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Biomedical subjects

R Epelbaum

Publications and source records attributed to R Epelbaum.

At least 55 records · Page 3Linked to original sources
PubMed1991

In vivo measurements of the fraction of dose of bleomycin labeled with cobalt 57 delivered to human tumors.

Concentrations of bleomycin labeled with cobalt 57 (Co-bleo) over time were measured in vivo in 17 patients with 32 sites of lymphoma and 18 patients with lung tumors after administration of the same dose of bleomycin. There were marked variations in individual tumor drug concentrations even among tumors with the same histologic type, indicating that the tumor concentration of this drug in individuals cannot be predicted from the administered dose. Also, tumor concentration could not be predicted from the area under the concentration over time curve (AUC) of Co-bleo in the blood; there was no correlation (r = 0.53) between the AUC and the concentration in the tumor at any point in time between 30 minutes and 8 hours after injection. There was no significant difference in the percent of the injected dose per milliliter (%ID/ml) which was delivered to the tumor when low and high amounts of bleomycin were administered to the same patient. Also, a good correlation (r = 0.88) between the %ID/ml over time was found when injection of low and high doses of bleomycin were compared. The results indicate that using quantitative single photon emission computed tomography (SPECT) and a labeled tracer dose it is possible to predict what fraction of the dose of a chemotherapeutic drug will concentrate in an individual patient's tumor in vivo. They also show that, for bleomycin, escalation of dose will result in a proportional increase of tumor concentration. This increase depends on individual properties of tumors which can be measured quantitatively in vivo by SPECT and are expressed as percent of %ID/ml of tumor tissue.

Adolescent↗
PubMed1991

Lonidamine as a modulator of alkylating agent activity in vitro and in vivo.

We are searching for relatively nontoxic compounds that can positively modulate the efficacy of antitumor alkylating agents. Lonidamine inhibits cellular energy metabolism and could potentially increase damage by alkylating agents if cellular defenses are energy requiring. Exposure of cells to lonidamine (500 microM) for 2 h under hypoxic conditions followed by 1-h exposures to lonidamine plus alkylating agents under normally oxygenated conditions in vitro significantly increased the cell kill achieved by cis-diamminedichloroplatinum(II) (CDDP) approximately 5-fold and by D-tetraplatin approximately 10-fold at 90% inhibitory concentration in MCF-7/CDDP (CDDP-resistant) cells. Carboplatin cytotoxicity, however, was little changed. In the MCF-7 parent cell line, treatment with lonidamine increased CDDP cytotoxicity by approximately 10-fold, D-tetraplatin by approximately 10-fold, and carboplatin by approximately 8-fold at the 90% inhibitory concentration. For L-phenylalanine mustard (melphalan), N,N',N"-triethylenethiophosphoramide (thiotepa), and N,N'-bis(2-chloroethyl)-N-nitrosourea, little resistance was evident in the MCF-7/CDDP lines compared with the parent line. Treatment with lonidamine increased the cytotoxicity of each drug by 1.5- to 3-fold in both cell lines. When exposure to lonidamine was extended to 24 h before and 12 h after drug exposure in MCF-7 normally oxygenated cultures, CDDP (250 microM) cytotoxicity was increased by approximately 100-fold, but melphalan cytotoxicity was increased only 2- to 3-fold over the concentration range tested. In the FSaIIC murine fibrosarcoma tumor system, five i.p. injections of 50 mg/kg of lonidamine over 36 h increased the tumor cell kill by CDDP and carboplatin approximately 2- to 3-fold over the dose range tested when the platinum complexes were given i.p. immediately after the third lonidamine injection. When cyclophosphamide and thiotepa were given in the same schedule, 10-fold increases in tumor cell killing were evident on tumor excision assay over the dosage ranges. The increase in bone marrow toxicity caused by lonidamine in addition to the alkylating agents was less than for tumor cells. Finally, in the EMT6 murine mammary carcinoma, use of lonidamine at 500 mg/kg twice daily along with CDDP, carboplatin, thiotepa, and cyclophosphamide significantly increased tumor growth delays by approximately 1.6- to 3.0-fold. The results suggest that lonidamine can positively modulate antitumor alkylating agent cytotoxicity and may be a clinically useful adjunctive therapy with these drugs.

