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Abramson Cancer CenterNCI CANCERLIT® Search: Therapy of Pancreatic Cancer - October 2001
National Cancer Institute®
Last Modified: November 21, 2001
Table of Contents
1
UI - 21417774
AU - Gazdar AF; Minna JD
TI -
Targeted therapies for killing tumor cells.
SO - Proc Natl Acad Sci U S A 2001 Aug 28;98(18):10028-30
AD - Hamon Center for Therapeutic Oncology Research and Department of
Pathology, University of Texas Southwestern Medical Center, Dallas, TX
75390, USA.
2
UI - 21271459
AU - Kobayashi S; Asano T; Ochiai T
TI -
A proposal of no-touch isolation technique in pancreatoduodenectomy for
periampullary carcinomas.
SO - Hepatogastroenterology 2001 Mar-Apr;48(38):372-4
AD - Second Department of Surgery, Chiba University School of Medicine, 1-8-1
Inohana, Chuoh-ku, Chiba 260-8670, Japan. kobayasi@med.m.chiba-u.ac.jp
BACKGROUND/AIMS: The procedure of pancreatoduodenectomy for
periampullary cancers accompanies a risk to shed cancer cells into a
portal vein while handling the pancreas head lesion. This manipulation
may subsequently cause a liver metastasis. We devised the no-touch
isolation technique for pancreatoduodenectomy without removing a portal
vein, for the purpose of preventing the manipulated shedding of cancer
cells into a portal vein and liver metastasis. METHODOLOGY: The
fundamental procedure of this technique is that isolation of portal vein
precedes the handling of tumor mass. Isolation of a portal vein is
carried out with the ligature of its surrounding veins after dividing of
duodenum and pancreas. We applied the no-touch isolation technique for
10 cases, which consisted of 6 cases of distal bile duct carcinoma and 4
There was neither operative mortality nor liver metastasis cases in
these cases. CONCLUSIONS: The no-touch isolation technique without
removing a portal vein might be recommended as a safe and reasonable
procedure for periampullary cancer patients who have the potential for
subsequent liver metastasis.
3
UI - 21271502
AU - Fujino Y; Suzuki Y; Kamigaki T; Mitsutsuji M; Kuroda Y
TI -
Evaluation of gastroenteric bypass for unresectable pancreatic cancer.
SO - Hepatogastroenterology 2001 Mar-Apr;48(38):563-8
AD - Department of Surgery I, Kobe University School of Medicine, 7-5-2
Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
BACKGROUND/AIMS: It is controversial as to whether gastroenteric bypass
is helpful for patients with unresectable pancreatic cancer. This study
was designed to evaluate the effects of gastroenteric bypass on dietary
intake and the symptoms of gastric outlet obstruction in these patients.
METHODOLOGY: We reviewed the cases of 101 patients with unresectable
pancreatic cancer surgically treated at the Kobe University Hospital.
The effects of gastroenteric bypass were examined by comparing the
dietary intake and the symptoms of gastric outlet obstruction on
admission, 1 month and 3 months after the operation. RESULTS: The
analyses of dietary intake and the symptoms indicated that the
gastroenteric bypass operation was not helpful for most of the patients
with unresectable pancreatic cancer. Multivariate logistic regression
model revealed that dietary intake on admission was the strongest
parameter for dietary intake at one month after operation. The patients
with a low dietary intake on admission often required a nasogastric tube
after the bypass operation, reflecting progression of the disease.
CONCLUSIONS: Gastroenteric bypass had no advantage to improve dietary
intake and symptoms for almost all the patients with unresectable
pancreatic cancer. It was effective only for patients with a high
dietary intake without symptoms of gastric outlet obstruction on
admission.
4
UI - 21271503
AU - Kato K; Morita T; Miyasaka Y; Fujita M; Kondo S; Katoh H
TI -
Modified Devine exclusion for unresectable pancreatic head carcinoma.
SO - Hepatogastroenterology 2001 Mar-Apr;48(38):569-71
AD - Department of Surgery, Hokkaido Gastroenterological Hospital, Honcho
1-1, Higashiku, Sapporo, 065-0041, Japan.
