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Biomedical subjects

A Macciò

Publications and source records attributed to A Macciò.

At least 37 records · Page 2Linked to original sources
PubMed1994

Study of peripheral blood lymphocyte subset distribution and IL-2 receptor (IL-2 R) p55-p75 subunit expression in patients with cancer of different sites.

The aim of the study was to evaluate the subset distribution and the IL-2 R p55-p75 subunit expression on unstimulated and phytohemagglutinin (PHA)-stimulated (at 3-d) peripheral blood mononuclear cells (PBMC), of patients with solid cancers of different sites. Indeed the expression of the two subunits of IL-2 R is an essential prerequisite for the action of the IL-2 on CD8+, CD16+ lymphocytes as effectors in antitumor activity (LAK-cell). The subset distribution (CD3, CD4, CD8, CD16, DR) was assessed by cytofluorometry with specific monoclonal antibodies (MAbs); the p55 (CD25) and p75 subunit expression was evaluated by specific MAb (OKT26a and anti-p75). Ninety patients with advanced cancer (mainly non-small cell lung cancer [NSCLC], head and neck cancer, and gynecological cancer; mean age 55 yr; range 27-80) were studied. Thirty-five age- and sex-matched healthy subjects were studied as controls. Our data show that there is no significant difference in the subset distribution between cancer patients and controls. Furthermore, no difference has been found in the expression of p55 subunits on unstimulated PBMC between cancer patients and controls. No difference has been found in the expression of both p55 and p75 subunits on PHA-stimulated PBMC between cancer patients and controls. Our results can support the rationale for further clinical trials with IL-2 in solid malignancies.

Adult↗
PubMed1994

Preovulatory human follicular fluid in vitro inhibits interleukin (IL)-1 alpha, IL-2, and production and expression of p55 chain IL-2 receptor of lymphomonocytes.

OBJECTIVE: To evaluate the immunoactivity of human follicular fluids (FFs) of ovaries stimulated with exogenous gonadotropins. PARTICIPANTS: Follicular fluids and peripheral blood mononuclear cells (PBMCs) were obtained at the time of ovum pick-up from 15 women (25 to 34 years of age) undergoing gonadotropin stimulation for GIFT. METHODS: The evaluation of the blastic response of PBMC to phytohemagglutinin (PHA), PHA plus recombinant interleukin (IL)-2, and recombinant IL-2 alone was performed by measuring 3H-thymidine (3H-TdR) incorporation by the cells cultured in media with or without FF. The percentage of CD25 expression on PHA-stimulated T lymphocytes was evaluated by flow cytofluorometry. The levels of IL-1 alpha and IL-2 in supernatants from PHA-stimulated PBMC were evaluated by an ELISA. RESULTS: The PBMC blastic response to PHA, to recombinant IL-2 alone, and to PHA plus recombinant IL-2 was suppressed by the addition of FF. However, the percentage of inhibition of 3H-TdR incorporation induced by FF in cultures performed in the presence of PHA alone was significantly higher than that obtained in cultures performed in the presence of PHA plus recombinant IL-2. The percentage of expression of the CD25 on PHA-stimulated lymphocytes was also significantly lower in presence of FF in comparison with the controls. Similarly, the production of IL-1 alpha and IL-2 in culture media of PHA-stimulated PBMC was significantly lower when FF was added in culture medium. CONCLUSIONS: The present data confirm that preovulatory FFs obtained by gonadotropin-stimulated ovaries contain unknown factors that induce immunosuppression. Furthermore, our study explains that the immunosuppressive activity of FF is mediated by the specific inhibition of the production of IL-1 alpha and IL-2 and by the decreased expression of the CD25.

Adult↗
PubMed1993

Evidence that granulosa cells inhibit interleukin-1 alpha and interleukin-2 production from follicular lymphomonocytes.

