Search PubMed⌕ Search

Biomedical subjects

S Van Belle

Publications and source records attributed to S Van Belle.

At least 19 recordsLinked to original sources
PubMed2003

Differential involvement of neurotransmitters through the time course of cisplatin-induced emesis as revealed by therapy with specific receptor antagonists.

Advances in antiemetic therapy for chemotherapy-induced emesis have resulted in improved protection against symptoms occurring within 24 h of chemotherapy. However, the vomiting which tends to occur beyond 24 h after chemotherapy (delayed-phase vomiting) is still relatively poorly controlled by the currently available drugs, suggesting that more than one mechanism may mediate these symptoms. The standard antiemetic regimen currently recommended for prevention of chemotherapy-induced emesis includes a serotonin (5-HT(3)) antagonist and a corticosteroid. The neurokinin-1 (NK(1)) antagonist aprepitant represents a new class of antiemetic currently in clinical development. Using data obtained in 2 Phase II clinical trials of aprepitant in patients receiving chemotherapy based on the highly emetogenic chemotherapeutic agent cisplatin, we compared the time course of antiemetic effect of aprepitant, a 5-HT(3) antagonist, or a combination of both. Over the entire observation period (up to 7 days post-cisplatin), patients who received the NK(1) antagonist had a superior prevention of emesis. However, in the first 24 h after cisplatin, emesis occurred in fewer patients who received the 5-HT(3) antagonist than in patients who did not receive this class of drug. Furthermore, the majority of treatment failures in patients who received the NK(1) antagonist occurred within the first 8-12 h of chemotherapy, whereas the treatment failures in patients who received a 5-HT(3) antagonist were more evenly distributed over time. Patients who received both drugs had superior control of symptoms compared with patients who received one or the other. The difference in the time course of emesis blockade observed with two different classes of receptor antagonists provides substantial evidence for involvement of separate pathophysiological mechanisms in chemotherapy-induced vomiting. Serotonin mediates the early vomiting process that occurs within 8-12 h following cisplatin-based chemotherapy, after which time substance P acting at NK(1) receptors becomes the dominant mediator of vomiting

Antiemetics↗
PubMed2003

Influence of neo-adjuvant chemotherapy with 5-fluorouracil on colonic anastomotic healing: experimental study in rats.

PURPOSE: We studied the effect of neo-adjuvant chemotherapy on the operative outcome and colonic anastomotic healing in a rat model. METHODS: Firstly, we determined the maximum tolerated dose (MTD) of intraperitoneal 5-flurorouracil (5-FU) in Wistar rats. Secondly, animals were randomly divided into 3 groups: group CT-H received the MTD of 5-FU, group CT-L received 50% of the MTD and a control group received an equivalent volume of 0.9% saline, intraperitoneally. Colonic anastomosis was performed 4 days after chemotherapy. Animals were sacrificed 10 days after surgery. Evaluations were made of: weight evolution, surgical complications, anastomotic bursting pressure (BP) and histological analysis of the anastomotic site. RESULTS: A dose of 20 mg/kg 5-FU, intraperitoneally, for 5 consecutive days was found to be the MTD. A significant weight loss occurred in group CT-H in comparison to the control group either during chemotherapy (p < 0.01) or after surgery (p = 0.01). Postoperative complications were seen only in group CT-H (30% versus 0% in CT-L and control groups). More intense adhesion formation was observed in group CT-H in comparison to the control group (p < 0.01). Intraperitoneal 5-FU induced more inflammation and fibrosis in the submucosa, either with the low or the high-dose, compared to the control animals (p < 0.05) and more pronounced vascular sclerosis was noticed with a dose of 20 mg/kg (p = 0.03). No significant differences in BP were found between the chemotherapy groups and the control group. CONCLUSION: Neoadjuvant chemotherapy with 5-FU does not alter the strength of colon anastomosis in this rat model. A dose of 20 mg/kg induces significantly more intra-abdominal adhesions and histological alterations at the anastomotic site.

