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Abramson Cancer CenterNCI CANCERLIT® Search: Therapy of Colorectal Cancer - April 2002
National Cancer Institute®
Last Modified: April 1, 2002
Table of Contents
1
UI - 10910241
AU - Tocchi A; Mazzoni G; Lepre L; Costa G; Liotta G; Agostini N; Miccini M
TI -
Prospective evaluation of omentoplasty in preventing leakage of
colorectal anastomosis.
SO - Dis Colon Rectum 2000 Jul;43(7):951-5
AD - First Department of Surgery, Rome La Sapienza University Medical School,
Italy.
PURPOSE: The aim of this study was to investigate the role of
omentoplasty, by means of intact omentum, in preventing anastomotic
leakages after rectal resection. METHODS: Between 1992 and 1997 a total
of 112 patients (64 males) with a mean age of 64.7 (range, 39-83) years
were randomly assigned to undergo omentoplasty (Group A) or not (Group
B) to reinforce the colorectal anastomosis after anterior resection for
rectal cancer. The primary end point was anastomotic leakage; the
secondary end point included morbidity and mortality related to
omentoplasty. RESULTS: The two groups were comparable in terms of
preoperative and intraoperative characteristics. Staple-ring disruption
at plain abdominal radiographs was detected in seven instances in Group
A and in ten in Group B patients (P = not significant). Two leakages
were evident clinically in Group A and seven in Group B (P < 0.05).
Three leaks were documented radiologically in Group A and eight in Group
B (P = not significant). No complications related to omentoplasty were
observed in Group A. There were two repeat operations for anastomotic
leakage in Group B. At followup, one stricture developed in Group A and
three in Group B (P = not significant) CONCLUSIONS: Despite a similar
incidence of staple-ring defects, a strikingly lower rate of clinically
and radiologically detected leaks developed in patients submitted to
omentoplasty. Although not affecting the incidence of anastomotic
disruption, omentoplasty seems to contain the severity of anastomotic
leakage.
2
UI - 11552476
AU - Carlomagno N; Scarano MI; Gargiulo S; De Rosa M; Panariello L; Izzo P;
TI -
Renda A
[Familial colonic polyposis: effect of molecular analysis on the
diagnostic-therapeutic approach]
SO - Ann Ital Chir 2001 Mar-Apr;72(2):207-14
AD - Chirurgia Generale ad Indirizzo Addominale, Universita Federico II,
Napoli. renda@unina.it
Germline mutations of the Adenomatous polyposis gene (APC) are
responsible for Familial Adenomatous Polyposis (FAP), an inherited
condition that predisposes to the development of hundreds to thousands
benign adenomas in the colo-rectum. If not surgically removed, they
inevitably progress into malignant adenocarcinoma. To date more than 450
germline mutations have been described allowing the establishment of
genotype/phenotype correlation between the site and type of molecular
defects and their morbid consequences. Authors reviewed their experience
concerning 22 FAP affected patients and their 26 first degree relatives,
in whom the mutational analysis of the APC gene had been carried out.
Site and type of mutations were associated with clinical parameters (age
of onset, rectal involvement, extracolonic manifestations, presence of
colorectal cancer) and treatments. The impact of mutational analyses on
the clinical approach could be very interesting in the future, modifying
both surveillance programs and therapeutical choices.
3
UI - 11786782
AU - Kaya A; Hazar H
TI -
Preoperative neoadjuvant therapy for rectal cancer also enables
autologous transfusion.
SO - Dis Colon Rectum 2002 Jan;45(1):143-4
4
UI - 11805575
AU - Giordano P; Renzi A; Gervaz P
TI -
Colorectal anastomosis and omentoplasty: re-evaluation of statistical
analysis.
SO - Dis Colon Rectum 2001 Jan;44(1):145
5
UI - 11805563
AU - Mehta VK; Poen J; Ford J; Edelstein PS; Vierra M; Bastidas AJ; Young H;
TI -
Fisher G
Radiotherapy, concomitant protracted-venous-infusion 5-fluorouracil, and
surgery for ultrasound-staged T3 or T4 rectal cancer.
SO - Dis Colon Rectum 2001 Jan;44(1):52-8
AD - Department of Radiation Oncology, Stanford University Medical Center,
Stanford, California 94305, USA.
BACKGROUND: A prospective study was undertaken to evaluate the response
and toxicity of neoadjuvant chemoradiotherapy for ultrasound-staged T3
or T4 rectal cancer. PATIENTS AND METHODS: Since 1995, 30 patients (18
males; median age, 56 (range, 25-83) years) have received preoperative
chemoradiotherapy for ultrasound-staged T3 or T4 rectal cancer. All
patients underwent an endorectal ultrasound, CT scan, and review in our
multidisciplinary Gastrointestinal Tumor Board before treatment. All
patients had pathology-demonstrated invasive adenocarcinoma of the
rectum. Eleven patients were Stage T3N0, 14 were T3N1, and five were
T4N1. Patients received radiotherapy to the primary tumor and draining
lymph nodes (45 Gy) followed by a tumor boost (50.4-54 Gy).