OBJECTIVE: Relationships between immune and endocrine systems seem to occur in ovarian follicular fluids (FF). Lymphomonocytes have been found in preovulatory follicles and their specific products, cytokines [interleukin-1 (IL1), IL2], were demonstrated to inhibit steroidogenesis. Ovarian steroids, in turn, reduce the cytokine production from immune-competent cells. In the present study we evaluated whether lymphomonocytes are present in FF, and if both their subset distribution and their IL1 alpha and IL2 secretions, after activation with phytohemagglutinin (PHA), are similar to those of peripheral blood. Interferences of IL1 alpha and IL2 production by FF lymphomonocytes caused by isolated granulosa cells were also evaluated. PARTICIPANTS: The study was performed on 86 FFs obtained from follicles containing mature oocytes that were aspirated at the time of ovum pickup from 27 women undergoing controlled ovarian hyperstimulation with exogenous gonadotropins for an in vitro fertilization (IVF) program [IVF-embryo transfer (IVF-ET) or gamete intrafallopian transfer (GIFT)]. RESULTS: Lymphocytes were found in FF. The distribution of CD8+ and CD3+ lymphocyte subsets is equal to that in peripheral blood, but the percentage of CD11b+, CD16+, and CD4+ cells (its trend) is higher in FF than in peripheral blood. The amount of IL2 and IL1 alpha deriving from PHA-activated FF lymphomonocytes is similar to that of peripheral blood PHA-activated lymphomonocytes. Granulosa cells significantly blunt IL2 and IL1 alpha production by FF lymphomonocytes. CONCLUSIONS: These results suggest that preovulation, a migration of lymphomonocytes from the peripheral compartment to the follicle occurs. However, unfavorable effects of IL2 and IL1 alpha, cytotoxic and antisteroidogenetic activities, are counteracted by the products of granulosa cells. The higher amounts of CD11b+, CD16+, and CD4+ in FF suggest that they could be involved in other immune processes.

Adult↗
PubMed1993

[p55 and p75 subunits of the IL 2 receptor, membrane bound and soluble, in peripheral lymphocytes in patients with solid tumors].

The aim of the investigation was to directly study the IL 2 receptor (IL 2 R) and its subunits, p55 and p75 chains, either membrane-bound or soluble, on peripheral blood mononuclear cells (PBMC) of patients with solid malignancies and, indirectly, the same patients' PBMC ability to produce IL 2. Fifty-eight cancer patients, 29 men and 29 women, were studied: their mean age was 57.3 years, range 35-79. Twenty-two healthy age-sex-matched subjects served as controls. The tumors were the most common and the most representative among human cancers, i.e. breast, lung, head and neck, digestive tract and liver, prostate and gynecologic cancers: they were generally in advanced stages and in 23 cases metastatic. The PBMC proliferative response to PHA, PHA plus IL 2 and IL 2 was evaluated along with the response to PHA in presence of anti-p55, anti-p75 monoclonal antibodies, or both. Moreover, membrane-bound IL 2 R, p55 and p75 chains, on PHA-stimulated PBMC were detected, along with soluble IL 2 R in the serum and in the culture supernatants. The conclusions suggest that in solid malignancies: the membrane-bound IL 2 R s, both p55 and p75 chains, are expressed normally, there is an high serum level of soluble IL 2 R, there is a normal release of soluble IL 2 R in culture, and there is an indirect evidence of a lack of IL 2 production. Therefore, no primary impairment of IL 2 R was found in solid tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Functional and surface phenotype study of lymphocyte subsets in peripheral blood and lymph nodes of breast cancer patients.

In an attempt to identify lymphocyte subsets possibly involved in the response to malignant cells, we have studied the lymphocyte surface phenotype by using a panel of monoclonal antibodies on both peripheral blood lymphocytes (PBL) and histologically proven metastatic and nonmetastatic (i.e., "hyperplastic") axillary lymph node lymphocytes (LNL) from eight breast cancer patients. Furthermore, we carried out a functional study by evaluating the response to polyclonal mitogens of the PBL and of the LNL of the same patients. A group of 30 healthy subjects, age and sex matched, were selected as controls for PBL. Six of them, who underwent surgery for nonneoplastic conditions, were selected as controls for LNL. The responsiveness of breast cancer patients' PBL to polyclonal mitogens phytohemagglutinin (PHA) and concanavalin A (Con A) was significantly lower as compared with the control response. The responsiveness of breast cancer patients' metastatic LNL was not different from control LNL for PHA, and it was lower than control LNL for Con A, while the responsiveness of the same metastatic LNL was higher than that of nonmetastatic (i.e., hyperplastic) LNL of patients. Furthermore, the response of hyperplastic LNL was always lower than that of control LNL. The responsiveness of patients' PBL was always lower than that of metastatic LNL, while the responsiveness of patients' PBL vs. hyperplastic LNL was at variance. Regarding the surface phenotype of PBL, there was no difference between those of breast cancer patients and controls concerning the T-cells subsets, while the Leu 7, CD 21 and DR antigens were significantly higher among the breast cancer patients. No significant differences were found between patient metastatic and hyperplastic LNL or between control LNL and patient metastatic or hyperplastic LNL, respectively; only the CD 4 antigen was higher in metastatic than in hyperplastic LNL. A comparison of this surface phenotype between PBL and either metastatic or hyperplastic LNL of breast cancer patients showed values almost constantly significantly higher for PBL vs. either metastatic or hyperplastic LNL, respectively. The results of our study suggest that there is no change in the local-regional immunocompetent cell subsets that may be related to metastasis of breast cancer to regional nodes and to the progression of disease and that circulating T cells in breast cancer include cells expressing activation markers but not showing significant changes in the proportion of entire subpopulations.

