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Abramson Cancer CenterNCI CANCERLIT® Search: Therapy of Colorectal Cancer - August 2002
National Cancer Institute®
Last Modified: August 1, 2002
- Synergy between the non-classical thymidylate synthase inhibitor AG337 (Thymitaq) and cisplatin in human colon and ovarian cancer cells.
- Perioperative radiotherapy in rectal cancer.
- Radiotherapy in rectal cancer.
- Indications for and results of combined modality treatment of colorectal cancer.
- Combination studies of antifolates with 5-fluorouracil in colon cancer cell lines.
- Thymidylate synthase inhibitors in colorectal cancer.
- [Treatment of colonic cancer in the elderly]
- Effects of ursolic acid and oleanolic acid on human colon carcinoma cell line HCT15.
- Circulating levels of interleukin-10 and interleukin-6 in gastric and colon cancer patients before and after surgery: relationship with
- [Laparoscopic surgery of the colorectum: analysis of the results of the National Registry of the SICE]
- Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel
- Impact of surgery on survival in palliative patients with metastatic colorectal cancer after first line treatment with weekly 24-hour
- Capecitabine and oxaliplatin in advanced colorectal cancer: a dose-finding study.
- Increased endocrine cells in treated rectal adenocarcinomas: a possible reflection of endocrine differentiation in tumor cells induced by
- [The prevention of negative side effects in homeochemotherapy]
- Diffusion MRI for prediction of response of rectal cancer to chemoradiation.
- Pharmacia's SU5416 not effective.
- MedImmune initiates phase I/II clinical study with Vitaxin.
- Therapeutic advances in the management of metastatic colorectal cancer.
- Prognostic biomarkers in resected colorectal cancer: implications for adjuvant chemotherapy.
- A prospective, randomized clinical trial of preoperative bowel preparation for elective colorectal surgery--comparison among oral,
- Gender differences in long-term survival of patients with colorectal cancer.
- Prospective analysis of quality of life and survival following mesorectal excision for rectal cancer.
- Randomized clinical trial of the effect of open versus laproscopically assisted colectomy on systemic immunity in patients with colorectal
- Randomized clinical trial of the effect of open versus laproscopically assisted colectomy on systemic immunity in patients with colorectal
- Right hemicolectomy: mechanical bowel preparation is not required.
- Differential cytostatic effect of sodium salicylate in human colorectal cancers using an individualized histoculture system.
- Targeted drug delivery to chemoresistant cells: folic acid derivatization of FdUMP[10] enhances cytotoxicity toward 5-FU-resistant
- Clinical trials referral resource. Clinical trials and NCI resources for cancer in HIV-positive patients.
- New studies highlight benefit of Xeloda in new combination treatments for colorectal cancer.
- ERBITUX as a single agent and in combination in colorectal carcinoma.
- [Error in an article on rectal cancer]
- Parents with colorectal cancer: 'What do I tell the children?'.
- Efficacy and cost of risk-adapted follow-up in patients after colorectal cancer surgery: a prospective, randomized and controlled trial.
- A prospective, blinded assessment of the impact of preoperative staging on the management of rectal cancer.
- Extended lymphadenectomy and preoperative radiotherapy for lower rectal cancers.
- Another NICE mess.
- A national strategic change in treatment policy for rectal cancer--implementation of total mesorectal excision as routine treatment
- Laparoscopic colorectal surgery for cancer: intermediate to long-term outcomes.
- Salvage radical surgery after failed local excision for early rectal cancer.
- T-level downstaging and complete pathologic response after preoperative chemoradiation for advanced rectal cancer result in decreased recurrence
- Surgeon specialty is associated with outcome in rectal cancer treatment.
- Effects of preoperative radiotherapy for primary resectable rectal adenocarcinoma on male sexual and urinary function.
- Defunctioning stoma in low anterior resection with colonic pouch for rectal cancer: a comparison between two hospitals with a different
- Multivisceral resection for colon cancer.
- Large bowel lymphoma: an analysis of prognostic factors and therapy in 53 patients.
- Comparison of J-pouch and coloplasty pouch for low rectal cancers: a randomized, controlled trial investigating functional results and
- Long-term prognostic significance of extent of rectal cancer response to preoperative radiation and chemotherapy.
- [Subtotal colectomy for the treatment of obstructive left colon cancer. Follow-up results]
- Clinical determinants of survival in patients with 5-fluorouracil-based treatment for metastatic colorectal cancer: results of a multivariate
- The role of the epidermal growth factor receptor in the treatment of colorectal carcinoma.
- Outcomes and toxicity in african-american and caucasian patients in a randomized adjuvant chemotherapy trial for colon cancer.
- Retrospective comparison of single-agent chemotherapy with weekly 5-fluorouracil or weekly irinotecan in previously treated patients with
- A rationale for the clinical development of the thymidylate synthase inhibitor ZD9331 in ovarian and other solid tumours.
- Restaging of locally advanced carcinoma of the rectum with MR imaging after preoperative radio-chemotherapy plus regional hyperthermia.
- Retrospective study of acute toxicity following short-course preoperative radiotherapy.
- Oxaliplatin and UFT combination chemotherapy in patients with metastatic colorectal cancer.
- [Rectal cancer surgery--to preserve urosexual function and radicality]
- [Therapy of elderly patients with colorectal carcinoma]
- Simultaneous colorectal and hepatic resections for colorectal cancer: postoperative and longterm outcomes.
- Laparoscopic total mesorectal excision.
- Laparoscopic vs open hemicolectomy for colon cancer.
- Results of laparoscopically assisted colon resection for carcinoma.
- Monoterpenes inhibit proliferation of human colon cancer cells by modulating cell cycle-related protein expression.
- Light-induced adenovirus gene transfer, an efficient and specific gene delivery technology for cancer gene therapy.
- Results of long-term follow-up after curative resection of Dukes A colorectal cancer.
- Restorative proctocolectomy with ileal reservoir.
- FDA evaluating oxaliplatin for advanced colorectal cancer treatment.
