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Biomedical subjects

H Bleiberg

Publications and source records attributed to H Bleiberg.

At least 73 records · Page 4Linked to original sources
PubMed1994

[Adjuvant chemotherapy in cancers of the colon and rectum].

The high incidence of recurrence in patients with resected colorectal cancer at Dukes' stages B2, B3 and C indicates that these patients have micrometastases at the time of surgery and demonstrates the need for adjuvant therapy. Studies using 5-FU alone led to negative results. The combination of 5-FU and levamisole given every week during 1 year was shown to be an effective adjuvant treatment, significantly increasing survival at 5 years from 55% to 71% (p = 0.006). Other treatment modalities are under investigation. Leucovorin increases 5-FU activity in advanced cancers. A combination of the two could thus play an important role in adjuvant treatment. No results are available regarding the compared effects of 5-FU/folinic acid, 5-FU folinic acid/levamisole to 5-FU/levamisole. Portal vein chemotherapy with 5-FU administered during 7 days after surgery has been studies as well, and could also be effective. An association of a short postoperative course of intraportal chemotherapy with intravenous chemotherapy over several months may lead to a further improvement of survival in patients with colorectal cancer. Despite the substantial advances made in the adjuvant treatment of colorectal cancer, progress will be obtained only through continual research.

Chemotherapy, Adjuvant↗
PubMed1994

Cost-effectiveness analysis of antiemetic treatment.

To address the economic issues posed by the introduction of 5-hydroxytryptamine3 receptor antagonist (5-HT3 RA), we performed a cost-effectiveness analysis based on clinical trial data published in the recent literature. Cost calculations include initial treatment and a second-line salvage treatment. The average cost and incremental cost were established. Incremental cost corresponds to the extra cost involved in achieving total control of emesis in 1% extra patients. If 5-HT3 RA is not part of the initial treatment, salvage treatment with ondansetron is not cost-effective. Moreover, starting with the combination of ondansetron plus dexamethasone saves more money than starting with ondansetron alone. However, if the difference in emesis control is only minimal, treatment with the 5-HT3 RA remains more expensive.

Antiemetics↗
PubMed1994

Dose-finding study of tropisetron in cisplatin-induced nausea and vomiting.

BACKGROUND: The purpose of these two studies was to define the optimal therapeutic dose of the 5-HT3 receptor antagonist tropisetron (Navoban, ICS 205-930) in cisplatin-induced nausea and vomiting. PATIENTS AND METHODS: In two multicentre, dose-finding studies of tropisetron in the prevention of cisplatin-induced emesis, cancer patients naïve to chemotherapy or who had not vomited previously were randomly assigned to tropisetron 5, 10, 20 or 40 mg (study I, 143 patients) or 2 or 5 mg (study II, 74 patients), administered as a single intravenous dose over 15 minutes just before the start of chemotherapy. RESULTS: In study I total control of acute symptoms (no nausea and no vomiting) was achieved in, respectively, 66%, 50%, 64% and 50% in the 5-, 10-, 20- and 40-mg groups of patients. A total absence of vomiting alone was seen in, respectively, 71%, 51%, 61% or 58% of patients. None of the differences were statistically significant. In study II there was total acute control in 57% of patients in the 2-mg group and 63% in the 5-mg group (p = NS). Total or major control of vomiting (< or = 2 emetic episodes) was the primary endpoint in study II and was seen in 68% of patients for the 2-mg and 86% for the 5-mg group (p = 0.055). In this study failures ( > 3 vomiting) were rescued with a second infusion of tropisetron (5-mg fixed dose). Three of 8 rescue infusions administered in the 2-mg group prevented further vomiting whereas none of 5 were successful in the 5-mg group during course 1 of chemotherapy. The most frequently reported adverse effects (over all three courses) were headache (6.0% of 217 patients) hypertension (3.7%) and diarrhoea (2.8%). None of the 25 deaths which occurred during the two studies were attributable to tropisetron. CONCLUSIONS: Thus, a single dose of tropisetron provides 24-hour protection against cisplatin-induced nausea and vomiting and is well tolerated. These studies do not allow a firm conclusion but suggest that 2 mg may be subtherapeutic and that 5 mg is as effective as higher doses.

Adult↗
PubMed1994

Optimal combination therapy with tropisetron in 445 patients with incomplete control of chemotherapy-induced nausea and vomiting.

