Tenascin-C in primary malignant melanoma of the skin.

AIMS: To investigate the expression and the prognostic role of glycoprotein Tenascin-C (Tn-C) in primary melanoma of the skin. METHODS AND RESULTS: The immunohistochemical expression of Tn-C was studied in 98 primary melanomas and related to inflammation, invasion, and patient outcome. Patients were followed up for disease recurrence for 0.04-7.4 years (median 3.9) and for survival for 0.5 to 12.1 years (median 9.3). The expression of Tn-C was evaluated for each tumour invasion border; the stromal and intracytoplasmic Tn-C of the melanoma islets were also recorded. Tn-C is widely expressed in primary melanoma samples, the staining pattern varying from focal to diffuse in different parts of the tumour. No correlation existed between intensity of Tn-C staining and inflammation. No stromal Tn-C was detected at the upper dermal lateral border in 12 patients, nor at the deep, dermal or subcutaneous border in 14 patients. These patients showed better disease-free survival (DFS) than did those cases with focal or diffuse staining (P = 0.06, P = 0.05). Also, absence of intracytoplasmic Tn-C was a beneficial prognostic factor for DFS (P = 0.04). In multivariate analysis, tumour ulceration and intracytoplasmic Tn-C expression of melanoma cells were independent adverse prognostic factors for DFS. CONCLUSIONS: In primary melanoma of the skin, absence of Tn-C in the stroma of invasion fronts and within tumour cells seems to be related to a more benign disease behaviour with a lower risk of developing metastases.

Prognosis of primary melanoma.

MATERIALS AND METHODS: To investigate the prognosis of primary melanoma, we studied a Finnish population of 298 primary melanoma patients, the majority with stage I or II tumours. The median clinical follow-up (4.8 years) was acquired from the patients' records, and the overall survival thereafter was collected from patient registries. The median follow-up for overall survival was 9.5 years. RESULTS: The overall survival rate was 66.8%. 24.5% developed metastasis, 17.8% died of melanoma, and 15.4% died of some other cause. Surgical margins had no effect on survival. In univariate analysis the most significant prognostic factors for disease-free and overall survival were stage of tumour (p < 0.0001), thickness of tumour (p < 0.0001), depth of tumour invasion (p < 0.0001) and tumour ulceration (p = 0.0005, p < 0.0002). Ulceration was an unfavorable prognostic marker. Younger patients had better survival outcomes than older ones (p = 0.04). Accordingly, in the multivariate Cox model the independent prognostic factors for both disease-free and overall survival were stage of tumour and thickness of tumour. Tumour location on trunk was an independent adverse prognosticator for overall survival. CONCLUSION: We conclude that the prognosis of primary melanoma has improved in Finland in the last decades being in line with a global tendency.

Financial compensation for radiotherapy-related adverse events in a judicial system where proof of medical negligence is not required.

PURPOSE: To examine the frequency of adverse events related to radiation therapy that lead to financial compensation in a judicial system that is not based on litigation in court but on statutory insurance where proof of medical negligence is not required for obtaining compensation. METHODS AND MATERIALS: In Finland, an injured patient does not sue through the courts, but submits an insurance claim to the Patient Insurance Association. Proof of medical negligence is not required for obtaining compensation. We reviewed all filed claims associated with radiotherapy presented to the Patient Insurance Association from May 1987 to January 1999. During this time period, 1,732,000 patient visits to radiation therapy units were made, and the estimated number of radiotherapy treatments was 86,600. The data collected included descriptions of the adverse events, examination of the radiation therapy procedures followed, assessment of the causal relation of the event to radiotherapy by the therapists involved and by independent reviewers, and the sums used for compensation. RESULTS: Only 102 patients (about 0.1%) had filed a claim for financial compensation, and in 18 (0.02%) cases the claim led to compensation. The mean national annual expenditure used for compensation was $35,200, and the sums paid in single cases ranged from $310 to $287,430 (median, $1,970). The expenditure used for compensating adverse radiation events was about $4 per treated patient, which is about 0.3% of all radiation therapy costs. CONCLUSIONS: The frequency of radiation therapy injuries that are financially compensated can remain low in an insurance-based judicial system where no litigation or attorneys are involved.

Patients with severe depression may benefit from buspirone augmentation of selective serotonin reuptake inhibitors: results from a placebo-controlled, randomized, double-blind, placebo wash-in study.