Anastomosis, Surgical↗
PubMed2003

Long-term medical costs of postmenopausal breast cancer therapy.

BACKGROUND: Since the incidence of breast cancer is growing, prevention programs can be expected to have a large economic impact on the health care system. From a health economic point of view, one is interested in the costs saved by disease prevention. PATIENTS AND METHODS: To predict 10-year cumulative incidence-based costs of postmenopausal breast cancer, a state transitional model was developed based on published clinical data. The model simulates disease progression and includes nine health states of 1 year: node-negative and node-positive early cancer; local relapse; metastasis, each with its follow-up states; and death. The cost per state was obtained from a chart review in 118 patients with different disease states. Costs were calculated from the health insurance perspective and discounted at 3%. RESULTS: The cumulative 10 year cost per patient was equal to 31,774 euro [95% confidence interval (CI) 30,536-33,012 euro] of which 30% was hospital costs, 28% systemic treatment, surgery and radiotherapy and 14% testing. Costs were at their highest following diagnosis and before death. CONCLUSIONS: This incidence-based approach identified the cost of postmenopausal breast cancer over time and may serve as a valid baseline for assessment of new interventions in prevention or early treatment.

Adult↗
PubMed2002

Quality of life assessment in radionuclide therapy: a feasibility study of the EORTC QLQ-C30 questionnaire in palliative (131)I-lipiodol therapy.

The good tolerance of radionuclide therapy has frequently been proposed as a major advantage. This study explored the feasibility of using the EORTC QLQ-C30 questionnaire in palliative iodine-131 lipiodol therapy for hepatocellular carcinoma. Questionnaires were completed during interviews in which all symptoms, co-morbidity and medication were assessed at baseline within 1 week before (131)I-lipiodol therapy, and subsequently after 1 and 3 months, in 20 patients treated with locoregional, intra-arterial (131)I-lipiodol therapy with or without cisplatin. Principal observations were that (1) a number of important scales, i.e. overall quality of life, physical functioning and pain, worsened between 0 and 3 months after (131)I-lipiodol therapy, irrespective of tumour response, and (2) the occurrence of clinical side-effects was associated with a negative impact on quality of life and physical functioning 1 and 3 months after (131)I-lipiodol. The QLQ-C30 can be regarded as a feasible method for quality of life assessment in (131)I-lipiodol therapy for hepatocellular carcinoma and possibly in other radionuclide therapies. These observations should be related to the impact of other treatment modalities on quality of life.

Aged↗
PubMed2002

Randomised, phase II trial comparing oral capecitabine (Xeloda) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines.

Capecitabine, an oral fluoropyrimidine carbamate, was designed to generate 5-fluorouracil preferentially at the tumour site. This randomised, phase II trial evaluated the efficacy and safety of capecitabine or paclitaxel in patients with anthracycline-pretreated metastatic breast cancer. Outpatients with locally advanced and/or metastatic breast cancer whose disease was unresponsive or resistant to anthracycline therapy were randomised to 3-week cycles of intermittent oral capecitabine (1255 mg m(-2) twice daily, days 1-14, (22 patients)) or a reference arm of i.v. paclitaxel (175 mg m(-2), (20 patients)). Two additional patients were initially randomised to continuous capecitabine 666 mg m(-2) twice daily, but this arm was closed following selection of the intermittent schedule for further development. Overall response rate was 36% (95% CI 17-59%) with capecitabine (including three complete responses) and 26% (95% CI 9-51%) with paclitaxel (no complete responses). Median time to disease progression was similar in the two treatment groups (3.0 months with capecitabine, 3.1 months with paclitaxel), as was overall survival (7.6 and 9.4 months, respectively). Paclitaxel was associated with more alopecia, peripheral neuropathy, myalgia and neutropenia, whereas typical capecitabine-related adverse events were diarrhoea, vomiting and hand-foot syndrome. Twenty-three per cent of capecitabine-treated patients and 16% of paclitaxel-treated patients achieved a > or =10% improvement in Karnofsky Performance Status. Oral capecitabine is active in anthracycline-pretreated advanced/metastatic breast cancer and has a favourable safety profile. Furthermore, capecitabine provides a convenient, patient-orientated therapy.