Animals↗
PubMed1991

[Primary malignant lymphoma of the testis].

Among 715 patients with non-Hodgkin's lymphoma referred to this oncology center between 1973-1989, there were 7 (0.9%) with primary lymphoma of the testis. The mean age was 55 (range 23-78). The presenting symptom in all the 7 was testicular mass or swelling. 6 of them underwent inguinal orchiectomy and 1 had a testicular biopsy. The pathological subtype of the lymphoma in all 7 was the diffuse large cell type. The disease stage was IE in 3, IIE in 3 and IVE in 1. Only 1 had bilateral testicular involvement. 6 were treated primarily with various combinations of chemotherapy and 1 by radiotherapy. 3 developed recurrent disease (2 treated primarily with chemotherapy and 1 by radiotherapy) and died 14, 19 and 27 months, respectively, after diagnosis. 3 are alive with no evidence of recurrent lymphoma. Follow-up in an additional patient has been too short for evaluation. Primary testicular lymphoma is a relatively rare form of extranodal lymphoma. It has a tendency to early systemic progression and is potentially curable by aggressive combination chemotherapy.

Adult↗
PubMed1991

Total-skin electron irradiation for cutaneous T-cell lymphoma: the Northern Israel Oncology Center experience.

Total-skin electron irradiation (TSEI) is effective and frequently used in the treatment of cutaneous T-cell lymphoma. A treatment technique has been developed at our center, using the Philips SL 75/10 linear accelerator. In our method, the patient is irradiated in a recumbent position by five pairs of uncollimated electron beams at a source to skin distance of 150 cm. This method provides a practical solution to clinical requirements with respect to uniformity of electron dose and low X-ray contamination. Its implementation does not require special equipment or modification of the linear accelerator, 19 of 23 patients (83%) with mycosis fungoides, treated by this method, achieved complete regression of their cutaneous lesions.

Adult↗
PubMed1990

Survival of diffuse large cell lymphoma. A multivariate analysis including dose intensity variables.

Ninety-five newly diagnosed patients with diffuse large cell lymphoma (DLCL) treated by cyclophosphamide (CTX), doxorubicin (ADM), vincristine (VCR), and prednisone (CHOP regimen) chemotherapy were evaluated for survival factors including dose intensity (DI). DI calculations were done for the initial cycles needed to achieve maximal response. The medians of the relative DI for CTX, ADM, and VCR were 0.9, 0.86, and 0.79, respectively. The median of the average relative DI (ARDI) was 0.83 (range, 0.28 to 1.14). The univariate analysis of potential prognostic variables showed that the following significantly decreased the survival rate: age older than 60 years (P = 0.0005), Stage III to IV (P = 0.02), male sex (P = 0.03), and all four DI variables (CTX, ADM, VCR, and ARDI) less than the median (P = 0.01 to 0.0001). A multivariate analysis by the stepwise proportional hazards model of Cox indicated that the factors predicting a poor prognosis were ARDI less than the median (P = 0.0003) and age older than 60 years (P = 0.02). A multivariate survival analysis of those who achieved complete remission showed ARDI less than the median (P = 0.0003), CTX less than the median (P = 0.02), and Stage III to IV (P = 0.02) to be the most negative factors regarding survival. In conclusion, a high DI in the initial cycles of CHOP chemotherapy for DLCL has a significant positive impact on survival.

Adolescent↗
PubMed1990

Normal and abnormal Ga-67 SPECT anatomy in patients with lymphoma.

The appearance of normal Ga-67 SPECT images in the coronal, sagittal and transaxial planes is described. The normal tomographic appearance of bone, liver, spleen, and gut is shown and compared with disease involvement above and below the diaphragm.

Gallium Radioisotopes↗
PubMed1990

Ga-67 SPECT before and after treatment of lymphoma.

The results of planar and single photon emission computed tomography (SPECT) gallium-67 scintigraphy performed before and after treatment were compared in 77 patients with lymphoma at 240 sites. Before treatment, the sensitivity of planar scintigraphy was 78% and the specificity was 97%; after treatment, 84% and 96%, respectively. Before treatment, SPECT had a sensitivity of 85% and a specificity of 98%; after treatment, 92% and 99%, respectively. In addition, SPECT allowed better anatomical localization and showed the entire extent of lesions at 36 sites. SPECT was of special value after treatment in excluding disease at 16 sites with residual masses seen at computed tomography (CT). Long-term follow-up in these patients showed that their condition was in complete remission and that the CT appearance of a residual mass does not always mean residual cancer. Thus, Ga-67 SPECT is a suitable imaging technique for monitoring the response of lymphoma to treatment.