Adult↗
PubMed1988

Role of interleukin-2 (IL-2) in cancer-related immune deficiency: in vitro response to IL-2, production of IL-2, and IL-2 receptor expression in patients with advanced cancer.

The aims of the investigation were 1) to determine if there are defects in interleukin-2 (IL-2) regulation on either phytohemagglutinin (PHA)-activated or non-PHA-activated peripheral blood mononuclear cells (PBMC) in cancer patients to ascertain the role of IL-2 in this disease; 2) to carry out preliminary experiments for a direct quantitative evaluation of endogenous IL-2 production by PBMC cultures; and 3) to evaluate the IL-2 receptor expression by PBMC of cancer patients. An assessment of lymphocyte subsets was also performed with monoclonal antibodies in a selected group of patients. A total of 170 patients entered the study. Cancer sites were larynx (48), breast (44), lung (30), colorectal(23), and gynecologic (25). Staging showed in the former three cancer sites predominantly localized or only locally advanced disease and in the latter two sites disseminated disease. PBMC cultures were performed with microtiter plate technique and 3H-thymidine uptake evaluation using polyclonal mitogens, IL-2, and a monoclonal antibody against IL-2 receptor. Our results provided evidence that the cancer patients exhibit a T-cell functional immunodepression, which, to some extent, progresses during tumor growth so that the localized disease shows a low-grade defect and advanced disease a high-grade defect. Our data also clearly suggest that IL-2 deficiency is the primary factor involved in this functional immune impairment. We found no significant defect in the IL-2 receptor expression by PBMC of cancer patients. Our data also seem to support the in vivo therapeutic administration of IL-2 and lymphokine-activated killer cells to cancer patients.

Antibodies, Monoclonal↗
PubMed1987

Peripheral blood lymphocyte response to recombinant and non-recombinant interleukin 2 in previously treated patients with Hodgkin's disease, long-time off-therapy.

13 patients with Hodgkin's disease (HD) previously treated, 9 of whom were long-time (more than 2 yr) off-therapy, were studied for peripheral blood lymphocyte response to interleukin 2 and for lymphocyte subpopulations by means of in vitro cultures and monoclonal antibodies. The aim of the study was to ascertain the role played by interleukin 2 in the impaired cell-mediated immunity of HD patients. The results show a response of peripheral blood mononuclear cells of HD patients to either the T cell-specific polyclonal mitogens PHA and Con A or to the T cell-dependent, although B cell-specific, PWM, most significantly decreased compared to the normal response. As far as the interleukin 2 involvement in HD is concerned, our study suggests: an impaired endogenous interleukin 2 production by T lymphocytes, a most probable deficiency of the interleukin 2 receptor (Tac) expression and 3) a decrease of the number and/or of the function of NK cells no longer responsive in vitro to interleukin 2. The phenotypic analysis of peripheral blood mononuclear cells showed a slight decrease of total T cells (T3+), of the helper/inducer subset (T4+) and of the T4+/T8+ cells ratio. Our data seem to support the rationale for a therapeutical approach with interleukin 2 in controlled clinical trials also in HD patients, according to the experiments in progress in solid tumor patients.

Adolescent↗
PubMed1987

Interleukin 2 (IL 2) relationships with the cancer-related immunodeficiency: in vitro response to exogenous IL 2 by PHA-activated and non PHA-activated peripheral blood mononuclear cells from cancer patients.

