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Biomedical subjects

A Sulkes

Publications and source records attributed to A Sulkes.

At least 37 records · Page 2Linked to original sources

HLA-DR and beta 2 microglobulin expression in medullary and atypical medullary carcinoma of the breast: histopathologically similar but biologically distinct entities.

AIMS: To examine the expression of HLA-DR and beta 2 microglobulin in medullary carcinoma and atypical medullary carcinoma of the breast to determine if the effective presentation of tumour antigens to the immune system can differentiate between these two histopathologically similar entities. METHODS: Expression of HLA-DR and beta 2 microglobulin was examined by immunohistochemical methods in five samples of medullary carcinoma of the breast, which has a relatively favourable prognosis, six samples of atypical medullary carcinoma of the breast, which has a prognosis closer to that of regular invasive duct carcinoma, and 20 samples of invasive duct carcinomas, 10 with an accompanying lymphocytic infiltrate. RESULTS: A positive and significant correlation was found between tumour type and both HLA-DR and beta 2 microglobulin expression. Expression was most prominent in medullary carcinoma, followed by atypical medullary carcinoma and invasive duct carcinoma with and without lymphocytic infiltrates. The mean intensity and percentage of HLA-DR tumour immunostaining were significantly higher in medullary carcinoma than in the other three tumour groups, as was the mean intensity of beta 2 microglobulin immunostaining. Mean percentage of beta 2 microglobulin immunostaining was significantly higher in medullary carcinoma than in invasive duct carcinoma without lymphocytic infiltrates, and showed a trend to increase from invasive duct carcinoma with lymphocytic infiltrates to atypical medullary carcinoma and medullary carcinoma. CONCLUSIONS: Medullary carcinoma and atypical medullary carcinoma of the breast differ in their expression of HLA-DR and beta 2 microglobulin. The relatively favourable prognosis of medullary carcinoma of the breast may be related to effective tumour antigen presentation to the immune system through MHC-I and MHC-II expression. Immunotherapy aimed at MHC-I and MHC-II induction might have a beneficial effect in breast cancer.

Adult↗

Low PSA metastatic androgen- independent prostate cancer.

OBJECTIVES: To describe the clinical parameters of low PSA, progressive metastatic androgen-independent prostate cancer. METHODS: From April 1995 to May 1999, we selected 18 patients with clinically progressive androgen-independent prostate cancer and low PSA (</=10 ng/ml). Patients received cisplatin-based therapy. Specimens from the primary tumor were reviewed and neuroendocrine differentiation was determined with chromogranin-A and neuron-specific enolase immunocytochemical staining. RESULTS: The median initial PSA level was 1.6 ng/ml (0-9.5). Each patient demonstrated elevation of at least one of the following markers: carcinoembryonic antigen, CA 19-9, CA15-3 and CA 125 CA. Metastases involved bone in 11 patients (61.1%) - 5 (27.7%) blastic, 2 (11.1%) lytic, and 4 (22.2%) combined - liver in 10 patients (55.5%), lymph nodes in 8 (44.4%), and lung in 6 (33.3%); solitary sites as orbit, skin and spleen were noted as well. A prostatic pelvic mass was detected in 13 patients (72.2%). Of the 12 patients who consented to chemotherapy, 8 (66.6%) achieved an objective response (95% CI, 34. 8-90%), including 1 patient with complete response. Hematoxylin and eosin evaluation revealed two major groups: neuroendocrine tumors, either pure small cell cancer in 6 patients (37.5%) or combined small cell cancer and adenocarcinoma in 8 (50%), and predominant poorly differentiated prostate cancer in 2 (12.5%). Neuroendocrine immunoreactivity was detected in all the specimens. CONCLUSIONS: Progressive androgen-independent prostate cancer with low serum PSA is characterized by visceral metastases, high proportion of lytic bone disease, sensitivity to cisplatin-based chemotherapy, and histological features of small cell or poorly differentiated prostate cancer. In this subgroup of patients, selection of the therapeutic approach can be based on clinical parameters. The rise of the serum markers may aid in the diagnosis and follow-up of these patients.

Androgens↗

Combination chemotherapy following adrenal suppression in androgen- independent prostate cancer.