PURPOSE: This study evaluated tropisetron (Navoban; Sandoz Pharma, Basle, Switzerland)-based combination therapy in patients who had incomplete control of chemotherapy-induced nausea or vomiting when using tropisetron as a single antiemetic agent. PATIENTS AND METHODS: One thousand seventy-two patients, who were scheduled to receive at least two identical cycles of emetogenic chemotherapy, were treated with 5 mg tropisetron once daily in their first chemotherapy course. A 2 x 2 x 2 factorial design was used to evaluate three additional treatments to the recommended 5 mg once daily (intravenously [i.v.] on day 1; orally on days 2 through 6) tropisetron regimen during course 2 in those patients who had shown incomplete control of nausea and/or vomiting on any day of course 1. Four hundred forty-five patients were centrally randomized to receive, in addition, open-label dexamethasone (day 1, 0.2 mg/kg i.v.; days 2 through 6, 8 mg orally) and/or open-label alizapride (day 1, 100 mg i.v. and 4 x 50 mg orally; days 2 through 6, 4 x 50 mg orally) and/or double-blind tropisetron (ie, doubling the dose to 10 mg once daily) or corresponding placebo. RESULTS: Complete response rates (no nausea and no vomiting) were 72% for day 1 and 48% for days 1 through 6 of course 1. During course 2, more complete responders were observed when dexamethasone was added, both for day 1 (76% v 66%, P = .020) and for days 1 through 6 (50% v 34%, P = .0004). A moderate increase in the complete response rate was seen with the addition of conventional-dose alizapride (day 1, 75% v 68%, P = .14; days 1 through 6: 47% v 37%, P = .041). Doubling the dose of tropisetron did not change the complete response rate. CONCLUSION: The addition of dexamethasone significantly increases the complete response rate of both acute and delayed emesis in patients who have incomplete disease control with tropisetron alone.

Administration, Oral↗
PubMed1993

Non-surgical treatment of hepatocarcinoma.

Hepatocellular carcinoma (HCC) is one of the most common tumors affecting man. It is the general feeling that only hepatectomy can give a chance for cure. However, less than 20% of patients can be resected, and other treatment modalities are required. Systemic (chemotherapy, hormonotherapy, immunotherapy) and loco-regional (intratumoral injection of alcohol, intra-arterial chemotherapy embolization, internal radiotherapy) approaches have been developed. In view of the small number of patients, tumor and patient heterogeneity, and difficulties in assessing tumor response, the real place of these treatments is difficult to evaluate. A review of the literature suggests that embolization with Gelfoam, even when given without chemotherapy, has an effect on response rate and on survival, and could be considered, at the present time, as the most attractive treatment in non-operable HCC. Chemotherapy seems effective only if combined with embolization. When administered alone by the systemic or the intra-arterial hepatic route, no clinically significant activity can be found. Unexpectedly, Lipiodol by itself seems inactive, and the co-administration of chemotherapy does not improve activity. Other approaches such as intratumoral injection of alcohol, immunotherapy, hormonotherapy, and radioimmunotherapy are still experimental, and well-designed studies are needed to identify their role.

Antineoplastic Agents↗
PubMed1993

Correlation between [3H]thymidine and proliferating cell nuclear antigen (PCNA)/cyclin indices in archival, formaldehyde-fixed human colorectal tissues.

Sections were obtained from archival colorectal tissue samples preserved in paraffin since 1974, after an in vitro incubation with [3H]thymidine and fixation in formaldehyde. These sections were submitted to immunohistochemical staining with the 19A2 monoclonal antibody against proliferating cell nuclear antigen (PCNA) (i.e. the PCNA identified as the auxiliary protein to DNA polymerase delta), followed by autoradiography. Analysis of this double-labelled material revealed an excess of PCNA-labelled over 3H-labelled nuclei, as expected from our previous studies with this fixative. On the other hand, PCNA positive nuclei showed the same overall topographical distribution as the [3H]thymidine-labelled ones, eventually revealing the same heterogeneity or abnormality in the spatial distribution of proliferative cells. Finally, there was a highly significant correlation (r = 0.898; P < 0.0001) between the [3H]thymidine labelling index (TLI) and the proportion of PCNA-positive nuclei (PCNAF-LI). PCNA immunostaining after formaldehyde fixation thus appears as a valid approach for mapping the proliferative compartment and demonstrating tumour heterogeneity or abnormalities in the distribution of proliferative cells. The excellent correlation between the PCNAF-LI and the TLI also makes PCNA immunostaining a simple tool for retrospective or prospective studies on pathological material aimed at evaluating the potential relevance of proliferative indices to clinical prognosis or prediction of cancer risk.