Protracted-venous-infusion 5-fluorouracil (225 mg/m2 per day, seven days
per week) was administered throughout treatment. Surgical resection was
performed six to ten weeks after completing chemoradiotherapy. Using
endorectal ultrasound measurements, the primary tumor was a median of 4
(range, 0-12) cm from the anal verge, encompassed 50 (range, 20-90)
percent of the rectal circumference, and was 6 (range, 3-12) cm in
diameter. RESULTS: No Grade 4 toxicity was observed during
chemoradiotherapy. Three patients experienced Grade 3 toxicity
(diarrhea), and four patients required a treatment interruption of
greater than three days. All patients completed at least 90 percent of
the prescribed radiotherapy dose. All patients underwent surgical
resection. Ninety-four percent had clear surgical margins. All
pathologic specimens had significant evidence of necrosis,
hyalinization, and fibrosis. Thirty-three percent of the specimens had a
complete pathologic response (defined as no evidence of viable tumor
cells). Of the 19 patients with ultrasound-staged N1 disease, only five
had pathologic evidence of nodal involvement after chemoradiotherapy. Of
the 25 patients with ultrasound-staged T3 disease, pathologic staging
revealed eight with T0, two with T1, five with T2, and ten with T3
disease. Of the five patients with ultrasound-staged T4 disease,
pathologic staging revealed two with T0, one with T2, and two with T3
disease. No patient developed progressive disease while on treatment.
Two patients have experienced local failure at 6 and 20 months, and one
patient failed in the liver at seven months. Twenty-seven patients
remain free of disease with a median follow-up of 20 (range, 3-53)
months. CONCLUSION: Our experience suggests that preoperative
chemoradiotherapy is well tolerated, down-stages tumors, and sterilizes
regional lymph nodes.
6
UI - 11776494
AU - Onaitis MW; Noone RB; Fields R; Hurwitz H; Morse M; Jowell P; McGrath K;
TI -
Lee C; Anscher MS; Clary B; Mantyh C; Pappas TN; Ludwig K; Seigler HF;
Tyler DS
Complete response to neoadjuvant chemoradiation for rectal cancer does
not influence survival.
SO - Ann Surg Oncol 2001 Dec;8(10):801-6
AD - Department of Surgery, Duke University Medical Center, Durham, North
Carolina 27710, USA.
BACKGROUND: Up to 30% of patients with locally advanced rectal cancer
have a complete clinical or pathologic response to neoadjuvant
chemoradiation. This study analyzes complete clinical and pathologic
responders among a large group of rectal cancer patients treated with
neoadjuvant chemoradiation. METHODS: From 1987 to 2000, 141 consecutive
patients with biopsy-proven, locally advanced rectal cancer were treated
with preoperative 5-fluorouracil-based chemotherapy and radiation.
Clinical restaging after treatment consisted of proctoscopic examination
and often computed tomography scan. One hundred forty patients then
underwent operative resection, with results tracked in a database.
Standard statistical methods were used to examine the outcomes of those
patients with complete clinical or pathologic responses. RESULTS: No
demographic differences were detected between either clinical complete
and clinical partial responders or pathologic complete and pathologic
partial responders. The positive predictive value of clinical restaging
was 60%, and accuracy was 82%. By use of the Kaplan-Meier life table
analysis, clinical complete responders had no advantage in local
recurrence, disease-free survival, or overall survival rates when
compared with clinical partial responders. Pathologic complete
responders also had no recurrence or survival advantage when compared
with pathologic partial responders. Of the 34 pathologic T0 tumors, 4
(13%) had lymph node metastases. CONCLUSIONS: Clinical assessment of
complete response to neoadjuvant chemoradiation is unreliable.
Micrometastatic disease persists in a proportion of patients despite
pathologic complete response. Observation or local excision for patients
thought to be complete responders should be undertaken with caution.
7
UI - 11862418
AU - Andoh A; Shimada M; Araki Y; Fujiyama Y; Bamba T
TI -
Sodium butyrate enhances complement-mediated cell injury via
down-regulation of decay-accelerating factor expression in colonic
cancer cells.
