A randomized controlled trial of oral 5-FU versus placebo in colorectal cancer: results of 10 years observation time.
Explore the source record for details and available documents.
Colorectal Neoplasms↗
Biomedical subjects
L Hafström
Publications and source records attributed to L Hafström.
Adjuvant chemotherapy with 5-fluorouracil, vincristine and CCNU for patients with Dukes' C colorectal cancer. The Swedish Gastrointestinal Tumour Adjuvant Therapy Group.
A prospective controlled randomized trial testing adjuvant postoperative combination chemotherapy (5-fluorouracil, lomustine (CCNU) and vincristine) versus no adjuvant therapy in patients operated on for Dukes' C colorectal cancer is reported. In total 334 patients aged less than 70 years were recruited: 205 patients with colonic and 99 with rectal cancer, but there were three protocol violations and these cases are excluded from further consideration. Twenty-seven patients had a limited resection of their cancer. After 5 years' follow-up there was no significant difference in the tumour-free survival rate or in the survival rate between the treated and control groups. Twenty-nine of the 147 patients who started chemotherapy discontinued this treatment because of side-effects, mainly from the gastrointestinal tract. In 30 patients treatment was discontinued because of recurrent disease. The conclusion is that systemic administration of combination chemotherapy for colorectal cancer after operation is not worthwhile in routine clinical practice.
Antineoplastic Combined Chemotherapy Protocols↗
Vascular clearance by the reticuloendothelial system--measurements using two different-sized albumin colloids.
Normal and reticuloendothelial system (RES) stimulated rats were examined with dynamic liver RES scintigraphy using a computerized gamma camera. 99Tcm-labelled albumin colloid, albures (radius 250 nm) or nanocoll (radius 25 nm), or both were used as test substances to study the kinetics of vascular clearance after RES stimulation. Registrations were made of 30 s per frame for 5 min and 300 s per frame for 15 min or 25 min and a region of interest (ROI) was indicated over the liver. Whole body and liver RES clearance rate constants (k) were calculated from the liver uptake vs time curve. Liver parenchyma blood flow was estimated with 133Xe washout technique. The blood clearance rate constant of albures in non-activated rats was twice that for nanocoll (1.08 +/- 0.05 vs 0.49 +/- 0.02 10(-2)s-1). There was no mutual interaction between the two colloids, implying that they may be eliminated from the blood-stream by slightly different processes. In zymosan-stimulated animals, nanocoll given in a single injection showed a significantly increased k-value. Neither the albures clearance rate constant nor the nanocoll/albures k-value ratio revealed RES macrophage activation. By contrast the nanocoll/albures ratio, calculated for the liver, rose significantly. The final colloid uptake in the liver revealed RES macrophage activation. No changes in liver parenchyma blood flow per g tissue could be registered after administration of zymosan. The nanocoll and albures colloid particles did not impair the normal liver parenchyma blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Albumins↗
Evaluation of blood flow measurements with microspheres and rubidium--an experimental study in rats.
The microsphere method has been widely used for blood flow measurements in normal and tumour tissues. The microsphere method was evaluated for repeated measurements of cardiac output and regional blood flow in anesthetised rats and in anesthetised rats given noradrenalin and thereby having altered haemodynamics with special emphasis on liver blood flow. Comparing the microsphere method with the soluble indicator method (86Rubidium) gave equal cardiac output values. The liver blood flow was lower and the spleen blood flow was higher with the microsphere method. Two microsphere injections at 10 min intervals were performed on anesthetised rats. In one group 817 +/- 10(3) microspheres were injected each time, in a second group 436 +/- 10(3) and in a third noradrenalin was added and then 430 +/- 10(3) microspheres injected twice. There was good reproducibility for cardiac output and for most organ and tissue blood flows between first and second microsphere injection. No influence on arterial liver blood flow was seen. A blood pressure fall and a decreased heart rate was registered after the first injection in the group given 817 x 10(3) spheres. There was also a blood pressure fall in the group given noradrenalin after the first microsphere injection. The microsphere method with two injections of 436 x 10(3) microspheres seems adequate to use in arterial blood flow studies of the liver and simultaneous cardiac output measurements.
