Download 高 雄 榮 民 總 醫 院 Kaohsiung Veterans General Hospital

高 雄 榮 民 總 醫 院
直
腸
癌
診
療
指
引
大腸直腸癌醫療團隊 制定
2014 年二月修訂
Kaohsiung Veterans General Hospital
Rectal Cancer Clinical Practice Guidelines
Colorectal Cancer Multidisciplinary Team
February 2014version 1
1
Rectal Cancer Clinical Practice Guidelines
Content
P3
P. 4
P. 5
P. 6
P. 7
P. 8
P. 9
P. 10
P. 11
P. 12
P. 13
P. 14
P. 15
P. 16-20
P. 21-22
P. 23
P. 24
Revision summary
Malignant polyp
Resectable primary rectal cancer
Adjuvant therapy for Stage I-II rectal cancer
Adjuvant therapy for T4 or stage III rectal cancer
Resectable synchronous liver and/or lung metastases only
Unresectable synchronous liver and/or lung metastases only
Surveillance
Workup for recurrence
Resectable metachronous metastases
Unresectable metachronous metastases
Intensive chemotherapy for advanced or metastatic disease
Non-intensive chemotherapy for advanced or metastatic disease
Chemotherapy regimens
TNM classification of colorectal cancer
7th AJCC colorectal cancer staging
Reference
2
<Revision Summary>
1. Presentation and workup (p.5):
Footnote 2 is new to the page: PET-CT does not supplant a contrast- enhanced diagnostic CT scan. PET-CT should only be used to evaluate an
equivocal finding on a contrast-enhanced CT scan or in patients with strong contraindications to IV contrast.
2. Adjuvant therapy for stage III or unresectable T4 lesion (p.7):
T3(a,b) at middle and high rectum : Transabdominal resection add as an option.
T4 and/or locally unresectableb
ØØ Added “or medically inoperable”.
ØØ The option of “resection contraindicated” added after primary treatment with the treatment options as per active chemotherapy regimens for
advanced disease REC-E.
3. Resectable stage IV disease (p.8):
Primary treatment option of staged or synchronous resection of metastases + rectal lesion removed.
4. Surveillance (p.10):
Consider proctoscopy recommendation modified to every 6 mo x 3-5 y for patients status post LAR or transanal excision.
5. Resectable metachronous metastases (p.12):
“Repeat” neoadjuvant therapy changed to “reinitiate” neoadjuvant therapy.
6. Add TMN classification and 7th AJCC staging st.atement.
7. Add Ufur as option of treatment in stage II, III and IV.
Clinical Presentation
Pedunculated
or sessile
polyp
(adenoma:
tubular,
tubulovillous,
or villous)
with invasive
cancer
Workup
ll
Pathology review
ll
Colonoscopy
ll
Marking of
cancerous polyp
site (at time of
colonoscopy or
within 2 weeks)
Findings
Single
specimen
completely
removed with
favorable
histological
features and
clear margins
(T1 only)
Surgery
Pedunculated polyp
with invasive cancer
Observe
Sessile polyp with
invasive cancer
Observe or see
primary
treatment
(page 6)
Fragmented
specimens or
margin cannot
be assessed or
unfavorable
histological
features
See primary
and adjuvant
treatment
(page 6)
Favorable histological features: Grade 1 & 2, no angiolymphatic invasion and negative margin of resection
Unfavorable histological features: Grade 3 & 4, or angiolymphatic invasion, or a “positive” margin
4
Clinical Presentation
Workup
Clinical Stage
T1-2, N0
ll Biopsy
See primary
treatment (page 6)
ll Pathology review
ll Colonoscopy
T3, N0 or
ll Rigid proctoscopy
T any, N1-2
See primary
treatment (page 7)
ll Chest/abdominal/pelvic CT1
Rectal cancer
ll CEA
appropriate for
ll Endorectal ultrasound or pelvic
resection
MRI
ll Enterostomal therapist as
T4 and/or locally
Unresectable or
See primary
treatment (page 7)
medically inoperable
indicated for preoperative
marking of site, teaching
ll PET-CT scan is not routinely
T any, N any, M1
Resectable metastases
See primary
treatment (page 8)
indicated
T any, N any, M1
Unresectable metastases
or medically inoperable
See primary
treatment (page 9)
PS: 1. CT should be with IV and oral contrast. Consider abd/pelvic MRI with MRIR contrast plus a non-contrast chest CT if either CT of abd/pelvis is
inadequate or if patient has a contraindication to CT with IV contrast.
