Biomedical subjects

G Gasparini

Publications and source records attributed to G Gasparini.

At least 37 records · Page 2Linked to original sources

PubMed2001

Angiogenesis sustains tumor dormancy in patients with breast cancer treated with adjuvant chemotherapy.

Experimental studies performed in Folkman laboratories suggest that angiogenesis is involved in the biology of tumor dormancy. We determined the vascular index in a series of 190 women operated of node-positive invasive breast cancer treated with adjuvant chemotherapy (CMF schedule) and we studied the relationship between vascularity of primary tumors with the behaviour in time of metastasis. The study of the hazard function of recurrence (in any site) was performed resorting to a generalized linear modelling approach with a binominal error according to Efron. A total of 80 cases developed recurrences during the period of observation. We found that the hazard function of metastasis in time presented two peaks of incidence at 20 and 60 months, respectively. We also plotted the curves of the hazard function by considering three values of microvessel counts corresponding to the quartiles of their distribution. The risk of first recurrence was associated with vascular index, and the patients of the third quartile of distribution of microvessels had the highest risk. In the final full model for the risk of recurrence at 5 years vascular index provided the highest prognostic contribution followed by the number of involved axillary lymph nodes. The observation that the patients with highly angiogenic tumors are at high risk of recurrence coupled with the identification of the second peak of incidence after 5 years which was also mainly sustained by angiogenic tumors suggest that a fraction of breast cancers promote metastasis after a period of tumor dormancy. The clinical and therapeutic implications of our results are discussed.

Adult↗

PubMed2001

Pacemapping of the triangle of Koch: a simple method to reduce the risk of atrioventricular block during radiofrequency ablation of atrioventricular node reentrant tachycardia.

Slow pathway ablation in common AVNRT can be complicated by total AV block. When radiofrequency energy is delivered to the posterior aspect of the triangle of Koch, total AV block may be the consequence of the absence of anterograde conduction along the fast pathway or of inadvertent damage to a fast pathway abnormally located close to the slow pathway. To localize the anterogradely conducting fast pathway, the triangle of Koch was pacemapped in 72 patients who underwent the ablation of common AVNRT. In all cases, before ablation the St-H interval was calculated by stimulating the anteroseptal (AS), mid-septal (MS), and posteroseptal (PS) aspect of the triangle of Koch at a rate slightly faster than the sinus rate. In all patients, common AVNRT was induced. In 64 (89%) of 72 patients (group A) the shortest St-H interval was recorded on stimulating the AS region. In six (8%) patients (group B) the shortest St-H interval was recorded on stimulating the MS region. Finally, in two (3%) patients (group C) the shortest St-H interval was recorded stimulating in the PS region. In group C, AH interval, calculated on stimulating in the AS region, was significantly longer than in patients of groups A and B (200 +/- 99 ms vs 64 +/- 18 and 62 +/- 3, respectively). In group A, on stimulating in the AS, MS, and PS regions, the AH interval remained constant in all patients. In contrast, in groups B and C on stimulation in the MS and PS regions, AH interval shortened (in group B from 56 +/- 8 to 27 +/- 37 and 37 +/- 14, respectively; in group C from 200 +/- 99 to 170 +/- 100 and to 137 +/- 109, respectively). In groups A and B, a posteroseptal slow pathway, and in group C, an anteroseptal retrograde fast pathway were successfully ablated without AV block. Pacemapping of the triangle of Koch can help to recognize patients in whom the anterograde conducting fast pathway is abnormally located far from the anteroseptal region or in whom anterograde conduction of the fast pathway is absent. In these cases the risk of AV block can be reduced by performing slow pathway ablation in a site sufficiently far from the site of the anterograde fast pathway or ablating the retrogradely conducting fast pathway.

Cardiac Pacing, Artificial↗

PubMed2001

Low-energy internal cardioversion in patients with long-lasting atrial fibrillation refractory to external electrical cardioversion: results and long-term follow-up.