Table of Contents
1
UI - 8949986
AU - Raymond E; Djelloul S; Buquet-Fagot C; Mester J; Gespach C
TI -
Synergy between the non-classical thymidylate synthase inhibitor AG337
(Thymitaq) and cisplatin in human colon and ovarian cancer cells.
SO - Anticancer Drugs 1996 Sep;7(7):752-7
AD - Unite INSERM U55, Institut Federatif de Recherches du Centre
Hospitalo-Universitaire Paris Saint-Antoine, Hopital Saint-Antoine,
France.
AG337 is the recent non-classical thymidylate synthase inhibitor with
promising activity and manageable toxicity in phase I clinical trials.
In this study, we investigated the cytotoxic activity of AG337 alone and
in combination with cisplatin in cultured human colon (HT29) and ovarian
(2008) cancer cell lines and their derived counterparts selected for
their resistance to 5-fluorouracil (5-FU) (HT29-5-FU) and cisplatin
(2008C13). We observed that AG337 had potent cytotoxic effects in colon
(IC50 = 0.17 MicroM) and ovarian cancer cells (IC50 = 0.65 microM). The
cytotoxic activity of AG337 was higher than that of 5-FU in the two
models. The Activity of AG337 was not significantly affected in
5-FU-resistant HT29-5-FU colon cancer cells characterized by an
amplification of the thymidylate synthase gene (IC50 = 0.27 microM, p =
0.15). Combinations of cisplatin and AG337 exert synergistic activity in
both ovarian and colon cancer cells. Interestingly, this synergism was
maintained in 5-FU- and cisplatin-resistant cells. Therefore, our data
encourage further examination of combinations of AG337 with cisplatin in
cancer chemotherapy.
2
UI - 10090685
AU - Glimelius B; Pahlman L
TI -
Perioperative radiotherapy in rectal cancer.
SO - Acta Oncol 1999;38(1):23-32
AD - Department of Oncology, University of Uppsala, Akademiska Sjukhuset,
Sweden.
Local failure of rectal cancer is one of the principal causes of
morbidity and mortality. In order to lower unacceptably high local
failure rates, pre- or postoperative radiotherapy has been extensively
investigated. The collected information from all controlled trials
reported so far shows that the proportion of local recurrences is
reduced to less than half when radiotherapy up to moderately high doses
is given preoperatively. This reduction is smaller after postoperative
radiotherapy, even if higher doses are used. In addition, there is a
positive influence on survival from preoperative radiotherapy. Improved
survival has also been seen in trials using postoperative radiotherapy,
but only when combined with chemotherapy. With proper radiation
techniques, sufficiently high doses can be given preoperatively with
little, if any, increase in postoperative mortality and morbidity.
Furthermore, late toxicity can be anticipated to be low provided the
technique is optimal. The beneficial effects noted so far have been
achieved in trials where 'standard' surgery has been used, followed by a
local recurrence rate of more than 20% (average 29%, range 23-46%) of
the patients. It is, however, possible that the reduction in local
failure rates is proportionally even greater added to 'optimal' surgery,
although the absolute number of failures prevented is lower.
3
UI - 10090683
AU - Tveit KM
TI -
Radiotherapy in rectal cancer.
SO - Acta Oncol 1999;38(1):5-6
4
UI - 10090684
AU - Gunderson LL
TI -
Indications for and results of combined modality treatment of colorectal
cancer.
SO - Acta Oncol 1999;38(1):7-21
AD - Mayo Medical School and Mayo Clinic, Rochester, MN 55905, USA.
Combined modality chemoirradiation is commonly used as a component of
treatment in combination with maximum resection for both high-risk
resectable and locally advanced primary or recurrent rectal cancers.
With surgically resected but high-risk rectal cancers, postoperative
chemoirradiation has been shown to improve both disease control (local
and distant) and survival (disease-free and overall) and was recommended
as standard adjuvant treatment at the 1990 National Institute of Health
(NIH) Consensus Conference on Adjuvant treatment for patients with
rectal and colon cancers. Subsequent intergroup trials are being
conducted to help define optimal combinations of postoperative
chemoirradiation for resected high-risk rectal cancers and to test
sequencing issues of preoperative versus postoperative chemoirradiation.
With locally unresectable primary or recurrent colorectal cancers,
standard therapy with surgery, external beam irradiation (EBRT) and
chemotherapy is often unsuccessful. When intraoperative electron
irradiation (IOERT) is combined with standard treatment, local control
and survival appear to be improved in separate analyses from the Mayo
Clinic and the Massachusetts General Hospital (MGH). However, routine
use of systemic therapy is also needed as a component of treatment, in
view of high rates of systemic failure.
5
UI - 10803742
AU - van der Wilt CL; Kuiper CM; Peters GJ
TI -
Combination studies of antifolates with 5-fluorouracil in colon cancer
cell lines.
SO - Oncol Res 1999;11(8):383-91
AD - Department of Medical Oncology, University Hospital Vrije Universiteit,
Amsterdam, The Netherlands.
The combined cytotoxic effects of the thymidylate synthase (TS)
inhibitors 5-fluorouracil (5FU) and different antifolates were studied
in seven colon cancer cell lines. Growth inhibition of the antifolates,
Nolatrexed, Raltitrexed, GW1843U89, or MTA in combination with 5FU, was
determined and multiple drug effect analysis showed that the drugs acted
mostly additively. The only synergistic interaction was found for 5FU
and Nolatrexed in the LS174T cell line. Also Raltitrexed and 5FU were
slightly synergistic in WiDr/F cells grown at low folate levels, but for
the other cell lines grown at high folate levels this combination was
more antagonistic. GW1843U89 and 5FU were mainly additive, while 5FU and
MTA showed antagonism in WiDr and additivity in LS174T. The effect of
the drugs at their target was evaluated by in situ TS inhibition. We
observed lower TS activity in all cells when two drugs were used instead
of one. Statistical analysis revealed that none of the values of the
combinations was higher or lower than could be expected from the product
of the effect of single drugs. We concluded that the effects on TS
inhibition were additive for all 5FU/antifolate combinations in all cell
lines. DNA strand break formation, as a result of TS inhibition, was
measured by means of a fluorometric analysis of DNA unwinding.