BACKGROUND/AIMS: Gastrojejunostomy is generally performed for
unresectable pancreatic head carcinoma. However, in the case of
conventional gastrojejunostomy, the bypass does not always function
effectively. METHODOLOGY: For unresectable pancreatic head carcinoma
accompanied by severe duodenal stenosis, conventional gastrojejunostomy
was performed in 5 cases, and modified Devine exclusion was performed in
7 cases. There were no significant differences between the groups
regarding their backgrounds. RESULTS: There were no significant
differences between the two groups for the average operation time, the
days before peroral ingestion and the hospital stay. The state of
peroral ingestion showed better results for modified Devine exclusion.
The discharge rates were better for modified Devine exclusion, showing a
significant difference (P = 0.028). The 50%-survival periods were 65
days and 159 days, respectively. The bleeding from the tumor occurred in
2 patients from the conventional gastrojejunostomy group, but none in
modified Devine exclusion group. CONCLUSIONS: Modified Devine exclusion
is a simple and effective technique for unresectable pancreatic head
carcinoma.
5
UI - 21348129
AU - Kawarada Y; Das BC; Naganuma T; Isaji S
TI -
Surgical treatment of pancreatic cancer. Does extended lymphadenectomy
provide a better outcome?
SO - J Hepatobiliary Pancreat Surg 2001;8(3):224-9
AD - First Department of Surgery, Mie University School of Medicine, 2-174
Edobashi, Tsu, Mie 514-8507, Japan.
The rate of curative resection of pancreatic cancer has increased as a
result of extended operations, but this has not led to any significant
improvement in postoperative outcome. No definite conclusions were drawn
in retrospective studies comparing outcome after standard and extended
operations, and there was almost no difference in outcome between the
two groups in a recent prospective randomized study. In addition,
extended procedures are very stressful operations that, in most
instances, impair the patient's quality of life (QOL). As a result, the
need for performing extended surgery to treat pancreatic cancer has come
into question. The outcome of advanced cancer in patients in whom
curative resection cannot be achieved by extended operations is
extremely poor, and we believe that, in such patients, priority should
be given to QOL, by selecting bypass or limited operations instead. It
is hoped that the value of extended surgery will be clarified by a very
carefully planned multicenter prospective randomized study in the
future.
6
UI - 21424855
AU - Stanford P
TI -
Surgical approaches to pancreatic cancer.
SO - Nurs Clin North Am 2001 Sep;36(3):567-77, xi
AD - Texas A&M University, Corpus Christi, Texas, USA.
Pancreatic cancer continues to be a significant health problem. Recent
advances in medical technologies allow patients with pancreatic cancer
to undergo diagnosis, staging, treatment, and palliation, and to
minimize the traditional use of laparotomy as a method of obtaining
information to facilitate treatment planning. Pancreatic surgery, which
can impact duration and quality of life, can be reserved for that subset
of patients likely to benefit from a surgical approach tailored to the
specific needs of the individual patient.
7
UI - 21381718
AU - Wolff RA; Evans DB; Gravel DM; Lenzi R; Pisters PW; Lee JE; Janjan NA;
TI -
Charnsangavej C; Abbruzzese JL
Phase I trial of gemcitabine combined with radiation for the treatment
of locally advanced pancreatic adenocarcinoma.