AIM: Low-energy internal cardioversion is a new electrical treatment for patients with persistent atrial fibrillation. This paper evaluates the efficacy and safety of low-energy internal cardioversion in patients with long-lasting atrial fibrillation refractory to external electrical cardioversion, and the clinical outcome of such patients. METHOD AND RESULTS: The study population consisted of 55 patients [32 male, mean age 65 +/- 10 years, 48 (87%) with underlying heart disease] with long-lasting (mean 18 +/- 34 months) atrial fibrillation in whom external cardioversion had failed to restore sinus rhythm. Two custom-made catheters were used: one positioned in the right atrium and one in the coronary sinus or the left pulmonary artery. A standard catheter was inserted into the right ventricular apex to provide R wave synchronization. Sinus rhythm was restored in 52 patients (95%) with a mean defibrillating energy of 6.9 +/- 2.6 J (320 +/- 60 V). No complications were observed. During follow-up (mean 18 +/- 9 months), 16 patients (31%) suffered early recurrence (< or = 1 week) of atrial fibrillation and 20 patients (38%) had late recurrence (> 1 week, mean 3.5 +/- 3.6 months) of atrial fibrillation. Six patients with a late recurrence again underwent cardioversion and five of these maintained sinus rhythm. Therefore, a total of 21/52 patients (40%) were in sinus rhythm at the end of follow-up. No clinical difference was found between patients with and without recurrences. CONCLUSIONS: Low-energy internal cardioversion is a useful means of restoring sinus rhythm in patients with long-lasting atrial fibrillation refractory to external electrical cardioversion. More than one-third of patients maintained sinus rhythm during long-term follow-up.

Aged↗

PubMed2001

Abrikossoff's tumor.

Abrikossoff's tumor is a disease that more commonly affects the oral cavity but can also occur at other sites. It develops between the second and sixth decades of life, more frequently among women and blacks. The neoplasm can affect all parts of the body. The head and neck areas are affected in 45% to 65% of cases and of these, 70% are located interorally (tongue, oral mucosa, hard palate). The benign form shows polygonal cells with granular, eosinophilic cytoplasm and small nuclei. The malignant form, however, is associated with a high mitotic index and pleomorphic cellular tissue. The clinical aspect of the neoformation is a swelling covered by mucus of normal appearance. Studies of the neoformation show that in addition to the objective examination, further instrumental research is necessary, i.e., with nuclear magnetic resonance or computed tomography with contrast CT scan. However, the only examination that can confirm the clinical diagnosis is the histological examination. The only treatment for Abrikossoff tumor is surgery. The surgical treatment provides for an extirpation of the neoformation with the overhanging mucus and the underlying periosteum. In this work, the authors discuss a case of Abrikossoff tumor affecting the mucus of the right side of the hemipalate in a 53-year-old patient and present a review of the literature.

Granular Cell Tumor↗

PubMed2001

Angiodysplasia with osteohypertrophy affecting the oromaxillofacial area: clinical findings.

The authors report a case of oro-facial port-wine stain angiomatosis with cutaneous and mucosal lesions localized in the first and the second branch surface distribution areas of the right trigeminal nerve in association with right upper and lower lip, cheek, and hemimaxillary true hypertrophy leading to a severe dento-skeletal malocclusion with openbite and facial asymmetry. The authors through a revision of the Bibliography locate nosologically this case among the rare congenital angiodysplastic syndromes affecting the maxillo-facial district as the Sturge-Weber and the Klippel-Trenaunay syndromes. They debate also about etiopathogenetic, clinical, differential diagnosis, and therapeutic aspects concerning the treatment of patients affected by this kind of malformation.

Adult↗

PubMed2001

Thrombospondin-1 and -2 in node-negative breast cancer: correlation with angiogenic factors, p53, cathepsin D, hormone receptors and prognosis.

