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Abramson Cancer CenterNCI CANCERLIT® Search: Therapy of Pancreatic Cancer - April 2002
National Cancer Institute®
Last Modified: April 1, 2002
Table of Contents
1
UI - 11776483
AU - Wolff RA
TI -
Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas:
great logic, grim reality.
SO - Ann Surg Oncol 2001 Dec;8(10):747-8
2
UI - 11776488
AU - White RR; Hurwitz HI; Morse MA; Lee C; Anscher MS; Paulson EK; Gottfried
TI -
MR; Baillie J; Branch MS; Jowell PS; McGrath KM; Clary BM; Pappas TN;
Tyler DS
Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas.
SO - Ann Surg Oncol 2001 Dec;8(10):758-65
AD - Department of Surgery, Duke University Medical Center, Durham, North
Carolina 27710, USA.
BACKGROUND: The use of neoadjuvant (preoperative) chemoradiotherapy
(CRT) for pancreatic cancer has been advocated for its potential ability
to optimize patient selection for surgical resection and to downstage
locally advanced tumors. This article reports our experience with
neoadjuvant CRT for localized pancreatic cancer. METHODS: Since 1995,
111 patients with radiographically localized, pathologically confirmed
pancreatic adenocarcinoma have received neoadjuvant external beam
radiation therapy (EBRT; median, 4500 cGy) with 5-flourouracil-based
chemotherapy. Tumors were defined as potentially resectable (PR, n = 53)
in the absence of arterial involvement and venous occlusion and locally
advanced (LA, n = 58) with arterial involvement or venous occlusion by
CT. RESULTS: Five patients (4.5%) were not restaged due to death (n = 3)
or intolerance of therapy (n = 2). Twenty-one patients (19%) manifested
distant metastatic disease on restaging CT. Twenty-eight patients with
initially PR tumors (53%) and 11 patients with initially LA tumors (19%)
were resected after CRT. Histologic examination revealed significant
fibrosis in all resected specimens and two complete responses. Surgical
margins were negative in 72%, and lymph nodes were negative in 70% of
resected patients. Median survival in resected patients has not been
reached at a median follow-up of 16 months. CONCLUSIONS: Neoadjuvant CRT
provided an opportunity for patients with occult metastatic disease to
avoid the morbidity of resection and resulted in tumor downstaging in a
minority of patients with LA tumors. Survival after neoadjuvant CRT and
resection appears to be at least comparable to survival after resection
and adjuvant (postoperative) CRT.
3
UI - 11854545
AU - Wayne JD; Abdalla EK; Wolff RA; Crane CH; Pisters PW; Evans DB
TI -
Localized adenocarcinoma of the pancreas: the rationale for preoperative
chemoradiation.
SO - Oncologist 2002;7(1):34-45
AD - The Department of Surgical Oncology, The University of Texas M. D.
Anderson Cancer Center, Houston, Texas 77030, USA.
Pancreatic adenocarcinoma is the fifth leading cause of cancer-related
death in the U.S. In spite of advancements in surgical treatment, nearly
80% of patients thought to have localized pancreatic cancer die of
recurrent or metastatic disease when treated with surgery alone.
Therefore, efforts to alter the patterns of recurrence and improve
survival for patients with pancreatic cancer currently focus on the
delivery of systemic therapy and irradiation before or after surgery.
Postoperative adjuvant therapy appears to improve median survival.
However, more than one-fourth of patients do not complete planned
adjuvant therapy due to surgical complications or a delay in
postoperative recovery of performance status. Utilizing a preoperative
(neoadjuvant) approach, overall treatment time is reduced, a greater
proportion of patients receive all components of therapy, and patients
with rapidly progressive disease are spared the side effects of surgery
as metastatic disease may be found at restaging following chemoradiation
(prior to surgery). This paper examines the factors pertinent to
clinical trial design for resectable pancreatic cancer, and carefully
reviews the existing data supporting adjuvant and neoadjuvant therapy
for potentially resectable disease.
4
UI - 11875725
AU - Evans TR; Colston KW; Lofts FJ; Cunningham D; Anthoney DA; Gogas H; de
TI -
Bono JS; Hamberg KJ; Skov T; Mansi JL
A phase II trial of the vitamin D analogue Seocalcitol (EB1089) in
patients with inoperable pancreatic cancer.
SO - Br J Cancer 2002 Mar 4;86(5):680-5
AD - CRC Department of Medical Oncology, Beatson Oncology Centre, Western
Infirmary, Dumbarton Road, Glasgow G11 6NT, UK.
J.Evans@beatson.gla.ac.uk
Inoperable cancer of the exocrine pancreas responds poorly to most
conventional anti-cancer agents, and new agents are required to palliate
this disease. Seocalcitol (EB1089), a vitamin D analogue, can inhibit
growth, induce differentiation and induce apoptosis of cancer cell lines
in vitro and can also inhibit growth of pancreatic cancer xenografts in
vivo. Thirty-six patients with advanced pancreatic cancer received once
daily oral treatment with seocalcitol with dose escalation every 2 weeks
until hypercalcaemia occurred, following which patients continued with
maintenance therapy. The most frequent toxicity was the anticipated
dose-dependent hypercalcaemia, with most patients tolerating a dose of
10-15 microg per day in chronic administration. Fourteen patients
completed at least 8 weeks of treatment and were evaluable for efficacy,
whereas 22 patients were withdrawn prior to completing 8 weeks'
treatment and in 20 of these patients withdrawal was due to clinical
deterioration as a result of disease progression. No objective responses
were observed, with five of 14 patients having stable disease in whom
the duration of stable disease was 82-532 days (median=168 days). The
time to treatment failure (n=36) ranged from 22 to 847 days, and with a
median survival of approximately 100 days. Seocalcitol is well tolerated
in pancreatic cancer but has no objective anti-tumour activity in
advanced disease. Further studies are necessary to determine if this
agent has any cytostatic activity in this malignancy in minimal disease
states. Copyright 2002 Cancer Research UK
5
UI - 11915724
AU - Ishikawa O; Ohigashi H; Yokoyama S; Yamada T; Sasaki Y; Imaoka S
TI -
[Present and future in the surgical treatment of pancreatic cancer]
SO - Gan To Kagaku Ryoho 2002 Mar;29(3):364-9
AD - Dept. of Surgery, Osaka Medical Center for Cancer and Cardiovascular
Disease, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan.
