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Adjuvant
therapy in pancreatic cancer
Paula Ghaneh, John Slavin, Robert Sutton, Mark Hartley, John P Neoptolemos
Department of Surgery, University of Liverpool, 5th
Floor UCD Building, Daulby Street, Liverpool, L69 3GA, UK
Correspondence to Professor JP Neoptolemos, Department of Surgery,
University of Liverpool, 5th
Floor UCD Building,
Daulby Street, Liverpool, L69
3GA, UK. j.p.neoptolemos@liverpool.ac.uk
Tel: 0044-151-706-4175,
Fax:
0044-151-706-5798
Received
2001-05-15
Accepted
2001-06-15
Abstract
The outlook for patients with pancreatic cancer has been grim. There have been
major advances in the surgical treatment of pancreatic cancer, leading to a
dramatic reduction in postoperative
mortality from the development of high volume specialized centres. This stimulated the study of
adjuvant and neoadjuvant treatments in pancreatic cancer including
chemoradiotherapy and chemotherapy. Initial protocols have been based on the
original but rather small GITSG study first reported in 1985. There have been
two large European trials totalling over 600 patients (EORTC and ESPAC-1) that
do not support the use of chemoradiation as adjuvant therapy. A second major
finding from the ESPAC-1 trial (541 patients randomized) was some but not
conclusive evidence for a survival benefit associated with chemotherapy. A third
major finding from the ESPAC-1 trial was that the quality of life was not
affected by the use of adjuvant treatments compared to surgery alone. The
ESPAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a
randomized controlled trial of 990 patients.
Subject headings pancreatic
neoplasms/drug therapy; pancreatic neoplasms/radiotherapy; human; review
Ghaneh P, Slavin J, Sutton R, Hartley M, Neoptolemos JP. Adjuvant therapy in
pancreatic cancer.
World J Gastroenterol, 2001;7(4):482-489
INTRODUCTION
Pancreatic cancer is the 5th
most common site of deaths due to cancer among all cancer sites in the Western world. Low cure
rates ensure that the mortality is nearly as high as the incidence. It is
responsible for 7000 deaths per year in the UK[1],
40000
per
year in Europe and 28000
in the USA[2].
The peak mortality ages are estimated to be between 65 and 72 years in Europe and 55 and 75 years
in the USA[2]. The incidence of this deadly disease has been
rising during the last century. In the past 20 years however, there have been
vast improvements in the surgical management of patients with pancreatic cancer.
The surgical procedures have been improved and become more standardized between
centres and countries. The level of pre- and post-operative
support for these patients has been optimized, particularly in established centres with a high
throughput[3]. These measures have ensured that the outlook for
patients with resectable disease has certainly improved, particularly in the
short term. Extending patient survival still remains a problem. The overall five-year
survival for all patents with pancreatic cancer is only 0.4%[4].
Patients who are suitable for resection have five-year
survival rates of between 10% and 24%[5-8] and are
virtually never cured. Therefore, even for the 10% to 15% of patients who
undergo surgery, there appears to be no guarantee of cure or indeed long- term
survival. These outcomes would suggest a role for the use of additional or
adjuvant therapy to attempt to improve patient survival and
quality of life.
RADICAL SURGERY
Japanese groups amongst others have been enthusiastic in pursuing radical
resection as means of increasing disease free margins and thus hopefully
improving patient survival. Radical surgery includes extensive lymph node
dissection and retroperitoneal connective tissue clearance as well as pancreatic
resection. The Japanese groups have suggested that these approaches are superior
to conventional Kausch-Whipple resection but
several studies have not shown significant survival advantages when compared with conventional
resection[9-13]. Kayahara
et al
found that radical resection in patients with Stage Ⅰ
and Ⅱ disease
(Japanese classification) and clear margins (R0) resulted in a reduction of
local recurrence but did not translate into improved survival because of hepatic
metastases[14].
Interestingly highly detailed serial section analysis of presumed
R0 specimens has revealed microscopic margin disease (R1) in up to 38% of
specimens[14].
Difficulties are encountered when comparing survival figures of Western
and Japanese studies because of the different staging systems used (UICC
vs
JPS respectively). This is because of the phenomenon
of ‘staging
system migration’ that may give apparently better survival for each
stage in one system compared to the other even though there is no overall
difference in survival. Satake et al[15] compared the Japanese and UICC staging
systems in a large cohort of patients. Stage for stage the Japanese system
revealed a better survival from Stage Ⅰ to Ⅳ
compared with UICC system. The overall five-year survival however, was the same (11%) because the
systems had been analysed in identical patients.