Raltitrexed-induced DNA damage was significantly increased by 5FU in
WiDr cells [single agent: 67% double stranded (ds) DNA, combination: 39%
ds DNA, P<0.0001]. In LS174T a trend for antagonistic effects was
observed for combinations of MTA, GW1843U89, or Raltitrexed and 5FU. The
combinations showed additive effects in WiDr/F cells. The overall
conclusion of the three assays in each of the cell lines indicated that
5FU and antifolate combinations were predominantly additive in colon
cancer cells.
6
UI - 11049037
AU - Cassidy J
TI -
Thymidylate synthase inhibitors in colorectal cancer.
SO - Semin Oncol 2000 Oct;27(5 Suppl 10):83-7
AD - University of Aberdeen, Aberdeen Royal Infirmary, Institute of Medical
Sciences, Foresterhill, UK.
7
UI - 12092086
AU - Gislerud G
TI -
[Treatment of colonic cancer in the elderly]
SO - Tidsskr Nor Laegeforen 2002 Mar 20;122(8):853; discussion 853
8
UI - 12046077
AU - Li J; Guo WJ; Yang QY
TI -
Effects of ursolic acid and oleanolic acid on human colon carcinoma cell
line HCT15.
SO - World J Gastroenterol 2002 Jun;8(3):493-5
AD - Department of Oncology, Cancer Center, Xin Hua Hospital, Shanghai Second
Medical University, Shanghai 200092, China. ljee@citiz.net
AIM: Ursolic acid (UA) and oleanolic acid (OA) are triperpene acids
having a similar chemical structure and are distributed wildly in plants
all over the world. In recent years, it was found that they had marked
anti-tumor effects. There is little literature currently available
regarding their effects on colon carcinoma cells. The present study was
designed to investigate their inhibitory effects on human colon
carcinoma cell line HCT15. METHODS: HCT15 cells were cultured with
different drugs. The treated cells were stained with hematoxylin-eosin
and their morphologic changes observed under a light microscope. The
cytotoxicity of these drugs was evaluated by tetrazolium dye assay. Cell
cycle analysis was performed by flow cytometry (FCM). Data were
expressed as means +/-SEM and Analysis of variance and Student' t-test
for individual comparisons. RESULTS: Twenty-four to 72 h after UA or OA
60 micromol/L treatment, the numbers of dead cells and cell fragments
were increased and most cells were dead at the 72nd hour. The
cytotoxicity of UA was stronger than that of OA. Seventy-eight hours
after 30 micromol/L of UA or OA treatment, a number of cells were
degenerated, but cell fragments were rarely seen. The IC(50) values for
UA and OA were 30 and 60 micromol/L, respectively. Proliferation assay
showed that proliferation of UA and OA-treated cells was slightly
increased at 24h and significantly decreased at 48 h and 60 h, whereas
untreated control cells maintained an exponential growth curve. Cell
cycle analysis by FCM showed HCT15 cells treated with UA 30 and OA 60
for 36 h and 72 h gradually accumulated in G(0)/G(1) phase (both drugs
P<0.05 for 72 h), with a concomitant decrease of cell populations in S
phase (both drugs P<0.01 for 72 h) and no detectable apoptotic fraction.
CONCLUSION: UA and OA have significant anti-tumor activity. The effect
of UA is stronger than that of OA. The possible mechanism of action is
that both drugs have an inhibitory effect on tumor cell proliferation
through cell-cycle arrest.
9
UI - 12034030
AU - Galizia G; Lieto E; De Vita F; Romano C; Orditura M; Castellano P;
TI -
Imperatore V; Infusino S; Catalano G; Pignatelli C
Circulating levels of interleukin-10 and interleukin-6 in gastric and
colon cancer patients before and after surgery: relationship with
radicality and outcome.
SO - J Interferon Cytokine Res 2002 Apr;22(4):473-82
AD - Division of Surgical Oncology, F. Magrassi and A. Lanzara Department of
Clinical and Experimental Medicine, Second University of Naples School
of Medicine, Naples, Italy. gennaro.galizia@unina2.it
Elevated interleukin-10 (IL-10) and IL-6 serum levels in advanced
gastrointestinal cancer patients have been shown previously. To
investigate the behavior and the prognostic role of IL-10 and IL-6 serum
levels in gastric and colon cancer patients undergoing surgery, we
studied the relationship between these cytokine levels and surgical
radicality and outcome. Seventy-eight patients with gastric or colon
cancer were admitted to the study, and 50 underwent radical surgery.
Cytokine serum levels were measured by ELISA the day before surgery and
16 days after surgery. Circulating levels of IL-10 and IL-6 were found
to be higher in cancer patients than in controls. Both IL-10 and IL-6
serum levels were demonstrated to be able to predict likelihood to
perform radical surgery. IL-10 serum levels returned to normal in all
but 8 radically resected patients. These 8 patients had tumor
recurrence. In contrast, IL-6 serum levels were shown to significantly
decrease in all patients but not to normalize regardless of the
radicality of the operation. On multivariate analysis, basal IL-10 serum
levels were found to be among the variables significantly affecting the
disease-free survival rate. Stepwise regression selected tumor stage,
number of metastatic resected nodes, and basal IL-10 serum level as the
best combination of variables for prediction of likelihood of tumor
recurrence. Preoperative IL-10 serum levels may be a useful marker to
predict likelihood of performing radical surgery. Abnormally high
postoperative IL-10 values negatively affected disease-free survival and
tumor recurrence. IL-6 serum levels were found to have a more limited
prognostic role.
10
UI - 11828998
AU - Gennari L
TI -
[Laparoscopic surgery of the colorectum: analysis of the results of the
National Registry of the SICE]
SO - Chir Ital 2001 Nov-Dec;53(6):913
11
UI - 11843249
AU - Gray B; Van Hazel G; Hope M; Burton M; Moroz P; Anderson J; Gebski V
TI -
Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone
for treating patients with liver metastases from primary large bowel
cancer.