Owing to the recent advances in surgical techniques and postoperative
care, the operative indication for adenocarcinoma of the pancreas has
been widened in Japan. In our institution, we have extended lymphatic
and connective tissue clearance during surgical resection of this
cancer. As a result, the 5-year survival rate has increased from 8% to
25% due to a significant decrease in the incidence of locoregional
recurrence. The prognostic benefit gained by this procedure is seen
mainly in those patients with stage III cancer or in whom no positive
nodes were detected beyond the pancreatic head region. Thus, our
extended surgery seems to have been useful due to eradicating the
microinvasion in the peripancreatic connective tissues, rather than
dissecting the positive lymph nodes. More advanced cancers should be
treated by effectively combining chemo- and/or radiation-therapies with
surgery. In order to cure the patients more easily with less-invasive
surgery in the future, we should develop both an early diagnosis system
and sensitive examinations of micrometastases or microinvasions.
6
UI - 11915725
AU - Doi R; Fujimoto K; Wada M; Imamura M
TI -
[Current status of adjuvant therapy for pancreatic cancer]
SO - Gan To Kagaku Ryoho 2002 Mar;29(3):370-5
AD - Dept. of Surgery & Surgical Basic Science, Kyoto University Graduate
School of Medicine, 54 Shogoinkawara-cho, Sakyo-ku, Kyoto 606-8507,
Japan.
Pancreatic cancer is considered to be one of the malignancies most
resistant to therapy. It is characterized by early local invasion and
distant spread. Therefore, resection with curative intent is limited to
a very small proportion of patients. Even in these selected patients,
long-term survival remains very poor because of liver and local
recurrence. Therefore, control of occult liver metastasis and local
residual tumor with perioperative radiotherapy and chemotherapy may
provide some palliative benefits, and should have some impact on overall
survival. However, none of the studies to date are considered
definitive. Japanese pancreatic surgeons have developed a number of
adjuvant therapies which theoretically could be good enough to prolong
long term survival, however, they have not been tested in randomized
controlled trials. Planning co-operative studies on this important issue
in pancreatic cancer therapy is urgently needed.
7
UI - 11915726
AU - Okada S
TI -
[Radiotherapy and chemotherapy for unresectable pancreatic cancer]
SO - Gan To Kagaku Ryoho 2002 Mar;29(3):376-82
AD - Hepatobiliary and Pancreatic Oncology Division, National Cancer Center
Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Despite many advances in the diagnosis of pancreatic cancer (PC), only a
small minority of patients are candidates for surgical resection with
curative intent. Moreover, even for these selected patients, the
prognosis remains unfavorable because of postoperative recurrence.
Accordingly, to improve the prognosis of PC, there is an urgent need to
develop effective non-surgical treatments for this disease. Radiotherapy
(RT) alone does not have a significant clinical impact in PC, but when
combined with chemotherapy (CHT), it provides a survival benefit in
locally unresectable PC. However, to establish optimal methods of
combining RT with CHT, newer approaches such as specialized RT
techniques and new CHT agents are actively being pursued. At present CHT
for PC has only limited value in clinical practice due to the lack of
any individual agent with a truly high level of activity. The strategies
for effective CHT in PC include biochemical modulation of anticancer
agents, multi-agent CHT, and new agents with different mechanisms of
action. Among these strategies, the identification of more effective new
agents is a high priority in developing a truly effective CHT for PC.
The novel nucleoside analog gemcitabine has the potential to produce
better results than those achieved with 5-FU, and has been accepted as
first-line CHT for patients with advanced PC. Moreover, increased
understanding of the biology of PC should facilitate the development of
entirely novel treatment options. We must continue to actively search
for more effective non-surgical treatments for PC.
8
UI - 11915727
AU - Homma H; Niitsu Y
TI -
[A new regional arterial infusion chemotherapy for patients with
advanced pancreatic cancer]
SO - Gan To Kagaku Ryoho 2002 Mar;29(3):383-9
AD - Gastroenterology Center, Tokeidai Hospital, 2-3 North 1 East 1, Chuo-ku,
Sapporo 060-0031, Japan.
Various arterial infusion chemotherapies have been tried for the purpose
of local control of advanced pancreatic carcinoma. However, these
treatments were not effective against the primary lesion because of its
special anatomical position and the complex hemodynamics, although they
were effective against the liver metastases. Therefore, the vascular
supply distribution was altered by superselective embolization to
control the primary legion in the pancreas, after transcatheter
peripancreatic arterial embolization toward the primary site.
Furthermore, bilateral (hepatic and splenic) arterial infusion
chemotherapy was applied to both the primary site and liver metastasis.
As a result, the response rate was 73.9%, with a mean survival period
18.26 +/- 10.06 months. We believe that the current chemotherapy was an
effective treatment for unresectable pancreatic cancer since it was
possible to treat patients with little harm to their quality of life.