Adenocarcinoma↗
PubMed1993

Compassionate use of tropisetron in patients at high risk of severe emesis.

Tropisetron is a 5-HT3 receptor antagonist which suppresses nausea and vomiting induced by cancer chemotherapeutic agents. In this study, tropisetron was evaluated on a compassionate-need basis in 545 cancer patients who had either proved refractory to antiemetic treatment during previous chemotherapy or who were at high risk of emesis as a result of current therapy. Tropisetron (5 mg or 10 mg) was administered as a 15-minute infusion prior to chemotherapy, with the further possibility of an additional dose, either orally or parenterally, on one or more subsequent days. In some patients the drug was administered orally on the day before treatment. On Day 1 of Course 1, 64.7% of patients had a complete response to tropisetron, i.e. no nausea or vomiting, and 26.9% of patients had a partial response. More than 80% of patients with a complete response in Course 1 had a complete response in Course 2 and of the partial responders in Course 1, 37% achieved a complete response in Course 2. Of the 7.6% failures in Course 1, a further 26% achieved a complete response in Course 2. Tropisetron was well tolerated, with adverse effects recorded in only 45 (8%) patients.

Adolescent↗
PubMed1993

Phase II trial of mitomycin C (MMC) in advanced gallbladder and biliary tree carcinoma. An EORTC Gastrointestinal Tract Cancer Cooperative Group Study.

BACKGROUND: Based on a recent pharmacokinetic study suggesting that high biliary levels of mitomycin C (MMC) may be achieved as a result of an entero-hepatic recycling mechanism, we conducted a Phase II EORTC trial which involved MMC administration to patients with non-resectable biliary tract carcinoma. PATIENTS AND METHODS: Of the 34 patients entered in the study, 30 were eligible (11m + 19f, median age 58 yrs). I.V. bolus injections of 15 mg/m2 MMC were administered at six-week intervals. The tumors were confined to the liver in 17 patients and 13 had extra-hepatic localizations. RESULTS: All 30 eligible patients were evaluable for toxicity and response. Mild thrombocytopenia was the main toxic side effect. Severe, WHO grade III/IV thrombocytopenia was limited to 4 patients. The haemolytic uraemic syndrome was not observed and there were no toxic deaths. Of 30 patients, 3 had partial remissions (overall response 10%, 95% confidence interval 2%-27%). CONCLUSIONS: This study, the largest such ongoing phase II trial, shows no significant activity of single-agent MMC in patients with advanced biliary tract carcinoma.

Biliary Tract Neoplasms↗
PubMed1993

Natural history of the colorectal cancer.

Colorectal cancer appears as a continuous process, starting with the normal cells and progressively growing towards malignancy. The aim of this review is to focus on the stages of that transformation and the means available for reducing the risk of this particular cancer. Although genetic factors have been identified, dietary pattern, the presence of inflammatory bowel disease and adenomas seem to play the most important role in the occurrence of colorectal cancer. The prevention of colorectal cancer should include changes in dietary habits, resection of adenomatous polyps as well as early detection of cancer. Studies testing these approaches are few and so far, none has proven effective in improving survival.

Cell Transformation, Neoplastic↗
PubMed1993

[Adjuvant treatments in resectable cancer of the rectum: preoperative radiotherapy, postoperative radiation- and chemotherapy or nothing?].

In addition to curative surgical resection, which remains the treatment of choice in rectal cancer, are there any other effective adjuvant treatments capable of increasing the life expectancy of patients by decreasing the frequency of local recurrences and distant metastases? Analysis of the results and clinical arguments in favour of adjuvant treatments demonstrates the efficacy of preoperative radiotherapy which decreases the pelvic recurrence rate in patients with T2T3T4NxM0 tumours. Postoperative administration of a combination of radiotherapy and chemotherapy (5-FU, methyl CCNU) also improved the survival rate and disease-free interval in patients operated for rectal cancer. However, the adverse effects and toxicity of this adjuvant treatment limit its routine administration. Lastly, the efficacy of postoperative radiotherapy and postoperative chemotherapy, administered separately, has not been clearly demonstrated to date.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Efficacy of twice daily versus three times daily oral ondansetron in the prevention of chemotherapy induced emesis: a randomized, single-blind, multicentre study. The Ondansetron International Emesis Study Group.

