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Biomedical subjects

H Bleiberg

Publications and source records attributed to H Bleiberg.

At least 109 records · Page 6Linked to original sources
PubMed1988

Activity of a new antiemetic agent: alizapride. A randomized double-blind crossover controlled trial.

Alizapride is a methoxy-2-benzamide derivative three times more potent than its parent compound, metoclopramide, as an antagonist of apomorphine-induced emesis in dogs. The antiemetic activity of alizapride plus dexamethasone (DXM) was compared with that of placebo plus DXM in a randomized, double-blind, crossover study in cancer patients receiving cisplatin (DDP). Alizapride, given at the maximally tolerated dose of 4 mg/kg x 5, or placebo was given in a sequence determined by randomization during two successive, identical courses of antitumor chemotherapy. The antiemetic treatment was given 30 min before and 1.5, 3.5, 5.5, and 7.5 h after starting. DXM, in a dose of 12 mg, was given IV with the first administration of alizapride or placebo. A total of 39 patients completed the two courses of chemotherapy. The severity of gastrointestinal symptoms was influenced by previous treatment but not by the treatment sequence. Although our overall results suggest that alizapride does not add to the activity of DXM against DDP-induced amesis, a statistically significant difference favoring alizapride plus DXM was found among patients with the lowest gastrointestinal tolerance to DDP: women, patients under 50 years of age, and patients pretreated with chemotherapy including DDP and non-DDP agents. Side effects consisted of orthostatic hypotension, which was symptomatic in two patients, and a single occurrence of severe extrapyramidal syndrome. We conclude that alizapride is more active than placebo when combined with DXM for DDP-induced emesis in patients at high risk of severe nausea and vomiting. The severity of the side effects in this study indicates that a dose reduction of alizapride might be appropriate for further studies.

Adolescent↗
PubMed1988

Hepatic artery ligation or embolization and locoregional chemotherapy of liver metastases from colorectal cancer.

If liver metastases are diffuse and spread out in the two lobes of the liver, the question remains as to which treatment should be given. Experimental studies showed that when a tumor grows, its vascular pattern becomes mainly arterial. However, if the tumor is still increasing, its center becomes progressively necrotic. After hepatic artery ligation the blood flow of the liver metastases decreases by 90% in the tumor but depriving the arterial circulation of the tumor is not sufficient to achieve a complete cure since the portal blood supply always saves a rim of neoplastic cells around the necrotic area. On the other hand, local infusion of chemotherapy for liver metastases by the arterial route showed a response rate varying between 34 and 70% and the median survival varying between 8 and 17 months. When FUdR chemotherapy was administered using a totally implantable drug infusion pump no improvement in the survival was observed and moreover a high level of toxicity was described including hepatitis and biliary sclerosis. A combined therapy seems a rational approach to treat tumor cells in surviving to the arterial ligation by perfusing the liver with cytotoxic drugs via the portal vein. Taylor's study was very promising but a randomized phase III clinical trial led by the gastrointestinal cancer group of the EORTC with the aim to evaluate the effectiveness of hepatic artery ligation and portal infusion of 5-FU did not show any difference in the survival of the treated patients when compared with patients treated by hepatic artery ligation alone. 77 patients were registered. Data are now available for 55 patients, respectively 30 and 25 patients in the treated group and in the control group. In both groups the median time to progression was 6 months and the median survival time was 12 months. 20% of the patients treated by hepatic artery ligation and portal chemotherapy had a response, one of them with a complete response, 5 with partial response and 14 patients without significant change in the size of their metastases. On the contrary, in the group treated by hepatic artery ligation alone, only one patient had a partial response with 13 patients having no change in the size of their metastases.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

An EORTC Gastrointestinal Group phase II evaluation of epirubicin combined with 5-fluorouracil in advanced adenocarcinoma of the pancreas.

The EORTC Gastrointestinal Group has conducted a phase II trial in 47 patients with locally advanced or metastatic adenocarcinoma of the pancreas with epirubicin 90 mg/m2 intravenously on day 1 in combination with 5-fluorouracil 500 mg/m2 in a 2 hr infusion day 1-4, every 4 weeks. Of 43 evaluable patients there were six early deaths due to tumour progression and one due to a cerebrovascular accident. There were six partial responses for a response rate of 14% including early deaths. The median survival for all patients was 4 months. It is concluded that the addition of 5-fluorouracil to epirubicin does not appear to enhance the therapeutic results of epirubicin alone.