SO - Cancer Immunol Immunother 2002 Feb;50(12):663-72
AD - Department of Internal Medicine, Shiga University of Medical Science,
Seta-Tukinowa, Otsu 520-2192, Japan. andoh@belle.shiga-med.ac.jp
Decay-accelerating factor (DAF) expressed on the surface of colonic
cancer cells presents a barrier to complement-mediated clearance by
contributing to the ineffectiveness of the humoral immune response. In
this study, to investigate the mechanisms responsible for the anti-tumor
effects of butyrate, we evaluated how butyrate modulates DAF expression
in colonic cancer cells. Three colonic cancer cell lines (HT-29, Caco-2,
and T84 cells) were studied. DAF protein expression was assessed by
western blot, and DAF mRNA expression was evaluated by northern blot.
Complement C3 deposition on the surface of colonic cancer cells was
determined by enzyme-linked immunosorbent assay (ELISA). The promoter
activity of the DAF gene was assessed by a reporter gene-luciferase
assay. Butyrate reduced the basal and interleukin-4 (IL-4)- and tumor
necrosis factor-alpha (TNF-alpha)-induced expression of DAF protein and
mRNA in HT-29 cells. It increased the susceptibility to complement
attack and enhanced C3 deposition on HT-29 cells. The inhibitory effect
of butyrate on DAF mRNA expression was also observed in T84 and Caco-2
cells. Butyrate decreased basal DAF expression at both transcriptional
and post-transcriptional levels. The inhibitory effect of butyrate on
IL-4-induced DAF expression was closely associated with a blockade of
IL-4-induced DAF mRNA stability. TNF-alpha-induced transcriptional
activation and the increased stability of the DAF gene were also blocked
by butyrate. Similar but weak effects were induced by trichostatin A, a
potent histone deacetylase inhibitor, suggesting that histone
acetylation might participate in butyrate activity. These observations
indicate that both a down-regulation of DAF expression and the induction
of susceptibility to complement attack contribute to the anti-tumor
effects of butyrate in colonic cancer.
8
UI - 11905733
AU - Twelves C; Hargreaves D; Nguyen-Van-Tam J; Ng T
TI -
Capecitabine monotherapy in metastatic colorectal cancer.
SO - Lancet Oncol 2001 Jul;2(7):400
9
UI - 11290635
AU - Borras JM; Sanchez-Hernandez A; Navarro M; Martinez M; Mendez E; Ponton
TI -
JL; Espinas JA; Germa JR
Compliance, satisfaction, and quality of life of patients with
colorectal cancer receiving home chemotherapy or outpatient treatment: a
randomised controlled trial.
SO - BMJ 2001 Apr 7;322(7290):826
AD - Cancer Prevention and Control Unit, Catalan Institute of Oncology, Gran
Via Km 2,7 s/n, 08907-Hospitalet, Spain. jmborras@ico.scs.es
OBJECTIVE: To compare chemotherapy given at home with outpatient
treatment in terms of colorectal cancer patients' safety, compliance,
use of health services, quality of life, and satisfaction with
treatment. DESIGN: Randomised controlled trial. SETTING: Large teaching
hospital. PARTICIPANTS: 87 patients receiving adjuvant or palliative
chemotherapy for colorectal cancer. INTERVENTIONS: Treatment with
fluorouracil (with or without folinic acid or levamisole) at outpatient
clinic or at home. MAIN OUTCOME MEASURES: Treatment toxicity; patients'
compliance with treatment, quality of life, satisfaction with care, and
use of health resources. RESULTS: 42 patients were treated at outpatient
clinic and 45 at home. The two groups were balanced in terms of age,
sex, site of cancer, and disease stage. Treatment related toxicity was
similar in the two groups (difference 7% (95% confidence interval -12%
to 26%)), but there were more voluntary withdrawals from treatment in
the outpatient group than in the home group (14% v 2%, difference 12%
(1% to 24%)). There were no differences between groups in terms of
quality of life scores during and after treatment. Levels of patient
satisfaction were higher in the home treatment group, specifically with
regard to information received and nursing care. There were no
significant differences in use of health services. CONCLUSIONS: Home
chemotherapy seemed an acceptable and safe alternative to hospital
treatment for patients with colorectal cancer that may improve
compliance and satisfaction with treatment.