2. PET-CT does not supplant a contrast-enhanced diagnostic CT scan. PET-CT should only be used to evaluate an equivocal finding on a
contrast-enhanced CT scan or in patients with strong contraindications to IV contrast.
5
Clinical Stage
cT1, N0
Primary Treatment
Adjuvant Treatment (6 months peri-OP treatment preferred)
Transanal
T1, NX;
excision, if
Margins
appropriate1
negative
Surveillance (page 10)
Observe
5-FU ± LV or FOLFOX or capecitabine ± oxaliplatin, then
T1, NX with high risk features
pT1-2,
infusional 5-FU/RT (preferred) or bolus 5-FU + LV/RT, or
N0,M0
UFUR/RT 4,6or capecitabine/RT (preferred), then 5-FU ±
Trans-
(positive margins,
lymphovascular invasion, poorly
differentiated tumors, or sm3
LV or FOLFOX or
abdominal
pT3, N0, M0
capecitabine ± oxaliplatin
resection
or
or
pT1-3, N1-2
Infusioinal 5-FU/RT (preferred) or bolus 5-FU + LV/RT or
invasion) or T2,NX
UFUR/RT4,6 or capecitabine/RT (preferred) followed by
5-FU ± LV or FOLFOX or capecitabine ± oxaliplatin
pT3, N0, M0
or
cT1-2, N0
Transabdominal
or T2,Nx
resection
pT1-3, N1-2
pT1-2, N0,
M0
Observe
NHI regulations for CRC adjuvant chemotherapy
1. Oxaliplatin: Stage III colon cancer
2. 5-FU: High risk stage II, stage III and stage IV colorectal cancer
3. Xeloda: Stage III colon cancer, stage IV colorectal cancer
4. UFUR: High risk stage II, stage III and stage IV colorectal cancer
Surveillance
PS1: unfavorable histopathologic features:
>3cm in size, T1, with grade III, lymphovascular
invasion, positive margin, or sm3 depth of tumor
invasion.
6
Clinical Stage
Primary Treatment
Adjuvant Treatment
(6 months peri-OP treatment preferred)
Pre-op infusional 5-FU/RT or
T3, N0
capecitabine/RT (preferred for
Transabdominal
or T any, N1-2
both) or bolus 5-FU + LV/RT
resection
FOLFOX or
capecitabine ± oxaliplatin
or Ufur7/RT
pT1-2,
5-FU ± leucovorin or
Surveillance
Observe
N0, M0
Patients with medical
contraindication to
Transabdominal
Reconsider
combined modality
resection
5-FU ± LV or FOLFOX or capecitabine ± oxaliplatin, then infusion
therapy
5-FU/RT(preferred) or bolus 5-FU + LV/RT or capecitabine/RT
pT3, N0, M0
or pT1-3, N1-2
(preferred) or UFUR7/RT
T3(a,b) at middle or
, then 5-FU ± LV or FOLFOX or capecitabine ± oxaliplatin
high rectum can
or
consider
Infusional 5-FU/RT (preferred) or bolus 5-FU + LV/RT or
capecitabine/RT(preferred) or UFUR7 /RT followed by 5-FU ± LV
T4 and/or
Infusional IV
Locally
5-FU/RT or bolus 5-
unresectable
FU + LV/RT or
or medical
inoperable
capecitabine/RT
or FOLFOX or capecitabine ± oxaliplatin
5-FU ± LV or FOLFOX or
Resection,
if possible
Any T
capecitabine ± oxaliplatin
Surveillance
or UFUR7/RT
Resection
contraindicated
Active chemotherapy
regimen for advanced
disease (page 14)
7
Clinical Stage
Primary Treatment
Adjuvant Treatment (resected metastatic disease)
(6 months peri-OP treatment preferred)
Combination chemotherapy
Staged or synchronous
(2-3 months) (FOLFIRI or
resection of metastases
FOLFOX or CapeOX) ±
and rectal lesion
Consider
Infusional IV 5-FU/ pelvic RT
or capecitabine/RT
or bolus 5-FU + LV/pelvic RT
bevacizumab or (FOLFIRI
or FOLFOX) ±panitumumab
Infusional IV 5-FU/ pelvic RT
Staged or synchronous
(KRAS wild-type gene only)
or capecitabine/RT
resection of metastases
or FOLFIRI ± cetuximab
or bolus 5-FU + LV/pelvic RT
and rectal lesion
(KRAS wild-type gene only)
S
U
R
V
E
T any,
I
N any, M1
L
Resectable
L
synchronous
A
metastases
N
C
E
Infusional IV 5FU/
pelvic RT
or capecitabine/RT
or bolus 5FU +
Leucovorin/Pelvic RT