SO - Ann Oncol 2001 Dec;12(12):1711-20
AD - Royal Perth Hospital, Sir Charles Gairdner Hospital, University of
Western Australia, Australia. bgray@sirtex.com
PURPOSE: SIR-Spheres are radioactive yttrium90 microspheres
(SIR-Spheres, Sirtex Medical Limited, Australia) used to selectively
target high levels of ionising radiation to tumors within the liver.
This trial was designed to measure any increased patient benefit by
adding a single administration of SIR-Spheres to a regimen of regional
hepatic artery chemotherapy (HAC) administered as a 12 day infusion of
floxuridine and repeated at monthly intervals, vs. the same chemotherapy
alone. PATIENTS AND METHODS: A phase III randomised clinical trial
entering 74 patients was undertaken on patients with bi-lobar
non-resectable liver metastases from primary adenocarcinoma of the large
bowel. Patient benefit criteria assessed in the trial were tumor
response, time to disease progression in the liver, overall survival,
quality of life, and treatment related toxicity. Tumor response was
measured by serial changes in both cross-sectional tumor areas and total
tumor volumes, provided any response lasted not less than three months
as well as changes in serum carcino-embryonic antigen (CEA). RESULTS:
The partial and complete response rate (PR + CR) was significantly
greater for patients receiving SIR-Spheres when measured by tumor areas
(44%) vs. 17.6%, P = 0.01) tumor volumes (50% vs. 24%, P = 0.03) and CEA
(72% vs. 47%, P = 0.004). The median time to disease progression in the
liver was significantly longer for patients receiving SIR-Spheres in
comparison to patients receiving HAC alone when measured by either tumor
areas (9.7 vs. 15.9 months, P = 0.001), tumor volumes (7.6 vs. 12.0
months, P = 0.04) or CEA (5.7 vs. 6.7 months, P = 0.06). The one, two,
three and five-year survival for patients receiving SIR-Spheres was 72%,
39%, 17% and 3.5%, compared to 68%, 29%, 6.5% and 0% for HAC alone. Cox
regression analysis suggests an improvement in survival for patients
treated with SIR-Spheres who survive more than 15 months (P = 0.06).
There was no increase in grade 3-4 treatment related toxicity and no
loss of quality of life for patients receiving SIR-Spheres in comparison
to patients receiving HAC alone. CONCLUSION: The combination of a single
injection of SIR-Spheres plus HAC is substantially more effective in
increasing tumor responses and progression free survival than the same
regimen of HAC alone.
12
UI - 11843250
AU - Wein A; Riedel C; Kockerling F; Martus P; Baum U; Brueckl WM; Reck T;
TI -
Ott R; Hansler J; Bernatik T; Becker D; Schneider T; Hohenberger W; Hahn
EG
Impact of surgery on survival in palliative patients with metastatic
colorectal cancer after first line treatment with weekly 24-hour
infusion of high-dose 5-fluorouracil and folinic acid.
SO - Ann Oncol 2001 Dec;12(12):1721-7
AD - Department of Internal Medicine I, Friedrich-Alexander-University
Erlangen-Nuremberg, Erlangen, Germany.
Axel.Wein@med1.imed.uni-erlangen.de
BACKGROUND: In palliative first-line treatment of colorectal cancer, the
secondary resection of distant metastases after downstaging has
constantly gained in importance. The objective of this prospective study
was to examine the tumor response rate, the toxicity, the median
survival time and the prognostic impact of metastatic resection after
downstaging of consecutively enrolled patients with primary
nonresectable colorectal cancer treated with once weekly 24-hour (24-h)
infusion of high-dose 5-fluorouracil (5-FU) and folinic acid. PATIENTS
with primary nonresectable metastases were recruited for a prospective
phase II study. The patients received in out-patient care 500 mg/m2
folinic acid in the form of a 1-2-hour infusion followed by 2600 mg/m2
5-FU administered as a 24-h infusion once weekly. One treatment cycle
comprised six weekly infusions followed by a two week rest. Three cycles
were administered, and in the event of complete remission (CR) or
partial remission (PR) and good tolerability, a fourth cycle was
undertaken. Thereafter, the possibility of performing a curative
metastatic resection was investigated. RESULTS: Of the 53 patients
treated, 7 showed a CR (13%), 15 patients a PR (28%), 26 patients stable
disease (SD) (49%), and 5 patients progressive disease (PD) (10%). As
the main symptom of toxicity, diarrhea (CTC grade 3 + 4) was observed in
11 patients (21%), followed by leucocytopenia (CTC grade 3 + 4) in 2
patients (4%), and the hand-foot syndrome in 1 patient (2%). The median
survival time was 17 months with a median follow-up of 41 months (range:
28-59 months). In 9 patients (17%), a secondary metastatic resection was
considered; in 6 patients (11%) curative resection was performed, and 4
patients (8%) showed no evidence of disease for at least three years.
CONCLUSION: In this phase II study, we have been able to show
prospectively that, after downstaging by palliative treatment using a
weekly 24-h infusion of high-dose 5-FU and folinic acid, secondary
curative metastatic resection was technically feasible in 11% of the
patients. For some of these patients, long-term survival is therefore
possible. Secondary metastatic resection should be carried out in close
interdisciplinary cooperation, and should be further investigated in
prospective phase III studies.
13
UI - 11843252
AU - Zeuli M; Costanzo ED; Sdrobolini A; Gasperoni S; Paoloni FP; Carpi A;
TI -
Moscetti L; Cherubini R; Cognetti F; Gruppo Oncologico Italiano per la
Ricerca Clinica (GOIRC) and Gruppo Oncologico Laziale (GOL)
Capecitabine and oxaliplatin in advanced colorectal cancer: a
dose-finding study.