10
UI - 11852390
AU - Bedenne L
TI -
[Follow-up after resection for cure of colorectal cancer: searching for
the missing rationale]
SO - Gastroenterol Clin Biol 2001 Oct;25(10):879-80
AD - Service d'Hepato-Gastroenterologie, CHU Le Bocage, Dijon, France.
lbedenne@u-bourgogne.fr
11
UI - 11852391
AU - Borie F; Daures JP; Millat B; Folschveiller-Bruggeman M; Tretarre B
TI -
[Follow-up of patients with colorectal cancer resected for cure in the
Herault area. A medico-economical study]
SO - Gastroenterol Clin Biol 2001 Oct;25(10):881-4
AD - Service de Chirurgie Digestive A, Hopital Saint-Eloi, Montpellier,
France. fborie@yahoo.com
Optimal modalities of surveillance of colorectal cancers (CRC) resected
for cure have not been determined so far and the overall improvement of
5-year survival related to surveillance has not been demonstrated. AIM
OF THE STUDY: To retrospectively evaluate modalities, results and costs
of follow-up of patients during the 5 years following the resection for
cure of CRC. METHODS: We studied medical and economical data from
records of 256 patients registered in the cancer registry of the Herault
area who underwent a potentially curative resection of CRC in 1992. We
analyzed comparatively modalities of follow-up in patients who were
followed according to recommendations from the 1998 French consensus
conference (standard follow-up) and in those who had a simplified
follow-up. We evaluated cumulative costs of follow-up. RESULTS: Nine
patients died in the postoperative period. Recurrence rate was 27% (69
patients). Sixty-nine patients had a standard follow-up (30% of the 231
classified patients) and 162 patients (70%) had a simplified follow-up.
The specific survival rate (taking into account only death related to
CRC) 5 years after resection for cure was 75%. The 5-year specific
survival rate after diagnosis of recurrence was 12% in the patients with
recurrent disease within the 5 years after initial therapy. The 5-year
survival rate after standard and simplified follow-up were 85% and 79%,
respectively (P=0.25). Total cost of follow-up of the 256 patients was 1
085 507 French francs (FF). Mean follow-up cost per patient was 5 527
FF. Cost of the examinations not recommended by the consensus conference
represented 30% of the expenses. Individual total cost of the follow-up
of patients alive 5 years after the diagnosis of the recurrence was 120
356 FF. CONCLUSION: In Herault area, clinicians carried out in 70% of
the patients a simplified follow-up and in 30% of the cases a reinforced
follow-up in comparison with French recommendations. Survival rates were
not significantly different between the 2 groups.
12
UI - 11778366
AU - Lengyel L; Szakats T; Koti C
TI -
[Primary resection of obstructive left-sided colon and rectal tumors
without intraoperative lavage]
SO - Orv Hetil 2001 Dec 2;142(48):2681-5
AD - Teruleti Korhaz Berettyoujfalu, Sebeszeti Osztaly.
Of the study is to show the results of early postoperative period of
left-sided large bowel obstruction (LBO) and methods of decompression
without colonic lavage and primary resection. Retrospective analysis of
28 patients admitted to the Surgical Department with LBO between years
1996 and 2000 were treated with ortograde decompression, and primary
resection without on table colonic lavage. The surgical method,
complications and mortality are pointed out. The patients average age
were 71 +/- 9.7 years and only one was free of comorbidity. The average
time of operative interventions was 116 +/- 42 minutes. 9 patients out
of 28 had rectum cancer their anastomosis were made by instrumental way
and the others by hand. The bowel movement was restored (in 89%) on the
fourth day of operation. Surgical complications were observed at 3/28
patients (10.7%), and non surgical complication at three patients.
Mortality rate 3.5%, one patient was lost. The average hospital stay was
12 +/- 5 days, 70% of the patients were at home within 11 days. The
emergency surgical treatment of left-sided colonic obstruction caused by
cancer treated by ortograde decompression and primary resection without
colonic lavage is a safe method in experienced surgeon hand. The
patients have a short recovery period and better quality of life.
13
UI - 11855920
AU - Gunther K; Dworak O; Remke S; Pfluger R; Merkel S; Hohenberger W;
TI -
Reymond MA
Prediction of distant metastases after curative surgery for rectal
cancer.
SO - J Surg Res 2002 Mar;103(1):68-78
AD - Department of Surgery, Biometry and Epidemiology of the University of
Erlangen, Erlangen, D-91054 Germany.
BACKGROUND: This study was performed to define selection criteria for
adjuvant therapy in rectal cancer. MATERIALS AND METHODS: An
immunohistochemical analysis using nine monoclonal antibodies against
CEA, CD15s, CD44v6, DCC, E-cadherin, EGF-R, NM23, PAI-1, and P53 was
performed on paraffin sections of two matched (age, gender, UICC stage
[I-III], year of operation [1982-1991]) groups of patients (n = 2 x 64)
with rectal carcinoma curatively treated by surgery alone. The two
groups differed only with regard to metachronous distant metastatic
spread. In order to exclude the influence of surgery, all patients had
to meet the selection criterion "free of locoregional disease."
Follow-up was prospective (median 80 months). Conventional staining
procedures and immunohistochemical evaluation were used. Tumor grading
and lymphatic and extramural venous invasion were also investigated.