Adolescent↗
PubMed1990

Residual mass and negative gallium scintigraphy in treated lymphoma.

Two patients with treated lymphoma demonstrated a residual mass on CT following treatment. In both cases gallium-67 (67Ga) scintigraphy demonstrated increased uptake in the original tumor mass and no uptake in the mass after treatment. In both cases the entire residual tumor mass was resected and found to contain no cancer tissue. This is further evidence of the role 67Ga scintigraphy may play in monitoring response of lymphoma patients to treatment. In contrast, other imaging modalities such as ultrasound, plain film x-rays, or CT only show the presence of a mass but not its nature.

Abdominal Neoplasms↗
PubMed1989

[Treatment of large cell lymphoma].

During 1977-1985, 50 patients with Stages III and IV large cell lymphoma (diffuse histiocytic [DH] and diffuse mixed [DM] types, Rappaport classification) were treated with the CHOP regimen (cyclophosphamide, adriamycin, Oncovin and prednisone). The male:female ratio was 1:1, the mean age at treatment 57 years, and mean follow-up 37 months. 80% had the DH type and 20% the DM type. 46% were in Stage III and 54% in Stage IV. The average relative dose intensity of CHOP was 0.68, which was well tolerated. In 68% a complete response was achieved after a mean of 4 treatment cycles. The average number of cycles for all patients was 7.2. The 5-year survival for those in Stage III was 50% and in Stage IV, 34%. Females survived better than males (60% vs 23%, respectively; p less than 0.02). The 5-year survival of the complete responders was 60% and their relapse-free survival 44%. In our experience, CHOP is a useful combination in the treatment of DH and DM lymphoma; it has yet to be proved in a randomized fashion that the current third generation of combinations is superior to it.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Competitive ELISA for detection of native ras gene-related products in sera of cancer patients.

A solid phase, enzyme-linked immunosorbent assay (ELISA) competition kit was developed to detect circulating native ras gene-related products in sera of 151 healthy volunteers and cancer patients. This assay uses monoclonal antibody (mAb) BST-6A generated against a yeast-derived, native ras-related polypeptide Yp20. Only 2% (1 of 58) of normal control sera showed strong competition, as compared to 15% (5 of 34) of patients with early stage or no evidence of disease, and 44% (26 of 59) of patients with advanced disease. These differences were statistically significant (x2, P less than 0.05-0.001). Eleven sera samples of cancer patients found to be strong competitors in the ELISA competition kit were tested for the presence of anti-ras antibodies by ELISA. None showed higher ELISA values as compared with pooled normal human serum and control sera. It is thus suggested that our procedure detected circulating ras-related onco-proteins in sera of cancer patients mainly with advanced disease.

Antibodies, Monoclonal↗
PubMed1989

Non-Hodgkin's lymphoma in northern Israel: a study of 481 patients with emphasis on ethnic-related patterns.

During the period between 1970-1984, 481 patients with previously untreated non-Hodgkin's lymphoma were referred to the Northern Israel Oncology Center, Haifa. There were 264 (54.9%) Ashkenazi Jews, 123 (25.6%) non-Ashkenazi Jews, and 86 (17.9%) Arabs. The mean age at diagnosis was 60 +/- 15 years for Ashkenazi Jews, 45 +/- 22 years for non-Ashkenazi Jews, and 36 +/- 22 years for Arabs. Ashkenazi Jews had a higher rate of nodular lymphoma compared to non-Ashkenazi Jews and Arabs. Extranodal lymphoma occurred more frequently in non-Ashkenazi Jews and Arabs. Lymphoma of the small intestine was more common in Arabs than in Ashkenazi and non-Ashkenazi Jews. Despite these differences in the pattern of disease, 5 year actuarial survival figures for the various ethnic groups were similar.

Adult↗
PubMed1989

Results of radiotherapy in stage I to II extranodal non-Hodgkin's lymphoma of the head and neck.

