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
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
Forty-one
patients with locally advanced PC were treated with external beam radiation
(50.4 Gy in 28 fractions) and daily cisplatin (CDDP, 5mg/m2/day, 30-min infusion
just before each radiation fraction) (Okusaka T, et al.). Maintenance 5-FU
(500mg/m2) once weekly was performed until disease progression or unacceptable
toxicity. Four patients (10%) achieved a partial response, and the median
survival time was 7.7 months. Radiotherapy with daily CDDP did not offer any
advantage over conventional chemoradiotherapy using 5-FU for locally advanced
PC.
A phase
I study of gemcitabine (GEM) was conducted to confirm the tolerability of
GEM at a dose of 1000 mg/m2 in Japanese patients with advanced PC (Okada S,
et al.). GEM was administered over 30 minutes weekly in the two schedules;
GEM x 3 every 4 weeks (Schedule 1) and GEM x 7 followed by a week of rest,
and then GEM x 3 every 4 weeks (Schedule 2). At Schedule 1, no dose-limiting
toxicity was observed in the 3 patients. At Schedule 2, 2 of 6 patients showed
dose-limiting toxicity such as neutropenia and GOT/GPT increase. GEM at Schedule
2 may be tolerated in Japanese patients with advanced PC.
A phase
II study of sequential administration of methotrexate and 5-FU (sequential
MTX/5-FU) was conducted in chemo-naive patients with measurable metastatic
PC (Ikeda M, et al.). MTX (100 mg/m2) bolus infusion was given, followed 3
hour later by 5-FU (600 mg/m2) infusion over 30 minutes. Four (13%) of the
21 enrolled patients achieved a partial response, and the median survival
time was 4 months. The main toxicities were neutropenia and diarrhea. The
sequential MTX/5-FU had marginal anti-tumor activity with mild toxicity against
metastatic PC.
Early detection of PC was prospectively evaluated by the combination of ultrasonography (US) and computed tomography (CT) in outpatients with signs and/or symptoms highly suggesting PC (Okada S, et al.). One hundred eighty-eight (12.0%) of 1,567 patients enrolled in this prospective study were eventually found to have PC. Seventy-five (39.9%) patients underwent pancreatic resection, and the 4-year survival rate after study entry was 49.9%. The screening method using both US and CT may be useful in selected patients with signs and/or symptoms highly suggesting PC.
Clinical Trials
Thirteen clinical trials are ongoing, including one phase III trial (TAE versus intra-arterial chemo-therapy in advanced HCC patients). Three clinical trials were started in 2000: a phase II trial of S-1 (oral fluoropyrimidine-based anti-cancer agent) in patients with advanced biliary tract cancer, a phase II trial of S-1 in patients with metastatic PC, and a phase I trial of radiotherapy combined with GEM in patients with locally advanced PC.
|
Protocols |
|
|
|
Treatment |
phase I |
3 |
|
|
phase II |
9 |
|
|
phase III |
1 |
|
PEI for Small HCC* (1990-2000) |
|
|
||
|
|
No. pts |
Survival |
||
|
|
1-yr |
3-yr |
5-yr |
|
|
Primary pts |
169 |
100% |
87% |
60% |
|
Post-op. pts |
106 |
98% |
85% |
58% |
|
*Three or less nodules, all smaller than 3 cm |
|
|||
|
Chemoradiotherapy for Pancreatic Cancer
(1993-2000) |
||
|
No. pts |
Median
survival |
1-yr survival |
|
127 |
10 months |
35% |
|
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 patients |
|||
(S. OKADA)