Analysis was performed with Fisher's exact test and Kaplan-Meier
estimates of disease-free survival (log rank). The Cox model was used
for multivariate analysis. RESULTS: In univariate analysis only grading
(P < 0.001) and extramural venous invasion (P < 0.001) correlated
significantly with metachronous metastases. In multivariate analysis,
beside grading (P = 0.010) and extramural venous invasion (P = 0.011),
CD15s (P = 0.042) was also of significance. All other
immunohistochemical markers failed. CONCLUSIONS: The histopathological
parameters grading and extramural venous invasion appear to be
acceptable predictors of metachronous distant spread in curatively
resected rectal cancer. In contrast to the immunohistochemical markers,
grading seems to better reflect the individual tumor phenotype and its
behavior.
14
UI - 11902527
AU - Adlard JW; Richman SD; Seymour MT; Quirke P
TI -
Prediction of the response of colorectal cancer to systemic therapy.
SO - Lancet Oncol 2002 Feb;3(2):75-82
AD - Academic Department of Pathology, University of Leeds, UK.
jwa@doctors.org.uk
Adjuvant chemotherapy with fluorouracil and folinic acid improves
overall survival for resected carcinoma of the colon of Dukes' stage C
by 10-12%. In metastatic disease, response rates with fluorouracil-based
regimens are about 25%. Combination with newer agents such as irinotecan
and oxaliplatin can improve response rates to more than 50% in selected
patients. New treatments with novel molecular targets will soon be
entering clinical use. Despite these improvements, many patients undergo
chemotherapy for resistant cancer, thus incurring side-effects without
benefit. Expression of particular genes can be tested at the protein or
RNA level and can be correlated with response or resistance to
particular systemic therapies. Thus, predictive-factor testing of tumour
biopsy samples may allow us to select chemotherapy or immunotherapy
treatments with a high likelihood of benefit for the individual patient.
15
UI - 11788909
AU - Munemoto Y; Iida Y; Abe J; Saito H; Fujisawa K; Kasahara Y; Mitsui T;
TI -
Asada Y; Miura S
Significance of postoperative adjuvant immunochemotherapy after curative
resection of colorectal cancers: Association between host or tumor
factors and survival.
SO - Int J Oncol 2002 Feb;20(2):403-11
AD - Department of Surgery, Prefecture of Saiseikai Fukui Hospital, Fukui
918-8503, Japan. y-munemoto@fukui.saiseikai.or.jp
We examined the relationship between host as well as tumor factors and
postoperative survival rate in patients who received combination therapy
of mitomycin C + fluoropyrimidine oral antineoplastics + protein-bound
polysaccharide K (PSK) (MFP therapy) after curative resection of
colorectal cancer. Markers that determine prognosis, such as
preoperative humoral factors (complement 3 and 4), immunosuppressive
acidic protein (IAP), lymphocyte transformation (cellular factors)
induced by phytohemagglutinin (PHA), pokeweed mitogen (PWM), and PSK,
and various tumor markers (CEA, CA19-9) were measured. For each
parameter, patients were divided into a high-level and a low-level group
according to a predetermined cut-off value, and survival rates were
compared between the two groups. The host factors that determined
prognosis were 1-month postoperative IAP level [IAP(1M)], preoperative
PHA value, and preoperative CA19-9 level. The levels of IAP(1M) <740
microg/ml, preoperative PHA > or =210 (SI value), and preoperative
CA19-9 <13 U/ml were associated with a favorable prognosis. When
combined with the tumor factors, the prognosis was favorable in Dukes
A+B cases with preoperative CA19-9 <13 U/ml, and in Dukes C cases with
preoperative PHA > or =210 SI. By the Cox proportional hazard model
analysis, among IAP, PHA and CA19-9, CA19-9 was the strongest host
factor associated with the prognosis of MFP therapy.
16
UI - 11865378
AU - Liang JT; Shieh MJ; Chen CN; Cheng YM; Chang KJ; Wang SM
TI -
Prospective evaluation of laparoscopy-assisted colectomy versus
laparotomy with resection for management of complex polyps of the
sigmoid colon.