SO - Ann Oncol 2001 Dec;12(12):1737-41
AD - Department of Medical Oncology A, Regina Elena Cancer Institute, Rome,
Italy. massimozeuli@tiscalinet.it
PURPOSE: Capecitabine and oxaliplatin are both active anticancer agents
in the treatment of patients with advanced colorectal cancer (ACRC). The
aim of this dose-finding trial was to determine the maximum-tolerated
dose (MTD), the dose-limiting toxicities (DLTs) and the activity of the
combination in patients with advanced colorectal cancer. PATIENTS AND
METHODS: Twenty-five chemotherapy-pretreated patients received the
combination of capecitabine and oxaliplatin. Capecitabine was
administered orally twice a day continuously for 14 days in doses
ranging from 1,650 to 2,500 mg/m2/d, and oxaliplatin was administered as
a two-hour infusion on day 1 using dose, ranges from 100 to 130 mg/m2
repeated every three weeks. RESULTS: Twenty-five patients were
assessable for toxicity, and DLTs were diarrhea (grade > or = 3: 27%)
and stomatitis (grade > or = 3: 9%) at dose level VI. Dose level V
(capecitabine 2500 mg/m2 and oxaliplatin 120 mg/m2) was found to be the
MTD. Hematological toxicity was minimal, overall neurotoxicity (grade
1-4) was 27% with 1% grade 3-4. A global response rate was 17% (95%
confidence interval (95% CI): 2%-32%) and the median overall survival
was 12 months. CONCLUSION: The recommended dose for further phase II
studies is capecitabine 2,500 mg/m2/d with intermittent schedule and
oxaliplatin 120 mg/m2 every three weeks. The toxicities were mainly
gastrointestinal: diarrhea, stomatitis and vomiting. This combination
should be studied in phase II trials in advanced colorectal.
14
UI - 12131153
AU - Shia J; Tickoo SK; Guillem JG; Qin J; Nissan A; Hoos A; Stojadinovic A;
TI -
Ruo L; Wong WD; Paty PB; Weiser MR; Minsky BD; Klimstra DS
Increased endocrine cells in treated rectal adenocarcinomas: a possible
reflection of endocrine differentiation in tumor cells induced by
chemotherapy and radiotherapy.
SO - Am J Surg Pathol 2002 Jul;26(7):863-72
AD - Department of Pathology, Memorial Sloan-Kettering Cancer Center, New
York, New York 10021, USA.
The presence of focal endocrine cells in colorectal adenocarcinoma is a
relatively common phenomenon. However, endocrine differentiation in
treated adenocarcinomas of the gastrointestinal tract has received
little attention. We noted striking numbers of cells with endocrine
morphology and phenotype in the residual tumor of six randomly
encountered cases of rectal adenocarcinoma that were subjected to
neoadjuvant therapy. All six cases had a substantial treatment response
(> or =50%). To validate our initial observation and to explore its
clinicopathologic significance, further morphologic and
immunohistochemical studies were performed on 53 cases of rectal
adenocarcinomas treated with preoperative radiation with (33 cases) or
without (20 cases) chemotherapy. Pretreatment biopsies from 20 of the 53
cases and 79 resection specimens of rectal adenocarcinoma that received
no neoadjuvant therapy were used as controls. Chromogranin positivity
was identified in the posttreatment resection specimens in 36 of the 53
study cases (67.9%). Twenty of the 36 showed positive staining in > or
=20% of the residual tumor cells. The chromogranin-positive cells in
these cases often formed cords or nests. On hematoxylin and eosin
sections these cells had markedly eosinophilic cytoplasm and round and
uniform or sometimes pleomorphic nuclei with an often dense chromatin
pattern. The proportion of chromogranin-positive cells was significantly
associated with the extent of treatment response (p = 0.0005). Tumors
treated with both chemotherapy and radiotherapy were more likely to have
abundant chromogranin-positive cells compared with tumors treated with
radiotherapy alone (p = 0.0004). In contrast, only 30% of the
pretreatment biopsies and 17.7% of the control resection specimens of
untreated rectal carcinomas showed chromogranin-positive cells,
predominantly arranged as scattered individual positive cells,
constituting <10% of the tumor. No significant correlation was observed
between pretreatment and posttreatment specimens with regard to
chromogranin positivity (p = 1.0). Ten of 15 patients (66.7%) whose
resection specimens showed positive chromogranin staining failed to
demonstrate any chromogranin positivity in their pretreatment biopsy
specimens. In addition, groups or nests of chromogranin-positive cells
noted in posttreatment specimens showed a very low Ki67 labeling index
(<5%) but showed a frequency of abnormal p53 protein expression
comparable with that observed in tumor foci resembling conventional
adenocarcinoma (66.7% vs 62.5%). Our findings demonstrate that there is
an increased frequency and density of cells with an endocrine phenotype
in rectal adenocarcinomas that were subjected to neoadjuvant therapy and
that the extent of endocrine cells appears proportional to the degree of
treatment response. The possible mechanism for the increased endocrine
cells in treated rectal adenocarcinomas may be related to induction of
endocrine differentiation in tumor cells by cytotoxic insult.
15
UI - 12146017
AU - Takahashi K; Mori T; Ohue M; Yamaguchi T
TI -
[The prevention of negative side effects in homeochemotherapy]
SO - Gan To Kagaku Ryoho 2002 Jul;29(7):1311-8
AD - Dept. of Surgery, Tokyo Metropolitan Komagome Hospital.
The purpose of the present study was to identity ways to prevent
negative side effects in homechemotherapy. We conducted continuous
hepatic arterial infusion chemotherapy (CHAI) in 122 cases of
unresectable hepatic metastases from colorectal cancer. We continuously
administered 5-FU at 250 mg/day for 7 days using a pump system. We also
conducted systemic chemotherapy (FP therapy) in 145 cases of advanced or
recurrent colorectal cancer in our outpatient clinic. Based on these
experiences, we analyzed the problems of homeochemotherapy. The rate of
negative side effects was 15.1% with CHAI. More than half were cases of
abdominal pain. Because we had established an observation system for
emergency cases, there were no fatal accidents. With FP therapy, about
40% of patients had gastrointestinal discomfort, but the rate of those
with higher than grade 3 was low (1-2%). We conclude that it is very
important to establish a hospital system to respond quickly to any
negative effects of homeochemotherapy.