Staged or synchronous
resection of metastases
and rectal lesion
Active chemotherapy regimen
for advanced disease (page 14)
8
Clinical Stage
Primary Treatment
Combination systemic chemotherapy
or 5-FU/RT or Capecitabine(or Ufur7)/RT
or Resection of involved rectal segment
Symptomatic
or Laser recanalization
or Diverting colostomy
T Any, N Any, M1
Active chemotherapy regimen
for advanced or metastatic
disease (page 14)
or Stenting
Unresectable
synchronous
metastases
or Medically
inoperable
Asymptomatic
Active chemotherapy regimen
for advanced or metastatic
disease (page 14)
Reassess response to
determine resectability
9
Surveillance
ll History and physical every 3-6 months for 2
years, then every 6 months for a total of 5 years
ll CEA every 3-6 mo for 2 years, then every 6
months for a total of 5 years for T2 or greater
lesions
ll Chest/abdominal/pelvic CT annually for up to 5
years for patients at high risk for recurrence
ll Colonoscopy in 1 years except if no preoperative
colonoscopy due to obstructing lesion,
colonoscopy in 3-6 months
Serial CEA elevation or
documented recurrence
See workup and treatment for
recurrence (page 11)
nn If advanced adenoma, repeat in 1 year
nn If no advanced adenoma, repeat in 3
years, then every 5 years
ll Consider proctoscopy every 6 months x 3-5 y for
patients status post LAR or transanal excision
ll PET-CT scan is not routinely recommended
10
Recurrence
Serial
CEA
elevation
Isolated pelvic/
anastomotic
recurrence
Workup
ll Physical exam
ll Colonoscopy
ll Chest/Abdomen/Pelvis
CT
ll Consider PET-CT scan
Potentially resectable
Unresectable
Documented
CT, MRI
and/or biopsy
Positive finding
Negative finding
Positive finding
See treatment for isolated
pelvic/anastomotic
recurrence or documented
metachronous metastases
Resection
Chemotherapy + RT
Pre-OP 5-FU + RT, If
not given previously
Resection + IORT
Chemotherapy ± RT
Resectable
Consider PET-CT
scan
Unresectable
(potentially
convertible or
unconvertible)
See primary
treatment on
page 13
metachronous
metastases by
Negative finding
ll Consider PET-CT scan
ll Re-evaluate
Chest/Abdominal/Pelvic
CT in 3 months
Resectable
See primary treatment
on page 12
Unresectable
11
Resectable
Metachronous
metastases
Primary treatment
Resection
Adjuvant treatment
FOLFOX/CapeOx
preferred
No previous
chemotherapy
Neoadjuvant
chemotherapy
(2-3 months)
(see page 7)
Resection
Reinitiate neoadjuvant
therapy
or FOLFOX
Growth on
neoadjuvant
chemotherapy
Active chemotherapy
regimen (page 14)
or observation
Resection
Observation (preferred for previous
oxaliplatin-Based therapy)
or Active chemotherapy regimen(page 14)
Previous
chemotherapy
Neoadjuvant
chemotherapy
(2-3 months)
(see page 14)
No growth on
neoadjuvant
chemotherapy
Resection
No growth on
neoadjuvant
chemotherapy
Growth on
neoadjuvant
chemotherapy
Reinitiate neoadjuvant therapy
o r
F O L F O X
or observation
Active chemotherapy regimen
(page 14)
or observation
12
Unresectable
Metachronous metastases
Previous adjuvant
FOLFOX within past 12
months
Primary treatment
ll
ll
ll
ll
ll
Active chemotherapy
regimen (page 14)
or observation
FOLFIRI ± bevacizumab
FOLFIRI ± ziv-aflibercept
Irinotecan ± bevacizumab
Irinotecan ± ziv-aflibercept
FOLFIRI ±(Cetuximab or
panitumumab )(KRAS WT
gene only)
ll (Cetuximab or panitumumab)
Resection
(KRAS WT gene only) +
irinotecan
ll Previous adjuvant
FOLFOX > 12
months
ll Previous 5-FU/LV
or Capecitabine
ll No previous
chemotherapy
Reevaluation for conversion