29 patients with previously untreated clinical stage I and II extranodal non-Hodgkin's lymphoma of the head and neck received involved or extended field radiotherapy at the Northern Israel Oncology Center during the years 1968 to 1979. Complete initial locoregional control was achieved in all patients; however, 18 patients (62%) relapsed. Two of the relapsing patients (11%) had "in field" failure, and one (6%) had "marginal" failure, with no evidence of disease elsewhere. 13 of the relapsing patients (72%) failed at distant sites, and two of these (11%) both locally and systemically. 13 of 15 patients (87%) with lymphoma of Waldeyer's ring relapsed, most commonly in the abdominal cavity. Only one of seven patients (14%) with lymphoma of the paranasal sinuses recurred. The five- and ten-year actuarial survival of all patients was 50% and 46%, respectively. While patients with lymphoma of the paranasal sinuses had a survival probability of 86% at ten years, patients with disease originating in Waldeyer's ring had an actuarial ten-year survival of 18% only. The prognosis of younger patients was better than the prognosis of patients older than 65. Although this series is too small and heterogeneous to derive definite treatment recommendations, it is suggested that radiotherapy to doses of 4000 to 6000 cGy can control most local disease. The overall results of radiation therapy alone have been unsatisfactory in our patients with lymphoma of Waldeyer's ring and the parotid gland due to failure outside the locally treated area, frequently in the abdominal cavity. Precise staging procedures are needed to detect sites of occult disease which require the use of systemic chemotherapy. It is felt that adequately staged, localized, small size non-Hodgkin's lymphoma of the paranasal sinuses can be treated by radiotherapy alone without loss of curability.

Actuarial Analysis↗
PubMed1988

Carcinoma of the nasopharynx in Northern Israel: epidemiology and treatment results.

Between 1968 and 1984, 49 patients with carcinoma of the nasopharynx were treated at the Northern Israel Oncology Center. There were 6 stage I-II patients (12%) and 43 stage III-IV patients (88%). According to ethnic origin, there were 27 (55%) non-Ashkenazi Jews, 9 (18%) Ashkenazi Jews, and 13 (27%) Arabs. This distribution is different from the percentages of these ethnic groups in Northern Israel. All patients received combined cobalt 60 and 8-10 MeV electron beam radiotherapy to the primary tumor and the entire neck. Twelve stage III-IV patients received three courses of chemotherapy using bleomycin, methotrexate, and cisplatin (BMP) prior to definitive radiotherapy. The following 5-yr actuarial survival figures were achieved: all patients, 42%; stage I-II, 63%; stage III-IV, 37%; Arabs, 53%, non-Ashkenazi Jews, 47%; Ashkenazi Jews, 22%; BMP+radiotherapy, 54%; radiotherapy alone, 42%. It is concluded that there is an ethnic-related pattern of nasopharyngeal carcinoma in Northern Israel. Prognosis is better in non-Ashkenazi Jews and Arabs with early-stage lymphoepithelioma or anaplastic carcinoma, younger than 45 yr old, and receiving more than 5,500 cGy. Chemotherapy by BMP improves initial control rates with questionable benefit to long-term survival.

Adolescent↗
PubMed1988

Whole abdominal irradiation following chemotherapy in advanced ovarian carcinoma.

One hundred and sixteen patients with advanced ovarian carcinoma, who underwent primary cytoreductive surgery, received 6-11 courses of chemotherapy by cis-platin (50 mg/m2) and adriamycin (50 mg/m2) every 21 days. This was followed by second look laparotomy in 66 patients with no clinical evidence of disease. Consolidation abdominal irradiation was administered to 43 patients. Two techniques of irradiation were employed: between 1980-1983 whole abdominal irradiation was used and patients were to receive 3000 cGy in 4 weeks (Schedule I). Due to myelosuppression only 13 of 26 patients (50%) completed the planned dose of radiation. Between 1983-1985 the target volume was divided into upper and lower parts. First, the lower abdomen received 3000 cGy in 3 weeks, and then the upper abdomen received the same dose (Schedule II). Sixteen of seventeen patients (94%) thus treated, completed the planned dose of radiation. The actuarial survival for all 116 patients was 28% of 5 years. Irradiated patients with negative second look laparotomy had a survival probability of 100% at 24 months. Irradiated patients with microscopic disease at second look operation had an actuarial 5-year survival of 66%. Patients with minimal residual disease at second look laparotomy, receiving consolidation abdominal irradiation, had an actuarial survival of 5% only at 36 months. It is concluded that consolidation radiotherapy is effective in patients with negative or microscopic residual disease at second-look laparotomy. In regard to bone marrow tolerance, split field technique of irradiation is preferred.