BACKGROUND: Although case reports and open studies have reported augmentation with buspirone to be beneficial in the treatment of depression refractory to treatment with a selective serotonin reuptake inhibitor (SSRI), a recently published randomized, placebo-controlled, double-blind study failed to show superiority of buspirone over placebo in this respect. METHOD: One hundred two outpatients who fulfilled DSM-IV criteria for a major depressive episode and who had failed to respond to a minimum of 6 weeks of treatment with either fluoxetine or citalopram were included in this double-blind, randomized, placebo-controlled study. After a single-blind placebo wash-in period of 2 weeks while continuing their SSRI, the patients were randomly assigned to adjunctive treatment with either buspirone, 10 to 30 mg b.i.d., or placebo for 6 weeks. Patients were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impressions scale (CGI), and visual analogue scales. RESULTS: After the first week of double-blind treatment, there was a significantly greater reduction in MADRS score (p = .034) in the buspirone group as compared with placebo. At endpoint, there was no significant difference between treatment groups as a whole, although patients with initially high MADRS scores (> 30) showed a significantly greater reduction in MADRS score (p = .026) in the buspirone group as compared with placebo. CONCLUSION: Patients with severe depressive symptoms may benefit from augmentation with buspirone. It cannot be excluded that augmentation with buspirone may speed up the antidepressive response of patients refractory to treatment with fluoxetine or citalopram.

MIB-1 immunoreactivity correlates with blood vessel density and survival in disseminated malignant melanoma.

The purpose of our current work was to evaluate the prognostic significance of tumor cell proliferation in advanced metastatic melanomas and to investigate a possible correlation between the proliferation index and blood vessel density in metastatic tissue. Sixty patients with disseminated malignant melanoma treated with four-drug chemotherapy combined with interferon-alpha were included in this study. Proliferative activity and vascularity in metastatic tissues were examined by immunohistochemistry with anti-Ki-67 (MIB-1) and anti-CD31 antibody, respectively. A significant relationship between MIB-1 index and blood vessel number was detected (rho = 0.323, p = 0.013). In survival analysis, the overall survival and disease-free survival were significantly longer (58 and 38 vs. 38 and 17 months) for patients with low MIB-1 immunoreactivity (p = 0.012 and p = 0.023, respectively). Likewise, the low MIB-1 labeling index was associated with the prolonged survival calculated from the initiation of the chemoimmunotherapy (12 vs. 7 months, p = 0.032). In multivariate Cox's proportional hazard analysis, MIB-1 positivity was an independent prognostic factor both for overall survival and for survival after beginning of the chemoimmunotherapy (p = 0.016 and p = 0.029).

The burden of genetic disease and attitudes towards gene testing in Alport syndrome.

We evaluated the burden of Alport syndrome (AS) and the attitudes towards gene testing in patients with AS and their healthy family members from 37 families using a multiple-choice questionnaire. We also evaluated how the disease affected the decision to have children and the information received about the syndrome. A total of 53 individuals responded to this questionnaire. The risk of renal insufficiency and the uncertainty of the prognosis were considered the worst components of AS. Many of the respondents felt that children should be informed about AS as soon as they start asking (45%), preferably by a parent (74%). Almost all of the respondents (96%) had a positive attitude towards genetic research, which in the opinion of the majority should be aimed at better treatment and diagnosis of the disease rather than developing methods for prenatal diagnosis (89% and 75% versus 43%). AS seems to be well tolerated; 28% and 19% of the respondents found abortion acceptable in cases of an affected male and female fetus, respectively. Our study indicates a desire for prenatal tests in order to predict the health of a future child rather than for selective abortion.

Prognostic value of tumour vascularity in primary melanoma.

To investigate the prognostic value of tumour vascularity we studied 84 patients with primary melanomas ranging in tumour thickness (Breslow) from 0.37 to 7 mm and in depth of tumour infiltration (Clark) from II to V. Vascularization was assessed by immunohistochemistry with a CD-31 antibody recognizing endothelial cells. The CD-31-positive vessels were counted and the degree of vascularization was correlated with the survival of the patients. In addition, the relationship between blood vessel density and some histopathological data is discussed. In our study, the multivariate Cox model showed that the only independent variable in disease-free survival was tumour thickness (Breslow classification) and the only one in overall survival was depth of tumour infiltration (Clark classification). In disease-free survival, tumour thickness (Breslow classification) was a clear prognostic factor (P = 0.004) after 4 years' follow-up, as were depth of tumour infiltration (Clark classification) (P = 0.04) and ulceration (P = 0.04). In overall survival, tumour vascularity was the strongest prognostic factor at 4 years, high vascularity being associated with a good prognosis (P = 0.06). Clark classification was also a prognostic factor (P = 0.02) in overall survival. We conclude that high vascularization is associated with a better prognosis but is not an independent prognostic indicator.