OBJECTIVE: Thrombospondins (TSP(s)) are a multigene family of five secreted glycoproteins involved in the regulation of cell proliferation, adhesion and migration. Two members of the TSP family, namely TSP-1 and TSP-2, are also naturally occurring inhibitors of angiogenesis. The aim of the present study was to determine the prognostic significance of the determination of TSP-1 and -2 and their correlation with the angiogenic peptides vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP), as well as with other biological and clinicopathological features investigated. METHODS: We evaluated a series of 168 women with node-negative breast cancer with a median follow-up period of 66 months, not treated with adjuvant therapy. The cytosolic levels of TSP-1 and -2 were determined in the primary tumour by a commercially available immunometric assay. RESULTS: We found that 166 tested tumours had measurable levels of TSP-1 and -2 protein (median value 5.978, range 0.579-31.410 ng/mg of protein). On the basis of Spearman's rank correlation coefficient, a weak inverse association of TSP-1 and -2 with tumour size and cathepsin D was found. Moreover, principal component analysis on ranks evidenced a poor association between TSP-1 and -2, VEGF and TP. The results of the clinical outcome were analysed by both univariate and multivariate [for relapse-free survival (RFS) only]) Cox regression models. TSP-1 and -2 were not significant prognostic factors in univariate analysis for either RFS (p = 0.427) or overall survival (p = 0.069). To investigate the 'angiogenic balance hypothesis', bivariate analyses were performed to investigate the interactions of TSP-1 and -2 with VEGF, TP or p53, but none were included in the selected models. Finally, in multivariate analysis for RFS a baseline model, previously defined in a larger case series and inclusive of VEGF, TP and their interaction was adopted. It was highly significant (p = 0.002, Harrell c statistic value of 0.703); but when TSP-1 and -2 were added, their contribution was negligible (p = 0.731, Harrell c statistic value of 0.705). CONCLUSIONS: The results of this study suggest that TSP-1 and -2 do not provide additional prognostic contribution to the joint effects of VEGF and TP. In the series of node-negative breast cancer patients investigated, determination of the angiogenic peptides VEGF and TP gave significant prognostic information. On the contrary, TSP-1 and -2, potential naturally occurring negative regulators of angiogenesis, lacked prognostic value.

Biomarkers, Tumor↗

PubMed2001

Angiogenesis and angiogenesis inhibitors: a new potential anticancer therapeutic strategy.

Tumor cells cannot grow as a mass above 2 to 3 mm3 because diffusion is insufficient for oxygen and glucose requirements, unless the tumor induces a blood supply. This mechanism of induction of a new blood supply from pre-existing vascular bed is called angiogenesis. Furthermore, tumor invasiveness and metastasis require neovascularization. In fact, recent published studies suggest that acquisition of the angiogenic phenotype is a common pathway for tumor progression and neovascularization is linked with other molecular steps leading to tumor progression. Angiogenic process is a complex multi-step cascade under the control of positive and negative soluble factors. A paracrine interaction occurs between tumor and endothelial cells. Angiogenesis involves: endothelial cell proliferation, migration and tubule formation with associated changes in the extra-cellular matrix, allowing subsequent new vessel growth toward the tumor. Each of the above steps may represent a target for antiangiogenic therapy. Antiangiogenesis is to be distinguished from direct targeting and destruction of tumor vasculature (vascular targeting). Inhibition of angiogenesis represents one of the more promising, new approaches, to anticancer treatment and its already in early clinical trials. This review takes into consideration: (i) the biological mechanism underlining angiogenesis process; (ii) the method to assess tumor angiogenesis activity; (iii) inhibition of angiogenesis as an anticancer therapy; (iv) the methodology for the clinical development of angiogenesis inhibitors, that should be considered biological response modifiers; (v) some angiogenesis antagonists that are in development and leader compounds that are under clinical trial.

Angiogenesis Inducing Agents↗

PubMed2001

Thalidomide: an old sedative-hypnotic with anticancer activity?

Thalidomide is a synthetic derivative of glutamic acid with sedative-hypnotic activity, which caused devastating teratogenic effects in the 1960s. This paper reviews the possible mechanisms of its teratogenic effect, its new therapeutic indications, the proposed mechanisms for its antitumor activity and, finally, reviews published studies of its application in oncology. Current data demonstrates that thalidomide is clinically promising in multiple myeloma, glioblastoma multiforme and renal cell cancer. Furthermore, a beneficial effect of the drug has been proposed in cancer-related cachexia, which merits further investigation. Well-designed, randomized studies are warranted to establish the possible indications of thalidomide as an antitumor compound.

Animals↗

PubMed2000

Behaviour of metastasis in relation to vascular index in patients with node-positive breast cancer treated with adjuvant tamoxifen.