SO - Clin Cancer Res 2001 Aug;7(8):2246-53
AD - The Pancreatic Tumor Study Group, The University of Texas M. D. Anderson
Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
rwolff@mdanderson.org
Gemcitabine has modest activity in the treatment of advanced pancreatic
cancer and is a potent radiosensitizer. We conducted a Phase I trial to
determine the maximum tolerated dose of weekly gemcitabine delivered
concurrently with radiation therapy for the treatment of locally
advanced adenocarcinoma of the pancreatic head and to assess the
treatment-related toxic effects associated with such a regimen. Eighteen
patients with pathologically proven, locally advanced adenocarcinoma of
the pancreatic head were enrolled in this study. Patients received seven
weekly doses of gemcitabine with 3000 cGy of external beam radiation
therapy delivered during the first 2 weeks of therapy. Six patients
received gemcitabine at 350 mg/m(2)/week, nine at 400 mg/m(2)/week, and
three at 500 mg/m(2)/week. Grade 3-4 hematological toxicity was observed
in over half the patients treated. Nonhematological toxicities were
significant and included fatigue, anorexia, nausea, vomiting, and
dehydration. Forty-four % of the patients required admission to the
hospital for management of nausea/vomiting and dehydration. The risk of
hospitalization appeared to be dose-related; all of the three patients
treated at 500 mg/m(2)/week required hospital admission during
treatment. Seventeen patients were evaluated for response, and eight
patients (47%) had evidence of a local anticancer effect. Four of these
eight patients (24%) had a partial response to therapy. The median
survival for the entire group was 6 months. The 1-year survival rate for
patients with an objective response to therapy was 66%. The clinical
responses observed in this group of patients suggest gemcitabine is a
clinically relevant radiosensitizer in patients with pancreatic
adenocarcinoma. However, the toxic effects are significant, suggesting
that until dose and scheduling issues are explored further, concomitant
administration of gemcitabine and radiation therapy should still be
considered investigational.
8
UI - 21387639
AU - Ianniello GP; Orditura M; Rossi A; De Vita F; Maiorino L; Carrozza F;
TI -
Manzione L; Catalano G
Gemcitabine plus epirubicin in advanced pancreatic cancer: a phase II
multicenter trial.
SO - Oncol Rep 2001 Sep-Oct;8(5):1111-5
AD - Division of Medical Oncology, G. Rummo Hospital, Benevento, Italy.
orditura@sirio-oncology.it
The aim of this phase II multicenter trial was to evaluate the activity
of a novel combination of gemcitabine (GEM) and epirubicin (EPI) in
advanced pancreatic cancer patients. Clinical benefit and response rate
30 consecutive patients with measurable advanced pancreatic cancer were
enrolled. Gemcitabine was administered intravenously in 30 min at a dose
of 800 mg/m2 on days 1, 8, 15 followed by i.v. injection of epirubicin
25 mg/m(2); treatment was repeated every 28 days. With regard to
clinical benefit response, 8/21 patients (38%) experienced significant
palliation of tumor-related symptoms; the median symptom control time
was 25 weeks. No complete responses were recorded while 6 patients
achieved a partial remission, for an overall response rate of 20%; 10
patients (30%) had a stable disease and 14 (46%) had progressive
disease. The median time to progression was 14 weeks. Median survival
was 26 weeks, with 6 patients (20%) having long-term survival at 46
weeks. In general, chemotherapy was well tolerated; 9 patients (30%)
suffered from WHO grade 3-4 haematological toxicity and 5 patients
(16.6%) suffered from grade 3 non-haematological toxicity. In
conclusion, the GEM plus EPI regimen represent a feasible approach for
improvement of clinical benefit in advanced pancreatic cancer patients,
but confirmatory investigations are required.
9
UI - 98333945
AU - Brown NK; Thompson DJ; Prentice RL
TI -
Nontreatment and aggressive narcotic therapy among hospitalized
pancreatic cancer patients.
SO - J Am Geriatr Soc 1998 Jul;46(7):839-48
AD - Department of Medicine, University of Washington School of Medicine,
USA.