The majority of
radical resection studies have been non-randomized and performed in
single institutions. The radical lymph node dissection allows more accurate
staging of disease and these tumours will tend to be upstaged because of this.
Thus it is necessary to examine overall group survival within the context of
randomized studies by an intention to treat analysis. There has been one
multicentre prospective randomized trial comparing traditional partial
pancreatoduodenectomy with and without a more extensive lymph node dissection[16]. Eighty-one patients were randomized
to receive a standard (n=40)
or extended (n=41)
lymphadenectomy and retroperitoneal soft tissue clearance.
The standard
lymphadenectomy included removal of lymph nodes situated at the anterior and
posterior pancreatoduodenal, pyloric, main bile duct, superior and inferior
pancreatic head and pancreatic body stations. The extended lymphadenectomy also
included the removal of lymph nodes from the hepatic hilum, along the aorta from
the diaphragmatic hiatus to the inferior mesenteric artery, laterally to both
renal hila and clearance of the coeliac trunk and superior mesenteric artery.
There was no significant difference of overall survival between the two groups.
Patients who had lymph node positive disease demonstrated better survival
following an extended resection compared to those who did not have an extended
lymphadenectomy but must be regarded as a statistically invalid manoeuvre as
this was a posthoc
subgroup analysis. In light of these findings the ultimate benefit of
extended lymphadenectomy surgery still needs to be proven with further critical
evaluation.
There appears to be no
additional survival benefit associated with total pancreatectomy compared to
Kausch-Whipple
pancreatoduodenectomy and at the present time the pylorus preserving pancreatoduodenectomy has
been shown to produce similar results to the more traditional Kausch Whipple
procedure[17,18]. The
latter approach is now the procedure of choice in most centres.
The lack of survival
benefit associated with radical resection may be due in part to the pattern of
disease recurrence in resected pancreatic cancer. Most tumour recurrences are
local, peritoneal and hepatic[19-24].
The early appearance of hepatic metastases following resection almost
certainly indicates the presence of hepatic micrometastases at the time of
surgery. Microscopic peritoneal disease also tends to occur early in contrast to
the relatively later presentation of local recurrence. Pancreatic cancer cells
tend to spread within a range of peripancreatic tissues. Lymphatic infiltration
and perineural invasion may be found in 90%-100% of resected
specimens[25].
Reasons for recurrence following an apparently
curative resection include residual retroperitoneal disease, perineural
invasion, hepatic micrometastases and lymph node involvement. The pattern of
relapse after surgery reflects the natural course of the disease without
resection. The most commonly
affected organs include abdominal lymph nodes (72%-83%), liver (64%-80%),
peritoneum (40%-53%) and lung (27%-50%)[14].
An R0 resection in patients with no lymph node metastases cannot be
achieved in more than about half of the patients undergoing resection. Kayahara et
al[14]
at post mortem examined 15 patients who had undergone
radical resection. The local recurrence rate in this group of patients was 80%.
The local recurrences were associated with perineural invasion, lymphatic
invasion and soft tissue infiltration. High rates of local recurrence have been
confirmed in numerous studies of patients who have undergone
pancreatoduodenectomy and the majority occur within 1 to 2 years of surgery[23,24].
Identification of extrapancreatic disease at the preoperative
stage has improved due to accurate imaging techniques[26]and
laparoscopy[27]. Peritoneal cytology has been shown to be positive
in 58% of patients who may have unresectable tumours or have a limited
postoperative survival[27]. The best predictors of outcome following surgery
also reflect the causes of disease relapse. These include tumour stage (which
also includes the lymph node status), grade of primary tumour and resection
margin status[28-32]. Not surprisingly patients with stage Ⅰ
or Ⅱ
disease and negative resection margins tend to demonstrate the best survival.
The poor overall survival
of patients with pancreatic cancer, even following optimal surgical
intervention, and the pattern of disease progression and recurrence are clear
indications for the use of additional treatment modalities.
CHEMOTHERAPY
Advanced pancreatic cancer
There have been many studies of chemotherapy in patients with advanced
pancreatic cancer. Single agents and combination regimens have been used. At the
present time there is no accepted standard chemotherapeutic agent for the
treatment of pancreatic cancer. 5-fluorouracil (5-FU)
remains the most effective and most frequently used single chemotherapy agent. 5-FU
works partly by interference with enzymes
such as thymidylate synthase and partly by incorporation of 5-FU
metabolites into DNA and RNA. The response rates of ~15%
with a median survival of 3-5 months[33].