Some experimental studies suggested that one possible oestrogen-receptor-unrelated mechanism of action of tamoxifen involves inhibition of angiogenesis. We evaluated the correlation of the degree of vascularisation of the primary tumour and we assessed it by using the panendothelial marker anti-CD31 and immunohistochemistry with microvessels count, performed at the vascular 'hot spot' of each single cancer, with the risk of recurrence in time. A cohort of 176 consecutive patients with node-positive invasive breast cancer treated with adjuvant tamoxifen (30 mg/daily for 3 years) and a median follow-up of 72 months was studied. Sixty-two patients developed metastasis (30 visceral, 18 skeletal and 14 in soft tissues) during the time of observation. The study of the hazard function for metastasis was performed by a generalized linear modelling approach with a binomial error according to Efron. The risk of first recurrence was strictly associated with vascular index, having the patients with the highest microvessel counts the highest risk of metastasis during all the period of observation. We did not find an interaction of vascularity with oestrogen receptor (ER) status. However, in the subgroup of patients with ER-positive tumours the hazard of metastasis was almost constant in time, while in that with ER-negative tumours it increased rapidly up to 20 months and, thereafter, decreased sharply. The results of our study are an indirect evidence that the patients with highly vascularized breast cancers may gain poor benefit of adjuvant tamoxifen and, therefore. that this antioestrogen is unlikely to retain a clinically relevant antiangiogenic activity in human breast cancer. Our data need confirmation by a prospective randomized clinical trial.

Antineoplastic Agents, Hormonal↗

PubMed2000

TNP-470 and recombinant human interferon-alpha2a inhibit angiogenesis synergistically.

The hypothesis that the combination of two known antiangiogenic agents TNP-470 and interferon (IFN)-alpha exerts synergistic effects has been investigated in vitro and in vivo. In vitro, TNP-470 and recombinant human IFN-alpha2a (rhIFN-alpha2a) resulted in a dose-dependent inhibition of proliferation of human umbilical vein endothelial cells (HUVECs) and EA.hy926 endothelial cells. Compared with the two agents used singly at their lowest or ineffective doses, combined treatment with the same doses inhibited more intensely in the absence of cytotoxicity and displayed similar behaviour on cell chemotaxis and capillary morphogenesis on Matrigel. However, the secretion of matrix metalloproteinase 2 (MMP-2) and MMP-9 was not influenced by the two agents, either alone or in combination, even when they were applied at their lowest efficacious doses or at higher cytotoxic doses. Experiments in vivo with the chick embryo chorioallantoic membrane (CAM)-sponge assay revealed the same dose-dependent inhibition and synergy. As the basic fibroblast growth factor (bFGF)-induced angiogenesis in the CAM-sponge model was strongly inhibited by the combined treatment, TNP-470 and rhIFN-alpha2a would appear to exert antiangiogenesis synergistically, perhaps by interfering with the bFGF-mediated pathway.

Angiogenesis Inhibitors↗

PubMed2000

Gemcitabine plus vinorelbine in advanced non-small cell lung cancer: a phase II study of three different doses. Gem Vin Investigators.

Our aim was to study the activity and toxicity of the gemcitabine plus vinorelbine (Gem Vin) combination and to identify the optimal dose. Previously untreated patients aged < 70 years, with stage IV or IIIb (not candidates for radiotherapy) non-small cell lung cancer were eligible. Studied dose-levels of Gem Vin, administered on days 1 and 8 every 3 weeks, were (mg m(-2)): level I = 1000/25; level II = 1200/25; level III = 1000/30; level IV = 1200/30. A feasibility study was performed at each dose-level, followed by a single-stage phase II study. Dose-level IV was unfeasible because of grade 4 neutropenia. Overall, out of 126 patients enrolled in phase II studies, there were one complete and 32 partial responses (response rate 26%: 95% CI 18-34%). Response rates were 27.9%, 21.4% and 29.3% at levels I, II and III, respectively. The treatment was well tolerated. Toxicity was less frequent and severe at level I. Overall median survival was 33 weeks (95% CI 28-40). Descriptive quality of life analysis showed that patients with a worse baseline global health status score tended to drop out of the study earlier than those with a better score. Gem Vin is feasible at different doses. It is sufficiently active and well tolerated. A phase III study to compare the effect on quality of life of Gem Vin (level I) vs cisplatin-based chemotherapy is ongoing.

Adult↗

PubMed2000

The long styloid process syndrome or Eagle's syndrome.

Eleven cases of Eagle's syndrome or long styloid process syndrome are presented. It is a rare entity, which is not commonly suspected in clinical practice. Symptoms were dull and persistent pharyngeal pain, dysphagia, and facial pain. In addition to careful clinical examination, the use of plain radiographs, orthopantomograms or CT scan has allowed accurate preoperative diagnosis of this syndrome. Surgical treatment has positively resolved the symptoms in these cases. The International literature is discussed regarding anatomy, symptoms and treatment of the long styloid process syndrome.

Adult↗

PubMed2000

A unique case of eccrine porocarcinoma with pulmonary lymphangitis and pericardial involvement: biological characterization and clinical aggressiveness.