OBJECTIVES: Recent trials with modern chemotherapy have demonstrated activity in androgen-independent prostate cancer, but all focused on patients with progression following androgen suppression or antiandrogen withdrawal. Limited data are available on the activity of chemotherapy in androgen-independent, hormone-refractory (progressing following adrenal suppression) prostate cancer. We evaluated the activity of estramustine combined with vinblastine in this subset of androgen-independent prostate cancer. METHODS: From January 1995 until April 1999, 19 patients with hormone-refractory prostate cancer received estramustine 140 mg p.o., three times daily along with weekly vinblastine 5 mg/m(2). RESULTS: A decrease in prostate-specific antigen of 50% or more was noted in 12 patients (63.1%, 95% CI 38.3-83.7%). The median decrease in prostate-specific antigen was 71.2% (range 50.5-85.2%). None of the 7 patients with measurable soft-tissue disease showed an objective response. The median survival from onset of chemotherapy was 6 (range 1.4-27.7) months and from initiation of adrenal suppression 16.9 (range 3.8-40. 5) months. CONCLUSIONS: The combination of estramustine and vinblastine is capable of inducing activity in androgen-independent prostate cancer progressing after adrenal suppression. In our small sample, the survival rate was low, and we obtained no response in soft-tissue sites. Future prospective trials are needed to determine the benefit of sequential versus simultaneous incorporation of adrenal suppression with chemotherapy in the management of androgen-independent prostate cancer.

Adult↗

Prognostic factors for local control of early glottic cancer: the Rabin Medical Center retrospective study on 207 patients.

PURPOSE: Different radiation therapy schedules and devices have been used over the last 20 years at Rabin Medical Center in patients with early glottic cancer. The aim of the present retrospective analysis was to identify the subgroup of patients at high risk of failure of radiation treatment. MATERIALS AND METHODS: Between 1974 and 1994, 207 patients with squamous cell carcinoma of the glottis, 182 Stage T1 and 25 Stage T2, underwent definitive radiation therapy. During this period, treatment was administered with different radiation devices (60Co or 6-MV X ray), using different dose/fraction protocols (1.8 or 2 Gy per day, 5 or 6 fractions per week), total doses (42-77.4 Gy), overall radiation times, and delays. These treatment variables, in addition to certain patient and tumor characteristics, were correlated with local control at a median follow-up of 57 months (range 18-265 months). RESULTS: The 5-year local control rates for T1 and T2 tumors were 88% and 73%, respectively. Univariate analysis showed that smoking, diabetes mellitus, anterior commissure involvement, T stage, and extension of tumor to one third or more of the vocal cord were highly significantly correlated with decreased local control. None of the treatment variables, including dosage at which complete tumor regression was noted, were found to be predictive. By multivariate analysis, only anterior commissure involvement was found to be highly significant (risk ratio 1.9, 95% CI 1.2-3.0, p = 0.027), and T stage was borderline significant (risk ratio 1.6, 95% CI 1.0-2.5, p = 0.054). CONCLUSION: This study suggests that only two tumor characteristics are predictive of local failure of early glottic cancer: anterior commissure involvement and T stage. Treatment variables apparently do not influence local control.

Adult↗

[Combination chemotherapy with M-VAC protocol in metastatic urothelial cancer].

The treatment of metastatic urothelial cancer is based on the combination of cisplatin, methotrexate, vinblastine and adriamycin (M-VAC). From November 1994 to May 1997 we treated 25 patients (51 men, 3 women, aged 50-77) with M-VAC. The tumor originated from the urinary bladder in 14 (56%) and the upper urinary tract in 11 (44%). Disease sites included: primary--5 (25%), lymph nodes--17 (68%), lungs--10 (40%), bones--8 (32%), pelvic mass and liver each--4 (16%), with an overall median of 2 (1-5) sites per patient. 9 patients (38%) had complete responses and 8 (32%) had partial responses, for an overall response rate of 68% (95% CI 48.5%-85%). The median duration of response was 15.3 (1.6-29.6+) months. Median survival of responders was 19.1 (4.8-35.7+) months compared to 6.2 (0.7-11.2) for the non-responders (p < 0.05). 13 (52%) of patients are alive, of whom 8 (32%) are free of disease and 5 with a single metastatic site on presentation at follow-up. In the 118 treatment cycles we observed grade III-IV toxicity: myelosuppression 53 (45%), thrombocytopenia 4 (3%), stomatitis 8 (6.7%), diarrhea 3 (2.5%). There were 22 infectious episodes and 1 patient died of sepsis. We achieved a high response rate with the combination M-VAC. However, only a third had long-term disease-free states and treatment was associated with excessive toxicity. Therapeutic approaches with new agents are required to improve the response rate and toxicity.

Aged↗

Role of radiation therapy in the management of cutaneous malignant melanoma.