OBJECTIVES: Strong feelings about patient autonomy as expressed in
living wills, polls, and legislative referenda have been challenging the
medical establishment to increase nontreatment, defined as foregoing a
life-prolonging treatment, and even to provide treatments having
life-shortening potential to selected patients. Because there are little
data about the actual practice of these procedures, including aggressive
narcotic therapy as defined herein, we studied the terminal management
of 417 pancreatic cancer patients. DESIGN AND PARTICIPANTS: The medical
records of 417 residents of King County, Washington, who died of
pancreatic cancer in the time periods 1959-1962, 1969-1972, and
1985-1990, were reviewed to study the frequency of, and risk factors
for, end-of-life nontreatment decisions and aggressive narcotic therapy
decisions, defined here as the decision to administer treatment doses of
narcotics or major sedatives to already comatose patients within 4 hours
of death. RESULTS: Antibiotics were not provided to 71% of the 70
febrile patients (two readings >38.33-38.83 degrees C or one reading of
38.88 degrees C), intravenous fluid was not provided to 43% of 294
dehydrated patients (oral intake <500 mL/24 hours), transfusions were
not provided to 39% of 57 severely anemic patients (hematocrit <20%),
and laparotomy was not performed for 86% of 36 patients with abdominal
emergencies (obstruction, bleeding, dehiscence). Also, 46% of the 118
patients who were comatose for at least 24 hours before death received
aggressive narcotic therapy, as defined above. A total of 335 of the 417
patients had documentation of at least one of the above life-threatening
conditions or were comatose for at least 24 hours before death, and 289
(86%) of these patients experienced nontreatment of one or more of these
conditions or received aggressive narcotic therapy. Nontreatment
decisions for febrile, dehydrated, or anemic patients tended to be more
frequent if the patient was comatose (P=.004, .010, and .065,
respectively), if there was a nontreatment statement in the medical
record (P=.009, .035, and .001, respectively), or if the patient was
described as terminal (P=.262, .029, and .002, respectively). Aggressive
narcotic therapy in comatose patients was more common among patients who
had regular visitors (P=.002), who had pre-coma pain (P=.006), who had
nontreatment statements in their charts (P=.031), whose in-charge
physician was an oncologist (P < .001), who were treated in a community
nonprofit hospital compared with a Catholic hospital (P=.007), or who
were treated in recent years (P=.011). CONCLUSION: Both nontreatment and
aggressive narcotic therapy forms of medical management have been
occurring commonly in terminal pancreatic cancer patients in King
County, Washington, during the past 3 decades, the latter with greater
frequency in recent years.
10
UI - 21323881
AU - Evans DB; Wolff RA; Crane CH
TI -
Neoadjuvant strategies for pancreatic cancer.
SO - Oncology (Huntingt) 2001 Jun;15(6):727-37; discussion 741-4, 747
AD - University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Recent prospective and retrospective data suggest that the use of
multimodality therapy combining pancreaticoduodenectomy with
postoperative adjuvant chemotherapy (fluorouracil) and external-beam
radiation therapy maximizes local tumor control and improves the length
of survival in pancreatic cancer patients, compared with surgery alone.
Since postoperative chemoradiation is often delayed in these patients
due to the morbidity and prolonged recovery time associated with
surgery, investigators are assessing the efficacy of administering
chemoradiation before pancreaticoduodenectomy in patients with
potentially resectable pancreatic adenocarcinoma. When given prior to
surgery, chemoradiation is not delayed and patients found to have
disease progression after chemoradiation are not subjected to an
unnecessary laparotomy.
11
UI - 21523827
AU - Carrio M; Mazo A; Lopez-Iglesias C; Estivill X; Fillat C
TI -
Retrovirus-mediated transfer of the herpes simplex virus thymidine
kinase and connexin26 genes in pancreatic cells results in variable
efficiency on the bystander killing: implications for gene therapy.
SO - Int J Cancer 2001 Oct 1;94(1):81-8
AD - Centre de Genetica Medica i Molecular, Institut de Recerca Oncologica
(IRO), L'Hospitalet de Llobregat, 08907-Barcelona, Spain.
Currently, there is no effective treatment for pancreatic cancer and
prodrug-activating gene therapy with the herpes simplex virus thymidine
kinase gene (HSV-tk) in combination with ganciclovir (GCV) has been
suggested as a candidate approach against this disease. In the present
study, we have evaluated the efficacy of the HSV-tk/GCV treatment in a
panel of pancreatic tumor cells (NP-9, NP-18, NP-31) and the
potentiation of the cytotoxic effect in combination with the
overexpression of the connexin 26 gene (Cx26). Pancreatic cells
transduced with a retrovirus containing the HSV-tk gene showed different
sensitivities to GCV that seemed to be independent of HSV-tk expression
levels. The extent of the bystander effect also varied among the
pancreatic tumor cells and correlated with the level of gap junction
intercellular communication (GJIC). Transduction of the pancreatic tumor
cells with a retrovirus carrying the connexin 26 gene resulted in high
levels of connexin 26 expression and in an increase in the GJIC that
correlated to an extent in the bystander effect in both NP-9Cx26 and
NP-18Cx26 cells. Neither an increment in GJIC nor an increase in the
bystander killing was detected in NP-31Cx26. The bystander effect in
NP-18 Cx26 cells was also prevented by the long term inhibitor of GJIC,
18-alpha-glycyrrhetinic acid (AGA). Together, these results demonstrate
that pancreatic tumor cells are highly different as regards the
susceptibility to HSV-tk/GCV treatment. Moreover, they indicate that
overexpression of the Cx26 gene does not always correspond to an
increase in GJIC although they clearly suggest the role of GJIC in
mediating the bystander effect. Copyright 2001 Wiley-Liss, Inc.