16
UI - 12147376
AU - Dzik-Jurasz A; Domenig C; George M; Wolber J; Padhani A; Brown G; Doran
TI -
S
Diffusion MRI for prediction of response of rectal cancer to
chemoradiation.
SO - Lancet 2002 Jul 27;360(9329):307-8
AD - UK Cancer Research Clinical Magnetic Resonance Research Group, Institute
of Cancer Research, Royal Marsden NHS Trust, Downs Road, Sutton SM2 5PT,
UK. andrzej@icr.ac.uk
Prediction of tumour response before onset of treatment could have
considerable clinical benefit. Since the apparent diffusion coefficient
(ADC) of a tumour's water content can show the extent of necrosis, we
looked for a possible correlation of ADC with response to treatment. We
measured mean tumour water ADC before and after chemotherapy and
chemoradiation in 14 patients with locally advanced rectal cancer, with
a quantitative magnetic resonance diffusion imaging sequence. We found a
strong negative correlation between mean pretreatment tumour water ADC
and percentage size change of tumours after chemotherapy (r=-0.67,
p=0.01) and chemoradiation (r=-0.83, p=0.001). Persistence of low ADC in
responders after chemotherapy could represent loss of a non-viable
fraction of the treated tumour.
17
UI - 12113066
AU - Anonymous
TI -
Pharmacia's SU5416 not effective.
SO - Expert Rev Anticancer Ther 2002 Feb;2(1):5
18
UI - 12113018
AU - Anonymous
TI -
MedImmune initiates phase I/II clinical study with Vitaxin.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):166
19
UI - 12113029
AU - Freyer G; Ligneau B; Kraft D; Descos L; Trillet-Lenoir V
TI -
Therapeutic advances in the management of metastatic colorectal cancer.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):236-46
AD - Medical Oncology Unit, Centre Hospitalier Lyon-Sud, 69495 Pierre-Benite,
France. Gilles.Freyer@chu-lyon.fr
Metastatic colorectal cancer has long been considered as a short-term,
poor prognosis, chemoresistant disease. Until the early 1990s, the
impact of systemic chemotherapy on patient outcome was debated.
Recently, the emergence of new therapeutic modalities (5-FU modulations
and associations with oxaliplatin and irinotecan) has led to a
significant improvement in tumor response rates and patient survival.
Thus, the indications of curative surgery of visceral metastases,
frequently preceded and followed by chemotherapy, systemic or
intra-arterial or both, have become more frequent. In this paper we will
review and comment on the results of the major clinical trials published
in the past 5 years and propose some decision strategies regarding the
main clinical situations met in daily practice.
20
UI - 12113030
AU - Graziano F; Catalano V; Baldelli AM; Cascinu S
TI -
Prognostic biomarkers in resected colorectal cancer: implications for
adjuvant chemotherapy.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):247-57
AD - University Hospital of Parma, via Gramsci 14, 43100 Parma, Italy.
Knowledge of the prognostic role of biomarkers in colorectal cancer is
limited and the routine determination for clinical practice is not
warranted. However, for some of these markers, data are promising enough
for further evaluation. This review addresses a comprehensive analysis
of prognostic biomarkers in colorectal cancer. Data from published
studies were collected and analyzed. A sufficient level of evidence
suggests that DNA indexes, angiogenesis indicators and some
genetic/biochemical markers identity prognostic differences in patients
with early-stage colorectal cancer. High-risk patients could be the
target for future adjuvant chemotherapy trials and one or more of these
markers may identify prognostic subgroups with the same TNM stage
category.
21
UI - 12160204
AU - Yabata E; Okabe S; Endo M
TI -
A prospective, randomized clinical trial of preoperative bowel
preparation for elective colorectal surgery--comparison among oral,
systemic, and intraoperative luminal antibacterial preparations.
SO - J Med Dent Sci 1997 Dec;44(4):75-80
AD - First Department of Surgery, Faculty of Medicine, Tokyo Medical and
Dental University, Yushima, Japan.
During a one year and six month period, 137 patients undergoing elective
colorectal surgery for carcinoma were randomly allocated to three
groups. Patients in group A received oral tobramycin and metronidazole
for three days prior to surgery. Patients in groups B and C received
systemic antibiotic, a second generation cephem cefmetazole, every 3
hours during surgery. Patients in group C also received a luminal
preparation of tobramycin during surgery. All patients received
mechanical bowel preparation in the same manner. The incidence of
postoperative wound sepsis was 10.9% in group A, 9.8% in group B, and
10.0% in group C. There were no significant differences in postoperative
wound sepsis among the three groups. The oral antibiotic regimen induced
a greater change in intestinal flora and was associated with more
frequent postoperative diarrhea. Although the preoperative bowel
preparation taken for patients in group A could not sufficiently reduce
the intestinal bacterial count, systemic antibiotic prophylaxis was
simple and cost-effective. There was no additional advantage in
combining the systemic and luminal antibiotic preparations. Therefore,
for elective colorectal surgery, we recommend intravenous infusion of
second generation cephem cephmetazole with mechanical bowel preparation.
22
UI - 11952598
AU - Dharma-Wardene MW; de Gara C; Au HJ; Hanson J; Hatcher J
TI -
Gender differences in long-term survival of patients with colorectal
cancer.
SO - Br J Surg 2002 Apr;89(4):490
23
UI - 11952609
AU - Huang AA; Hindle KS
TI -
Prospective analysis of quality of life and survival following
mesorectal excision for rectal cancer.
SO - Br J Surg 2002 Apr;89(4):495
24
UI - 11952614
AU - Wu FP; Cuesta MA; Sietses C
TI -
Randomized clinical trial of the effect of open versus laproscopically
assisted colectomy on systemic immunity in patients with colorectal
cancer.