The aims of the investigation were: 1) to determine if there are defects in interleukin 2 (IL 2) regulation either on phytohemagluttinin (PHA)-activated or non PHA-activated peripheral blood mononuclear cells (PBMC) in cancer patients, in order to ascertain the role of IL 2 in this disease, and 2) to carry out preliminary experiments for a direct quantitative evaluation of endogenous IL 2 production by PBMC cultures of cancer patients. An assessment of lymphocytes subsets was also performed with monoclonal antibodies in a selected group of patients. A total of 159 patients entered the study. Cancer sites were: larynx, 49; breast, 42; lung (NSC), 25; colorectal, 18; and gynecologic, 25. In the former 3 cancer sites, staging showed localized or only locally advanced disease and in the later 2 sites it showed disseminated disease. Our results provided evidence that the cancer patients exhibit a T cell functional immunodepression, which progresses during tumor growth, so that the localized disease shows a low-grade defect and advanced disease shows a high-grade defect. Our data also clearly suggested that the factor involved with a primary role in this functional immune impairment is the IL 2 deficiency. In our study we have not found a substantial difference of activity between recombinant and nonrecombinant IL 2, although the comparison of the relative activities of the two types of IL 2 is not easy to make, since they are expressed in different ways; however the recombinant one appeared to be slightly more active, probably for the higher purity. Our data also seem to support the perspective of the in vivo therapeutic administration of IL 2 in cancer patients.

Breast Neoplasms↗
PubMed1986

Peripheral blood lymphocyte response to exogenous interleukin 2 by PHA-prestimulated and non-PHA-prestimulated cells in patients with cancer.

The study aims were to assess the response of peripheral blood lymphocytes (PBL) of cancer patients to exogenous Interleukin 2 (IL 2) either by PHA-prestimulated or non PHA-prestimulated PBL, and to carry out preliminary experiments for a direct quantitative evaluation of endogenous IL 2 production by PBL cultures of cancer patients in order to define the actual role of IL 2 in the disease. Analysis of PBL subsets was also carried out with monoclonal antibodies in a selected group of patients. A total of 134 patients entered the study. Cancer sites were: larynx 32, breast 36, lung (NSC) 24, colorectal 17 and gynecologic 25. In the former 3 cancer sites staging showed localized or only locally advanced disease, and in the last 2 sites disseminated disease. Our results provided evidence that cancer patients exhibit a T-cell functional immunodepression, which progresses during tumor growth, so that the localized disease shows a low-grade defect, and advanced disease a high-grade defect. Our data also clearly suggested that the factor involved with a primary role in this functional immune impairment is the IL 2 deficiency. A perspective may be drawn on the therapeutic administration in vivo of IL 2 and IL 2-activated lymphokine-activated killer cells in controlled clinical trials of selected groups of cancer patients.

Cells, Cultured↗
PubMedDate not supplied

Membrane-bound and soluble IL-2 receptors (p55 and p75 chains) on peripheral blood mononuclear cells from patients with solid malignancies.

The aim of the investigation was to study directly the IL-2 receptor (IL-2R) and its subunits, p55 and p75 chains, either membrane-bound or soluble, on PBMC of patients with solid malignancies and, indirectly, the same patients' PBMC ability to produce IL-2. Fifty-eight cancer patients, 29 men and 29 women, were studied: their mean age was 57.3 yr, range 35-79. Twenty-two healthy age-sex-matched subjects served as controls. The tumors were the most common and the most representative among human cancers, i.e., breast, lung, head and neck, digestive tract and liver, prostate and gynecologic cancers: they were generally in advanced stages and in 23 cases metastatic. The PBMC proliferative response to PHA, PHA plus IL-2, and IL-2 was evaluated along with the response to PHA in the presence of anti-p55, anti-p75 monoclonal antibodies, or both. Moreover, membrane-bound IL-2R (p55 and p75 chains) on PHA-stimulated PBMC was detected, along with soluble IL-2R in the serum and in the culture supernatants. The conclusions suggest that in solid malignancies: the membrane-bound IL-2Rs, both p55 and p75 chains, are expressed normally, there is an high serum level of soluble IL-2R, there is a normal release of soluble IL-2R in culture, and there is an indirect evidence of a lack of IL-2 production. Therefore, no primary impairment of IL-2R was found in solid tumors. Moreover, in our study we have found no difference in any parameter studied between patients with and patients without metastases.

Adult↗
PubMedDate not supplied

Results of a dose-intense phase 1 study of a combination chemotherapy regimen with cisplatin and epidoxorubicin including medroxyprogesterone acetate and recombinant interleukin-2 in patients with inoperable primary lung cancer.