9
UI - 11915728
AU - Yahara N; Oka M
TI -
[Immunotherapy for unresectable pancreatic cancer]
SO - Gan To Kagaku Ryoho 2002 Mar;29(3):390-7
AD - Dept. of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi
University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi
755-8505, Japan.
To treat unresectable pancreatic cancer, we have performed cell
therapies using lymphokine-activated killer cell, cytotoxic T
lymphocytes (CTLs) induced by mixed lymphocyte culture (MLC) with
autologous tumor cells, and CTL recognizing MUC1 induced by MLC with an
allogeneic pancreatic tumor cells line, YPK-1. CTL therapy was effective
in some cases. We also performed cell therapy using MUC1 peptide-pulsed
dendritic cells (MUC1-DCs) and MUC1-CTLs. This therapy was effective in
one of three cases so far. Cancer peptide vaccine therapy trials for
unresectable pancreatic cancer are also ongoing. Cell therapy and
peptide vaccine therapy may be promising approaches for unresectable
pancreatic cancer.
10
UI - 11900219
AU - Shojamanesh H; Gibril F; Louie A; Ojeaburu JV; Bashir S; Abou-Saif A;
TI -
Jensen RT
Prospective study of the antitumor efficacy of long-term octreotide
treatment in patients with progressive metastatic gastrinoma.
SO - Cancer 2002 Jan 15;94(2):331-43
AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive
and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
20892-1804, USA.
BACKGROUND: Malignant pancreatic endocrine tumors (PETs) have a poor
prognosis and existing antitumor treatments are unsatisfactory. Recent
studies have shown somatostatin analogues to have antitumor growth
effects in patients with malignant PETs; however, to the authors'
knowledge, little information exists regarding their efficacy or effect
on survival in patients with progressive malignant gastrinoma, the most
common symptomatic malignant PET. The purpose of the current study was
to study prospectively the efficacy, safety, and effect on survival of
long-term treatment with octreotide in consecutive patients with
progressive malignant gastrinoma. METHODS: Fifteen consecutive patients
with malignant gastrinoma with progressive hepatic metastases were
studied. All patients underwent conventional imaging studies (computed
tomography scan, magnetic resonance imaging, ultrasound, and, if needed,
selective angiography) and somatostatin receptor scintigraphy prior to
treatment and at 3-6-month intervals while receiving treatment. The
patients all were treated initially with octreotide, 200 microg every 12
hours, and at last follow-up were being maintained on long-acting
release octreotide, 20-30 mg every month. Tumor size and/or number were
used to classify patient responses as either no tumor response or tumor
response (stabilization or decrease in size). Treatment response was
correlated with tumor and clinical characteristics. RESULTS: Tumors in 8
of the 15 patients studied (53%) responded at 3 months, with 47% (7 of
15 patients) demonstrating tumor stabilization and 6% (1 of 15 patients)
demonstrating a decrease in tumor size. The mean duration of response
was 25.0+/-6.1 months (range, 5.5-54.1 months). Six of the eight
responders were continuing to respond at the time of last follow-up.
Tumor response did not correlate with any clinical parameter (e.g.,
tumor extent, fasting gastrin, or acid secretory rates). However,
slow-growing tumors were more likely to respond prior to treatment (86%
vs. 0%) (P < 0.0014). During follow-up (range, 4-8 years), 25% of the
responders died compared with 71% of the nonresponders, a difference
that approached statistical significance (P = 0.10). Two patients (13%)
developed serious side effects that required the withdrawal of
octreotide. CONCLUSIONS: Octreotide is an effective antitumor treatment
in patients with progressive malignant gastrinoma. In approximately 50%
of these patients octreotide has an antigrowth effect; treatment is
associated with a low incidence of serious side effects compared with
other antitumor treatments commonly used and, in contrast to many
studies, the growth response is long-lasting. The results of the current
study suggest that octreotide treatment should replace chemotherapy as
the standard treatment for these patients, especially those patients
with slow-growing tumors. Additional studies involving larger numbers of
patients will be needed to determine a convincing effect on survival.
11
UI - 11865376
AU - Jang JY; Kim SW; Park SJ; Park YH
TI -
Comparison of the functional outcome after pylorus-preserving
pancreatoduodenectomy: pancreatogastrostomy and pancreatojejunostomy.
SO - World J Surg 2002 Mar;26(3):366-71
AD - Department of Surgery, Seoul National University College of Medicine, 28
Yongon-dong Chongno-ku, Seoul 110-744, Korea.
To determine if there is any difference in pancreatic function after
pylorus-preserving pancreatoduodenectomy(PPPD) according to the type of
pancreatoenterostomy [pancreatojejunostomy (P-J) or pancreatogastrostomy
(P-G)], we evaluated the long-term functional status of 34 patients who
underwent PPPD and survived for more than 1 year without clinical
evidence of recurrence. Altogether 20 patients underwent P-J and 14 P-G.
To compare the two groups, we analyzed the (1) general nutritional
status; (2) quality of life using three scoring systems; (3)
gastrointestinal symptoms; and (4) pancreatic exocrine function by the
stool elastase I test and endocrine function by oral glucose tolerance
test (GTT). After PPPD, body weight decreased in both groups, with no
difference between the two groups. No statistical differences were found
in triceps skinfold thickness or serum protein/albumin. Regarding the
quality of life and postoperative gastrointestinal symptoms, there were
no differences between the two groups except steatorrhea. There were 4
mild and 15 severe cases of pancreatic exocrine insufficiency among
those who underwent P-J, whereas all of the patients who underwent P-G
showed severe pancreatic insufficiency. On GTT, excluding preoperative
diabetes patients, 43.8% (7/16) of the P-J group had abnormal results
after surgery, whereas 75.0% (9/12) of the PG group had an abnormal
postoperative GTT (p = 0.11). Severe exocrine and endocrine pancreatic
insufficiency developed after PPPD in both the P-J and P-G groups, but
there was more functional deterioration in the P-G group than in the P-J
group. General nutritional status and quality of life were not affected
by the pancreatoenterostomy method in either group.