Traditionally, cutaneous malignant melanoma is regarded as a radioresistant tumor. Recently, however, an increasing number of clinical studies have refuted this notion. The authors examined the role of radiation therapy in the palliative and/or adjuvant treatment of cutaneous malignant melanoma. The records of 69 patients with cutaneous malignant melanoma were reviewed. Twenty-five patients with extensive regional lymph node involvement received adjuvant radiation therapy after primary surgical treatment, and the remainder received palliative radiation therapy. The therapeutic significance of fraction size was analyzed. In the palliative radiation therapy group, the response rate was 52% with a fraction size < or = 300 cGy and 35% with a larger fraction size (p > 0.05, NS). Local regional control rates after adjuvant radiation therapy using conventional fractionation and larger fraction size were 87% and 82%, respectively (p > 0.05, NS). Radiation therapy is effective in the management of cutaneous malignant melanoma. It plays an important role in the palliation of metastatic disease and as an adjuvant treatment. No advantage in using a large fraction size over conventional dose schedules was found.

Adult↗

Tailoring treatment for classical Kaposi's sarcoma: comprehensive clinical guidelines.

Classical Kaposi's sarcoma (CKS) is a rare indolent proliferative disease which is particularly prevalent among Jews of Ashkenazi and Mediterranean origin. To define guidelines for its comprehensive management, we conducted a retrospective analysis of 123 patients, focusing mainly on treatment modalities. The CKS-related mortality was 4% (5 patients). Of the 39 patients for whom observation only was the primary approach, 15 (38%) remained progression-free for 1-83 months (median, 4 months). Twenty-nine of the 52 (56%) patients who underwent surgery as the primary approach remained recurrence-free for 1-162 months (median, 15 months). Radiotherapy achieved an objective response in 74 courses (85%), including 50 (58%) complete responses. Symptomatic relief was reported in 95% of the patients. Vinblastine (27 series) achieved an objective response in 73% of series, including 22% complete responses. Multivariate analysis of time to progression with observation alone identified immunosuppression as the only significant independent factor that predicted disease progression. Our study suggests that observation alone may be sufficient for immunocompetent asymptomatic patients; symptomatic resectable lesions are suitable for simple excision; and more advanced disease or unresectable lesions require radiotherapy. If disease is extensive or the other approaches fail, chemotherapy is appropriate. Tailoring the treatment for CKS is an integrative process, requiring good understanding of the role of each available modality in the different clinical disease settings.

Adult↗

Coronary artery operation in patients after breast cancer therapy.

OBJECTIVE: The purpose of this investigation was to retrospectively study the outcome of patients undergoing coronary artery operation who were previously treated for breast cancer. METHODS: Between July 1992 and December 1996, 28 patients with a history of breast cancer underwent coronary artery bypass graft operation and were randomly matched against a noncancer group of similar size (n = 36) to allow for comparison of their preoperative characteristics, operative course, and postoperative outcome. RESULTS: The incidence of sternal wound infection was significantly higher in the cancer group than in the control group (25% versus 6%; p = 0.027). Postoperative noncardiac chest pain occurred more frequently in the cancer group than in the control group (52% versus 31%; not significant). In the study group, radiotherapy and recent myocardial infarction were the only two independent factors associated with sternal wound complications. Patients with a less than 17-year interval between the breast cancer therapy and the coronary artery operation had a higher incidence of sternal wound infection (46%) as opposed to patients with a longer time interval (7%; p = 0.028; odds ratio = 12). Sternal wound complications were more frequent in patients with a history of right-sided breast cancer (50%) compared with left-sided lesions (12.5%; p = 0.068; odds ratio = 7). CONCLUSIONS: Coronary artery operation in patients after breast cancer therapy may be associated with an increased sternal wound infection rate. To decrease this risk of infection, an approach through a right thoracotomy, minimally invasive techniques, the use of skeletonized internal mammary artery, and broad spectrum antibiotic therapy may be considered.

Aged↗

Antiandrogen withdrawal syndrome with cyproterone acetate.

OBJECTIVES: To determine whether the antiandrogen withdrawal syndrome occurs with the steroidal antiandrogen cyproterone acetate. METHODS: Cyproterone acetate was withheld in 12 patients with progressing androgen-independent metastatic prostate cancer. Eight patients had been receiving cyproterone acetate concomitant with androgen ablation, and in 4 patients it was prescribed after failure of androgen suppression. Time to response and to disease progression were defined by serum prostate-specific antigen (PSA) levels and imaging studies. RESULTS: PSA levels decreased in 5 of the 1 2 patients; in 4 of them (33%), the decrease exceeded 50%. The decline lasted a median of 24 weeks (range 9 to 37.8). All 5 patients had received initial concomitant exposure to androgen ablation and cyproterone acetate. CONCLUSIONS: We recommend that the steroidal antiandrogen cyproterone acetate be added to the list of agents capable of inducing antiandrogen withdrawal syndrome.

Aged↗

A sequential four-drug chemotherapy and biotherapy with interferon alpha and GM-CSF--an innovative protocol for the treatment of metastatic melanoma.