Administration, Oral↗
PubMed2001

Healing of experimental colonic anastomoses: effects of combined preoperative high-dose radiotherapy and intraperitoneal 5-fluorouracil.

To study the effects of preoperative radiochemotherapy (RCT) on the healing of colonic anastomosis, the rectosigmoid colon in male Wistar rats was irradiated up to an end dose of 41.6 Gy (RT) or sham-irradiated (SR). During the last 5 days of the irradiation schedule, 5-fluorouracil (5-FU) was administered intraperitoneally in either a high dose (20 mg/kg, chemotherapy-high dose [CH]) or a low dose (10 mg/kg, chemotherapy-low dose [CL]). Animals were randomly arranged into six groups: group I, control (SR + saline intraperitoneally); group II, RT only; group III, SR + CL; group IV, RT + CL; group V, SR + CH; group VI, RT + CH. Four days after RCT, a side-to-side anastomosis was constructed between the irradiated rectosigmoid and the nonirradiated caecum. Animals were killed 10 days postoperatively. No significant differences were found in the anastomotic bursting pressure or the bursting wall tension. In group VI, mitoses were less (P < 0.01) and mucosal ulceration was more (P = 0.03) pronounced compared to group I. Sclerotic arteries were seen in all irradiated groups and in animals that received high-dose 5-FU alone. 5-FU administration in high or low dose, with or without RT, induced more inflammation in the submucosa compared to controls (P < 0.05). Conclusively, RCT has no detrimental effect on the mechanical strength of colonic anastomosis in this rat model. However, RCT with high-dose 5-FU induces more histological alterations at the anastomotic site.

Anastomosis, Surgical↗
PubMed2001

Influence of preoperative combined radiochemotherapy on surgical outcome and colonic anastomotic healing: experimental study in the rat.

PURPOSE: To study the influence of combined preoperative hyperfractionated irradiation with intraperitoneal 5-fluorouracil (5-FU) on surgical outcome and colonic anastomotic healing in a rat model. METHODS: Male Wistar rats were given 41.6 Gy of preoperative radiotherapy (RT) or sham irradiation, with intraperitoneal 5-FU at low dose (10 mg/kg) or high dose (20 mg/kg). Animals were arranged in 6 groups: RT + low-dose 5-FU (RCT-L), RT + high-dose 5-FU (RCT-H), sham RT + low-dose 5-FU (CT-L), sham RT + high-dose 5-FU (CT-H), RT alone (R), and a control group (sham RT + intraperitoneal saline). Side-to-side colonic anastomoses were constructed from one irradiated and one nonirradiated limb 4 days after radiochemotherapy. Animals were sacrificed 10 days after surgery. RESULTS: Compared to controls, more complications occurred in group RCT-H (50% versus 0%, p = 0.01). Adhesion formation was more intense in groups RCT-H and CT-H (p < 0.001 and p = 0.001, respectively). After therapy, white blood cell counts dropped significantly in all irradiated animals (p < 0.01), and platelet counts decreased significantly in group RCT-H (p = 0.01). No significant differences were noticed in anastomotic bursting pressure when the treated groups were compared to each other or to the control group. CONCLUSIONS: Neoadjuvant radiochemotherapy has no adverse effect on the strength of colonic anastomosis in this rat model. However, the combined RT with high-dose 5-FU does increase operative morbidity and adhesion formation.

Anastomosis, Surgical↗
PubMed2001

Comparison of L-758,298, a prodrug for the selective neurokinin-1 antagonist, L-754,030, with ondansetron for the prevention of cisplatin-induced emesis.