12
UI - 11870159
AU - Rocha Lima CM; Savarese D; Bruckner H; Dudek A; Eckardt J; Hainsworth J;
TI -
Yunus F; Lester E; Miller W; Saville W; Elfring GL; Locker PK; Compton
LD; Miller LL; Green MR
Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor
marker responses in patients with previously untreated advanced
pancreatic cancer.
SO - J Clin Oncol 2002 Mar 1;20(5):1182-91
AD - H. Lee Moffitt Cancer Center, University of South Florida,
Gastrointestinal Program Office, Tampa, FL 33612, USA.
rochalcm@moffitt.usf.edu
PURPOSE: This phase II, multicenter, open-label, single-arm study
evaluated the efficacy and safety of irinotecan and gemcitabine as
combination chemotherapy for previously untreated patients with
unresectable or metastatic pancreatic cancer. PATIENTS AND METHODS:
Patients received repeated 21-day cycles at starting doses of
gemcitabine 1,000 mg/m(2) over 30 minutes followed immediately by
irinotecan 100 mg/m(2) over 90 minutes, both given intravenously on days
1 and 8. Patients were evaluated for objective tumor response, changes
in the serum tumor marker CA 19-9, time to tumor progression (TTP),
survival, and safety. RESULTS: Forty-five patients were treated. Eleven
patients (24%) had 50% or greater reductions in tumor area. These were
confirmed one cycle later in nine patients (response rate, 20%; 95%
confidence interval, 8% to 32%). Among 44 patients with baseline CA 19-9
determinations, CA 19-9 decreased during therapy in 22 patients (50%)
and was reduced by 50% or more in 13 patients (30%). Median TTP was 2.8
months (range, 0.3 to 10.8 months). There were significant (P <.001)
correlations between proportional changes in CA 19-9 and radiographic
changes in tumor area with regard to extent of change (r =.67), timing
of minimum on-study values (r =.85), and tumor progression (r =.89).
Median survival was 5.7 months (range, 0.4 to 19.4+ months), and the
1-year survival rate was 27%. Severe toxicities were uncommon and
primarily limited to grade 4 neutropenia (2%), grade 4 vomiting (2%),
and grade 3 diarrhea (7%). CONCLUSION: Irinotecan/gemcitabine is a new
combination that offers encouraging activity in terms of radiographic
and CA 19-9 response and notable 1-year survival in pancreatic cancer.
The regimen was well tolerated, with minimal grade 3 and 4 toxicities
and excellent maintenance of planned dose-intensity.
13
UI - 11753801
AU - Hohenberger W; Schoolmann S; Kastl S
TI -
[Quality management in surgery: treatment of pancreatic carcinoma--What
is evidence-based?]
SO - Zentralbl Chir 2001 Nov;126(11):901-7
AD - Chirurgische Universitatsklinik Erlangen, Germany.
Summary.The term "evidence-based medicine" (EBM) - an Anglicism in
common use in modern medicine - has of the nature of a catchword, the
actual meaning of which is not always clear to all who use it. Generally
speaking it is taken to mean that decision-making in the areas of
diagnosis and treatment is based on data obtained from randomized,
preferably double-blind and controlled, studies involving sufficient
numbers of cases. This, however, is not always automatically equatable
with arriving at a decision at the highest level of confirmed scientific
knowledge, including the most recently acquired facts. Taking account of
the current literature, the present article attempts an analysis of the
following four aspects of surgical treatment of pancreatic carcinoma:
the required extent of lymph node dissection, the relevance of
multimodal treatment concepts, the significance of pylorus-preserving
partial duodenopancreatectomy and the relevance of portal vein
resection.
14
UI - 11753802
AU - Adam U; Makowiec F; Riediger H; Trzeczak S; Benz S; Hopt UT
TI -
[Distal pancreatic resection--indications, techniques and complications]
SO - Zentralbl Chir 2001 Nov;126(11):908-12
AD - Chirurgische Universitatskliniken Rostock und Freiburg, Germany.
AIM: Description of the indications, surgical technique and
postoperative complications of distal pancreatic resection. METHODS: We
analyzed the prospectively documented perioperative data of 41 patients
undergoing distal pancreatectomy between 1994 and 2001. Indications for
resection were chronic pancreatitis (n = 21), malignant or benign tumors
(n = 19) and others (n = 1). RESULTS: Median operation time was 4.5
hours, a Y-Roux-pancreaticojejunostomy was performed in 66 %. Further
organs were resected in 93 %, most frequently in form of splenectomy. A
malignant vascular invasion led to positive resection margins in three
patients. Mortality was 2 %. Postoperative complications occurred in 41
% with 15 % revealing pancreatic leakage. A relaparotomy was carried out
in 20 %. Pancreatic leakage was more frequently seen in the first part
of the study period and after oversewing of the pancreatic stump. A new
onset diabetes occurred postoperatively in 6 % of the patients.
CONCLUSIONS: Distal pancreatectomy can be carried out with low
mortality, despite a high complication rate. The probability of
postoperative diabetes is low. The frequency of pancreatic leakage may
be reduced significantly by increasing hospital experience. The
management of the pancreatic stump by pancreatojejunostomy should be
considered in patients with a high risk of pancreatic leakage.