The addition of the modulator folinic acid has produced marginal survival benefit over
5-FU
alone but this has not been a significant increase[33].
The addition of other modulators such as phosphonacetyl-L-aspartate (PALA), and interferon has also not
produced significant improvements in survival[34,35].
Comparisons of 5-FU alone and 5-FU with a combination of other agents have not shown any
advantage for the combination groups in randomized trials[33].
A new agent, gemcitabine
has been compared to 5-FU
in a randomized multi-centre phase Ⅲ clinical trial[36].
Gemcitabine is a deoxycytidine analogue that is phosphorylated to an active form and
competes with dCTP for incorporation into DNA. The study, in which over 70% of
patients had stage Ⅳ disease, randomized 63 patients to receive
gemcitabine and 63 patients to receive 5-FU. Median survival in the gemcitabine group was 5.7
months compared to 4.4 months in the 5-FU group but no patient
survived beyond 19 months. The clinical benefit response was also significantly
higher in the gemcitabine group[36]. Despite the fact that this is the only trial with a
straight comparison between the two agents gemcitabine has been recommended as
the drug of choice in the USA. Gemcitabine has also been combined with 5-FU in several phase Ⅱ studies. It is generally
well tolerated but can have unpredictable side effects such as neutropaenia, abnormal liver
function tests and nausea and vomiting. In patients who have had previous
radiotherapy to the mediastinum there have been unpredictable reactions[37].
There is good evidence
from several randomized controlled trials comparing chemotherapy with a no
treatment group that chemotherapy is of benefit in patients with advanced
pancreatic cancer. Mallinson et
al[38]
demonstrated a median survival of 11 months for patients treated with
5-FU,
cyclophosphamide, methotrexate, vincristine and mitomycin C compared to 2.2
months for the untreated control group. This regimen did not produce a
significantly greater survival when compared to 5-FU alone in a much larger
randomized control trial[39]. Another rather poorly controlled study compared 5-FU
and carmustine to untreated controls[40].
There was no significant survival benefit associated with this regimen but the majority of patients
in this study received only a single treatment and did not finish the course. A
further trial of the combination of 5-FU,
doxorubicin and mitomycin C (FAM) resulted in median survival of 33 weeks
compared with median survival of 15 weeks in untreated control patients[41].
A recent study compared the use of 5-FU + folinic acid (+/-
etoposide) with best supportive care and showed that the median survival in the treated group
was 6 months compared to 2.5 months in the control group[42].
Moreover there was better overall quality of life score for the treated patients.
Adjuvant chemotherapy
There have been only a few studies of adjuvant chemotherapy in pancreatic cancer and
(up until the ESPAC-1 trial) there was only one randomized controlled
trial comparing surgery and chemotherapy with surgery alone (Table 1)[43-46]. Splinter et al[43]reported
no evidence of improvement or survival using a
FAM regimen in 16 patients who had undergone pancreatoduodenectomy with a three
year survival of 24% compared to a three year survival of 28% in 36 patients who
had undergone surgery only. Patients from different time periods were
included in the two groups and there were only nine patients with pancreatic
ductal adenocarcinoma in the adjuvant group and 18 in the surgery only group.
Baumel et
al[46]
reported adjuvant chemotherapy in 43 selected patients with a median survival of 12 months but there
was no difference in median survival from those patients who underwent surgery
only (12 months). Bakkevold et
al[45]
randomized 61 patients who had undergone pancreatoduodenectomy for
pancreatic cancer or ampullary cancer to receive either six courses of FAM or no
chemotherapy. There was a significant difference in the median survival rates
between the two groups: 23 months. Unfortunately this did not translate into a
significantly improved long-term survival however: the 5-year
survival rates were 4% for the treatment arm versus 8% for the surgery only arm. There was
also considerable toxicity encountered with the FAM regimen. Only 24 out of 30
patients randomized to treatment actually started therapy. Sixteen patients
needed hospitalization after the first chemotherapy course and a total of 13
patients managed to complete all six cycles of FAM.
The European Study
Group for Pancreatic Cancer (ESPAC) has commenced the ESPAC-3 trial with the objective of definitively defining
the role of adjuvant chemotherapy following curative resection for pancreatic
ductal adenocarcinoma. Two adjuvant regimens are being studied against a no
chemotherapy control: ① 5-FU + folinic acid for 24 weeks versus ②
gemcitabine for 24 weeks versus ③ observation. All patients will have undergone
potentially curative resection for pancreatic ductal adenocarcinoma. A total of
990 patients (330 in each arm) will be recruited over the next few years and
survival analysis will be completed after two years of follow-up.