SO - Br J Surg 2002 Apr;89(4):497
25
UI - 11952615
AU - Schwenk W
TI -
Randomized clinical trial of the effect of open versus laproscopically
assisted colectomy on systemic immunity in patients with colorectal
cancer.
SO - Br J Surg 2002 Apr;89(4):497
26
UI - 12109610
AU - Jansen JO; O'Kelly TJ; Krukowski ZH; Keenan RA
TI -
Right hemicolectomy: mechanical bowel preparation is not required.
SO - J R Coll Surg Edinb 2002 Jun;47(3):557-60
AD - Department of Surgery, Aberdeen Royal Infirmary, Foresterhill, UK.
BACKGROUND: Mechanical bowel preparation before colonic surgery is
widely advocated but remains controversial. Recent guidelines published
by the Clinical Standards Board for Scotland recommend mechanical bowel
preparation prior to surgery for all colorectal cancers but this may be
inappropriate. This study examines the outcome of a policy of no
mechanical preparation before elective right hemicolectomy. METHOD: Data
on 102 consecutive patients undergoing elective right or extended right
hemicolectomy for colonic adenocarcinoma were extracted from a
prospective database. RESULTS: No clinical anastomotic leaks were
observed. Two patients developed wound infections and one patient died
with no autopsy evidence of anastomotic leak. CONCLUSION: Mechanical
bowel preparation can safely be omitted prior to right hemicolectomy in
patients with colonic cancer.
27
UI - 12107552
AU - Liu Y; Eu W; Seow-Choen F; Cheah Y
TI -
Differential cytostatic effect of sodium salicylate in human colorectal
cancers using an individualized histoculture system.
SO - Cancer Chemother Pharmacol 2002 Jun;49(6):473-8
AD - Department of Colorectal Surgery, Singapore General Hospital, Singapore
169608, Republic of Singapore.
PURPOSE: Tumor metastasis is the major cause of colorectal cancer (CRC)
mortality. Nonsteroidal antiinflammatory drugs (NSAIDs) such as aspirin
have been shown to have an antineoplastic effect in CRC cell lines.
Different patients, however, exhibit different chemosensitivity. In this
study, we assessed the chemotherapeutic potential of sodium salicylate,
an aspirin metabolite, by measuring its cytostatic effect in an
individualized three-dimensional histoculture system. METHODS:
Histocultured cancer tissues were treated with sodium salicylate at
concentrations from 1 to 10 m M for 24 or 48 h. Inhibition of DNA
synthesis was measured in terms of inhibition of bromodeoxyuridine
(BrdU) incorporation.RESULTS: The concentration response of individual
cancer tissues could be categorized into four groups ranging from the
most to the least sensitive to sodium salicylate. Of 20 cancer tissues,
12 (60%) showed a concentration-effect relationship with sodium
salicylate in the clinically relevant concentration range (IC50
1.2+/-0.4 to 3.8+/-0.5 m M). Doubling the exposure time decreased the
IC50 in four specimens, suggesting that a similar inhibition might be
achieved with a lower concentration over an extended time. None of the
right-sided cancers was sensitive to sodium salicylate ( P=0.002).
CONCLUSIONS: Sodium salicylate had a cytostatic effect on the majority
of histocultured CRC tissues. The varying chemosensitivity of the
cancers possibly reflected underlying differences, for example in
relation to cancer site, thus emphasizing further the usefulness of this
clinically relevant system in tailoring chemotherapy to the individual
patient.
28
UI - 11511236
AU - Liu J; Kolar C; Lawson TA; Gmeiner WH
TI -
Targeted drug delivery to chemoresistant cells: folic acid
derivatization of FdUMP[10] enhances cytotoxicity toward 5-FU-resistant
human colorectal tumor cells.
SO - J Org Chem 2001 Aug 24;66(17):5655-63
AD - Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska
68198-6805, USA.
Current chemotherapy protocols that include fluoropyrimidines, such as
5-fluorouracil (5-FU), are limited by the development of chemoresistance
during the course of treatment. Our laboratory has developed a novel
class of fluoropyrimidines, FdUMP[N], that are oligodeoxynucleotides
(ODNs) composed of some number, N, of
5-fluoro-2'-deoxyuridine-5'-O-monphosphate (FdUMP) nucleotides. Novel
synthetic procedures are described that permit conjugation of folic acid
to the 5'-OH of FdUMP[10] via a phosphodiester linkage using automated
synthesis. The synthetic methods developed are generally applicable for
ODN conjugation with folic acid. The folic acid conjugate FA-FdUMP[10]
showed improved cytotoxicity toward human colorectal tumor cells (H630),
and 5-FU-resistant colorectal tumor cells (H630-10). Enhanced
cytotoxicity was observed for FA-FdUMP[10] relative to nonconjugated
FdUMP[10] for cells grown under folate-restricted conditions, consistent
with cellular uptake being, in part, receptor-mediated. Folate receptor
alpha (FRalpha) mRNA was shown by RT-PCR to be overexpressed 26.3-fold
in 5-FU-resistant H630-10 cells relative to H630 cells. Thus,
FA-FdUMP[N] may prove useful for the treatment of 5-FU-resistant
malignancies.
29
UI - 11866136
AU - Black JB; Feigal EG; Gore-Langton RE
TI -
Clinical trials referral resource. Clinical trials and NCI resources for
cancer in HIV-positive patients.
SO - Oncology (Huntingt) 2002 Feb;16(2):200-2, 205, 207
AD - National Cancer Institute, USA.
30
UI - 12113038
AU - Anonymous
TI -
New studies highlight benefit of Xeloda in new combination treatments
for colorectal cancer.
SO - Expert Rev Anticancer Ther 2002 Jun;2(3):241-2
31
UI - 12113039
AU - Anonymous
TI -
ERBITUX as a single agent and in combination in colorectal carcinoma.
SO - Expert Rev Anticancer Ther 2002 Jun;2(3):242
32
UI - 11881564
AU - Bulow S
TI -
[Error in an article on rectal cancer]
SO - Ugeskr Laeger 2002 Feb 11;164(7):921-2
33
UI - 12048454
AU - Black PK; Hyde C
TI -
Parents with colorectal cancer: 'What do I tell the children?'.