15
UI - 11753803
AU - Stumpf M; Kasperk R; Bertram P; Truong S; Schumpelick V
TI -
[Role of surgical biliary bypass for palliation of pancreatic cancer - a
retrospective study of 107 cases]
SO - Zentralbl Chir 2001 Nov;126(11):913-6
AD - Chirurgische Klinik und Poliklinik, Medizinische Fakultat,
Rheinisch-Westfalische Technische Hochschule, Aachen, Germany.
BACKGROUNDS AND STUDY AIMS: At the time of diagnosis most patients with
pancreatic cancer are still irresectable for cure. The aim of this study
was to evaluate surgical palliation, in particular against the
background of endoscopic stent placement. PATIENTS AND METHODS: This
retrospective study analyses the therapeutic results in 107 patients
with an irresectable pancreatic carcinoma operated on between 1990 and
1998. RESULTS: 104 patients showed primary therapeutic success with
adequate bile drainage. In 97 % a simultaneous gastrojejunostomy was
performed. The overall complication rate was 24 % and the hospital
mortality 3.7 %. Median survival after surgical treatment was 201 days.
CONCLUSIONS: Because of a decrease in perioperative morbidity and
mortality, surgical palliation of irresectable pancreatic carcinoma
still remains an effective therapy, especially for patients expected to
survive 6 months or more. The surgical procedure offers the better
chance for long-term palliation of obstructive jaundice and duodenal
obstruction compared to the endoscopic approach. However, to consider
both, the surgical and the endoscopic treatment, complementing each
other, seems to be important to guarantee optimal palliation for the
individual patient.
16
UI - 11762810
AU - Halford S; Yip D; Karapetis CS; Strickland AH; Steger A; Khawaja HT;
TI -
Harper PG
A phase II study evaluating the tolerability and efficacy of CAELYX
(liposomal doxorubicin, Doxil) in the treatment of unresectable
pancreatic carcinoma.
SO - Ann Oncol 2001 Oct;12(10):1399-402
AD - Department of Medical Oncology, Guy's Hospital, London, UK.
BACKGROUND: Preclinical studies of liposomal doxorubicin (CAELYX) have
demonstrated significant inhibition of growth of human pancreatic cancer
explants in nude mice. This study evaluated the efficacy of CAELYX in
chemotherapy-naive patients with unresectable, histologically confirmed
pancreatic carcinoma. Secondary endpoints were quality of life (QOL).
time to progression and overall survival. PATIENTS AND METHODS:
Twenty-two patients (median age 65) were enrolled. CAELYX was
administered to the first five patients at a dose of 30 mg/m2
three-weekly. Two of these patients were dose escalated to 50 mg/m2
four-weekly. Subsequent patients were all treated on the latter
schedule. RESULTS: Two patients died after consenting to enter the study
but before treatment was commenced and are not included in the analysis.
Sixteen patients were evaluable for response. No objective responses
were seen. Six patients had stable disease. One patient experienced
grade 4 toxicity with palmar plantar dysaesthesia (PPE), but continued
treatment after dose reduction and delay. Four patients experienced
grade 3 stomatitis and two grade 3 nausea. Median survival from time of
starting chemotherapy was 3.2 months (range 21 days to 19 months) and
one year survival was 10%. Eight patients completed at least two EORTC
QLQ C-30 questionnaires. There was no significant change in either
global QOL or in any functional or symptom subscale score. CONCLUSION:
No objective responses were seen with CAELYX in this study. CAELYX was
however associated with stable disease, but data were inconclusive with
regard to clinical benefit. It warrants further investigation in the
context of combination trials.
17
UI - 11807364
AU - Murakami H; Suzuki H; Nakamura T
TI -
Pancreatic fibrosis correlates with delayed gastric emptying after
pylorus-preserving pancreaticoduodenectomy with pancreaticogastrostomy.
SO - Ann Surg 2002 Feb;235(2):240-5
AD - Department of Surgery, Kainan Hospital, Aichi, Japan.
OBJECTIVE: To show that residual pancreatitis delays gastric emptying,
the authors used surgical specimens and studied gastric stasis after
pylorus-preserving pancreaticoduodenectomy (PPPD). SUMMARY BACKGROUND
DATA: Delayed gastric emptying is a leading cause of complications after
PPPD, occurring in 30% of patients. The pathogenesis of delayed gastric
emptying remains unclear. METHODS: Surgical specimens of the pancreas
from 25 patients undergoing PPPD and pancreaticogastrostomy were
collected and examined by microscopy according to progressive pancreatic
fibrosis and divided into three groups: no fibrosis, periductal
fibrosis, and intralobular fibrosis. The authors then measured gastric
output from the nasogastric tube, pancreatic output from the pancreatic
tube, and the time until patients tolerated a solid diet. RESULTS:
Pancreatic juice output was significantly related to the degree of
pathologic findings, and gastric output was inversely related to them. A
significant prolongation of postoperative solid diet tolerance
correlated with increased pancreatic fibrosis and gastric fluid
production. CONCLUSIONS: Pancreatic fibrosis and increased gastric fluid
production correlate with delayed gastric emptying after PPPD with
pancreaticogastrostomy.
18
UI - 11807377
AU - Krouse RS; Chu DZ; Grant M; Ferrell B; Wagman LD
TI -
Evaluation of quality of life (QOL) in pancreaticoduodenectomy
survivors.
SO - Ann Surg 2002 Feb;235(2):310-1
19
UI - 11920457
AU - Colucci G; Giuliani F; Gebbia V; Biglietto M; Rabitti P; Uomo G;
TI -
Cigolari S; Testa A; Maiello E; Lopez M
Gemcitabine alone or with cisplatin for the treatment of patients with
locally advanced and/or metastatic pancreatic carcinoma: a prospective,
randomized phase III study of the Gruppo Oncologia dell'Italia
Meridionale.