SO - World J Surg 2002 Mar;26(3):377-83
AD - Department of Surgery, National Taiwan University Hospital, No. 7 Chung
Shan South Road, Taipei, Taiwan, R.O.C. jintung@ha.mc.ntu.edu.tw
Laparoscopy-assisted colectomy is technically feasible, but objective
evidence of its benefits remains scarce. This study was done to evaluate
the outcomes and operative stress of laparoscopy-assisted colectomy
versus the traditional open method in the management of sigmoid complex
polyps that cannot be safely or adequately removed by colonofibroscopy.
equally randomized to the laparoscopy group and the laparotomy group by
the blocked randomization method. Three patients randomized to the
laparoscopy group did not complete the trial; therefore 18 patients
treated by laparoscopy-assisted sigmoidectomy and the other 21 treated
by the open method were prospectively evaluated. These two groups of
patients were well matched in age, gender, symptoms, tumor location,
localization method, tumor size, morphology, histopathology, and the
accuracy of the clinical diagnosis. Two standardized surgical
strategies, the lateral-to-medial and medial-to-lateral dissection
sequences, were performed in 14 and 4 patients of the laparoscopy group,
respectively, according to whether their tumors were located above or
below 20 cm above the anal verge. After evaluating the surgical
outcomes, we found that the laparoscopy group was significantly better
than the laparotomy group in regard to parameters that included severity
of postoperative pain, wound size, postoperative complication rate, and
the duration of postoperative ileus, hospitalization, and disability.
There was no significant difference in the operating times for these two
groups. However, the costs of the laparoscopy group were significantly
higher. To evaluate the surgical stress, we measured the serum
C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR),
total lymphocyte count, and CD4+/CD8+ ratio 24 hours before and after
surgery. We found that the postoperative serum CRP level and the ESR
were significantly less elevated and the total lymphocyte counts and
CD4+/CD8+ ratio were significantly less depressed in the laparoscopy
group than in the laparotomy group. We thus concluded that
laparoscopy-assisted sigmoidectomy can be safely performed with shorter
convalescence and less operative stress but at a higher cost. We
strongly recommended the use of this technique in the management of
sigmoid complex polyps if the patient's economic status permits.
17
UI - 11870158
AU - Cure H; Chevalier V; Adenis A; Tubiana-Mathieu N; Niezgodzki G;
TI -
Kwiatkowski F; Pezet D; Perpoint B; Coudert B; Focan C; Levi F; Chipponi
J; Chollet P
Phase II trial of chronomodulated infusion of high-dose fluorouracil and
l-folinic acid in previously untreated patients with metastatic
colorectal cancer.
SO - J Clin Oncol 2002 Mar 1;20(5):1175-81
AD - Centre Jean Perrin and L'Institut National de la Sante et de la
Recherche Medicale U484, Clermont-Ferrand, France.
PURPOSE: To study tolerability and efficacy of an intensified
chronomodulated schedule of fluorouracil (5-FU) and l-folinic acid
(l-FA) as first-line treatment of metastatic colorectal cancer, 5-FU was
given near individually determined dose-limiting toxicity in a
multicenter phase II trial. PATIENTS AND METHODS: One hundred patients
(68 men and 32 women, median age 62 years, World Health Organization
performance status less-than-or-equal 2) with previously untreated and
inoperable metastases received chronomodulated daily infusion of
5-FU/l-FA (from 10:00 PM to 10:00 AM with peak at 4:00 AM). 5-FU dose
was escalated from 900 to 1,100 mg/m(2)/d with fixed dose of l-FA at 150
mg/m(2)/d for 4 days every 14 days. RESULTS: 5-FU dose escalation was
achieved in 66% of the patients. Grade 3 to 4 toxicities mainly
consisted of nausea or vomiting (14% of patients and 1.5% of courses),
hand-foot syndrome (38% of patients and 8% of courses), mucositis (26%
of patients and 4% of courses), and diarrhea (21% of patients and 2.3%
of courses). Objective response rate (ORR) was 41% (95% confidence
interval, 31.5% to 50.5%). Twenty patients underwent metastases surgery;
among these, 12 had a complete resection. Median progression-free
survival was 7 months. Median survival was 17 months; 28% of the
patients were alive at 2 years and 18.6% at 3 years. CONCLUSION: The ORR
achieved with intensified chronomodulated delivery of 5-FU/l-FA was
nearly twice as high as that earlier obtained by our cooperative group
using less intensive 5-FU/FA chronotherapy.
18
UI - 11870160
AU - Potosky AL; Harlan LC; Kaplan RS; Johnson KA; Lynch CF
TI -
Age, sex, and racial differences in the use of standard adjuvant therapy
for colorectal cancer.
SO - J Clin Oncol 2002 Mar 1;20(5):1192-202
AD - Division of Cancer Control and Population Sciences, National Cancer
Institute, National Institutes of Health, Bethesda, MD 20892, USA.
potosky@nih.gov
PURPOSE: Dissemination of efficacious adjuvant therapies for resectable
colorectal cancer has not been comprehensively described. Trends,
patterns, and outcomes of adjuvant therapy for colorectal cancer,
focusing on age, sex, and racial/ethnic differences, are reported.