At the present time recruitment is underway from centres across Europe with further centres in
Canada, Australia and New Zealand due to join.
RADIOTHERAPY (CHEMORADIOTHERAPY)
Advanced pancreatic cancer
External beam radiotherapy (EBRT) although used in the treatment of advanced
pancreatic cancer, has never been compared with an untreated control arm in any
randomized controlled trial. The most commonly used and probably the best
radiosensitizer used with EBRT for advanced pancreatic cancer is 5-FU.
Many retrospective studies of EBRT, usually in relatively small groups
of selected patients report median survival times of 10-15 months with good
palliation of symptoms[47,48].
The improved local
control of disease achieved with EBRT has not translated into significantly longer survival times, so there have been
various refinements in an attempt to enhance the effectiveness of radiotherapy.
Wide field irradiation has been used to address the problem of hepatic
micrometastases. A Radiation Therapy Oncology Group (RTOG) study of 79 patients
who received pancreatic and hepatic irradiation resulted in a median survival of
8.4 months but at the expense of considerable toxicity[49].
Intraoperative radiation therapy (IORT) aims to deliver higher doses of radiation with
greater precision and thus reducing the exposure of neighbouring organs.
Experimentally, its effectiveness may be as high as five times the equivalent
dose given by EBRT. In advanced pancreatic cancer the survival times achieved
using IORT have not been encouraging (median survival ~6 months) and it has been
mainly used to boost
EBRT[50,51]. A study comparing EBRT + IORT + 5-FU
with EBRT +5-FU demonstrated no significant survival difference
(12 and 13 months respectively)[50,51].
Complications encountered
during IORT include, duodenal and gastric ulceration, vascular sclerosis and
pancreatic abscess[52].
IORT offers good local control and pain relief but
cannot be recommended as a standard treatment as it has not been possible to
demonstrate any advantages over conventional therapy.
Adjuvant radiotherapy (chemoradiotherapy)
Adjuvant EBRT and IORT have been used alone and in
combination in the adjuvant setting (Table 2)[21,32,53-60].
The majority of studies indicate that EBRT alone or in combination with IORT has a
significant survival advantage over the use of IORT alone. In a randomized trial
IORT was observed to reduce the local recurrence rate by 50% following surgery,
but this did not translate into a significant survival advantage (3-year
survival with IORT=7% vs no IORT 3%)[21].
In selected patients IORT and resection produced 3 and 5-year survival rates of 53% and 29%[61,62].
The use of IORT however requires specialised facilities and can be
associated with severe complications.
EBRT (with concomitant
chemotherapy) following resection is generally well tolerated but the degree of
survival advantage, if any, is uncertain. To address this issue
a multicentre Phase Ⅲ trial organized by the European Organisation for
Research and Treatment of Cancer (EORTC) compared chemoradiotherapy in patients
following potentially curative surgery for pancreatic cancer with surgery alone[58]. Between 1987 and 1995, 218 patients were randomized
to receive either chemoradiotherapy or no chemoradiotherapy following curative
surgery for pancreatic or ampullary cancer. Ninety-three
out of 110 patients randomized to treatment received a total of 40 Gy with concomitant
continuous infusion of 5-FU. There were a total of 54 patients in the
observation group and 60 patients in the treatment group with pancreatic ductal
adenocarcinoma. There was no significant difference in median survival (with
treatment 171
months vs 12.6 months with
observation) and in five year survival [with treatment 20 (95% CI,
5-35)% vs 10 (0-20)% with observation].
Similarly there was no significant difference in survival between the treatment and
observation groups in patients with ampullary cancer. This study showed that
there was no survival advantage for adjuvant chemoradiotherapy for pancreatic
and ampullary cancer but has been criticized because it was almost certainly
underpowered.
REGIONAL THERAPY
Advanced pancreatic cancer
Regional therapy has been developed with the objective of delivering high doses
of cytotoxic drug to the tumour. The systemic side effects should be reduced
with this approach. The coeliac and hepatic arteries and portal vein have all
been used to deliver chemotherapeutic drugs to the tumour bed. Good control of
hepatic metastases has been reported, with disease progression mainly due to
local progression or peritoneal deposits. The combination of 5-FU,
folinic acid and cisplatin produced median survival times of 9-14 months
in selected patients[63,64]. It has
also been reported that some apparently irresectable tumours have become
resectable following regional therapy[64].