A unique case of eccrine porocarcinoma with pulmonary lymphangitis and pericardial involvement is reported. The clinical course was aggressive, leading to the death of the patient a few months after diagnosis. Certain pathologial markers of clinical aggressiveness were retrospectively investigated: p53 and Ki-67 expression were determined by means of immunohistochemistry. Angiogenesis was assessed by determination of intratumor microvessel density at the vascular 'hot spot' with the anti-CD34 monoclonal antibody and quantitative analysis using computerized image analyzer. Both primary tumor and metastatic lymph node presented immunostaining for p53 and Ki-67, with a higher degree of vascularization in the secondary lesions compared to the primary tumor. Our findings suggest a correlation between tumor vascularization and clinicopathological parameters of aggressiveness in malignant eccrine porocarcinoma. Taking into account the disappointing results of current treatments for metastatic eccrine porocarcinoma, the assay of microvessel density may be helpful in selecting the patients of high risk for recurrence or death who may benefit of anti-angiogenic therapies.

Acrospiroma↗

PubMed2000

Prognostic value of vascular endothelial growth factor in breast cancer.

Angiogenesis, the process leading to the formation of new blood vessels from a preexisting vascular network, is necessary for tumor growth, invasion, and metastasis. Data from experimental and clinical studies indicate that breast carcinoma is an angiogenesis-dependent tumor. Most retrospective studies evaluating the prognostic value of determination of intratumoral microvessel density (IMD) at the vascular "hot spot" (a surrogate marker of angiogenesis) found that IMD is a significant and independent prognostic indicator in patients with both node-negative and node-positive breast cancers. More recently, the expression of certain endothelial growth factors has been tested. Among these, vascular endothelial growth factor (VEGF), the most potent endothelial cell mitogen and also a regulator of vascular permeability, is emerging as a powerful new prognostic tool. Eight of the nine published retrospective studies reported that VEGF is significantly associated with relapse-free survival, overall survival, or both. Patients with early stage breast cancer who have tumors with elevated levels of VEGF have a higher likelihood of recurrence or death than patients with low-angiogenic tumors, even if treated with conventional adjuvant therapy. High levels of VEGF can differentiate the subgroups of patients with breast cancer with poor prognosis who benefit minimally from conventional adjuvant therapy but who may benefit from validated anti-VEGF treatments.

Biomarkers, Tumor↗

PubMed2000

Expression of vascular endothelial growth factor can predict event-free survival in stage II colon cancer.

The usefulness of chemotherapy in patients with stage II disease continues to be debated. Biological prognostic factors may allow further insight into the optimal treatment strategy for patients with node-negative disease. Vascular endothelial growth factor (VEGF) seems to be essential for angiogenesis and for the growth of colorectal cancer. Recently, it was shown able to predict disease recurrence in patients with stage II colon cancer. Specimens of surgically resected colon cancer were immunostained for VEGF. Consecutive patients referred to the study institutions were considered eligible for this study. The main inclusion criteria were stage II tumor, sufficient tumor material, and adequate follow-up information. Analysis was performed on 121 patients. The recurrence rate in the patients with VEGF-positive tumors was 50% (18 of 36 patients), which was significantly higher than that observed in patients with VEGF-negative tumors [11.7% (10 of 85 patients); P = 0.001]. Also the degree of VEGF immunoreactivity was significantly higher in 28 relapsing patients compared with 93 disease-free patients (mean VEGF score, 2.84 0.38 versus 0.66 +/- 0.17; P = 0.0001). VEGF may be used in a clinical setting to identify patients at high risk for relapse who may benefit from adjuvant treatment including new therapeutic strategies such as monoclonal antibody neutralizing VEGF.

Adult↗

PubMed2000

Cutaneous infection caused by Serratia marcescens.

An 86-year-old woman presented with a chronic granulomatous skin lesion on the dorsal aspect of her left hand. Histologic examination showed pseudoepitheliomatous hyperplasia and a dense dermal infiltrate largely composed of lymphocytes and histiocytes. Abscess formation and fibroblastic proliferation were also present. Use of Fite, Giemsa, and periodic acid-Schiff stains did not show specific organisms. The gram-negative bacillus Serratia marcescens was the only microorganism isolated from all cultures performed. Trimethoprim-sulfamethoxazole, 960 mg every 12 hours for 20 days (orally), was given and resulted in complete disappearance of the lesion and negative culture findings. Cutaneous infection by S marcescens may represent a distinctive entity, whose clinical and possible pathogenic features are presented here.