SO - Cancer 2002 Feb 15;94(4):902-10
AD - Medical and Experimental Oncology Unit, Oncology Institute, Bari, Italy.
colucci@goim.it
BACKGROUND: A prospective, randomized Phase III trial was performed to
determine whether, compared with gemcitabine (GEM) alone, the addition
of cisplatin (CDDP) to GEM was able to improve the time to disease
progression and the clinical benefit rate in patients with advanced
pancreatic adenocarcinoma. The objective response rate, overall survival
rate, and toxicity patterns of patients in the two treatment arms were
evaluated as secondary end points. METHODS: Patients with measurable,
locally advanced and/or metastatic pancreatic adenocarcinoma were
randomized to receive GEM (Arm A) or a combination of GEM and CDDP (Arm
B). In Arm A, a dose of 1000 mg/m(2) GEM per week was administered for 7
consecutive weeks, and, after a 2-week rest, treatment was resumed on
Days 1, 8, and 15 of a 28-day cycle for 2 cycles. In Arm B, CDDP was
given at a dose of 25 mg/m(2) per week 1 hour before GEM at the same
dose that was used in Arm A. On Day 22, only GEM was administered.
Patients were restaged after the first 7 weeks of therapy and then again
after the other 2 cycles. RESULTS: A total of 107 patients entered the
trial: Fifty-four patients were randomized to Arm A, and 53 patients
were randomized to Arm B. The median time to disease progression was 8
weeks in Arm A and 20 weeks in Arm B; this difference was statistically
significant (P = 0.048). In Arm A, one complete response and four
partial responses were recorded on the basis of an intent-to-treat
analysis, with an overall response rate of 9.2% (95% confidence interval
[95%CI], 3-20%). In Arm B, there were no complete responses, whereas 14
partial responses were achieved, with an overall response rate of 26.4%
(95%CI, 15-40%). This difference in the overall response rates was
statistically significant (P = 0.02). The tumor growth control rate
(i.e., total number of patients who achieved complete responses, partial
responses, and stable disease) was 42.6% (95%CI, 29-57%) in Arm A and
56.6% (95%CI, 42-70%) in Arm B. A clinical benefit was observed in 21 of
43 patients (49%) in Arm A and in 20 of 38 patients (52.6%) in Arm B
without any significant difference. The median overall survival was 20
weeks for patients in Arm A and 30 weeks for patients in Arm B (P =
0.43). Toxicity was mild in both treatment arms, with no significant
differences between the two groups except for the statistically higher
incidence of Grade 1-2 asthenia in Arm B (P = 0.046). CONCLUSIONS: The
addition of CDDP to GEM significantly improved the median time to
disease progression and the overall response rate compared with GEM
alone. The clinical benefit rate was similar in both arms, whereas the
median overall survival rate was more favorable for Arm B, although the
difference did not attain statistical significance. The authors conclude
that the combination of CDDP and GEM currently may be considered as an
optimal treatment for patients with locally advanced and/or metastatic
adenocarcinoma of the pancreas. Copyright 2002 American Cancer Society.
DOI 10.1002/cncr.10323
20
UI - 11875595
AU - Wiersema MJ
TI -
Identifying contraindications to resection in patients with pancreatic
carcinoma: the role of endoscopic ultrasound.
SO - Can J Gastroenterol 2002 Feb;16(2):109-14
AD - Eisenberg 8A, Mayo Clinic, 200 First Street SW, Rochester, MN 55905,
USA. wiersema.maurits@mayo.edu
OBJECTIVE: To present recently published material comparing the
performance of endosonography relative to other imaging modalities when
evaluating the patient with a suspected or known pancreas carcinoma.
METHODS: Medline was searched using the terms "endosonography" and
"pancreas neoplasms". References from retrieved papers were reviewed to
identify other reports. Emphasis was placed on peer-reviewed material
published within the past three years that included comparison with
other imaging modalities. RESULTS: Despite advances in cross-sectional
imaging modalities, endosonography remains the most sensitive and
specific method for identifying pancreatic mass lesions. The
resectability of pancreatic carcinoma is best determined with dual-phase
helical computed tomography, although endosonography may be slightly
more accurate for lymph node assessment. Endoscopic ultrasound-guided
fine needle aspiration biopsy has a high sensitivity (93%) and
specificity (100%) when used in patients with masses in whom pancreatic
cancer is suspected but prior biopsies have been negative. CONCLUSIONS:
Endosonography helps in the diagnosis of pancreatic neoplasms through
definitive inclusion or exclusion of a mass lesion as well as biopsy
confirmation of malignancy. The role of endosonography in the
determination of resectability has been eclipsed by dual-phase helical
computed tomography. However, endoscopic ultrasound with fine needle
aspiration of nonperitumoral lymph nodes may identify advanced disease
with sufficient frequency to justify its routine use in patients with
lesions that are thought to be resectable based on helical computed
tomography.
21
UI - 11875596
AU - Beger HG; Gansauge F; Leder G
TI -
Pancreatic cancer: who benefits from curative resection?
SO - Can J Gastroenterol 2002 Feb;16(2):117-20
AD - Department of General Surgery, University Hospital, University of Ulm,
Steinhovelstrasse 9, D-89075 Ulm Donau, Germany.
hans.beger@medizin.uni-ulm.de
Surgical resection is the only chance for cure of pancreatic cancer.
Unfortunately, the majority of patients have grossly unresectable
disease. Patients with stage I or II disease according to the criteria
of the International Union Against Cancer (UICC) should be considered
for potentially curative surgery. The goal of surgery is to remove the
entire tumour with no residual disease (oncological R0 resection), which
requires extensive resection of the surrounding tissues. Even if lymph
nodes are histologically free of disease, molecular biological
techniques reveal infiltration with cancer cells in 50% of cases.