Adjuvant regional therapy
There have been several studies which have demonstrated improved
survival in patients receiving regional chemotherapy following pancreatic
resection largely in comparison with historical controls (Table 3)[65-68].
Link et
al[69] found a median survival of 21 months in
18 patients who had undergone pancreatoduodenectomy for pancreatic ductal
adenocarcinoma and then coeliac artery infusion of 5-FU, folinic acid,
mitoxantrone and cisplatin compared to 9.3 months for historical controls. Disease progression
occurred principally locally or in the peritoneum and was rarely detected in the
liver. The rate of hepatic recurrence was greatly reduced using a combination of
hepatic artery and portal vein infusion in patients with resected pancreatic,
which in one study cancer produced a 54% three-year
survival compared to 34% in historical controls[65].
Ozaki et
al[66]
found a 5-year survival rate of 32% patients treated with
extended resection, IORT and hepatic artery and portal vein. The encouraging
results of these small studies have prompted the ESPAC-2 trial, which is a
multicentre, prospective randomized controlled Phase Ⅲ trial. This study will
compare adjuvant intra-arterial chemotherapy (cisplatin, 5-FU, folinic acid and
mitoxantrone) and radiotherapy (Arm A) with surgery alone (Arm B) in patients who have undergone
potentially curative resection for pancreatic ductal adenocarcinoma or ampullary
carcinoma. The trial will recruit 110 patients into each arm and will be
completed by 2007 aiming to provide a definitive answer to the role of adjuvant
regional therapy for
pancreatic cancer.
Table 1
Survival following surgery
and adjuvant chemotherapy
| Series | Period | Number | Regimen | Median survival (months) |
Actuarial survival (%) | |||
| Total | PDAC | 1 year | 3 year | 5 year | ||||
| Splinter et al[43] | 1977-1984 | 36 | 18 | 28 |
||||
| 1980-1984 | 16 | 9 | 5-FU/DOX/MMC | 24 |
||||
| Livingstone et al[44] | N/A | 285 | 285 | N/A | 9 | |||
| Bakkevold et al*[45] | 1984-1987 | 30 | 23 |
5-FU/DOX/MMC | 23 | 70 | 70 | 4 |
| 31 | 24 | 11 | 45 | 30 | 8 |
|||
| Baumel et al[46] | 1982-1988 | 43 | 43 | Not specified | 12 | |||
| 1982-1988 | 527 | 527 | 12 | |||||
5-FU = 5-fluorouracil; DOX =
doxorubicin; MMC = mitomycin C; * randomised cont
Table 2
Survival following surgery
and radiotherapy for
| Series |
Year |
Number |
EBRT(Gy) | IORT(Gy) | Median
survival (months) |
Actuarial survival (%) | ||
| 1 year | 3 year | 5 year | ||||||
| Willett et al[32] | 1993 | 16 (nm) | 40-50 | 21 | 29 |
|||
| 23 (pm) | 40-50 | 11 | 0 |
|||||
| Johnstone et al[53] | 1993 | 26 | 45-55 | 20 | 18 | |||
| Zerbi et al[21] | 1994 | 43 | 12.5-20 | 19 | 71 | 7 | ||
| 47 | 12 | 49 | 10 | |||||
| Di Carlo et al[54] | 1997 | 27 | 14 | |||||
| 27 | 12.5-20 | 17 | ||||||
| Dobelbower et al[55] | 1997 | 14 | 6.5 | 15 | 0 | 0 | ||
| 6 | 10-20 | 9 | 50 | 35 | 33 | |||
| 14 | 50-67 | 14.5 | 64 | 28 | 0 | |||
| 10 | 27-54 | 10-25 | 18 | 70 | 10 | 0 | ||
| Farrell et al[56] | 1997 | 14 | 60 | 12-25 | 16 | 62 | 22 | 15 |
| Hishinuma et al[57] | 1998 | 34 | 24 EBRT | 13
EBRT + IOR |
13 | 59 | 19 | |
| Klinkenbijl et al*[58] | 1999 | 54pdc | 12.6 | 10 | ||||
| 60pdc | 40 | 17.1 | 20 | |||||