Substance P is localised in brainstem regions associated with emesis. Based on studies in the ferret, it was postulated that a neurokinin-1 (NK1) receptor antagonist would have antiemetic activity as monotherapy in humans receiving chemotherapy. L-758,298 is a water-soluble, intravenous (i.v.) prodrug for L-754,030, a potent and selective NK1 receptor antagonist. This double-blind, randomised, active-agent (ondansetron)-controlled study enrolled 53 cisplatin-naïve patients and evaluated the prevention of both acute (0-24 h) and delayed (days 2-7) emesis after cisplatin treatment (50-100 mg/m(2)). All patients received i.v. L-758,298 (60 or 100 mg) (n=30) or ondansetron (32 mg) (n=23) before cisplatin and efficacy was evaluated up to day 7 post-cisplatin. Nausea was assessed by means of a four-point ordinal scale at intervals over the 7 day period. In the acute period, the proportion of patients without emesis in the L-758,298 and ondansetron groups was 37 and 52%, respectively (no significant difference between the groups). Comparing the distribution of average nausea scores over the entire first 24 h revealed no significant difference between the groups. In the delayed period, the proportion of patients without emesis in the L-758,298 and ondansetron treatment groups was 72 and 30%, respectively (P=0.005). The distribution of average nausea scores in the delayed period was lower in the L-758,298 group compared with the ondansetron group (P=0.15 for the entire delayed period and P=0.043 for day 2 only). No serious adverse events were attributed to L-758,298. A single dose of L-758,298 substantially suppressed the delayed nausea and vomiting characteristic of high dose cisplatin and also appeared to reduce acute emesis post-cisplatin. The data also support the proposition that the underlying mechanism(s) of acute and delayed emesis are different.

Acetals↗
PubMed2001

Iodine-labeled tamoxifen uptake in primary human breast carcinoma.

UNLABELLED: Assessing tumor uptake and retention of (123)I-labeled tamoxifen (TX) could increase our understanding of TX's action and the mechanisms involved in resistance to the drug. METHODS: Nine untreated primary breast carcinoma patients underwent whole-body planar and tomographic (SPECT) imaging 30 min and 4-5 h after injection of 185 MBq (123)I-TX. Tumor-to-normal tissue uptake ratios (T/N) derived from SPECT images were related to estrogen receptor (ER) and progesterone receptor (PR) status. RESULTS: In 4 of 9 patients, all of whom were ER+/PR+, (123)I-TX tumor uptake was clearly depicted. In 2 of them, involved axillary lymph nodes were also visualized. T/N consistently increased over time. All ER+/PR- and ER-/PR- tumors as well as 2 ER+/PR+ tumors were (123)I-TX-. CONCLUSION: These preliminary findings suggest that (123)I-TX is preferentially taken up in alpha-ER+/PR+ breast tumors known to be more likely to respond to endocrine treatment.

Breast Neoplasms↗
PubMed2000

Radiolabeled estradiol derivatives to predict response to hormonal treatment in breast cancer: a review.

Several radiolabeled steroidal and nonsteroidal estradiol derivatives of which the tumoral uptake is believed to relate quantitatively to the content and binding characteristics of the alpha-estrogen receptor (alphaER) receptor in the target tissue have been synthesized and their imaging potential and clinical usefulness evaluated in vivo in humans. Due to the use of different methodologies and cut-off values for the measurement of alphaER positivity, the use of both quantitative positron emission tomography and semiquantitative single-photon emission tomography, and the difference in patient populations studied, direct comparison of these data is not possible. Individual data, however, fail to substantiate a direct relationship between these radiolabeled estradiol derivatives and alphaER status, in keeping with recent pathophysiological findings demonstrating (1) estradiol sequestration and retention through other than alphaER-mediated, either membrane- or non-membrane-related, mechanisms and (2) an inverse relationship between estradiol uptake and local biosynthesis through aromatization and interconversion in alphaER-positive tumors. Additionally, given the discovery of very high affinity alphaER-like binding sites (Kd, dissociation constant, <0.1 nM), and the potential for underestimation of aER Kd when using ligand binding assays, at least part of the radiolabeled estradiol derivative uptake reflects tumoral perfusion rather than the ligand-receptor binding process. However, the reduction in cellular uptake, membrane sequestration and local biosynthesis of estradiol following tamoxifen treatment in alphaER-responsive tumors should allow early prediction of response to therapy through rapid sequential radiolabeled estradiol scintigraphy with higher accuracy than conventional alphaER estimations, as supported by recent data.