Following a single intravenous dose given pre-chemotherapy, the efficacy and tolerability of oral ondansetron treatment given twice daily was compared with the established three times daily oral supplementary regimen in the prophylaxis of nausea and vomiting induced by cyclophosphamide (greater than or equal to 500 mg/m2) in combination with doxorubicin (greater than or equal to 40 mg/m2) or epirubicin (greater than or equal to 40 mg/m2). Oral ondansetron given twice daily or three times daily was equally effective in controlling nausea and emesis. The twice daily oral treatment prevented emesis in 73% of patients in the first 24 hours and in 65% of patients over 3 days. Both dose schedules were safe and were tolerated well. Twice daily oral ondansetron showed good efficacy for controlling emesis and nausea in oncology outpatients.

Administration, Oral↗
PubMed1992

A phase I trial of a new antiemetic drug--clebopride malate--in cisplatin-treated patients.

Clebopride, a new benzamide derivative, has, in common with the other members of this group, antidopaminergic activity. In animals, its therapeutic ratio is superior to that of metoclopramide at doses free of side effects associated with hyperprolactinemia and extrapyramidal symptoms. The present study was designed to define the maximum tolerated dose (MTD) in patients with advanced histologically-proven cancer, treated with cisplatin at a dose of greater than 50 mg/m2. Most of them were pretreated and refractory to standard antiemetics. Clebopride was started at a dosage of 0.10 mg/kg in a group of 6 patients and escalated by 0.2 mg at each dose level. A total of 30 patients were included. Side effects include somnolence, diarrhea and extrapyramidal-like symptoms. The latter occurred at almost all dose levels in 14% of the cycles and limited continuation of the study. Activity in this group of patients was encouraging but, considering the rate of extrapyramidal symptoms, further dose escalation is not indicated and activity at lower, nontoxic levels should be investigated.

Adolescent↗
PubMed1992

Antiemetic agents.

Despite major progress in the treatment of chemotherapy-induced emesis, nearly one third of patients undergoing cisplatin-based regimens still experience emesis within the first 24 hours of chemotherapy. An adequate treatment of delayed and anticipatory emesis remains to be determined. For highly emetogenic chemotherapy, the combination of ondansetron and dexamethasone is superior to dexamethasone alone and protects most patients. For moderately emetogenic regimens, the high level of complete control that can be achieved with the use of standard antiemetics is comparable to that obtained with ondansetron. This would suggest that, to reduce the cost of antiemetic therapy, ondansetron can be limited in case of failure of standard therapy. Delayed emesis remains poorly controlled with no difference between metoclopramide, dexamethasone, ondansetron, and placebo. Although some data suggest an improved efficacy when combining ondansetron with dexamethasone, convincing confirmatory studies are needed.

Antiemetics↗
PubMed1992

Compassionate use of a 5-HT3-receptor antagonist, tropisetron, in patients refractory to standard antiemetic treatment.

The efficacy of tropisetron in the prevention of nausea and vomiting induced by chemotherapy of varying emetogenic potential was evaluated in 545 patients with a variety of malignancies who had either proved refractory to antiemetic treatment during previous chemotherapy courses or who were considered to be at high risk of nausea and vomiting. Tropisetron 5 or 10mg was administered intravenously just before chemotherapy, with the possibility of additional oral or intravenous doses on the day before chemotherapy and on 1 or more subsequent days. On day 1 of the first course of chemotherapy, a complete response (no nausea and no vomiting) was achieved in 62% of patients and a partial response (1 to 4 vomits and/or episodes of nausea) in 29%. Among the 325 patients who received a second course of chemotherapy, more than 80% of those with a complete response on day 1 of course 1 also had a complete response on day 1 of course 2; 37% and 26%, respectively, of patients with a partial response or failure (1 or more vomits and/or episodes of nausea) on day 1 of course 1 then had a complete response on day 1 of course 2.

Adolescent↗