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Biomedical subjects

L Y Dirix

Publications and source records attributed to L Y Dirix.

At least 55 records · Page 3Linked to original sources
PubMed1996

EO9 phase II study in advanced breast, gastric, pancreatic and colorectal carcinoma by the EORTC Early Clinical Studies Group.

In a phase II trial, the activity of EO9, a new bioreductive alkylating agent, was assessed. EO9 was used as second-line chemotherapy in breast cancer patients and as first-line chemotherapy for patients with gastric, pancreatic and colorectal cancer. EO9 was given as a 5 min i.v. infusion at a weekly dose of 12 mg/m2. 92 patients were entered; 22 with breast cancer, 26 with colon cancer, 24 with pancreatic cancer and 20 with gastric cancer. In general, the drug was well tolerated with nausea and vomiting occurring in 26.42 and 13.3% of courses, respectively. Reversible proteinuria was the main toxicity occurring in 45% of courses. Antitumour activity was not observed. At this dose and schedule, EO9 is not an active drug in the type of tumour studied.

Adult↗
PubMed1996

Tallimustine in advanced previously untreated colorectal cancer, a phase II study.

Tallimustine is a novel benzoyl mustard derivative from distamycin A with a unique mode of action. It is a DNA minor groove binder and produces highly sequence-specific alkylations. Previous studies have shown significant anti-tumour effects in animal models. We performed a phase II study in previously untreated patients with advanced colorectal cancer, using a schedule of i.v. bolus infusions of 900 microgram m-2 once every 4 weeks. Seventeen patients were enrolled, and no responses were documented in 14 evaluable patients. Toxicity mainly consisted a highly selective neutropenia, which warrants further investigation of this agent in combination with myeloid growth factors.

Adult↗
PubMed1996

Serum basic fibroblast growth factor and vascular endothelial growth factor and tumour growth kinetics in advanced colorectal cancer.

BACKGROUND: The development of new microvessels in the surrounding stroma is a prerequisite for tumour progression. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are angiogenic factors expressed in a broad range of human tumours. We have measured the concentrations of both cytokines in the serum of patients with advanced colorectal cancer. We questioned whether these levels are related to the number of tumour sites, the volume of liver and/or lung involvement and the growth kinetics. PATIENTS AND METHODS: 44 untreated colorectal adenocarcinoma patients who had developed metastatic and/or recurrent disease were evaluated. Serum levels of bFGF and VEGF were repeatedly measured using ELISA. The extent of target organ involvement and the kinetics of tumour volume growth were determined on consecutive computer tomography (CT) images. RESULTS: Patients with a tumour volume doubling time of less than 6 months showed a higher bFGF and VEGF serum level than others, independent of the number of sites involved and the extent of the metastatic disease. CONCLUSIONS: The data suggest a predictive value of serum bFGF and VEGF levels for the progression of disease in patients with untreated metastatic colorectal cancer. The results corroborate the importance of angiogenesis in the process of tumour growth. The serum levels might prove a useful tool in the quantification of angiogenesis and might be of valuable information in the decision process of initiating palliative chemotherapy. It will be of considerable importance to investigate whether the serum bFGF and VEGF levels have a predictive value on the probability of response to cytotoxic therapy.

Adenocarcinoma↗
PubMed1996

Diagnosis and treatment of soft tissue sarcomas in adults.

Soft tissue sarcomas account for approximately 1% of all malignancies. They constitute a wide range of different tumor types with very different clinical courses and treatment sensitivities. Our understanding of the molecular mechanisms of tumor growth in sarcomas is increasing rapidly. These new data will probably lead to drastic changes in our current classification systems, which are primarily based on routine microscopy. This might also bring about a more detailed and reliable prognostic evaluation in individual tumors. Hopefully, this knowledge will guide us towards a more rational and more successful development of new therapies. Current surgical approaches and treatment protocols are more or less well defined. Knowledge on when to use ionizing radiation for local control is reasonably clear. Major difficulties however remain for both these treatment modalities in cases of both truncal and retroperitoneal sarcomas. The lack of new very active chemotherapeutic agents against this group of diseases has remained unchanged in the past years, although both the taxanes and the topoisomerase I inhibitors show some activity.

Adult↗
PubMed1996

Long-term results of continuous treatment with recombinant interferon-alpha in patients with metastatic carcinoid tumors--an antiangiogenic effect?