Binding Sites↗
PubMed2000

Mutation analysis of P73 and TP53 in Merkel cell carcinoma.

The p73 gene has been mapped to 1p36.33, a region which is frequently deleted in a wide variety of neoplasms including tumours of neuroectodermal origin. The p73 protein shows structural and functional homology to p53. For these reasons, p73 was considered as a positional and functional candidate tumour suppressor gene. Thus far, mutation analysis has provided no evidence for involvement of p73 in oligodendrogliomas, lung carcinoma, oesophageal carcinoma, prostatic carcinoma and hepatocellular carcinoma. In neuroblastoma, two mutations have been observed in a series of 140 tumours. In view of the occurrence of 1p deletions in Merkel cell carcinoma (MCC) and the location of p73 we decided to search for mutations in the p73 gene in five MCC cell lines and ten MCC tumours to test potential tumour suppressor function for this gene in MCC. In view of the possible complementary functions of p73 and TP53 we also examined the status of the TP53 gene. Sequence analysis of the entire coding region of the p73 gene revealed previously reported polymorphisms in four MCCs. In one MCC tumour, a mis-sense mutation located in the NH2-terminal transactivation region of the p73 gene was found. These results show that p73, analogous to neuroblastoma, is infrequently mutated in MCC. This is also the first report in which the role of TP53 in MCC has been investigated by sequencing the entire coding region of TP53. TP53 mis-sense mutations and one non-sense mutation were detected in three of 15 examined MCCs, suggesting that TP53 mutations may play a role in the pathogenesis or progression of a subset of MCCs. Moreover, typical UVB induced C to T mutations were found in one MCC cell line thus providing further evidence for sun-exposure in the aetiology of this rare skin cancer.

Base Sequence↗
PubMed2000

[A comparative randomized phase-II study of Xeloda (capecitabine) and paclitaxel in patients with breast cancer progressing after anthracycline antibiotics].

A randomized study of the effectiveness of treatment with capecitabine (Xeloda) (22) and paclitaxel (taxol) (19) was carried out in breast cancer patients resistant to anthracycline antibiotic drugs. Capecitabine and paclitaxel showed comparable effectiveness, although the former appeared less toxic, particularly, in hematologic complication situations. Therefore, it may be administered to out-patients who previously received several courses of chemotherapy.

Adult↗
PubMed1999

Marimastat in recurrent colorectal cancer: exploratory evaluation of biological activity by measurement of carcinoembryonic antigen.