Based on the role of cytokines in the pathogenesis of cancer-related anorexia-cachexia and the ability of progestins, such as medroxyprogesterone acetate, to reduce cytokine production and relieve cancer-related anorexia-cachexia symptoms, the authors designed an open, dose-finding phase I study of a combined chemotherapy regimen (cisplatin [CDDP], epidoxorubicin [EPI]), including recombinant interleukin-2 (IL-2) and medroxyprogesterone acetate for patients with stage IIIB to IV inoperable primary lung cancer. The end points were clinical response and toxicity with definition of dose-limiting toxicity and maximal tolerable dose; relief of cancer-related anorexia-cachexia symptoms; the assessment of patient serum levels of IL-1beta, IL-6, tumor-necrosing factor-alpha (TNF-alpha), and soluble IL-2 receptor (sIL-2R). From March to October 1997, 16 patients (M:F ratio, 14:2; mean age, 60.5 years; age range, 41 to 74 years) were enrolled. All patients were evaluable for toxicity and 14 of them for response. The patients were assigned to increasing dose levels of drugs according to a dose-escalation schedule. The weekly schedule consisted of a combination of CDDP given intravenously on day 1, EPI given intravenously on day 1, 1 g/day medroxyprogesterone acetate given orally on days 1 to 7, and recombinant IL-2 1.8 MIU administered subcutaneously on days 2 to 7 plus 300 microg granulocyte-colony stimulating factor support given subcutaneously on days 2 to 5. Administration of medroxyprogesterone acetate began 1 week before the first cycle. Dose escalation of the drugs was as follows: 30 mg x m2 x week(-1) CDDP and 25 mg x m2 x week(-1) EPI (first level, two patients); 30 mg x m2 x week(-1) CDDP and 33 mg x m2 x week(-1) EPI (second level, 2 patients); 40 mg x m2 x week(-1) CDDP and 33 mg x m2 x week(-1) EPI (third level, 6 patients); and 40 mg x m2 x week(-1) CDDP and 40 mg x m2 x week(-1) EPI (fourth level, 6 patients). Six cycles were planned for each patient. The actual dose intensity delivered was more than 80% of the projected dose intensity of all drugs. After six cycles, clinical response (according to World Health Organization criteria), toxicity (according to World Health Organization criteria), Eastern Cooperative Oncology Group (ECOG) performance status, body weight, appetite, and serum levels of cytokines were evaluated. After six cycles, 9 of 14 patients (64.3%) had partial response, 3 of 14 (21.4%) had stable disease, and 2 of 14 (14.3%) had progressive disease, and the objective response rate was 64.3%. ECOG performance status and body weight did not change significantly after treatment, whereas appetite showed an increase that was of borderline statistical significance. Toxicity was acceptable and only hematologic. Dose-limiting toxicity was established at the fourth dose level; consequently, maximal tolerable dose was assessed at the third dose level. Before treatment, the serum levels of IL-1beta, IL-6, and TNF-alpha were significantly greater in the patients than in healthy persons. The comparison between pretreatment and posttreatment serum values of IL-1beta, IL-6, TNF-alpha, and sIL-2R did not reveal significant differences in the patients. Similar results were obtained when the patients were considered as responders (partial response) or non-responders (stable or progressive disease) to therapy. Only IL-6 serum levels were increased (p = 0.014) after treatment.

Adult↗
PubMedDate not supplied

Reactive oxygen species, antioxidant mechanisms and serum cytokine levels in cancer patients: impact of an antioxidant treatment.

OBJECTIVE: So far, it is not well established whether oxidative stress found in cancer patients results from an increased production of oxidants in the body or from a failure of physiological antioxidant systems. To further investigate this question we have assessed the blood levels of reactive oxygen species as a marker of free radicals producing oxidative stress and the most relevant of the physiological body enzymes counteracting reactive oxygen species, namely glutathione peroxidase and superoxide dismutase. Serum levels of proinflammatory cytokines and IL-2 were also investigated. All these parameters were studied in relation to the clinically most important index of disease progression, namely Performance Status (ECOG PS). We also tested the reducing ability of different antioxidant agents on reactive oxygen species levels by measuring the increase in glutathione peroxidase activity, and the reduction of serum levels of IL-6 and TNF. DESIGN, SETTING AND SUBJECTS: We carried out an open non randomized study on 28 advanced stage cancer patients (stage III, 10.7%, and stage IV, 89.3%) with tumours at different (8) sites: all were hospitalized in the Medical Oncology Dept, University of Cagliari Interventions. The patients were divided into 5 groups and a different antioxidant treatment was administered to each group. The selected antioxidants were: alpha lipoic acid 200 mg/day orally, N-acetylcysteine 1800 mg/day i.v. or carboxycysteine-lysine salt 2.7 g/day orally, amifostine 375 mg/day i.v., reduced glutathione 600 mg/day i.v., vitamin A 30000 IU/day orally plus vitamin E 70 mg/day orally plus Vitamin C 500 mg/day orally. The antioxidant treatment was administered for 10 consecutive days. RESULTS: Our results show that all but one of the antioxidants tested were effective in reducing reactive oxygen species levels and 2 of them (cysteine-containing compounds and amifostine) had the additional effect of increasing glutathione peroxidase activity. Comprehensively, the "antioxidant treatment" was found to have an effect both on reactive oxygen species levels and glutathione peroxidase activity. The antioxidant treatment also reduced serum levels of IL-6 and TNF. Patients in both ECOG PS 0-1 and ECOG PS 2-3 responded to antioxidant treatment.