12
UI - 21451474
AU - Tyler D
TI -
Adenocarcinoma of the pancreas: is surgery making a difference?
SO - Am J Gastroenterol 2001 Sep;96(9):2532-4
13
UI - 21451485
AU - Ahmad NA; Lewis JD; Ginsberg GG; Haller DG; Morris JB; Williams NN;
TI -
Rosato EF; Kochman ML
Long term survival after pancreatic resection for pancreatic
adenocarcinoma.
SO - Am J Gastroenterol 2001 Sep;96(9):2609-15
AD - Department of Medicine, Center for Clinical Epidemiology and
Biostatistics, University of Pennsylvania Cancer Center, Philadelphia,
Pennsylvania, USA.
OBJECTIVE: The aim of this study was to determine the long term survival
of patients with pancreatic adenocarcinoma who underwent surgical
resection and to assess the association of clinical, pathological, and
treatment features with survival. METHODS: Between January, 1990, and
December, 1998, 125 patients underwent a pancreaticoduodenal or partial
pancreatic resection for pancreatic ductal adenocarcinoma at our
institution. The records of these patients were reviewed for
demographics, tumor characteristics including size, histological grade,
margin status, lymph node status, surgical TNM staging, and
postoperative adjuvant therapy. The primary outcome variable analyzed
was survival. RESULTS: A total of 116 patients had complete follow-up
and were included in the final analysis. The median survival after
surgery was 16 months. The 1-, 3-, 5-, and 7-yr survival rates for all
116 patients were 60%, 23%, 19%, and 11%, respectively. The 1-, 3-, 5-,
and 7-yr survival rates for patients who received adjuvant therapy were
69%, 28%, 23%, and 18% compared with 20% and 0% in patients who did not
receive adjuvant therapy (p < 0.0001). The 1-, 3-, 5-, and 7-yr survival
rates for patients with negative lymph nodes were 73%, 38%, 26%, and 22%
compared with survival rates of 52%, 14%, 14%, and 9% in patients with
positive lymph nodes (p = 0.01). In multivariate analyses, adjuvant
therapy was the only feature found to be strongly associated with
survival (hazards ratio = 0.26, 95% CI = 0.15-0.44). CONCLUSIONS: The
overall 5- and 7-yr survival rates of 19% and 11% in our study further
validate that surgical resection in patients with pancreatic
adenocarcinoma can result in long term survival, particularly when
performed in association with adjuvant chemoradiation.
14
UI - 21523853
AU - Xu Z; Friess H; Solioz M; Aebi S; Korc M; Kleeff J; Buchler MW
TI -
Bcl-x(L) antisense oligonucleotides induce apoptosis and increase
sensitivity of pancreatic cancer cells to gemcitabine.
SO - Int J Cancer 2001 Oct 15;94(2):268-74
AD - Department of Visceral and Transplantation Surgery, University of Berne,
Inselspital, Berne, Switzerland.
Pancreatic cancer is one of the leading causes of cancer-related death
in Western countries. Bcl-x(L) is an anti-apoptotic factor of the Bcl-2
family, which is overexpressed in pancreatic cancer and its presence
correlates with shorter patient survival. In this study,
sequence-specific antisense oligonucleotides targeting the coding region
of Bcl-x(L) were designed to examine whether apoptosis could be induced
and chemosensitivity could be increased in pancreatic cancer cells. Five
pancreatic cancer cell lines, Panc-1, MIA-PaCa-2, Capan-1, ASPC-1 and
T3M4, were treated with Bcl-x(L) sense or antisense oligonucleotides and
gemcitabine and the cell viability was examined by the SRB method.