Marimastat is a specific inhibitor of matrix metalloproteinases that has been shown to be effective in cancer models. A pilot, escalating-dose study of oral marimastat was performed in patients with recurrent colorectal cancer, in whom evaluation of serological response was made by measurement of carcinoembryonic antigen (CEA) levels. The study assessed the safety and tolerability of 4 weeks administration of marimastat, and determined a dose range producing detectable serological effects. Patients were recruited with a serum CEA level greater than 5 ng ml(-1), and rising by more than 25% over a 4-week screening period. Patients were treated for 28 days and entered into a continuation protocol if a serological response or clinical benefit was observed. Pharmacokinetic and safety data determined that groups of patients were recruited sequentially at 25 mg and 50 mg twice daily, and, thereafter, 10 mg twice daily, 10 mg once daily, 5 mg once daily and 20 mg once daily. A biological effect (BE) was defined as a CEA value on day 28 no greater than on day 0; a partial biological effect (PBE) was defined as a rise in CEA over the 28-day treatment period of less than 25%. Of 70 patients recruited, 63 completed the 28-day treatment period, and 55 were eligible for cancer antigen analysis. Examination of the dose-effect relationships provides evidence for a causal relationship between marimastat and biological effects: the proportion of patients with BE or PBE was higher with twice daily dosing (16 out of 25, 64%) than with once daily dosing (11 out of 30, 37%) (P = 0.043, chi2 test). Furthermore, the median rates of rise of CEA fell markedly during treatment compared with the screening period for patients receiving twice daily marimastat (P<0.0001), but not for patients receiving marimastat once daily (P = 0.25). Musculoskeletal adverse events emerged as the principal drug-related toxicity of marimastat, occurring in a dose- and time-dependent fashion. It was concluded that marimastat was associated with dose-dependent biological effects in cancer patients. The occurrence of musculoskeletal side-effects define 25 mg twice daily as the upper limit of the dose range for continuous use in further studies. Therefore, a dose range of 20 mg once daily to 25 mg twice daily seems appropriate for further studies, which should aim to demonstrate the efficacy of the drug in terms of conventional clinical end points and describe the long-term tolerability of this novel agent.

Administration, Oral↗
PubMed1999

Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer.

PURPOSE: This phase III study compared docetaxel and doxorubicin in patients with metastatic breast cancer who had received previous alkylating agent-containing chemotherapy. PATIENTS AND METHODS: Patients were randomized to receive an intravenous infusion of docetaxel 100 mg/m(2) or doxorubicin 75 mg/m(2) every 3 weeks for a maximum of seven treatment cycles. RESULTS: A total of 326 patients were randomized, 165 to receive doxorubicin and 161 to receive docetaxel. Overall, docetaxel produced a significantly higher rate of objective response than did doxorubicin (47.8% v 33.3%; P =.008). Docetaxel was also significantly more active than doxorubicin in patients with negative prognostic factors, such as visceral metastases (objective response, 46% v 29%) and resistance to prior chemotherapy (47% v 25%). Median time to progression was longer in the docetaxel group (26 weeks v 21 weeks; difference not significant). Median overall survival was similar in the two groups (docetaxel, 15 months; doxorubicin, 14 months). There was one death due to infection in each group, and an additional four deaths due to cardiotoxicity in the doxorubicin group. Although neutropenia was similar in both groups, febrile neutropenia and severe infection occurred more frequently in the doxorubicin group. For severe nonhematologic toxicity, the incidences of cardiac toxicity, nausea, vomiting, and stomatitis were higher among patients receiving doxorubicin, whereas diarrhea, neuropathy, fluid retention, and skin and nail changes were higher among patients receiving docetaxel. CONCLUSION: The observed differences in activity and toxicity profiles provide a basis for therapy choice and confirms the rationale for combination studies in early breast cancer.

Adult↗
PubMed1998

Ossified retroperitoneal malignant Schwannoma with spinal leptomeningeal metastases.

A malignant retroperitoneal schwannoma in a patient without von Recklinghausen's disease is reported. Ossification in the tumour, shown on CT and MRI in this previously untreated patient is exceptional. MRI demonstration of spinal leptomeningeal metastases supports the hypothesis of haematogenous metastatic spread of systemic malignant tumours to the leptomeningeal spaces.

Female↗
PubMed1998

Abdominal pain with anorexia in patients with breast carcinoma.

Breast cancer is the second commonest primary tumour responsible for gastrointestinal metastases after malignant melanoma. The real incidence of gastrointestinal metastases in breast cancer patients is probably underestimated owing to the non-specific presenting symptoms and death of patients caused by other more obvious metastases. The predominant histological subtype of gastrointestinal metastases of breast cancer is invasive lobular carcinoma and the median interval from diagnosis of primary breast cancer to gastrointestinal metastases is five years. We report two cases of disseminated breast cancer with gastrointestinal involvement with a rather long survival.

Abdominal Pain↗