Prognostic value of tumour vascularity in metastatic melanoma and association of blood vessel density with vascular endothelial growth factor expression.

Tumour angiogenesis is essential for tumour growth and metastasis. Several lines of evidence indicate that vascular endothelial growth factor (VEGF) is a major regulator both of physiological and pathological angiogenesis. In this study we assessed the blood vessel density and VEGF expression of 94 melanoma metastases of 70 patients by immunohistochemistry, utilizing antibodies against human platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) and VEGF. The number of blood vessels ranged from 4 to 131 vessels/high power field (HPF), with a mean value of 32 vessels/HPF (+/-21) and a median of 29 vessels/ HPF. Survival since diagnosis of the primary disease and from the start of chemoimmunotherapy, as well as the disease-free survival period, was significantly shorter in the high vascularity group of patients compared with the low vascularity group (P< 0.05 and P< 0.01, respectively). A high overall expression of VEGF in the metastatic melanoma samples was observed. The degree of VEGF expression appeared to have a strong association with the blood vessel density (P= 0.017). This study demonstrates the clinical role of tumour vascularity in the prognosis of patients with metastatic melanoma. In addition, the strong association between vascularity and VEGF expression suggests a crucial role for this growth factor in the neovascularization of metastatic melanoma.

Regimens with or without interferon-alpha as treatment for metastatic melanoma and renal cell carcinoma: an overview of randomized trials.

The effect of interferon-alpha (IFN-alpha) as single agent or in combination in the treatment of metastatic malignant melanoma (MM) or of advanced renal cell carcinoma (RCC) has been widely explored in phase II trials. To evaluate the net benefit of IFN-alpha therapy in these diseases, we performed a meta-analysis comprising all available randomized trials comparing regimens with or without IFN-alpha. Data were obtained from the Medline data base, and from the data bases at the National Cancer Institute, Schering-Plough, and Hoffmann-La Roche. A total of six published and five unpublished studies on metastatic MM, as well as six published and two unpublished studies on advanced RCC, comprising altogether 1,164 and 525 patients, respectively, fulfilled our criteria. In MM, the overall response rate for the IFN-alpha-containing regimens was 24% (range, 10-46%), compared with 17% (range, 5-30%) for those without IFN-alpha. In RCC, the overall response rate for IFN-alpha-containing regimens was 14% (range, 4-33%), and 8% (range, 3-27%) for those without IFN-alpha. A meta-analysis showed that regimens including IFN-alpha improved response rates compared with regimens without IFN-alpha. The pooled odds ratio (OR) for improved response with IFN-alpha in metastatic MM was 0.65 [95% confidence interval (CI) 0.48 to 0.87], and in advanced RCC the OR was 0.47 (95% CI 0.26-0.85). In five metastatic MM trials and three RCC trials, enough data on survival were reported to estimate a pooled 1-year OR for survival. The pooled OR for improved survival with IFN-alpha was 0.69 (95% CI 0.50-0.94), and 0.46 (95% CI 0.28-0.75), respectively. The data on both metastatic MM and advanced RCC indicate that better response rates and prolonged survival can be achieved with regimens including IFN-alpha. The clinical relevance of these findings will be discussed.

Second cancer among long-term survivors from Hodgkin's disease.