Therefore, extensive local resection combined with radical resection of
lymphatic tissue, including lymph nodes around the head of the pancreas,
retroperitoneal tissue and neural plexus around the great vessels,
affords a longer median survival time than standard resection alone.
Even patients with UICC stage III disease can undergo aggressive
surgical treatment, but their chances for long term survival are low.
Some patients develop severe diarrhea after circumferential removal of
nerve tissue around the superior mesenteric artery. Adjuvant
radiochemotherapy also provides a modest prolongation of survival.
Despite these advances, the prognosis for pancreatic cancer is still
poor, and spread of tumour within the peritoneum and to the liver is
common postoperatively.
22
UI - 11875597
AU - Moore MJ
TI -
Pancreatic cancer: what the oncologist can offer for palliation.
SO - Can J Gastroenterol 2002 Feb;16(2):121-4
AD - Department of Medicine, Princess Margaret Hospital, University of
Toronto, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada.
malcolm.moore@uhn.on.ca
Because pancreatic cancer has a poor survival rate and only 20% of
patients present with potentially resectable disease, a key goal of
therapy is to provide palliation. The poor medical condition of many
patients interferes with their ability to tolerate traditional
chemotherapy. Recently, however, a nucleoside analogue, gemcitabine, has
been developed. This drug is more effective than 5-fluorouracil (5-FU),
can be used in patients who fail to respond to 5-FU and has only modest
toxicity. Combination therapies including gemcitabine and other agents
are being tested. Local radiotherapy seems to provide pain relief, but
gastrointestinal toxicity is significant. The effect of combined
modality therapy (5-FU with radiotherapy) on survival is unclear, and it
does not prevent local disease progression. Some novel biological
agents, including angiogenesis inhibitors, matrix metalloproteinase
inhibitors, antisense compounds, inhibitors of cell signalling such as
epidermal growth factor and vascular endothelial growth factor, and
inhibitors of oncogene activation, are undergoing phase II and III
trials in patients with pancreatic cancer. Among the most promising are
farnesyl protein transferase inhibitors, which modulate K-ras function.
Such an approach is promising for the treatment of pancreatic cancer
because this tumour frequently exhibits mutation of the ras gene.
23
UI - 11894005
AU - Heinemann V
TI -
Gemcitabine-based combination treatment of pancreatic cancer.
SO - Semin Oncol 2002 Feb;29(1 Suppl 3):25-35
AD - Klinikum Grosshadern, III Medical Clinic, Munich, Germany.
Since the introduction of gemcitabine (Gemzar; Eli Lilly and Company,
Indianapolis, IN), pancreatic cancer may no longer be regarded as a
completely chemotherapy-resistant tumor. Good treatment tolerability and
a low incidence of side effects are clear advantages of single-agent
gemcitabine and enable its integration into combination regimens.
Currently, the most widely used regimens involve combination partners
such as 5-fluorouracil (5-FU), cisplatin, and docetaxel. Combinations of
gemcitabine with cisplatin or 5-FU appear comparably active and
tolerable. Comparative analysis of multiple phase II studies performed
with gemcitabine/cisplatin showed response rates in the range of 11.4%
to 58% and median survival times of 7.4 to 10 months, whereas various
gemcitabine/5-FU-based regimens achieved response rates of 3.7% to 25%
and median survival times of 4.4 to 10.3 months. In view of the great
variety of schedules and inconclusive treatment results, an optimal
regimen for the combination of 5-FU and gemcitabine still needs to be
defined. Although the combination of gemcitabine with docetaxel has
demonstrated activity, data showing a clear survival benefit are not yet
available. It is also premature to evaluate the activity of combinations
with irinotecan or oxaliplatin. Four-drug regimens indicate a possible
improvement in treatment outcome. However, their application may be
limited to selected patients with good performance status. Copyright
2002, Elsevier Science (USA). All rights reserved.
24
UI - 11896099
AU - Louvet C; Andre T; Lledo G; Hammel P; Bleiberg H; Bouleuc C; Gamelin E;
TI -
Flesch M; Cvitkovic E; de Gramont A
Gemcitabine combined with oxaliplatin in advanced pancreatic
adenocarcinoma: final results of a GERCOR multicenter phase II study.
SO - J Clin Oncol 2002 Mar 15;20(6):1512-8
AD - Service d'Oncologie-Medecine Interne, Hopital Saint-Antoine, Service
d'Oncologie, Hopital Tenon, and GERCOR, Paris, France.
christophe.louvet@sat.ap-hop-paris.fr
PURPOSE: Based on preclinical in vitro synergy data, this study
evaluated the activity and toxicity of a gemcitabine/oxaliplatin
combination in patients with metastatic and locally advanced pancreatic
adenocarcinoma. PATIENTS AND METHODS: Previously untreated metastatic
and locally advanced unresectable pancreatic adenocarcinoma patients
were enrolled onto this multicenter phase II study. Patients received
gemcitabine 1,000 mg/m(2) as a 10-mg/m(2)/min infusion on day 1 and
oxaliplatin 100 mg/m(2) as a 2-hour infusion on day 2 every 2 weeks.
