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Biomedical subjects

L Israel

Publications and source records attributed to L Israel.

At least 37 records · Page 2Linked to original sources
PubMed1992

Fotemustine plus dacarbazine for malignant melanoma.

119 patients with metastatic melanoma received fotemustine 100 mg/m2 on days 1 and 8 and dacarbazine 250 mg/m2 on days 15-18. After a 5-week rest, fotemustine 100 mg/m2 on day 1 and dacarbazine 250 mg/m2 on days 2-5 was given every 3-4 weeks. 12 complete responses (11.6%) and 16 partial responses were observed in 103 evaluable patients (response rate 27.2%). The median duration of response was 21.5+ weeks (8+ to 53+). The response rate was 26.3% in CNS, 18.2% in visceral sites and 37.5% in non-visceral sites. The toxicity was mainly haematological: grade III-IV leukopenia in 27.4% and thrombocytopenia in 23.4%. The response rate was lower than that in 63 patients previously reported. The present series had a higher median age (54 vs. 40 years) without any differences in other population variables. However, activity on CNS metastases and on non-visceral sites was confirmed. Haematological toxicity was about 50% lower than that with fotemustine alone. Hence, this is an active outpatient regimen for metastatic melanoma, especially against cerebral and non-visceral metastases.

Adult↗
PubMed1992

Inhibitory effect of substituted dextrans on MCF7 human breast cancer cell growth in vitro.

Substituted dextrans can reproduce some of the properties of heparin and can thus be used to alter cellular growth. We studied the effect of heparin (H108), dextran (D), carboxymethylbenzylamide dextran (CMDB) and carboxymethylbenzylamide sulfonate dextran (CMDBS) on the growth of human mammary cells of the MCF7 tumor line. The cells were cultured in minimum Eagle's medium containing 2% fetal calf serum without biopolymer, or with increasing concentrations of H108, D, CMDB or CMDBS. Growth curves were accurately based on cell counting using a Coulter counter. Cell distribution in the various phases of the cycle was analyzed by flow cytometry. Dose-dependent growth inhibitory effects (400-4000 micrograms/ml) were observed. The effect on MCF7 tumor cells was most apparent with CMDBS. The percentage of cells in the S phase decreased with preferential blocking in the G0/G1 phase. Pre-clinical studies can be anticipated as there is an absence of in vivo toxicity.

Aged↗
PubMed1991

Fibrocystic disease of the breast in premenopausal women: histohormonal correlation and response to luteinizing hormone releasing hormone analog treatment.

Sixty-six patients with fibrocystic mastopathy were enrolled in the trial after being selected according to clinical, radioultrasonographic, and histologic criteria. No characteristic hormonal profile was noted in most patients (52%). Estrogen receptors or progesterone receptors, or both, were found in 57% of patients. Hormone receptor levels were correlated with atypical proliferative mastopathy (87.5%). Mastopathy was associated with a uterine fibroma or a fibromatous uterus in 73% of cases. All patients received intramuscular injections of a sustained delivery system (microcapsules) of luteinizing hormone releasing hormone agonist [D-Trp6]-LHRH, Ipsen-Biotech, Paris) for 3 to 6 months. In case of partial response at 3 months, an antiestrogen (tamoxifen, 40 mg/day, for estrogen receptor-predominant lesions) or a progestin (cyproterone acetate, 50 mg/day, for progesterone receptor-predominant lesions) was added to the luteinizing hormone releasing hormone agonist. A complete response was observed in more than half of the patients (n = 35, 53%) treated by [D-Trp6]-LHRH alone (n = 29) or associated with tamoxifen (n = 4) or cyproterone acetate (n = 2). A significant partial response was observed in 30 other patients (45%). Additionally, half of them received inhibitory drugs. The best responses were seen with cyst reformation (complete response, 100%) and fibrous block. Clinical responses to treatment with [D-Trp6]-LHRH alone were independent of hormone receptor status, but synergistic effects occurred with concomitant use of the corresponding inhibitory drugs. We conclude that chronic mastopathy, particularly when associated with uterine fibroma, can be successfully treated by luteinizing hormone releasing hormone analogs in premenopausal women.

Adult↗
PubMed1991

Recombinant interleukin-2 in metastatic renal cell carcinoma--a European multicentre phase II study.

This multinational, multicentre study represents the introduction of recombinant interleukin-2 (rIL-2) in Europe. From December 1987 to June 1989, 57 eligible patients with metastatic renal cell cancer were treated with rIL-2 administered as continuous intravenous infusion. 8 out of 51 evaluable patients responded (16%), 2 complete remission (CR) and 6 partial remission (PR). 10 patients had no change (20%). The response duration for CR was 209 and 394+ days. The median response duration for PR was 371 (range 140-506+) days. Dose-limiting grade 3-4 toxicities were hypotension in 52% of the patients, arrhythmia (4%), dyspnoea (8%), creatinine rise (4%), peripheral neurotoxicity (10%) and central neurotoxicity (10%). Toxicities most often recovered solely on interrupted therapy. 2 patients died due to catheter-related septicaemia and one patient died of rIL-2 induced renal failure. The study confirmed the antitumour efficacy of rIL-2 in renal cell cancer. Toxicities were numerous, but manageable by close observation in a normal oncology ward without routine use of an intensive care unit.

Adult↗
PubMed1991

[Interferon and interleukin 2 in metastatic cancer of the kidney. Apropos of 18 cases].

Eighteen patients with advanced renal cancer received a combination of IFN alpha 10 x 10(6) U/m2/Day (D) x 5D followed by Interleukin 2 (IL2) 18 x 10(6) UI/m2/D x 5 D. The median follow-up is 10 months. Four partial responses were observed lasting 7 to 13 months (22.2%). The clinical safety was satisfactory. The survival for responding patients is 12 months (median). The safety of treatment is an argument in favour of future trials in an attempt to demonstrate the benefit of combinations of biomodulators.