Animals↗
[A growing research interest in liver sinusoidal cells].
Explore the source record for details and available documents.
Humans↗
Effect on liver tumor growth in rats of allopurinol and 5-fluorouracil in combination with hepatic artery ligation.
Rats with an experimental solitary liver tumor of a nitrosoguanidine-induced colonic adenocarcinoma were subjected to hepatic artery ligation (HAL) alone or in combination with 5-fluorouracil (5-FU) in three different doses, with or without the addition of allopurinol. The drugs were injected i.p. on 3 consecutive days before or after the HAL procedure. HAL alone significantly reduced the tumor growth compared with the control procedure (P less than 0.001). This observation was correlated with a significantly prolonged survival for the ligated animals (P less than 0.01). The administration of a low dose of 5-FU (15 mg/kg per day) in combination with allopurinol (100 mg/kg per day) enhanced tumor growth compared with that in animals treated with 5-FU only (P less than 0.01) or nontreated animals (P less than 0.05). A significant increase in survival was observed in animals given a high dose of 5-FU (60 mg/kg per day) after HAL compared with non-treated animals (P less than 0.001) as well as animals subjected to HAL alone (P less than 0.02). All animals receiving more than 15 mg/kg per day 5-FU before HAL succumbed within 10 days. The addition of allopurinol did not protect the animals against this mortality. These observations indicate that the effect of HAL followed by 5-FU is dose-dependent and that, at least in this treatment modality, allopurinol does not modulate the toxicity of 5-FU.
Allopurinol↗
Dacarbazine versus dacarbazine-vindesine in disseminated malignant melanoma: a randomized phase II study.
In a phase II study 119 patients with disseminated malignant melanoma were randomized to receive treatment with dacarbazine alone or in combination with vindesine. The study was designed to reveal an additive response rate when the drugs were combined. Dacarbazine was given i.v. at 250 mg m-2 per day X V every 4 weeks. In the combination regimen vindesine given at 3 mg m-2 per week was included. One hundred and ten patients were available for evaluation of response. With dacarbazine 4/51 patients obtained a complete remission (8%) and 5/51 patients a partial remission (10%). Overall response rate was 18%. With dacarbazine-vindesine 8/59 patients obtained a complete remission (13%) and 7/59 patients a partial remission (12%). Overall response rate was 25%. The difference in response rates observed between the treatment arms is not statistically significant. Median response duration was 123 days for dacarbazine patients and 171 days for patients receiving dacarbazine-vindesine (difference not statistically significant).
Adult↗
Kinetics of radioiodinated monoclonal antibodies in the rat. Influence of tumour growth and reticuloendothelial system host modulation.
This experimental study in rats examines the influence of tumour growth and RES function modulation on the kinetics of iodinated MAb IgG1 C241. The study was designed to investigate unspecific accumulation in liver and blood. C241 is raised against human colon adenocarcinoma COLO 205 and reacts with SiLea tumour-associated antigen, also known as tumour-associated antigen 19-9. In 26 rats, 2 micrograms 125I MAb C241 (lodobead labelling method) was given i.v. Blood, organ and tumour content was measured at 0.5, 24, 72 and 144 h. In 61 rats, 10 micrograms 131I MAb C241 (lodogen labelling method) was given i.v. The rats were divided into a non-tumour and a tumour-bearing group and subjected to RES function modulation with Zymosan stimulation or methyl palmitate depression. A syngeneic nitrosoguanidine-induced colonic carcinoma--mean 11 g--was growing in back subcutaneous tissue and hind leg musculature. Serum content of tumour-associated antigen was not found on IRMA testing and tumour content of SiLea ganglioside antigen was found only on lipid binding phase assay. The half-time in blood of iodinated MAb C241 was three days. In-vivo release of iodine was tested by plasma separation on a gel column. More than 90% of the iodine was in the IgG fraction. The activity distribution was almost in equilibrium after 24 h. A tumour/blood activity concentration ratio of 0.5 and liver/blood ratio of 0.3 remained at 72 h and 144 h. Radionuclide accumulation was equally low in the macrophage-rich liver and the kidneys. Tumour-bearing animals had significantly lower blood content (0.37 versus 0.99% g-1) and liver content (0.09 versus 0.31% g-1) at 144 h than non-tumour-bearing rats. The whole body content at 144 h was also lower (24% versus 35% of administered activity) (p = 0.10). Modulation of RES function had no significant influence on the whole body, blood or liver content of 131I MAb C241 activity in non-tumour-bearing animals. In tumour-bearing animals, RES stimulation with Zymosan increased the whole body, liver and blood content of 131I activity. The two tested methods of iodination gave similar results.