Adult↗
PubMedDate not supplied

Medroxyprogesterone acetate and megestrol acetate reduce cisplatin-induced serotonin release from human peripheral blood mononuclear cells of cancer patients.

In the present study we evaluated the ability of either medroxyprogesterone acetate (MPA) or megestrol acetate (MA) to reduce cisplatin (CDDP)-induced serotonin (5-HT) release from peripheral blood mononuclear cells (PBMC) of cancer patients. Sixteen patients with cancer of different sites, all in advanced stage of disease, were studied (10 for MPA and 6 for MA). The levels of 5-HT in culture supernatants of PBMC stimulated with CDDP were higher than controls (100 nM vs 51 for MPA study and 123 vs 64 for MA study) and were in the same range of PHA-stimulated PBMC. The addition into cultures of MPA or MA was able to significantly reduce the CDDP-induced production of 5-HT (62 nM for MPA, and 46 for MA study). MPA as well as MA are able to inhibit 5-HT production and/or release by CDDP-stimulated PBMC of cancer patients: this finding to our knowledge has not been previously reported. The concentrations of MPA and MA used in cultures were in the same range as those raised in plasma following the clinical administration of daily doses of 1,000/2,000 mg of MPA and 320 to 960 mg of MA.

Aged↗
PubMedDate not supplied

Comparison of oral 5-HT3-receptor antagonists and low-dose oral metoclopramide plus i.m. dexamethasone for the prevention of delayed emesis in head and neck cancer patients receiving high-dose cisplatin.

A phase III, single-institution, open, prospective, randomized, parallel study was carried out on head and neck cancer patients to compare a combination of low-dose (20 mg q.i.d.) oral metoclopramide (M) + i.m. Dexamethasone (D) with an oral 5-HT3-Receptor Antagonist (5-HT3-RA) alone in the prevention of high-dose (HD > or = 80 mg/m2) cisplatin-induced delayed emesis. 51 consecutive patients, all but two with advanced stage of disease, were treated for a total of 198 chemotherapic cycles: 23 patients entered Group A (5-HT3-RA) receiving a total of 108 cycles, 28 patients entered Group B (M + D) receiving a total of 90 cycles. The treatment groups were well matched for age, sex (almost all patients were males), ECOG PSR, stage of disease and alcohol intake. The efficacy of M + D was significantly higher than that of 5-HT3-RA in achieving complete protection (CR 88.9% vs 72.2%, chi2 9.9, p = 0.002) and major efficacy (ME: CR + MR) (94.5% vs 85.2%, chi2 5.6, p = 0.02). Generally, for both treatments (5-HT3-RA and M + D) a good control of delayed emesis was achieved in patients who had complete protection on acute emesis. A good control of acute emesis had a highly positive predictive value of delayed emesis for both treatments without significant difference between them (CR 85% for M + D and 82% for 5-HT3-RA; ME 88% for M + D and 92% for 5-HT3-RA). The failure (F) on acute emesis had a significantly higher negative predictive value of delayed emesis for M + D (98%) than 5-HT3-RA (67%). Our study is, to our knowledge, the first comparing M + D vs one 5-HT3-RA alone in the prevention of HD cisplatin-induced delayed emesis in a properly designed clinical trial. Our results show that M + D are more effective than 5-HT3-RA alone in the prevention of HD cisplatin induced delayed emesis, whereas 5-HT3-RA may be the treatment of choice in patients who had acute vomiting. Our study demonstrated not only the persistence of antiemetic efficacy but also increasing efficacy, during subsequent courses. Our results confirm that protection from acute emesis plays a major role in the appearance and control of delayed emesis.

Administration, Oral↗