This study investigated the efficacy of long-term continuous and dose-escalated interferon-alpha (IFN) treatment in patients with progressive carcinoid tumors. In this single-institution, phase II study 16 chemotherapy-naive, eligible patients were entered. Interferon treatment consisted on 5 MIU IFN three times weekly s.c. until radiologic progression. In case of progression the dose was increased to 10 MIU. Radiologic and biochemical evaluation was done monthly and thereafter 3 monthly. We have treated 16 patients of whom 15 are evaluable for tumor response. Calculated by standard response criteria, three patients experienced a partial response. Another three had an important minor response. Median response duration was 24 months (range 18-51 months). Biochemical responses were observed in nine out of 12 patients with an elevated 5-hydroxyindoleacetic acid excretion. The serum neuron-specific enolase proved a reliable marker for both response and progression. In the one patient progressive after 3 months, a dose increment to 10 MIU was without effect. In patients initially not progressing or responding to 5 MIU, escalation to 10 MIU had a short lasting beneficial effect in three cases. The radiological characteristics and the kinetics of these responses are compatible with an anti-angiogenic effect of IFN. This study of IFN in carcinoid tumors confirms the activity in this disease. Our results demonstrate the necessity of initiating treatment only in radiologically progressive patients and continuing this treatment until progression. We feel that currently the activity of IFN in metastatic carcinoid tumors compares favorably with that of systemic chemotherapy in patients with progressive disease.

Adult↗
PubMed1996

The influence of hypoxia on the cytotoxicity of concomitant KW-2149 and ionizing irradiation in Chinese hamster fibroblasts.

7-N-((2-((2-(gamma-L-glutamylamino)ethyl)dithio)ethyl))-mitomycin C (KW-2149) is a newly synthesized water-soluble mitomycin C (MMC) analog. Preclinical testing showed an interesting activity profile and a superior hematological tolerance in murine models. The aim of this study was to investigate the interaction of this compound with ionizing radiation, both under normoxic and hypoxic conditions, in Chinese hamster fibroblasts (V79). V79 cells were irradiated both under normoxic conditions and after a 1 h period of hypoxia. Paired irradiation dose-response curves confirmed the significance of radioresistance under hypoxia with an oxygen enhancement ratio of approximately 3. In contrast to MMC, KW-2149 showed no increased cytotoxic effect on hypoxic V79 cells. The cytotoxic effect of KW-2149 increased with increasing concentration, irrespective of the ambient oxygen pressure. When KW-2149 was combined with irradiation under hypoxic conditions, cytotoxicity was significantly enhanced under these conditions. The difference in survival between normoxic and hypoxic conditions was statistically significant (p < 0.004). These data suggest a radiosensitizing effect of KW-2149, more pronounced under hypoxic conditions. This effect increases with radiation dose. It also corroborates earlier suggestions of a different mode of action of KW-2149 as compared to MMC.

Animals↗
PubMed1995

Microvessel quantification in primary colorectal carcinoma: an immunohistochemical study.

The vascularisation of human primary colorectal carcinomas was studied immunohistochemically using the endothelial cell markers CD31 and factor VIII-related antigen. Tumour sections were systematically scanned at a magnification of x 100 to find areas of intense neovascularisation. Microvessel counts within these vascular 'hotspots' were performed at magnification x 250. Regions in which tumour cords were surrounded by a collagen IV-positive basement membrane were compared with those in which this was absent and with normal mucosa. CD31 appeared to be a more sensitive marker for endothelial cells than factor VIII-related antigen (mean 185 +/- 59 and 120 +/- 38 microvessels mm-2). Within individual tumour sections microvessel counts in vascular hotspots with highest vessel density correlated significantly with microvessel counts in vascular hotspots with second highest vessel density (P < 0.01). Microvessel counts in tumour areas where collagen IV-positive basement membrane were absent exceeded those in areas where it was present (factor of 1.7) and those in normal mucosa (factor of 1.6). The differences in vessel density between individual tumours and the low variability in vessel density within individual tumours using this quantification technique allow us to investigate the prognostic value of vessel density in areas of intense neovascularisation in human primary colorectal carcinomas.

Adult↗
PubMed1995

Microvessel density, endothelial cell proliferation and tumour cell proliferation in human colorectal adenocarcinomas.