Adenocarcinoma↗
Prognostic significance of estrogen and progesterone receptors in stage II breast cancer.
Estrogen (ER) and progesterone receptors (PgR) were evaluated in samples from primary tumors in 539 patients with stage II breast cancer participating in a randomized multicenter controlled clinical trial on adjuvant therapy. At the cut-off points of 10 fmol ER/mg protein and 30 fmol PgR/mg protein, no significant difference in recurrence-free survival (RFS) existed between premenopausal patients with receptor-positive and negative tumors, respectively. After recurrence, premenopausal patients with receptor-positive tumors had a significant longer survival than patients with receptor-negative tumors. In postmenopausal patients not treated with adjuvant tamoxifen, no correlations between RFS and receptor status were found. Patients with ER+ tumors survived longer than patients with ER-tumors. In postmenopausal patients treated with adjuvant tamoxifen, highly significant differences in RFS and in survival were observed when receptor-positive patients were compared with receptor-negative patients. No differences in survival after recurrence were registered among these patients.
Breast Neoplasms↗
Phase II study of estramustine phosphate (Estracyt) in patients with metastatic melanoma.
Twenty-six patients with measurable metastatic melanoma were treated with estramustine phosphate (12 mg/mg body wt) orally every day. Tumor biopsies were assessed for estrogen receptors (ER) in 14 patients and for estramustine binding sites (EMBS) in 13 patients. ER and EMBS were measured with isoelectric focusing in polyacrylamide gels. Three partial responses (PR) (12%) and three no changes (NC) (12%) according to WHO criteria were registered. In one patient with NC and in four patients with progressive disease (PD) the tumors were ER positive. EMBS was found in one patient with PR and in two patients with PD. Because of the low frequency of antitumor activity and the low number of patients with ER and/or EMBS the number of patients is too low for any correlation between tumor response and ER and/or EMBS status.
Adult↗
Postoperative adjuvant therapy.
There is no proven significant benefit of adjuvant chemotherapy in colorectal cancer. Portal infusion of 5-FU in the immediate postoperative period has given some promising results but further trials of this treatment are necessary. Intraperitoneal administration should also be tested. All clinical studies of adjuvant chemotherapy must include control groups who do not receive adjuvant treatment.
Clinical Trials as Topic↗
Liver cancer--present status.
Explore the source record for details and available documents.
Antineoplastic Combined Chemotherapy Protocols↗
RES function and tumour take and tumour growth in the liver and in the kidney--an experimental study in rats.
This experimental study in rats examines tumour take and growth after RES modulation in an organ rich in macrophages--the liver--vs. an organ poor in macrophages--the kidney. A control group of 16 rats had 1.0 X 10(6) transplantable adenocarcinoma cells inoculated in the liver and the same number in the left kidney. They were compared with a RE-stimulated group of 16 rats treated i.v. with Zymosan (3 mg/100 g for 3 days) and a RE-depressed group of 16 rats treated with i.v. methylpalmitate (100 mg/100 g for 3 days) before tumour inoculation. Tumour size was measured on days 7 and 14. The animals were killed on day 14. Mortality was significantly higher in methylpalmitate-treated rats than in control groups. Tumour take in the kidney was not affected by RES stimulation or depression. In the liver, RES stimulation caused significantly less tumour take. Depression of RES with methylpalmitate did not increase tumour take or tumour growth in the liver, which was very high in the control group.
Adenocarcinoma↗
Techniques for measuring regional blood flow.
Explore the source record for details and available documents.
Animals↗
Phagocytosis and dynamic RES scintigraphy: an evaluation of commercial colloids in rats.