Adenocarcinoma↗
PubMed1990

Combination chemotherapy of dacarbazine and fotemustine in disseminated malignant melanoma. Experience of the French Study Group.

A total of 70 patients presenting with a disseminated malignant melanoma were entered into a multicentric study of combination chemotherapy using dacarbazine and fotemustine. In all, 63 patients were evaluable, 31.8% of whom had previously received cytotoxic chemotherapy. The protocol consisted of induction treatment with a weekly infusion of 100 mg/m2 fotemustine on days 1 and 8 and a daily infusion of 250 mg/m2 dacarbazine on days 15/18 followed by a 4- to 5-week rest period. Responding and stabilized patients were given maintenance treatment comprising fotemustine (100 mg/m2, day 1) and dacarbazine (250 mg/m2, days 2/5) every 3 weeks. The response rate was 33.3% (9 complete responses (CRs) and 12 partial responses (PRs)) and was outstanding among pretreated patients (34.9%). Responses were also documented in cerebral (28.6%), visceral (23.1%) and nonvisceral (43.3%) metastatic sites. Toxicity was mainly hematologic (22.2%, grade III/IV leukopenia; 20.3%, grade III/IV thrombocytopenia) and was acceptable. These results are encouraging in terms of the antitumor activity against nonvisceral metastases (43.3%) and the percentage of CRs obtained (23.3%), and they confirm the activity of fotemustine in cerebral metastatic sites.

Adult↗
PubMed1989

Reliability of clinical criteria for the diagnosis of dementia. A longitudinal multicenter study.

The reliability of the clinical diagnosis of dementia was estimated by comparing the diagnosis made at 1-year intervals on 55 consecutive subjects with suspected cognitive impairment seen at three different centers by neurologists and gerontologists. The diagnosis was based on history and clinical examination, the criteria of the Diagnostic and Statistical Manual of Mental Disorders (revised ed 3), the Modified Ischemic Score, and a computed tomographic scan. Fifty-two of 55 subjects were given the same diagnosis a year later indicating a reliability of 95%. The study shows that a diagnosis of dementia established by simple clinical criteria comparable to the NINCDS/ADRDA criteria affords sufficient reliability to allow the comparability of groups at different centers for purposes of research, including research on the evaluation of the efficacy of pharmacologic treatment.

Aged↗
PubMed1989

Interleukin-2 with or without LAK cells in metastatic renal cell carcinoma: a report of a European multicentre study.

Between October 1987 and November 1988, 95 European patients with metastatic renal cell carcinoma have been treated with recombinant interleukin-2 (rIL-2) (EuroCetus) at 18 X 10(6) IU/m2/day (equivalent to 3 X 10(6) Cetus Units/m2/day) according to the West schedule in two trials. 1. Forty-two patients received rIL-2 alone. Median time between initial diagnosis and metastases was three months. Eighty-one percent of the patients had at least two involved sites at inclusion and 86% underwent prior nephrectomy. Twenty-seven patients (64%) received two successive courses. Over 80% of the planned dose was administered in 69% and 44% of patients during courses 1 and 2, respectively. Fever, hypotension, weight gain, rise in creatinine level, hepatic disturbances, anaemia and thrombocytopenia were commonly observed but resolved promptly after completion of therapy. No toxic death was recorded. Two (6%) complete responses (CR), four (13%) partial responses (PR), four stable diseases (SD) and 22 progressive diseases (PD) were observed. The response rate is 6/32 (19%); the median progression-free survival time is not reached at 218+ days (92-394). 2. Fifty-three patients received rIL-2 with lymphokine-activated killer (LAK) cells. Median time from primary diagnosis to metastases was three months. Eighty-five percent of patients had at least two involved sites though 73% had previously undergone nephrectomy. Forty patients (75%) received two successive induction courses. Most patients, i.e. respectively, 77% and 60%, were given at least 80% of the planned dose during courses 1 and 2. Median numbers of LAK cells infused were 13.1 and 11.6 X 10(9) nucleated cells per course, respectively. Toxicity was not different from that described above; no toxic death occurred; five CR (10%), nine PR (18%), 11 SD and 26 PD were observed. The response rate is 14/51 (27%) and the median progression-free survival time is not reached at 7.2+ months (3-13.1). In conclusion, rIL-2, with or without LAK cells, is obviously active on metastatic renal cell carcinoma. The difference in response rate between the two trials is not statistically significant but has to be paralleled with the difference in dose received by the patients rather than with the addition of a cellular therapy. Toxicity was always manageable and reversible. The association of rIL-2 with other lymphokines should represent a major issue to improve the response rate and will be considered in further European studies.

Carcinoma, Renal Cell↗
PubMed1989

[Regression and slowing of the growth of human pulmonary metastases induced by piroxicam, an inhibitor of prostaglandin synthesis].

The action of piroxicam, an inhibitor of prostaglandin synthesis, was evaluated in 31 cases of measurable pulmonary metastases of several primary cancers. In each case, the spontaneous doubling time was measured prior to and after a minimum of 3 months of treatment with piroxicam as a single drug, 20 mg daily po. The doubling time of metastatic lung nodules was significantly increased in 18/31 cases (58%) of which 10 cases had their spontaneous doubling time multiplied by two. Minor regressions were observed in 5/31 cases (16%) and one case of metastatic fibrosarcoma had a complete radiologic response. No effect was observed in 8/31 cases (26%). Prostaglandin synthesis inhibitors may be useful for treating metastatic cancer. Possible mechanisms of action are discussed.

Adult↗