Adenocarcinoma↗
PubMed1987

An EORTC Gastrointestinal Group phase III evaluation of combinations of methyl-CCNU, 5-fluorouracil, and adriamycin in advanced gastric cancer.

In a prospective phase III multicenter trial, 189 patients with advanced measurable and nonmeasurable gastric cancer were randomized to receive 5-fluorouracil (5-FU) combined with Adriamycin (FA) or FA plus methyl-CCNU (MeFA). The response rate in patients with measurable disease was 10% (three of 29), and 18% (five of 28), respectively. No difference in the duration of survival was detected (P = .14; log rank test). Median survivals were 21 and 32 weeks, respectively. Toxicity was moderate, but there have been two toxic deaths among the patients who received FA. Because of the low response rate and the short survival, neither regimen can be recommended for the treatment of advanced gastric cancer.

Adenocarcinoma↗
PubMed1986

An EORTC Gastrointestinal Group evaluation of the combination of sequential methotrexate and 5-fluorouracil, combined with adriamycin in advanced measurable gastric cancer.

In a phase II multicenter trial, 71 patients with advanced measurable gastric cancer were registered to receive sequential high-dose methotrexate (MTX) and 5-fluorouracil (5-FU) combined with Adriamycin (A [Adria Laboratories, Columbus, OH]). The response rate was 33% (22 of 67), including all eligible patients. There were nine complete responders (CRs). The median survival for all patients was 6 months. There has been one toxic death; however, three other patients died from toxicity associated with major protocol violations. It is concluded that this protocol is active in gastric cancer. Toxicity, partly because of nonprotocol adherence, is considerable and is now under further investigation in a randomized trial comparing this schedule with a combination of 5-FU, Adriamycin, and mitomycin C (FAM).

Adult↗
PubMed1985

Cell kinetic indicators of premalignant stages of colorectal cancer.

Using an in vitro double labeling technique with two different levels of 3H-thymidine, the duration of the phase of DNA synthesis (S) and the labeling index (LI) were measured in the colorectal mucosa of three groups of patients: patients with colorectal neoplasms (adenomas and/or adenocarcinomas), patients with inflammatory bowel disease, and a control group of patients without gastrointestinal pathology. In those patients with colorectal neoplasms, samples were obtained from both the neoplastic mucosa and from the normal appearing mucosa at various distances from the lesions. One-way analyses of variance were used to test the equality of mean S-phase duration and LI in the various types of tissues. S-phase duration was significantly longer in the tumor than in the unaffected mucosa of patients with adenocarcinoma (18.65 hours +/- 2.3 versus 10.13 hours +/- 1.26 P less than 0.0001). However, S-phase duration was significantly longer in the unaffected mucosa of cancer patients than in the mucosa of patients without gastrointestinal pathology (10.58 hours +/- 1.84 versus 7.91 hours +/- 0.46, P = 0.013). Similarly, LI was significantly higher in the unaffected mucosa of patients with adenoma and adenocarcinoma than in the mucosa of patients without gastrointestinal pathology (19.1% +/- 3.0 versus 9.5% +/- 2.2, P less than 0.0001). There was a highly significant trend to a progressive increase of LI from flat histologically normal appearing mucosas to inflammatory mucosas, adenomas, and adenocarcinomas (P less than 0.0001). These results suggest that increased S-phase duration is specifically related to cancer. In mucosa without histologic sign of malignancy, an increased S-phase duration would indicate that the malignant process has started. An increased LI would appear to relate to the selective advantage that rapidly proliferating cells hold over less proliferating ones.

Adenocarcinoma↗
PubMed1985

Phase II study of epirubicin in advanced adenocarcinoma of the pancreas.

The EORTC Gastrointestinal Group has conducted a phase II trial in 41 patients with locally advanced or metastatic adenocarcinoma of the pancreas with epirubicin 90 mg/m2 intravenously every 4 weeks, with dose escalation if possible. Seven patients were not evaluable for response. In 34 evaluable patients there were two complete and six partial responses (response rate 24%). Nine patients had stable disease for at least 2 months, including one patient with a minor response. Median time to progression for responders was 7 months, for all patients 3 months. Median survival for responders was 9 months, for all patients 5 months. It is concluded that epirubicin is an active drug in pancreatic cancer.