Reticuloendothelial system (RES) phagocytic function or capacity can be measured by clearance studies with test substances. This study in the rat examines three commercially available 99Tcm-labelled test substances, and different methods of calculating RES capacity. Albures size 500 nm and sulphur colloid size 600 nm used for liver scintigraphic imaging and Nanocoll size 50 nm used for bone-marrow scintigraphic imaging were tested. The rats were examined under a gamma camera and the uptake by the liver, clearance from the heart and clearance from blood samples were recorded. Different amounts of substances were tested. The final uptake in different organs was recorded after the animals were sacrificed. Colloid size and stability were tested with a polycarbonate filter. (Nanocoll was found to have at least 10 times smaller colloid diameter, leading to a thousand times more particles per milligram). RES function was calculated as the uptake rate or clearance rate, k. In a logarithmic plot, the relationship between uptake or clearance and time was found to be linear between 90 and 300s and calculations of k in this interval are recommended. k-values selected from blood sample curves were 11 +/- 5 S.E.M. lower than those calculated from heart clearance curves or liver uptake curves. Increasing amounts of Nanocoll caused a decrease in uptake rate k. Albures and sulphur colloid could not be given in amounts that caused any change in k. Only Nanocoll could be given in sufficiently large amounts (above the critical dose) to challenge RES and avoid complete extraction from the circulation during first passage through RE organs. Nanocoll seems suitable for use in tests of RES function and the optimal amount was 0.03 mg per rat (0.6 X 10(12) particles).
Animals↗
Unresectable and locally recurrent rectal cancer treated with radiotherapy or bilateral internal iliac artery infusion of 5-fluorouracil.
Seventy-nine patients with histopathologically verified unresectable or locally recurrent rectal cancer were nonrandomly allocated to radiotherapy or regional intra-arterial infusion of 5-Fluorouracil (5-FU). Fifteen patients with unresectable and 32 with locally recurrent rectal cancer were subjected to radiotherapy. The absorbed dose was 30 Gy in patients with an unresectable tumor and 45 Gy in patients with locally recurrent rectal cancer. Six patients with unresectable and 26 with locally recurrent rectal cancer received bilateral internal iliac artery infusion of 5-FU in a median dose of 7.5 g. There was no difference in survival between the two methods of treatment. Resection of an initially unresectable tumor could be performed in 5 of 21 patients (4 after radiotherapy and 1 after chemotherapy). All except eight patients had pelvic or perineal pain before treatment. Forty of 43 (93%) patients reported pain relief after radiotherapy and 21 of 28 (75%) after infusion therapy. Ten nonresponders were subjected to alternative treatment (three to intra-arterial infusion and seven to radiotherapy). Five of these ten patients reported complete pain relief and five partial pain relief. After radiotherapy, no significant side effects or complications were observed. The infusion chemotherapy was the cause of death in one patient. In summary, similar palliation was achieved with bilateral iliac artery 5-FU-infusion and radiotherapy. Owing to the complications registered with infusion therapy, radiotherapy must be considered the treatment of choice for these patients. Patients who do not respond to radiotherapy or suffer recurrence of pelvic and perineal pain may receive further palliation from intra-arterial infusion.
Adult↗
[Liver transplantation--experiences from Gothenburg].
Explore the source record for details and available documents.
Adult↗
Adjuvant therapy of breast cancer: compliance and data validity in a multicenter trial.
Multicenter clinical trials are often large and complex, involving many institutions and investigators. The organizational structure is of vital importance in conducting and coordinating such trials. The present article describes the organization of a multicenter trial of adjuvant therapy of breast cancer. The trial is conducted since 1978 and involves all 15 hospitals in the Southern Swedish Health Care Region. The paper also describes methods of determining patient accrual rate, compliance with entrance criteria, diagnostic procedures, treatment, and follow-up. Comparison of data obtained from a population-based regional tumor registry revealed an accrual rate of more than 80%. Compliance with entrance criteria varied between the treatment groups from 85% to 97%. No patients were lost to follow-up. Compliance with diagnostic procedures and treatment was generally good. Reporting of recurrences was in accordance with data from patients' records in 98% of patients. One hundred thirteen patients died during the first 5 years of study. Twenty-one of these deaths were not reported to the secretariat. This strongly illustrates the necessity of matching to a population register before presenting data of such trials.
Antineoplastic Agents↗