Aged↗

PubMed1999

Left atrial filling volume can be used to reliably estimate the regurgitant volume in mitral regurgitation.

OBJECTIVES: The objective was to analyze the accuracy and diagnostic value of the estimated regurgitant volume of mitral regurgitation using 1) left atrial volume variation during ventricular systole (left atrial filling volume) and 2) the percent of systolic pulmonary vein velocity integral compared with its total. BACKGROUND: Left atrial filling volume (LAfill), which represents the atrial volume variation during ventricular systole, has been used for the assessment of mitral regurgitation severity. A good correlation with invasive semiquantitative evaluation was found, but with an unacceptable overlapping among grades. The reason could be the absence of information concerning the contribution of blood entering into the left atrium from the pulmonary veins. METHODS: Doppler regurgitant volume (Dpl-RVol) (mitral stroke volume - aortic stroke volume) was measured in 30 patients with varying degrees and etiological causes of mitral regurgitation. In each patient atrial volumes were measured from the apical view, using the biplane area-length method. The systolic time-velocity integral of pulmonary vein flow was expressed as a percentage of the total (systolic-diastolic) time-velocity integral (PVs%). These parameters were used in this group of patients to obtain an equation whose reliability in estimating Dpl-RVol was tested in a second group of patients. RESULTS: In the initial study group, with linear regression analysis the following parameters correlated with Dpl-RVol: end-systolic left atrial volume (R2=0.37, p=0.0004); LAfill (R2=0.45, p < 0.0001); PVs% (R2=0.56, p < 0.0001). In multiple regression analysis the combination of LAfill and the percent of the systolic pulmonary vein velocity integral (PVs%) provided a more accurate estimate of regurgitant volume (R2=0.88; SEE 10.6; p < 0.0001; Dpl-RV=6.18 + (1.01 x LAfill) - (0.783 x PVs%). The equation was subsequently tested in 54 additional patients with mitral regurgitation with a mean Dpl-RVol 27+/-37 ml. Estimated regurgitant volume and Dpl-RVol correlated well with each other (R2=0.90; SEE 12.1; p < 0.0001). In the test population, the equation was 100% sensitive and 98% specific in detecting a regurgitant volume higher than 55 ml. CONCLUSIONS: Left atrial filling volume and pulmonary vein flow give a reliable estimate of regurgitant volume in mitral regurgitation.

Adult↗

PubMed1999

A phase II study of Tomudex alternated with methotrexate, 5-fluorouracil, leucovorin in first-line chemotherapy of metastatic colorectal cancer.

PURPOSE: This multicenter phase II study was designed to assess the efficacy of the alternating schedule of tomudex with methotrexate (MTX)/5-fluorouracil (5-FU)/leucovorin (LV) in first-line chemotherapy for metastatic colorectal cancer. PATIENTS AND METHODS: Patients with histologically proven metastatic colorectal cancer and at least one bidimensionally measurable lesion, aged 18-70, with performance status < or = 2, normal baseline biological values, and no prior chemotherapy, were selected. Treatment was tomudex 3 mg/m2 and, after two weeks, MTX, 200 mg/m2 by 30' infusion after hydration with 1500 ml saline solution, followed on day 2 by 5-FU, 600 mg/m2 and leucovorin, orally, 15 mg for six times every 6 hours, beginning 24 hours after MTX. Cycles were repeated every four weeks. Tumor response assessment was performed after three cycles. RESULTS: Thirty-four patients were enrolled in this study, of whom twenty-four had liver metastases, nine local relapse, five lymph node involvement, four lung metastases, and three peritoneal carcinomatosis. Four patients achieved objective responses (one complete and three partial), for an overall response rate of 12% (95% CI: 0%-22%). Twelve patients had stable disease and 18 progressed on therapy. Median survival for all patients was 13 months. Two patients experienced grade 3 WHO neutropenia while hepatotoxicity was reported in 13 patients (6 grade 1, 3 grade 2, 3 grade 3, 1 grade 4), suggesting that this combination could increase hepatic toxicity in comparison to tomudex or MTX/5-FU alone. CONCLUSIONS: Our results suggest that this regimen does not warrant further investigation in advanced colorectal cancer patients, at least not with this schedule and doses.

Adenocarcinoma↗