SO - Br J Nurs 2002 May 23-Jun 12;11(10):679-85
AD - Stoma Care/Coloproctology, Coloproctology Department, The Hillingdon
Hospital, Uxbridge, Middlesex.
Whatever the age of the child, there is no easy way for a parent to
explain serious, life-threatening illness. For children to hear that
their parent is ill is devastating, especially if the parent has cancer
and needs a permanent colostomy. The diagnosis of cancer can produce
feelings of fear, confusion and uncertainty in patients and their close
relatives. How difficult does this then become for the child battling to
understand long medical words, alien hospital environments and an ill
parent? The social taboos that surround body matter elimination are
legion and therefore the surgical outcome of having a permanent stoma
changes the individual's body image perception long-term. The two case
studies presented in this article highlight this problem as well as the
lack of suitable available literature.
34
UI - 12099653
AU - Secco GB; Fardelli R; Gianquinto D; Bonfante P; Baldi E; Ravera G;
TI -
Derchi L; Ferraris R
Efficacy and cost of risk-adapted follow-up in patients after colorectal
cancer surgery: a prospective, randomized and controlled trial.
SO - Eur J Surg Oncol 2002 Jun;28(4):418-23
AD - DICMI - Sezione di Semeiotica Chirurgica I, University of Genoa School
of Medicine, Genoa, Italy.
AIMS: This paper aims to evaluate the diagnostic efficacy and costs of
follow-up tailored according to risk of recurrence compared with minimal
surveillance. METHODS: A total of 358 patients treated by surgery alone
for colorectal cancer were prospectively divided into two groups of 200
and 158 patients considered at high and low risk of recurrence
respectively, according to prognostic factors. They were further
randomized into two subgroups: group 1, 192 patients undergoing
risk-adapted follow-up, intensive and low-intensity; group 2, 145
patients undergoing minimal surveillance. Twenty-one cases dropped out.
Median follow-up was 61.5 months and 42 months for cases at high risk
(intensive follow-up) and at low risk (low-intensity follow-up)
respectively. RESULTS: At the end of the study, 52.6% of patients
undergoing risk-adapted follow-up and 57.2% undergoing minimal follow-up
had developed recurrence. In patients at high risk, a significant
difference in the incidence of curative re-operations was observed
between the subgroups undergoing risk-adapted follow-up and subgroups
undergoing minimal surveillance (P<0.05). The actuarial 5 year survival
of patients at high and at low risk of recurrence undergoing
risk-adapted follow-up is significantly better than that of cases
undergoing minimal follow-up. The economic costs for 34 patients in the
intensive follow-up group and for the 57 patients in the low-intensity
follow-up group who were free from disease after primary surgery was
very similar. CONCLUSIONS: Risk-adapted follow-up has significantly
improved the targeting of curative re-operations and overall survival of
patients independently of risk of recurrence and has allowed a reduction
in the costs of following up of disease-free patients.
35
UI - 12105829
AU - Harewood GC; Wiersema MJ; Nelson H; Maccarty RL; Olson JE; Clain JE;
TI -
Ahlquist DA; Jondal ML
A prospective, blinded assessment of the impact of preoperative staging
on the management of rectal cancer.
SO - Gastroenterology 2002 Jul;123(1):24-32
AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester,
Minnesota 55905, USA.
BACKGROUND & AIMS: The influence of preoperative staging of rectal
carcinoma on therapeutic decisions is uncertain. The use of fine-needle
aspiration (FNA) of perirectal nodes in this setting has not been
evaluated. The aim of this prospective, blinded study of patients with
rectal cancer was to assess the impact of preoperative staging on
treatment decisions and compare the tumor (T), nodal (N) staging
performance characteristics of pelvic computed tomography (CT), rectal
endoscopic ultrasonography (EUS), and EUS FNA. METHODS: Eighty
consecutive patients with newly diagnosed rectal cancer were
prospectively evaluated. Therapy decisions were recorded after
sequential disclosure of staging information to the patient's surgeon.
RESULTS: In 31% of patients (95% confidence interval, 21%-42%), EUS
staging information changed the surgeon's original treatment plan based
on CT alone. The further addition of FNA changed therapy in one patient.
T staging accuracy was 71% (CT) and 91% (EUS) (P = 0.02); N staging
accuracy was 76% (CT), 82% (EUS), and 76% (EUS FNA) (P = NS).
CONCLUSIONS: Preoperative staging with EUS results in more frequent use
of preoperative neoadjuvant therapy than if staging was performed with
CT alone. The addition of FNA only changed the management of one
patient, whereas FNA did not significantly improve N staging accuracy
over EUS alone. FNA seems to offer the most potential for impacting
management in those patients with early T stage disease, and its use
should be confined to this subgroup of patients. EUS is more accurate
than CT for determining T stage of rectal carcinoma.
36
UI - 12110792
AU - Watanabe T; Tsurita G; Muto T; Sawada T; Sunouchi K; Higuchi Y; Komuro
TI -
Y; Kanazawa T; Iijima T; Miyaki M; Nagawa H
Extended lymphadenectomy and preoperative radiotherapy for lower rectal
cancers.
SO - Surgery 2002 Jul;132(1):27-33
AD - Department of Surgery, University of Tokyo Hospital, the Cancer
Institute Hospital, Japan.
BACKGROUND: Extended lymphadenectomy including lateral node dissection
(EXT-L) contributes to a low incidence of local recurrence of lower
rectal cancer. However, EXT-L is frequently associated with impairment
of sexual and urinary function. We therefore compared the effectiveness
of preoperative radiotherapy with that of EXT-L. METHODS: One hundred
fifteen patients were studied. Seventy-eight patients underwent
preoperative radiotherapy with a total dose of 50 Gy (Rad[+] group), and
37 did not (Rad[-] group). Seventy-five patients received EXT-L
(EXT-L[+] group), and 40 did not (EXT-L[-] group). Patients wer
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