to resectable every 2 months
if conversion to
respectability is a
reasonable goal
Converted to
resectable
Remains
unresectable
Active chemotherapy
regimen (page 14)
Active chemotherapy
regimen (page 14)
13
Chemotherapy for advanced or metastastic disease
Initial therapy
FOLFOX ±bevacizumab
or
CapeOX ± bevacizumab
or
FOLFOX ±
panitumumab
(KRAS wild-type [WT]
gene only)
Patient
appropriate
for
intensive
therapy
FOLFIRI ± bevacizumab
or
FOLFIRI ± (cetuximab or
Panitumumab)
(KRAS wild-type [WT]
gene only)
Therapy after First Progression
FOLFIRI ± bevacizumab
or FOLFIRI ± ziv-aflibercept
or Irinotecan ± bevacizumab
or Irinotecan ± ziv-aflibercept
(Cetuximab or Panitumumab) +
FOLFIRI + (cetuximab or Panitumumab)
or (cetuximab or Panitumumab) + irinotecan
Regorafenib (if not given previously)
FOLFOX ± bevacizumab
care
or CapeOX ± bevacizumab
(Cetuximab or Panitumumab) +
bevacizumab
or Clinical trial or best supportive
irinotecan; for patients
not able to tolerate combination,
consider single agent (cetuximab or
panitumumab)
or Regorafenib
FOLFOX or CapeOX
or CapeOX ± bevacizumab
FOLFOXIRI±
irinotecan; for patients
not able to tolerate combination,
consider single agent
(cetuximab or panitumumab)
or Regorafenib
(Cetuximab or Panitumumab) +
irinotecan; for patients not able to
tolerate combination, consider single
agent (cetuximab or panitumumab )
(KRAS [WT] gene only)
FOLFOX ± bevacizumab
5-FU/LV or
Capecitabine ±
bevacizumab
Therapy after Second Progression
Irinotecan
or Irinotecan + oxaliplatin ± bevacizumab
Irinotecan ± bevacizumab
or Irinotecan ± ziv-aflibercept
or FOLFIRI ± bevacizumab
or FOLFIRI ± ziv-aflibercept
FOLFOX
or
(Cetuximab or Panitumumab)
+ irinotecan; for patients
not able to tolerate
combination,
consider single agent
(cetuximab or
panitumumab)
or Regorafenib
CapeOX
14
Chemotherapy for advanced or metastastic disease
Initial therapy
Patient not
appropriate
for
intensive
therapy
Infusional 5-FU + leucovorin
or
Capecitabine ± bevacizumab
or
Cetuximab (KRAS wild-type
gene only)
or
Panitumumab (KRAS wildtype
gene only)
or
Ufuf 5
Therapy after first progression
Improvement
in functional
status
No improvement
in functional status
Consider initial therapy
as patient appropriate
for intensive therapy on
page 14
Best supportive
care
15
Adjuvant Chemotherapy Regimen
Oxaliplatin base (including FOLFOX4, FOLFOX6, FOLFOX7, mFOLFOX, CapeOX)
5-FU base chemotherapy (IV form 5-FU, Capecitabine, Ufur)
Chemotherapy for advanced or metastatic disease
All CRC chemotherapy regimens according to patient’s condition and guidelines
NHI approve Bevacizumab combine with Irinotecan base or 5-FU base regimens at the 1st line treatment
NHI approve Cetuximab combine with Irinotecan base regimens at the 1st line & the 3rd line treatment
CRC Chemotherapy regimens
5-FU/leucovorin (dl-LV) (100 l-LV=200 dl-LV)
•de Gramont regimen (LV5FU2)
LV 400 mg/ m2 /2h in NS 250ml＋5-FU 400 mg/ m2 bolus and 600 mg/ m2 /22h in NS
500ml x 2 days every 2 weeks
•AIO regimen:
LV 500 mg/ m2 in NS 250ml run 2 hour + 5-FU 2600 mg/ m2 in NS 500ml run 24 hour
weekly x 6, followed by 2 weeks off (repeat every 8 weeks)
•mAIO regimen:
LV 200 mg/m2 in NS 250ml run 1 hour + 5-FU 2600 mg/ m2 in NS 500ml run 18 hour
weekly x 6, followed by 2 weeks off (repeat every 8 weeks)
•Simplified 5-FU/LV (sLV5FU2)
16
Leucovorin 400 mg/ m2 in NS 250ml IV over 2 hours on day 1,
5-FU bolus 400 mg/ m2 and then 2400-30000 mg/ m2 in NS 500ml 46hours IV continuous infusion
Repeat every 2 weeks.