Patients with metastatic disease were treated until evidence of
progressive disease, whereas patients with locally advanced disease
received six cycles in the absence of progression, followed when
appropriate by concomitant radiochemotherapy. RESULTS: Among 64 eligible
patients included in eight centers, 30 had locally advanced and 34 had
metastatic disease. Response rate for the 62 patients with measurable
disease was 30.6% (95% confidence interval, 19.7% to 42.3%), 31.0% for
locally advanced and 30.3% for metastatic patients. Among 58 assessable
patients, 40% had clinical benefit. Median progression-free survival and
median overall survival (OS) were 5.3 and 9.2 months, respectively, with
36% of patients alive at 1 year. Median OS for patients with metastatic
disease and locally advanced disease were 8.7 and 11.5 months,
respectively. With 574 treatment cycles (median per patient, nine;
range, zero to 27), grade 3/4 toxicity per patient was 11% for
neutropenia and thrombocytopenia, 14% for nausea or vomiting, 6.2% for
diarrhea, and 11% for peripheral neuropathy, with no toxic deaths.
CONCLUSION: Palliative effects, response rate, and survival observed
with this well-tolerated gemcitabine/oxaliplatin combination deserve
additional evaluation. A comparative study of combination therapy versus
gemcitabine alone is ongoing.
25
UI - 11819168
AU - Gebhardt C
TI -
[Pancreaticojejunal anastomosis. Indication, technique and results]
SO - Zentralbl Chir 2001;126 Suppl 1():29-31
AD - Klinik fur Abdominal, Thorax und Endokrine Chirurgie, Klinikum Nurnberg
Nord.
Pancreaticojejunal anastomosis. Indication, technique and
results.Pancreaticojejunal anastomoses are performed for the treatment
of chronic pancreatitis and after resection of pancreatic carcinomas. In
chronic pancreatitis by drainage procedures (Partington-Rochelle and
Puestow-Gillesby) one can expect good long term results, if the diameter
of the pancreatic duct is at least 1 cm and the length of the
anastomosis 6 cm. The duodenumpreserving head resection (Beger or Frey)
is a combination of resection and drainage and is significant in the
therapy of inflammatory head processes. In the surgical treatment of
pancreatic carcinomas pancreaticojejunostomies are applied after head
resection (Whipple-, pyloruspreserving modification). The end-to-side
mucosa-mucosa anastomosis offers the best results concerning
postoperativ complications and mortality rates.
26
UI - 11925720
AU - Ducreux M; Baudin E; Schlumberger M
TI -
[Treatment strategy of neuroendocrine tumors]
SO - Rev Prat 2002 Feb 1;52(3):290-6
AD - Unite de gastroenterologie Institut Gustave Roussy 94805 Villejuif.
ducreux@igr.fr
Therapeutic strategy of neuroendocrine tumours is complex, due to their
heterogeneity and to the fact that although generally slow growing, a
significant proportion demonstrates aggressive tumour growth.
Symptomatic carcinoid syndrome and various pancreatic endocrine tumours
with symptomatic syndromes are well controlled with somatostatin
analogues. Surgery remains the mainstay of treatment if the tumour can
be resected. Metastatic pancreatic neuroendocrine tumour are treated
when resection is not feasible with combination chemotherapy using
adriamycin and streptozotocin, which remains a standard of care. In well
differentiated tumour of the gut or the lung there is no clear standard
of chemotherapy and treatment vary according to the tumour course. In
indolent cases, somatostatin analogues are the best treatment, in case
of aggressive tumours chemoembolisation should be preferred when the
disease is located or predominant in the liver. Poorly differentiated
tumours are treated by combination chemotherapy with etoposide and
cisplatin, and surgery has no indication. Gastrinoma and other
pancreatic tumours arising in the context of multiple endocrine
neoplasia type I disease need a specific therapeutic strategy.
27
UI - 9717985
AU - Von Hoff DD; Goodwin AL; Garcia L
TI -
Advances in the treatment of patients with pancreatic cancer:
improvement in symptoms and survival time. The San Antonio Drug
Development Team.
SO - Br J Cancer 1998;78 Suppl 3():9-13
AD - Institute for Drug Development, Cancer Therapy & Research Center, San
Antonio, Texas 78245, USA.
Pancreatic cancer is a major cause of death from cancer in both men and
women in the USA and Europe. The disease causes pain and has a
significant impact on the performance status of the patient. In a
randomized trial vs 5-fluorouracil, the novel nucleoside analogue
gemcitabine (GEMZAR) has been shown to provide clinical benefit for
patients (decreased pain and improved performance status) as well as to
improve the time to tumour progression and survival for patients with
the disease. There are also other new agents that are presented in this
discussion, such as the multi-targeted antifolate MTA, capecitabine and
the ONYX-015 adenovirus, which replicates in, and kills, only
p53-abnormal cells, which have the potential to have an impact on this
terrible disease.
28
UI - 10226533
AU - Kornmann M; Kleeff J; Debinski W; Korc M
TI -
Pancreatic cancer cells express interleukin-13 and -4 receptors, and
their growth is inhibited by Pseudomonas exotoxin coupled to
interleukin-13 and -4.
SO - Anticancer Res 1999 Jan-Feb;19(1A):125-31
AD - Department of Medicine, University of California, Irvine 92697, USA.
mkorc@uci.edu
BACKGROUND: Interleukin (IL)-13 and -4 are multifunctional cytokines
that bind to specific cell-surface receptors. The aim of this study was
to determine whether pancreatic cancer cells express either receptor,
and to assess the growth suppressive effects of chimeric proteins
composed of a Pseudomonas exotoxin (PE) A mutant (PE38QQR) fused to
IL-13 (IL-13-PE38QQR) or IL-4 (IL-4-PE38QQR) in these cells. MATERIALS
AND METHODS: Northern and Western blot analysis were used to analyze the
expression of IL-4/-13 receptors and the common gamma chain (gamma c) in
pancreatic cancer cell lines. MTT growth assays were carried out to
assess the effect
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