| Mehta et al[59] | 2000 | 52 | 45-54 | 8 IORT | 32 | 75 | 38 | |
| Lee et al[60] | 2000 | 22 | 47 | |||||
| 13 | 49 | 81 | ||||||
EBRT = external beam radiotherapy; IORT =
intraoperative radiotherapy; nm = nega
Table 3
Adjuvant regional therapy
for pancreatic cancer
| Series |
Year |
Number |
Regimen | Median
survival (months) |
Actuarial survival (%) | ||
| 1 year | 3 year | 5 year | |||||
| Ishikawa et al[65] | 1994 | 20 | HAI + PVI | 54 |
|||
| Ozaki et al[66] | 1994 | 24 | IORT
+ HAI +/- PVI |
32 |
|||
| Link et al[67] | 1997 | 20 | CAI | 21 | |||
| 29 | 9.3 | ||||||
| Beger et al[68] | 1999 | 24 | CAI | 23 | 54
(4 year) |
||
| nd | 10.5 | 9.5 (4 year) | |||||
HAI = hepatic arterial infusion; PVI = portal vein
infusion; CAI = coeliac
NEOADJUVANT THERAPY
The rationale for pre-operative therapy includes
(a) the avoidance of long
The effect of any long
COMBINATION THERAPY
Advanced pancreatic cancer
The combination of chemoradiation and follow-on
chemotherapy may enable good lo
Adjuvant combination therapy
(Table 5)
A phase
The UK Pancreatic Cancer Trials Group (UKPACA)
The findings of these studies were instrumental in
the design of the ESPAC
wh
Series |
Year |
Number |
Regimen | Resection rate | Positive resection margin (n) |
Median survival(months) | Actuarial survival (%) |
||
| n | % | 3 year | 5 year | ||||||
| Ishikawa et al[70] | 1994 | 23 | EBRT | 17/23 | 74 |
22 |
|||
| Coia et al[71] | 1994 | 27 | EBRT + 5-FU + MMC | 13/27 |
48 | 0/13 | 16 | 43 |
|
| Staleyet al[72] | 1996 | 39 | EBRT + 5-FU + IORT | 39/39 | 100 | 7/39 | 19 | 19 (4 year) |
|
| Spitz et al[73] | 1997 | 41 | EBRT + 5-FU | 41/91 | 51 | 5/41 | 19.2 | ||
| Hoffman et al[74] | 1998 | 53 | EBRT + 5-FU + MMC | 24/53 | 45 | 15.7 | |||
| White et al[75] | 1999 | 25 | 5-FU + EBRT + MMC +CPP | 5/25 | 20 |
||||
| Wanebo et al[76] | 2000 | 14 | 5-FU + EBRT +CPP | 9/14 | 64 |
||||
| Snady et al[77] | 2000 | 68 | EBRT+5-FU+STREP+CPP | 20/68 | 29 | 32 | 32 | ||
| 48 NR | 71 | 21 | 13 | ||||||
EBRT = external beam radiotherapy; 5-FU =
5-fluorouracil; MMC= mitomycin C; IORT
Table 5
Results of combination
therapy in patients who have
| Series | Year | Number | Radiotherapy (Gy) |
Chemotherapy | Median
survival (months) |
Actuarial
survival (%) |
|||
| 1 year | 2 year | 3 year | 5 year | ||||||
| Kalser et al*[81] | 1985 | 21 | EBRT 40 | 5-FU | 20 | 67 | 42 | 24 | 18 |
| 22 | 11 | 50 | 15 | 7 | 8 | ||||
| GITSG[82] | 1987 | 30 | EBRT 40 | 5-FU | 18 | 46 |
|||
| Conlon et al[83] | 1996 | 56 | EBRT 45 | 5-FU | 20 |
35 |
|||
| Yeo et al[84] | 1997 | 53 | 13.5 | 30 |
|||||
| 99 | EBRT 40-45 | 5-FU | 21 | 44 |
|||||
| 21 | EBRT 50-57 | 5-FU + FA | 17.5 | 22 |
|||||
| UKPACA[85] | 1998 | 35 | EBRT 40 | 5-FU | 13 | 56 | 38 | 29 | 15 |
| Abrams et al[86] | 1999 | 23 | EBRT | 5-FU + FA | 15.9 |
||||
| Paulino et al[87] | 1999 | 30 | EBRT | 5-FU | 26 |
||||
| 8 | EBRT | 5.5 | |||||||
| André et al[88] | 2000 | 10 | EBRT | 5-FU + FA + CPP | 17 | ||||
EBRT = external bean radiotherapy; 5-FU =
5-fluorouracil; FA = folinic
CONCLUSION
This is a very encouraging time for the treatment of
pancreatic cancer. The resu
AKNOWLEDGEMENTS
We are grateful to the
Cancer
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