT to pelvis allowed
- Prior RT to chest must be above D5 vertebra
- Portal vein embolization ligation or pre-RT TACE allowed
- No concurrent treatment with steroids or non-steroidal anti-inflammatory drugs during
RT (proton-pump inhibitor allowed)