•Roswell-Park regimen
Leucovorin 500 mg/ m2 in NS 250ml IV over 2 hours + 5-FU 500 mg/ m2 IV bolus weekly x 6, followed by 2 weeks off
Repeat every 8 weeks
•Mayo Clinic Regimen
Leucovorin 20 mg/ m2 /day i.v. 30 minutes + 5-FU, 425 mg/ m2 /day i.v. bolus x 5 days
Repeat every 5 weeks
•CCRT
Leucovorin 20 mg/ m2 + bolus 5-FU 400 mg/ m2 at D1-4 during week 1 and 5 of XRT (radiotherapy)
•Ufur
Leucovorin 20-30 mg/ m2 + Ufur 300-500 mg/ m2 at D1-28 in every 35 days
•Xeloda
(Capecitabine)
Capecitabine 850-1250 mg/ m2 twice daily days 1-14 every 3 wks
Oxaliplatin Base
•FOLFOX 6
Oxaliplatin 85 mg/ m2 IV in D5W 250ml over 2 hours on day 1
Leucovorin 400 mg/ m2 IV in NS 250ml over 2 hours concurrently with Oxaliplatin on day 1
5-FU 400 mg/ m2 IV bolus day 1, then 1200 mg/ m2 /day x 2 days (total 2400 mg/ m2 over 46-48 hours ) IV continuous infusion
17
Repeat every 14 days
•mFOLFOX
Oxaliplatin 85-100 mg/ m2 IV in D5W 250-500 ml over 1.5hours on day 1
Leucovorin 200 mg/ m2 IV diluted in D5W/NS 250 ml over 1 hours concurrently with Oxaliplatin on day 1
5-FU 2600 mg/ m2 in NS 500 ml CIV over 18 hours on day 1
Repeat every 14 days.
•CapeOX / XELOX
Oxaliplatin 130 mg/ m2, Day 1
Capecitabine 850-1000 mg/ m2 Q12H Day 1-14
Repeat every 21 days
Irinotecan Base
•FOLFIRI
Irinotecan 180 mg/ m2 IV over 90 minutes, day 1
Leucovorin 400 mg/ m2 IV infusion for 2 hours concurrent with irinotecan infusion, day 1
5-FU 400 mg/ m2 IV bolus day 1, then 1200 mg/ m2/day x 2 days (total 2400 mg/ m2 over 46-48 hours) IV continuous infusion
Repeat every 2 weeks
•mFOLFIRI
Irinotecan 180 mg/ m2 IV over 90 minutes, day 1
Leucovorin 200 mg/ m2 IV infusion for 1 hours concurrent with irinotecan infusion, day 1
5-FU 2400-3000 mg/ m2 continuous infusion over 18 hours (start on day 1)
Repeat every 2 weeks
18
Bevacizumab (Avastin)
•Bevacizumab 5 mg/kg in NS 100ml IV 30-60 minutes every 2 weeks
Combine with FOLFIRI, FOLFOX, or 5-FU/LV
•Bevacizumab 7.5 mg/kg IV (over 15 minutes) every 3 weeks + CapeOX
Cetuximab (Erbitux) (KRAS wild-type gene only)
•Cetuximab 400 mg/ m2 1st infusion, then 250 mg/ m2 IV weekly or
•Cetuximab 500 mg/ m2 IV over 2 hours, day 1, every 2 weeks
FOLFOXIRI
Irinotecan 165 mg/ m2 IV day 1,
Oxaliplatin 85 mg/ m2 IV day 1,
Leucovorin 400 mg/ m2 IV day 1,
5-FU 1600 mg/ m2/day x 2 days (total 3200 mg/ m2 over 48 hours) IV continuous infusion
Repeat every 2 weeks
Panitumumab (KRAS wild-type gene only)
Panitumumab 6 mg/kg IV over 60 minutes every 2 weeks
19
Regorafenib regimen:
Regorafenib 160mg PO daily days 1-21, repeat every 28 days
ziv-aflibercept
Ziv-aflibercept 4 mg/kg IV, repeat every 2 weeks
Dosing Schedules for Concurrent Chemotherapy/RT:
2
XRT + continuous infusion 5-FU 5-FU 225 mg/m over 24 hours 5 or 7 days/week during XRT
2
2
XRT + 5-FU/leucovorin 5-FU 400 mg/m IV bolus + leucovorin 20 mg/m IV bolus for 4 days during week 1 and 5 of XRT
2
XRT + Capecitabine Capecitabine 825 mg/m twice daily 5 days/week + XRT x 5 weeks