Abdomen↗
PubMed1988

Treatment of diffuse histiocytic and diffuse mixed non-Hodgkin lymphomas with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP).

During 1977 to 1985 90 patients with large-cell non-Hodgkin lymphoma (diffuse histiocytic or diffuse mixed according to Rapport classification) were treated by the CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) with a mean follow-up of 41 months. Thirty-four patients were treated with radiation therapy as well. The mean number of CHOP cycles to achieve complete response was 4.0 and the mean total number of cycles was 6.6. For 78 patients it was possible to calculate relative dose intensity (RDI) for each drug and the average RDI. Sixty-four patients (71%) achieved CR. The actuarial 5-year survival rate of all patients was 52%. The median RDI for cyclophosphamide was 0.72, for doxorubicin 0.70, for vincristine 0.69 and the median average RDI was 0.69. The following favorable prognostic factors were found to be of statistical significance: female sex and stages I-III as compared to stage IV. The 5-year survival rate for stage I & II patients treated by CHOP plus radiotherapy was 70% as compared to 55% for those treated by CHOP only; this difference was not statistically significant.

Adolescent↗
PubMed1987

Treatment of advanced gastric cancer with DDP (cisplatin), adriamycin, and 5-fluorouracil (DAF).

Sixteen evaluable patients with advanced gastric cancer who had no prior therapy were treated intravenously with cisplatin (DDP) 20 mg/m2/day on days 1-5 and with Adriamycin 40 mg/m2 and 5-fluorouracil 600 mg/m2 on day 1 (DAF) every 3 weeks. There were five objective partial responses, giving a response rate of 31%. Five patients had minor responses, and 5 others achieved disease stabilization. The median duration of response for responders was 10 months, and the median time to tumor progression in nonresponders was 6 months. The overall median survival was 12 months (responders 14 months, nonresponders 9 months; NS). Most patients had a subjective improvement, including disappearance of abdominal pain (7/9) and gastrointestinal bleeding (5/7). The drug toxicity was moderate to severe. The primary nonhematologic toxicities were nausea and vomiting (in all patients), severe weakness (44%), and parasthesias (31%). Eight patients (50%) experienced significant bone marrow suppression. The DAF combination appears to have some activity in patients with advanced gastric cancer. However, further efforts in new drug development and other combinations are needed to improve the results of chemotherapy in stomach cancer.

Adenocarcinoma↗
PubMed1986

Non-Hodgkin's lymphoma presenting with spinal epidural involvement.

Cord compression was noted at presentation in 10 of 453 (2.2%) previously untreated non-Hodgkin's lymphoma patients seen at the Northern Israel Oncology Center between 1968 and 1983. A prodromal phase of local back pain occurred in eight patients, persisting up to 1 year, followed by a second phase of rapidly progressive signs of cord compression. Five of the ten patients presented with primary spinal epidural involvement (Stage IE), whereas the others had Stage IIE and IIIE (one patient each) and Stage IV, with bone and bone marrow involvement (three patients). All patients had unfavorable histologic diagnoses, mostly of the intermediate grade malignancy types according to the Working Formulation. The patients were treated by radiotherapy (two patients), chemotherapy (three patients), or both modalities (five patients). Seven of the ten patients achieved complete remission, but four of them have subsequently had relapses (two patients in bone, one in central nervous system, and one in mediastinum). The 5-year actuarial survival and 3-year relapse-free survival were 66% and 32%, respectively. Median survival has not been reached after a mean follow-up of 34 months. Non-Hodgkin's lymphoma with spinal epidural involvement at presentation is an aggressive disease. An intensive treatment combining irradiation with chemotherapy, and surgery as needed, is suggested in order to achieve good local response and long-term survival.

Actuarial Analysis↗