PURPOSE: There are limited data on the frequency of second cancer among long-term survivors from Hodgkin's disease. The aim of this study was to determine the frequencies of second cancers, and their locations with respect to radiotherapy portals. METHODS AND MATERIALS: Medical records of 202 consecutive patients who survived at least for 5 years after treatment for Hodgkin's disease, and who were treated with radiotherapy in Helsinki University Central Hospital between 1970 and 1979, were reviewed. Survival data were collected also from the Finnish Cancer Registry and records of other hospitals. The median follow-up time of the patients still alive was 22 years (range, from 13 to 26). All patients received radiotherapy; in addition, 65 patients received MOPP and 3 received MOPP and ABVD. RESULTS: During the follow-up consisting of 4020 person-years, 27 patients developed a second cancer. The cumulative risk for a second cancer was 17% (95% CI, from 10.4 to 23.1 %) at 20 years after the diagnosis of Hodgkin's disease. Of the 26, 20 (77%) solid second cancers were found within or adjoining the irradiated fields, and the 20-year cumulative risk for a second cancer within the irradiated fields was 12% (6.3-17.5%). The most common second cancers were lung (n = 7) and breast (n = 4) cancer. In a multivariate analysis, predictive factors for a second cancer were: age at diagnosis greater than the median (30 years, relative risk, 3.97, 1.6-12.5), treatment for recurrent lymphoma (RR, 2.75, 1.3-6.7) and primary treatment without splenectomy (RR 4.31, 1.7-11.0). However, portal size and inclusion of chemotherapy as part of the primary treatment were not significantly associated with second cancer in a univariate analysis. CONCLUSION: Patients treated with radiotherapy for Hodgkin's disease have a considerable risk for a second cancer in long-term follow-up. The majority of second cancers arise within or next to the irradiated portals, and particular attention should be paid to the irradiated sites in posttreatment follow-up.

Prognostic value of biomarkers in malignant melanoma.

Biopsy specimens from 12 patients with metastatic melanoma were longitudinally analysed to evaluate changes in proliferation activity and CD4+/CD8+ ratios during the course of the disease. The primary tumours of the patients who subsequently had metastatic disease were also each matched with tumours from two controls whose disease remained localized, and were compared with regard to tumour proliferation. Immunohistochemistry was performed using the avidin-biotin complex (ABC) immunoperoxidase technique, using bcl-2, p53, mdm-2 and Ki-67 as the primary monoclonal antibodies, and the percentage of positively stained melanocytic cells was calculated. Frozen sections were also available from metastatic lesions excised from eight of our patients before treatment initiation and at the time of disease progression. These specimens were prepared for microscopy, and quantitative characterization of CD4+ (OKT 4a) and CD8+ (OKT 8) cells was performed. Compared with the localized melanomas bcl-2 expression was higher in those primary melanomas that later metastasized (P = 0.068, Wilcoxon; P = 0.038, median test). Mdm-2 and Ki-67 expression did not differ in the primary tumours of patients and controls, but a statistically significant trend was observed towards increasing expression with the progression of the disease (two-sided exact P-values: 0.04 and 0.05, respectively). Patients with a low Ki-67 index in their first metastasis had a better prognosis when compared with patients with high indexes (P = 0.008, log-rank). Furthermore, most patients with decreasing CD4+/CD8+ ratios had increasing p53 immunoreactivity. Our findings suggest that Ki-67 and bcl-2 may be useful for predicting the prognosis of melanoma patients. Mdm-2 is a new but promising marker in melanoma and deserves further evaluation.

Urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion during multiple-day high-dose chemotherapy.

Highly emetogenic drugs such as cisplatin induce an increase in the urinary 5-hydroxyindoleacetic acid (5-HIAA) level, the main metabolite of serotonin (5-HT), within the first 24 h following a single infusion, thus providing a possible cause for acute emesis and an explanation for the action of 5-HT3 antagonists. No further excretion peaks have been observed, suggesting that additional or serotonin-independent mechanisms cause delayed emesis. Our aim was to study the mechanisms behind emesis seen during a highly emetogenic chemotherapy regimen given as a continuous infusion over several days. Seven women treated with a 4-day high-dose chemotherapy (HDCT) regimen for breast cancer entered the study. Pooled urine samples were collected prior to and during chemotherapy for determining 5-HIAA excretion. An excretion peak in the urinary 5-HIAA level was observed within the first 24 h with no further peaks thereafter. Thus, the mechanisms behind the emesis experienced during this highly emetogenic multiple-day chemotherapy regimen from days 2-3 onwards would appear to be at least partially serotonin independent and would not be expected to be completely relieved by 5-HT3 antagonists alone.

Tumor-infiltrating lymphocytes in patients with metastatic melanoma receiving chemoimmunotherapy.

