Hepatobiliary and Pancreatic Oncology Division
Introduction
The Hepatobiliary and Pancreatic
Oncology Division deals with tumors originating in the liver, biliary system,
or pancreas, for example, hepato-cellular carcinoma (HCC), gall bladder cancer,
and pancreatic cancer (PC). As part of the multi-disciplinary care given at
the National Cancer Center Hospital, we work closely with surgeons and radiologists
who have special expertise in these areas. We also conduct research to study
the patho-physiology of hepatobiliary and pancreatic tumors and to develop
new and more effective diagnostic methods and treatments.
Routine Activities
The division consists of three
staff oncologists and three to four residents. In 1990, the division began
using percutaneous ethanol injection (PEI) to treat patients with small HCCs.
Based on long-term observations of PEI-treated patients, we have employed
PEI as a valuable alternative to surgery for most patients with HCC nodules
equal to or less than 3, all of which are smaller than 3 cm in diameter. We
also perform transcatheter arterial embolization (TAE), mainly in patients
with multiple HCC nodules. Patients with locally advanced PC receive chemoradiotherapy,
which has shown some survival benefit and has improved symptoms such as upper
abdominal pain to a significant degree. Chemo-therapy, including transcatheter
arterial infusion, is also performed as a clinical trial in patients with
metastatic disease.
Patients with hepatobiliary
and pancreatic tumors, whether they undergo surgical or nonsurgical treatment,
are all hospitalized in the Hepatobiliary and Pancreatic Ward. Case conferences
are held weekly with surgeons to determine treatment strategies for these
patients. Rounds for patients admitted to the division are made by all the
staff oncologists and residents every morning and evening.
Research Activities
A phase II study of moderate-dose
(60 mg/m2) docetaxel was conducted in chemo-naive
patients with measurable metastatic PC (Okada S et al.). None of the 21 enrolled
patients achieved an objective response, and the median survival time was
118 days. The main grade 3-4 toxicities by patient were leukocytopenia (67%)
and neutropenia (86%). These results indicated that docetaxel, administered
on this schedule, did not show significant antitumor activity in patients
with metastatic PC.
Serial changes in serum CA19-9
levels in patients with PC or chronic pancreatitis (CP) were examined to clarify
whether these changes are useful in the diagnosis of PC (Tanaka N et al, in
press). The CA19-9 level increased more than two-fold (increased type) in
7 (64%) of the 11 PC patients, although only 1 (5%) of the 21 CP patients
showed the increased type. Serial changes in serum CA19-9 levels may be useful
to differentiate between PC and CP, and close follow-up may be required for
patients with the increased type.
Twenty patients who had HCC with no tumor stain were
treated by PEI (Ueno H et al, in press). Ten patients had intrahepatic recurrence
in other parts of the treated lesions, although no local recurrence was observed.
The 5-year recurrence-free survival rate and the overall survival rate after
PEI were 22% and 75%, respectively. A serum alpha-fetoprotein level of 20
ng/ml or less was the only factor that was significantly related to prolonged
recurrence-free survival. PEI
may be useful for the treatment of HCC with no tumor stain.
Clinical Trials
Sixteen clinical trials are
ongoing, including two phase III trials. Six clinical trials were started
in 1999: a phase II trial of radiofrequency ablation therapy in patients with
small HCC, a phase III trial comparing TAE with intra-arterial chemotherapy
in advanced HCC patients, a phase II trial of UFT (tegafur+uracil) in patients
with biliary tract cancer, a phase I trial of hyperfractionated chemoradiotherapy
in patients with locally advanced PC, a phase II trial of UFT in patients
with metastatic PC, and a dose-response trial of lactoferrin (an anti-hepatitis
C virus agent) in patients with chronic hepatitis C.
Two multi-institutional studies
have been conducted to improve the early detection of PC. First, a prospective
trial of early detection of PC by ultrasonography and computed tomography
has been performed. To date, about 1,600 patients older than 40 years with
symptoms suggestive of PC have been enrolled. Second, serum and urine were
collected from patients with pancreatic diseases to identify individuals at
increased risk for PC. We measured the levels of several markers, including
ICAM-1 and HCG beta core fragment.
|
Protocols |
||
|
Diagnosis |
2 |
|
|
Treatment |
phase
I |
2 |
|
phase
II |
10 |
|
|
phase
III |
2 |
|
PEI
for Small HCC* (1990-1999) |
||||
|
No. pts |
Survival |
|||
|
1-yr |
3-yr |
5-yr |
||
|
Primary pts |
129 |
100% |
88% |
60% |
|
Post-op. pts |
73 |
98% |
84% |
58% |
|
*Fewer than three nodules, all smaller
than 3 cm in |
||||
|
diameter. |
||||
|
Chemoradiotherapy
for Pancreatic Cancer |
||
|
(1993-1999) |
||
|
No. pts |
Median survival |
1-yr survival |
|
87 |
10 mo |
40% |
|
Systemic
Chemotherapy (1990-1999)* |
|||
|
No.
pts |
Response
rate |
Median
survival |
|
|
HCC |
91 |
20% |
6.5 mo |
|
Biliary tract ca. |
57 |
30% |
6.0 mo |
|
Pancreatic ca. |
116 |
9% |
3.2 mo |
|
*Data show the numbers of chemo-naive
pts. |
|||
(S. OKADA)