Adenocarcinoma↗
PubMed1985

cis-Platinum as second-line chemotherapy in advanced gastric adenocarcinoma. A phase II study of the EORTC Gastrointestinal Tract Cancer Cooperative Group.

Thirty-four patients with measurable metastatic gastric adenocarcinoma refractory to prior chemotherapy were treated with cis-platinum 100 mg/m2 in a 6-hr infusion at 3-week intervals. Thirty-one patients were evaluable for response. There were three complete and three partial responses. Median duration of response was 4 months. Toxicity consisted mainly of nausea and vomiting and was severe in 12 patients. One patient had a severe but reversible renal failure. These results confirm other data reported in the literature. Cis-platinum has activity in gastric adenocarcinoma and should now be further investigated in first-line chemotherapy.

Acute Kidney Injury↗
PubMed1985

Gastrointestinal metastases from extra-abdominal tumors.

Over a period of 4 years, metastatic lesions to the gastrointestinal tract were analysed in postmortem and clinical series. Melanoma, breast and lung cancers were the most common primary lesions. The topography of parietal involvement shows that all patients evidenced tumor involvement of the submucosa, but not all of them revealed invasion of the mucosa and serosa, suggesting a hematogenous route of dissemination. Although almost all cases had widespread disease at the time of referral for diagnosis, patients who were submitted to surgery had a median survival of 8 months (range 1-48). In selected cases, surgery offers good palliation and may permit resumption of otherwise active chemotherapeutic treatments.

Adult↗
PubMed1984

Cell cycle parameters and prognosis of colorectal cancer.

In vitro determination of S phase duration and labeling index were performed, in tumor and normal tissues, in 15 patients with rectal and colon cancer to determine if these cell cycle parameters can predict the clinical course of the disease. Microscopic analyses of the tumor and adequate follow-up were obtained for all patients. S phase duration and labeling index did not exhibit any obvious correlations with age, sex, tumor localization, Duke's classification or other microscopic prognostic features; neither did they show any difference between patients alive without cancer 5 yr after initial treatment and those dead from cancer or other causes.

Aged↗
PubMed1983

[Phase I study of alizapride in cancer patients treated with cisplatin].

Alizapride in a new methoxy-2 benzamide derivative with antiemetic properties. The dose-effect relationship of this compound was studied in 24 cancer patients treated with cisplatin regimens. Alizapride was administered as 15 min intravenous infusions at doses of 1 to 5 mg/kg repeated every 2 hours for 5 administrations. No adverse reactions were noted at doses of 1 to 3 mg/kg. Serious orthostatic hypotension was observed at the highest dose level. Other side effects were essentially mild to moderate and consisted of somnolence and diarrhea. The study indicated that the dosage level of 4 mg/kg is suitable for clinical use. The antiemetic activity of alizapride in patients receiving cisplatin therapy remains to be firmly established in a randomized study. This trial suggested a better antiemetic effect of alizapride in naive patients as compared to those previously treated with anticancer chemotherapy.

Adult↗
PubMed1983

Improving peritoneoscopic staging of patients with solid tumors.

Peritoneoscopy and guided needle biopsy were carried out as the staging procedure in patients with solid tumors. The disease was disseminated in 379 patients with various tumor types and limited in 109 with breast cancer and malignant melanoma. Adequate liver biopsies were obtained in all cases. Macroscopic liver tumors were demonstrated in 96 patients. Eleven additional patients had peritoneal or mesenteric tumors with normal livers. Attempts were made to improve the yield of positive findings of the procedure. The cytologic examination of cells adhering to the needle after biopsy or optimizing visualization of the liver surface by using a fiberoptic gastroscope did not answer this purpose. A 7.2% increase in liver tumor detection was obtained by taking 4-6 biopsies at random or towards deep palpated nodules in macroscopically normal livers. The data, although difficult to interpret in terms of accuracy of the method, suggest that in solid tumors random samplings of normal livers could contribute to the diagnosis of otherwise undetectable liver metastases.

Biopsy, Needle↗