Biopsies from 12 patients with progressive metastatic melanoma were excised during chemoimmunotherapy to evaluate and characterize the local immune response in situ in the metastases. These findings were compared with the distribution of lymphocyte subsets in the peripheral blood and correlated with the clinical data. The biopsy specimens were prepared for microscopic procedures, and the fields for analyses were chosen to involve a section of both stroma and the tumor area. The number of each lymphocyte subset was calculated and compared with the number of melanoma cells in the field, allowing quantitative characterization of the immune reaction in different samples. Comparison of the lymphocyte subsets of peripheral blood and metastatic lesions revealed equal relative amounts of CD4+ (helper) and CD8+ (suppressor/cytotoxic) cells in both tissues, but 10- to 20-fold fewer CD56+ (natural killer, NK) cells, and a total absence of CD20+ (B) cells in the metastatic lesions. The prognosis of patients was viewed at different stages of the disease. The median survival from the primary diagnosis of patients with a tumor CD4+/CD8+ ratio above the median was 4.4 years compared with 2.4 years for those with a ratio below the median (Logrank, p = 0.02). In the multivariate analysis, the only statistically significant prognostic factors were the CD4+/CD8+ ratio of the tumor (p = 0.010) and of the peripheral blood (p = 0.020). Monitoring of CD4+ and CD8+ cells may thus provide valuable information about the state of host defense, with a high CD4+/CD8+ ratio indicating more favorable prognosis.

DNA flow cytometry and the outcome of chemoimmunotherapy in metastatic melanoma.

DNA ploidy and S-phase fraction (SPF) were measured by flow cytometry on tumours from 80 patients with disseminated malignant melanoma. All patients received a four-drug chemotherapy regimen (dacarbazine, vincristine, bleomycin and lomustine) plus interferon. Specimens were taken for analysis from the latest metastases biopsied before the start of the treatment. In 13 patients we also analysed sequential samples taken after the treatment at the time of progression. DNA aneuploidy was observed in 65% of the patients. Among the 40 responders there were 26 with aneuploid tumours (65%). Aneuploidy did not reach statistical significance as a prognostic sign in the unstratified study population, but when stratified by response groups, DNA aneuploidy was a significant prognostic factor for a better response (P = 0.04). SPF could be calculated in 76 tumours. Out of 40 responding patients (complete or partial response), 23 had tumours with an SPF higher than the median. Accordingly, patients with a high SPF survived longer than those with a low SPF, with median survival times of 9.8 months and 8.7 months, respectively (P = 0.18). We conclude that DNA aneuploidy and a high SPF are associated with longer survival in patients with disseminated melanoma treated with a chemoimmunotherapy regimen. Based on our findings we claim that, among patients receiving chemoimmunotherapy, high SPF and aneuploidy are not signs of unfavourable prognosis, which is in contrast to previous observations in melanoma patients receiving heterogeneous therapy.

Vascularity and prognosis of metastatic melanoma.

The clinical role of vascularity was examined in metastatic melanoma, analyzing the correlation of the blood vessel density and prognosis. Our study included 51 specimens of metastatic melanoma tissue samples from 31 patients treated with combined chemo-immunotherapy. PECAM-1 (CD31) was used for assessing vascularity by immunohistochemical staining. On the basis of blood vessel counts, patients were classified into 2 main groups: low and high vascularity. A higher blood vessel density was found to be associated with shorter survival, estimated from the primary diagnosis of the disease (38 months), compared with patients with low blood vessel counts (68 months). A similar tendency was observed when vascularity was correlated to the survival period after the detection of the first metastases (13 vs. 30 months) and with survival since the initiation of chemo-immunotherapy (8 vs. 16 months). When vascularity and some common prognostic factors, such as age, sex, DNA ploidy and WHO tumor response, were used for a Cox multivariate analysis, vascularity turned out to be the most significant independent prognostic factor. Our results suggest that counting the blood vessels identified by immunohistochemical staining for the endothelial cell-specific CD31 is a powerful predictor for prognosis in patients with metastatic melanoma and should be considered when selecting patients for therapy.

A low proportion of BRCA2 mutations in Finnish breast cancer families.

One hundred breast cancer families were identified at the Helsinki University Central Hospital in Finland and were screened for germ-line mutations in the coding regions and splice boundaries of the BRCA2 gene. Eight families (8%) were found to carry five different mutations, all of which are predicted to prematurely truncate the protein product. These BRCA2 families have early-onset breast cancer (mean and median age = 49 years), with four of the eight families including ovarian cancer but with no families including male breast cancer. A wide spectrum of other cancers also is seen in these families. Three mutations were identified in more than one family, and haplotype analysis in the families suggested a common founder for each recurrent mutation. One recurrent mutation, 999del5, previously has been noted as a common mutation in Iceland. The relationship between the Icelandic 999del5 mutation and the Finnish 999del5 mutation was explored by comparison of families from both countries. A common haplotype covering a minimal region intragenic to the BRCA2 gene was shared between the Icelandic and the Finnish mutation carriers.