XRT + Leucovorin 20-30 mg/ m2 + Ufur 300-500 mg/ m2 combine with XRT
20
Definitions for T, N, M Primary Tumor (T)TX
Primary tumor cannot be assessedT0
No evidence of primary tumorTis
Carcinoma in situ:
intraepithelial or invasion of lamina propriaa
T1 Tumor invades submucosa
T2 Tumor invades muscularis propria
T3 Tumor invades through the muscularis propria into the pericolorectal tissues
T3a < 1mm
T3b 1-5mm
T3c 5-15mm
T3d ≧15mm
T4a Tumor penetrates to the surface of the visceral peritoneumb
T4b Tumor directly invades or is adherent to other organs or structuresb,c
Regional Lymph Nodes (N)NX
Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1a Metastasis in one regional lymph node
N1b Metastasis in 2-3 regional lymph nodes
21
N1c Tumor deposit(s) in the subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues without regional nodal metastasis
N2a Metastasis in 4-6 regional lymph nodes
N2b Metastasis in seven or more regional lymph nodes
Distant Metastasis (M)
M0 No distant metastasis
M1 Distant metastasis
M1a Metastasis confined to one organ or site (eg,
liver, lung, ovary, nonregional node)
M1b Metastases in more than one organ/site or the peritoneum
22
7th AJCC Colorectal cancer staging
Dukes
MAC
Group
T
N
M
0
Tis
N0
M0
-
-
I
T1
N0
M0
A
A
T2
N0
M0
A
B1
IIA
T3
N0
M0
B
B2
IIB
T4a
N0
M0
B
B2
IIC
T4b
N0
M0
B
B3
IIIA
T1-2
N1/N1c
M0
C
C1
T1
N2a
M0
C
C1
T3-4a
N1/N1c
M0
C
C2
T2-3
N2a
M0
C
C1/C2
T1-2
N2b
M0
C
C1
T4a
N2a
M0
C
C2
T3-4a
N2b
M0
C
C2
T4b
N1-2
M0
C
C3
IVA
anyT
anyN
M1a
-
-
IVB
anyT
anyN
M1b
-
-
IIIB
IIIC
23
Reference
1. Major base on NCCN Rectal Cancer Clinical Practice Guidelines Version 2.2014
2. NHI regulations for CRC chemotherapy
3. The ESMO Low Gastrointestinal Cancers guideline 2013
4. Efficacy of oral UFT as adjuvant chemotherapy to curative resection of colorectal cancer: multicenter prospective randomized trial. Kato T, Ohashi
Y, Nakazato H, Koike A, Saji S, Suzuki H, Takagi H, Nimura Y, Hasumi A, Baba S, Manabe T, Maruta M, Miura K, Yamaguchi A. Langenbecks
Arch Surg. 2002 Mar;386(8):575-81.
5. The role of UFT in metastatic colorectal cancer. Bennouna J, Saunders M, Douillard JY. Oncology. 2009;76(5):301-10.
6. Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results
from National Surgical Adjuvant Breast and Bowel Project Protocol C-06. Lembersky BC, Wieand HS, Petrelli NJ, O'Connell MJ, Colangelo LH,
Smith RE, Seay TE, Giguere JK, Marshall ME, Jacobs AD, Colman LK, Soran A, Yothers G, Wolmark N. J Clin Oncol. 2006 May 1;24
(13):2059-64.
7. Preoperative chemoradiotherapy for rectal cancer: randomized trial comparing oral uracil and tegafur and oral leucovorin vs. intravenous 5fluorouracil and leucovorin. de la Torre A, García-Berrocal MI, Arias F, Mariño A, Valcárcel F, Magallón R, Regueiro CA, Romero J, Zapata I, de
la Fuente C, Fernández-Lizarbe E, Vergara G, Belinchón B, Veiras M, Molerón R, Millán I. Int J Radiat Oncol Biol Phys. 2008 Jan 1;70
(1):102-10.
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