MATERIALS AND METHODS: Population-based random samples of patients
diagnosed with colorectal cancer diagnosed in nine geographic areas were
collected annually between 1987 and 1991 and in 1995 (n = 4,706). Data
were obtained from medical record reviews. Multiple logistic regression
was used to assess the use of standard adjuvant chemotherapy for colon
and rectal cancers. The Cox proportional hazards model was used to
assess 9-year mortality. RESULTS: From 1987 until 1995, the use of
adjuvant therapy increased in all age groups. There was an increase
starting in 1989 for colon and in 1988 for rectal cancer. Use of
standard therapy was 78% for those younger than 55 years and 24% for
those older than 80 years. White patients received standard therapy more
frequently than African-Americans (odds ratio, 1.75; 95% confidence
interval [CI], 1.09 to 2.83). All-cause and cancer-specific mortality
exceeding 9 years were lower in those who received standard therapy
(all-cause risk ratio [RR], 0.73; 95% CI, 0.61 to 0.88; cancer-specific
RR, 0.87; 95% CI, 0.70 to 1.09). CONCLUSION: Standard adjuvant therapies
for colorectal cancer disseminated into community practices during the
1990s. However, evidence exists of differential use of therapies by
older patients and by African-Americans. The use of standard therapies
in the general population is associated with lower mortality. Improved
dissemination of standard adjuvant therapies to all segments of the
population could help reduce mortality.
19
UI - 11875472
AU - Dove A
TI -
Promising drug is victim of bad business.
SO - Nat Med 2002 Mar;8(3):199
20
UI - 11875693
AU - McArdle CS; Hole DJ
TI -
Outcome following surgery for colorectal cancer: analysis by hospital
after adjustment for case-mix and deprivation.
SO - Br J Cancer 2002 Feb 1;86(3):331-5
AD - University Department of Surgery, Royal Infirmary, Alexandra Parade,
Glasgow G31 2ER, UK. wrh1k@clinmed.gla.ac.uk
Outcome, adjusted for case-mix and deprivation, in 3200 patients
undergoing resection for colorectal cancer in 11 hospitals in Central
Scotland between 1991 and 1994 was studied. There were significant
differences among individual hospitals in the proportion of elderly
(P<0.001) and deprived (P<0.0001) patients, the mode (P=0.007) and stage
(P<0.0001) at presentation, and the proportion of patients who underwent
apparently curative resection (P<0.001). There were no significant
differences in postoperative mortality. Cancer-specific survival at 5
years following apparently curative resection varied from 59 to 76%;
cancer-specific survival at 2 years following palliative resection
varied from 22 to 44%. The corresponding hazard ratios, adjusted for the
above prognostic factors, for patients undergoing apparently curative
resection varied among hospitals from 0.58 to 1.32; and the ratios for
palliative resection varied from 0.73 to 1.26. This study demonstrates
that, after adjustment for variations in case-mix and deprivation,
significant differences in outcome among hospitals following resection
for colorectal cancer persist. Copyright 2002 The Cancer Research
Campaign
21
UI - 11875709
AU - Werther K; Christensen IJ; Nielsen HJ; Danish RANX05 Colorectal Cancer
TI -
Study Group
Prognostic impact of matched preoperative plasma and serum VEGF in
patients with primary colorectal carcinoma.
SO - Br J Cancer 2002 Feb 1;86(3):417-23
AD - Department of Surgical Gastroenterology 435, Hvidovre University
Hospital, University of Copenhagen, 2650 Hvidovre, Denmark.
k.werther@ofir.dk
In serum, the major part of vascular endothelial growth factor derives
from in vitro degranulation of granulocytes and platelets. Therefore,
plasma may be preferred for vascular endothelial growth factor
measurements. However, which specimen is the best predictor of survival
is still debated. The present study analyzed the prognostic value of
matched preoperative serum and plasma vascular endothelial growth factor
concentrations in patients with colorectal cancer. To establish the
reference range among healthy people, vascular endothelial growth factor
was analyzed in 50 matched EDTA-plasma and serum samples from healthy
blood donors. Preoperatively, in 524 patients with colorectal cancer,
matched plasma and serum vascular endothelial growth factor
concentrations were analyzed. In the colorectal cancer patients, the
median plasma vascular endothelial growth factor concentration (44 pg
ml(-1)) was significantly (P=0.01) higher than the median plasma
vascular endothelial growth factor concentration (30 pg ml(-1)) in the
healthy blood donors. In serum, no significant (P=0.30) difference in
the median vascular endothelial growth factor concentration was found
between colorectal cancer patients (268 pg ml(-1)) and healthy blood
donors (220 pg ml(-1)). The preoperative vascular endothelial growth
factor concentrations were dichotomized by the 95th percentile of the
healthy blood donors (plasma=112 pg ml(-1), serum=533 pg ml(-1)). In
univariate survival analyses, both high plasma vascular endothelial
growth factor (>112 pg ml(-1)) and high serum vascular endothelial
growth factor (>533 pg ml(-1)) predicted a reduced survival. In
multivariate survival analyses, high serum vascular endothelial growth
factor (>533 pg ml(-1)) independently predicted a reduced survival
(HR=1.65, P=0.015), while high plasma vascular endothelial growth factor
(>112 pg ml(-1)) did not (HR=1.27, P=0.23). This study indicates that
preoperative serum vascular endothelial growth factor apparently is a
better predictor of overall survival than the preoperative plasma
vascular endothelial growth factor. Copyright 2002 The Cancer Research
Campaign
22
UI - 11807360
AU - Heuschen UA; Hinz U; Allemeyer EH; Autschbach F; Stern J; Lucas M;
TI -
Herfarth C; Heuschen G
Risk factors for ileoanal J pouch-related septic complications in
ulcerative colitis and familial adenomatous polyposis.