Can the CD4+/CD8+ ratio predict the outcome of interferon-alpha therapy for renal cell carcinoma?

BACKGROUND: In a randomised trial, patients with renal cell carcinoma (RCC) treated with vinblastine alone or in combination with interferon-alpha (IFN) were monitored for peripheral blood lymphocyte subsets (CD4+ and CD8+) prior to and during treatment to elucidate the influence of IFN on these cells, and the association of the change in the CD4+/CD8+ ratio with treatment outcome. PATIENTS AND METHODS: Blood samples were systematically obtained from 30 patients receiving either vinblastine or vinblastine + IFN-alpha-2a. Flow cytometry was used to detect CD4+ (T-helper) and CD8+ cells (T-suppressor) with monoclonal antibodies. RESULTS: Increasing CD4+/CD8+ ratios were seen in 10 of 17 patients in the vinblastine-IFN group and in 7 of 13 patients in the vinblastine group. Two of three patients achieving a complete response with the vinblastine-IFN treatment showed a dramatic increase in CD4+/CD8+ ratio concomitantly with regression of all metastases. Those treated with vinblastine-IFN who showed an increasing ratio had a better median survival (not reached at 28 months of follow-up) compared to those with a decreasing ratio (6.3-month survival) (P = 0.0037, log-rank). No such difference occurred in patients treated with vinblastine alone. In the multivariate analysis, the increase in CD4+/CD8+ ratio was the most important prognostic factor. CONCLUSION: In a proportion of patients receiving an interferon-based therapy, IFN seems to influence the host's immune system, resulting in an increased CD4+/CD8+ ratio concomitantly with tumour regression. Changes in the CD4+/CD8+ ratio of patients with metastatic RCC receiving such therapy, may provide valuable prognostic information and a basis for future improvements of immunotherapy.

Stage I non-Hodgkin's lymphoma treated with doxorubicin-containing chemotherapy with or without radiotherapy.

Seventy-six patients with stage I or IE intermediate-grade or immunoblastic non-Hodgkin's lymphoma were treated with a short course of doxorubicin-containing chemotherapy with (n = 58) or without (n = 18) involved field radiotherapy. Chemotherapy consisted of 3 or 4 cycles of M-BACOD or (bleo-)CHOP. Seventy-two (97%) of the 74 evaluable patients achieved a complete response. The 3-year overall survival was 89%, recurrence-free survival 94%, and lymphoma-specific survival 93%. Patients older than 60 years also had a 3-year lymphoma-specific survival rate of as high as 92%. The International Prognostic Index was associated with overall survival (p = 0.04), but not with lymphoma-specific survival (p = 0.18). We conclude that stages I and IE intermediate-grade or immunoblastic non-Hodgkin's Hodgkin's lymphoma is highly curable if treated with short doxorubicin-containing chemotherapy and involved field radiotherapy.

An overview of randomised studies comparing 5-HT3 receptor antagonists to conventional anti-emetics in the prophylaxis of acute chemotherapy-induced vomiting.

Ten years after it was demonstrated in the ferret that cisplatin-induced emesis could be blocked by the selective 5-HT3 receptor antagonist MDL 72222, 5-HT3 receptor antagonists have become routine anti-emetic agents for chemotherapy-induced emesis. However, although in association with highly emetogenic, mainly cisplatin-containing regimens, the use of these agents is well justified, the net benefit of 5-HT3 receptor antagonists in association with moderately emetogenic regimens has not been that well clarified. Here, we present an overview of 30 randomised studies comparing 5-HT3 antagonists with the conventional anti-emetics in the prophylaxis of acute vomiting induced by cytotoxic chemotherapy. A meta-analysis showed that 5-HT3 antagonists reduce the risk of acute vomiting in comparison to conventional anti-emetics both with cisplatin treatments (15 trials; odds ratio 0.60; 95% confidence interval 0.51-0.70) and with moderately emetogenic treatments (11 trials; odds ratio 0.47; 95% confidence interval 0.39-0.58). The risk of acute vomiting seems to be further reduced when 5-HT3 antagonists are combined with dexamethasone.