BACKGROUND: Thymidine incorporation studies performed in animal tumour models, revealed major differences in endothelial cell proliferation when tumour tissue was compared with normal tissue. The fraction of proliferating endothelial cells is reported to be increased by a factor of 30 to 40 in tumour tissue. PATIENTS AND METHODS: To make it possible to analyze the endothelial cell proliferation in human tumours, an immunohistochemical double staining technique comprising CD31, an endothelial cell marker, and Ki-67, a proliferation marker, was developed. Endothelial cell proliferation was analysed in 21 primary human colorectal adenocarcinomas and in the adjacent mucosa. RESULTS: Proliferating endothelial cells were found throughout the entire carcinoma. The mean overall endothelial cell labeling index (ECLI) was 9.9% (range, 5.4-18.0), and the labeling index of endothelial cells in areas of intense neovascularisation was even higher. Mean ECLI in the vascular hot spots was 21.0% (range, 6.8-35.0), and the mean tumour cell labeling index (TCLI) in the maximally Ki-67 immunostained areas was 78.3% (range 47.0-89.7). In 14 of 21 carcinomas, these areas were predominantly found at the luminal margin of the tumour, as were the vascular hot spots. A significant positive correlation was found between tumour vascularity, measured in the vascular hot spots, and tumour cell proliferation, measured in the maximally Ki-67 immunostained areas (p < 0.05). To analyse this relation in more detail, microvessel density (MVD), TCLI and ECLI were determined per x400 microscopic field by scanning in sequence from the luminal tumour margin to the invasive tumour base. In all tumours, the pattern of the MVD per x400 field, from the luminal margin to the tumour base, was similar to that of the TCLI and ECLI. CONCLUSIONS: These findings confirm that the fraction of cycling endothelial cells is higher in human colorectal carcinoma than in the adjacent mucosa which suggests that endothelial cells are proliferating in most of the individual capillaries in tumour tissue. Regional differences in MVD correlate with differences in tumour cell proliferation in these tumours.

Adenocarcinoma↗
PubMed1995

Phase II trial of CPT-11 in patients with advanced pancreatic cancer, an EORTC early clinical trials group study.

BACKGROUND: CPT-11 (irinotecan) is a semi-synthetic derivative of camptothecin and exerts its activity by inhibiting DNA topoisomerase I. A phase II study of this drug was performed in patients with pancreatic cancer. PATIENTS AND METHODS: Eligibility criteria included advanced non-chemotherapy-pretreated pancreatic cancer. CPT-11 was administered as a 30-minute i.v. infusion at a dose of 350 mg/m2 diluted in 250 ml normal saline every 3 weeks. RESULTS: Thirty-four eligible patients were enrolled in the study, thirty-two of them were evaluated, and three achieved partial responses (9%; 95% C.I. = 3%-25%). The duration of response was 7.2, 7.5 and 7.8 months, respectively. Thirteen patients had no change, fourteen patients had progressive disease and two had early progressive disease. The median duration of survival for all patients treated was 5.2 months. The main toxicities (CTC grade > or = 3) were diarrhea, leukocytopenia, asthenia, nausea and vomiting in, respectively, 7%, 16%, 8%, 6%, 4% of the courses. These toxicities were reversible and manageable with anti-emetics and prophylactic or curative antidiarrheal agents. CONCLUSION: CPT-11 is an interesting moderately effective drug in pancreatic cancer.

Adult↗
PubMed1995

Topotecan in colorectal cancer: a phase II study of the EORTC early clinical trials group.

PURPOSE: This phase II study with the topoisomerase I inhibitor topotecan was performed to determine its clinical activity and toxicity in patients with metastatic or locally unresectable colorectal cancer. PATIENTS AND METHODS: Topotecan 1.5 mg/m2 was administered intravenously by 30-minute infusion for 5 days. Fifty-nine patients entered the study, 2 were considered ineligible and 57 were evaluable for response and toxicity. RESULTS: Partial response was obtained in 4 of 57 evaluable patients (7%). The median duration of the response was 11 months (range 9.3 to 12.2). This topotecan regimen was very well tolerated. A total of 290 courses were given, with a median of 4 courses per patient (range, 1 to 18). The major toxic effects were leuko- and neutropenia (91%), grade 3-4 in 48% and 79% of courses, respectively, but with only 2 infectious complications. Other side effects were grade 1 alopecia (77%) in 46%, nausea (35%), vomiting (10%), and maculo-papular rash (6%). CONCLUSIONS: Topotecan administered as a daily-times-five regimen has only minor activity as a single-agent therapy in colorectal cancer.

Adult↗
PubMed1995

Diagnosis and treatment of soft tissue sarcomas in adults.

The optimal treatment of soft tissue sarcoma remains a challenge for the multidisciplinary approach in modern oncology. Only when a team of experienced clinicians, oncologists, radiotherapists, and oncologic orthopedic surgeons cooperates with the radiologist and the pathologist can optimal treatment be guaranteed. Recent advances in our knowledge of sarcomas have resulted from more detailed analysis of the cytogenetic and molecular changes in the different types of sarcoma. The prognostic significance of many biologic markers is still the subject of ongoing investigations, with sometimes conflicting results. The usefulness of adjuvant radiotherapy in the combined approach for optimal local control of both extremity and trunk sarcomas is confirmed in different studies. the discovery of antitumor activity of taxoids in this disease brings new chemotherapeutic combinations within reach.

Adult↗
PubMed1995

Cryptorchidism and extragonadal germ cell tumor.

A patient with an extragonadal germ cell tumor and a history of bilateral cryptorchidism is reported. The rarity of this concurrence in a single patient is discussed. The necessity for thorough investigation of the cryptorchid testes in patients with metastatic germ cell cancer remains essential.

Adult↗