SO - Ann Surg 2002 Feb;235(2):207-16
AD - Department of Surgery, University of Heidelberg, Heidelberg, Germany.
Udo_Heuschen@med.uni-heidelberg.de
OBJECTIVE: To analyze the association between pre- and perioperative
factors and pouch-related septic complications (PRSC) in ulcerative
colitis (UC) and in familial adenomatous polyposis (FAP) after ileal
pouch-anal anastomosis (IPAA). SUMMARY BACKGROUND DATA: For patients
with UC and FAP, IPAA is the surgical therapy of choice, but in some
patients the outcome is compromised by PRSC. METHODS: A total of 706
consecutive patients (494 UC, 212 FAP) were assessed in a study aimed at
identifying subgroups of patients who were at high risk for PRSC. The
rate of PRSC was analyzed as a time-dependent function (Kaplan-Meier
estimation). Patients with UC and FAP were stratified separately
according to associated factors (age, sex, surgeon's experience,
temporary ileostomy, colectomy before IPAA, anastomotic tension, and
several factors specific for UC). RESULTS: In all, 131 (19.2%) patients
had PRSC (23.4% UC, 9.4% FAP). In patients with UC, the estimated 1-year
PRSC rate was 15.6% and the estimated 3-year PRSC rate was 24.2%. In
patients with FAP, the estimated 1-year and 3-year PRSC rates were 9.2%.
The difference between the estimated rates of PRSC was significant (P
<.001). In the univariate analysis, patients with UC younger than 50
years, with severe proctitis, with preoperative hemoglobin levels less
than 10 g/L, or receiving corticoid medication had a significantly
higher risk for PRSC (P =.039, P =.037, P =.047, P =.003, respectively).
Multivariate analysis showed that patients with UC receiving a systemic
prednisolone-equivalent corticoid medication of more than 40 mg/day had
a significantly greater risk of developing pouch-related complications
than patients with UC receiving 1 to 40 mg/day and patients with UC who
were not receiving corticoid medication (RR: 3.78, 2.25, 1,
respectively, P <.001). Patients with FAP proved to have a significantly
higher risk for PRSC in the univariate and multivariate analyses if
anastomotic tension had occurred (RR 3.60, P =.0086). CONCLUSIONS:
Pouch-related septic complications occur as late complications and
should therefore be considered in regular, specific long-term follow-up
examinations. The authors identified significant risk factors for PRSC
specific to patients with UC and FAP; these must be considered for each
individual surgical strategy.
23
UI - 11807361
AU - Lehnert T; Methner M; Pollok A; Schaible A; Hinz U; Herfarth C
TI -
Multivisceral resection for locally advanced primary colon and rectal
cancer: an analysis of prognostic factors in 201 patients.
SO - Ann Surg 2002 Feb;235(2):217-25
AD - Section of Surgical Oncology, Department of Surgery, University of
Heidelberg, Heidelberg, Germany. thomas_lehnert@med.uni-heidelberg
OBJECTIVE: To review a single-center experience with 201 multivisceral
resections for primary colorectal cancer to determine the accuracy of
intraoperative prediction of potential curability, to identify
prognostic factors, and to examine the effect of surgical experience on
immediate outcome and long-term results. SUMMARY BACKGROUND DATA:
Locally advanced colorectal cancer may require an intraoperative
decision for en bloc resection of surrounding organs or structures to
achieve complete tumor removal. This decision must weigh the risk of
complications and death of multivisceral resection against a potential
survival benefit. Little is known about prognostic factors and the
influence of surgical experience on the outcome of multivisceral
resection for colorectal canc
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