Apoptosis was determined using DAPI staining. In all examined pancreatic
cancer cells, Bcl-x(L) expression was reduced after transfection of the
antisense oligonucleotides. Cell death analysis using DAPI staining
revealed that antisense, but not sense oligonucleotides caused apoptotic
cell death. Furthermore, Bcl-x(L) antisense oligonucleotides enhanced
the cytotoxic effects of gemcitabine in pancreatic cancer cells. Our
results indicate that Bcl-x(L) antisense oligonucleotides effectively
inhibited pancreatic cancer cell growth and caused apoptosis by reducing
Bcl-x(L) protein levels. Bcl-x(L) antisense oligonucleotides also
increased the chemosensitivity of pancreatic cancer cells, suggesting
that Bcl-x(L) antisense therapy might be a potential future approach in
this disease. Copyright 2001 Wiley-Liss, Inc.
15
UI - 21473283
AU - Yamaguchi K; Yokohata K; Ohkido M; Watanabe M; Ogawa Y; Chijiiwa K;
TI -
Tanaka M
Which is less invasive--distal pancreatectomy or segmental resection?
SO - Int Surg 2000 Oct-Dec;85(4):297-302
AD - Department of Surgery and Oncology, Graduate School of Medical Sciences,
Kyushu University, Fukuoka, Japan.
BACKGROUND: For a pancreatic body tumor, distal pancreatectomy (DP) has
been a standard operation. Segmental resection (SR) of the pancreas has
been introduced as a less invasive procedure in consideration of
preservation of the pancreatic functions and postoperative quality of
life. Surgical stress and exocrine and endocrine functions of the
residual pancreas were compared between DP and SR. METHODS: Clinical
findings including serum levels of C reactive protein (CRP), fasting
blood sugar, a 120 min value of the 75 g oral glucose tolerance test,
and N-benzol-L-tyrosyl-p-aminobenzoic acid excretion value (a pancreatic
exocrine function test) were compared between 47 patients with DP and 10
with SR performed for benign pancreatic diseases. RESULTS: Operation
time was longer in SR (356 min) than in DP (272 min; P = 0.0123).
Operative blood loss and peri-operative blood transfusion were not
different between the two groups. Serum levels of CRP increased after
the operation, reaching the peak on postoperative day 2 or 3, and
decreased thereafter The peak of serum CRP level was similar between the
two groups (13.4+/-1.8 mg/dl in SR and 14.8+/-1.1 mg/dl in DP).
Postoperative hospital stay in 10 patients with SR (65 days) was
significantly longer than that in 47 with DP (33 days; P = 0.0001). When
postoperative complications were compared between the two groups, the
incidence of pancreatic fistula was significantly higher in SR (4/10
[40%]) than in DP (4/46 [9%]; P = 0.0103). Abdominal abscess was seen in
30% of SR and in 11% of DP. Postoperative intra-abdominal hemorrhage was
seen only in one patient with SR After DP, glucose tolerance
deteriorated at short-term in nine of 24 patients examined and at
long-term in two of five patients examined. Only one patient showed
improvement of glucose intolerance at short-term after the operation. On
the other hand, SR showed no alteration of the pancreatic endocrine and
exocrine functions in eight patients examined. CONCLUSIONS: SR is
superior to DP from the view-point of preservation of the pancreatic
functions, although SR has a longer operation time, a longer hospital
stay and a higher incidence of postoperative complications.
16
UI - 21538334
AU - Tsukagoshi S
TI -
[Results of gemcitabine hydrochloride in the treatment for pancreatic
cancer]
SO - Gan To Kagaku Ryoho 2001 Oct;28(10):1461-7
AD - Cancer Institute, Japan Foundation Cancer Research.
Pancreatic cancer has extremely poor prognosis. However no satisfactory
effective chemotherapy for this cancer has been established. Gemcitabine
hydrochloride, a novel anti-tumor agent, had shown the remarkable
for pancreatic cancer of this agent has been approved in Japan and it is
expected to be widely and increasingly introduced for clinical use. This
review summarizes the study results of gemcitabine mono-therapy for
pancreatic cancer and discusses other possibility of the treatment by
Gemcitabine with the reported data about its combination therapy with
other anti-cancer drug or radiation.
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
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