We present the results of our chemo-biotherapy protocol for patients with metastatic melanoma. The rationale for the design of the combined therapy was induction of systemic anti-tumor immunity by: (a) priming with IFN-alpha for enhancement of tumor and histocompatibility antigen expression, (b) therapy by the 4-drug regimen (BCNU, DTIC, cisplatin and tamoxifen) for maximal tumor destruction, followed by (c) an immunomodulatory, low dose of GM-CSF. Treatment was given in cycles of three weeks: first IFN-alpha (3 x 10(6) U/day on days 1, 3, and 5); then the 4-drug regimen given according to Del Prete et al., (4); followed by GM-CSF (20 micrograms/m2/day on days 15 to 21). All patients were previously untreated by chemotherapy, and had a performance status of ECOG 0-2. Treatment was discontinued upon severe toxicity or disease progression. In responding patients--once maximal response was achieved-IFN alpha treatment (3 x 10(6) U/day, three times weekly) was continued for a period of two years or until disease progression. All 40 patients (28 males and 12 females) who received the above program were evaluable for response and toxicity and received at least two cycles of therapy. At a median follow-up of one year, 50% had achieved an objective response, with 22.5% complete responses (CR), and 27.5% partial remissions (PR). Median duration of response is 11 months (12 for CR and 9 for PR patients). Median survival for all patients is 14 months (range, 7-21), increasing to 22 months (range, 15-29) in responding patients. Activation of patients' peripheral blood Macrophages and Dendritic Cells was observed following GM-CSF treatment. The chemo-biotherapy protocol presented above--while associated with acceptable toxicity--resulted in a relatively high response rate with an increase in the number of durable responses in patients with metastatic melanoma.

Adolescent↗

Classic Kaposi sarcoma: experience at Rabin Medical Center in Israel.

Classic Kaposi sarcoma is an indolent cutaneous proliferative disease affecting mainly elderly people of Mediterranean and Jewish origin. The authors review the epidemiologic and clinical findings in Israeli patients with classic Kaposi sarcoma treated at the Institute of Oncology, Rabin Medical Center. A total of 123 patients were identified. The average age at diagnosis was 68 years (range, 20-90 years) and, as expected, there was a strong predominance of men (2.4:1). All but two patients were Jewish. The distribution of Ashkenazic Jews and Sephardic Jews was almost equal. Twenty-three patients (19%) had secondary malignancies that were mostly solid tumors. The clinical course was indolent and rarely fatal (4% disease-related mortality). Multivariate analysis revealed that non-Ashkenazic origin, age over 70 years, multiple lesions (>10), and immunocompromised conditions adversely affected survival. Radiotherapy for localized skin lesions yielded an 88% objective response, with symptomatic relief in 95% of patients. Chemotherapy was similarly effective (76% response rate) in patients with disseminated disease. These data demonstrate the indolent nature of classic Kaposi sarcoma which usually requires a less aggressive therapeutic approach than in the African and AIDS-related types of Kaposi sarcoma.

Adult↗

Uracil-ftorafur: an oral fluoropyrimidine active in colorectal cancer.

PURPOSE AND DESIGN: This review describes the early clinical development of uracil-ftorafur (UFT), an oral fluoropyrimidine, designed in 1978 by adding uracil to ftorafur. The review focuses on the treatment of colorectal cancer and summarizes the Japanese experience and the phase I and II trials performed in the United States and Europe. RESULTS: Clinical trials of UFT published in the Western world have included 581 patients with colorectal cancer. UFT has been administered in these trials as a single agent or biomodulated by leucovorin (LV). UFT was administered daily in split doses for periods that ranged from 14 to 28 days. The activity of oral UFT in large-bowel cancer when administered with oral LV (approximately 50 mg/dose) has resulted in objective response rates of approximately 40%. Response rates of approximately 25% (range, 17% to 39%) were reported when UFT was administered as a single agent or with lower doses of LV. The highest dose-intensities of UFT are achieved with 28-day schedules of administration. The maximum-tolerated dose (MTD) of UFT with this schedule, when administered concomitantly with oral LV 150 mg daily, is 300 mg/m2 daily. The dose-limiting toxicity (DLT) of UFT has generally been diarrhea. Other commonly described toxicities include nausea and vomiting, fatigue, and stomatitis. Myelosuppression occurs infrequently. Typically, hand-foot syndrome and neurologic toxicity are lacking. CONCLUSION: UFT is a fluoropyrimidine active in colorectal cancer. The oral route of administration and improved safety profile represent important advantages over both conventional and infusional fluorouracil (5-FU) regimens.

Administration, Oral↗

The role of radiation therapy and chemotherapy in the treatment of Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma is a rare and highly aggressive skin tumor. The purpose of this study was to determine the role of radiation therapy and chemotherapy in the treatment of patients with Merkel cell carcinoma. METHODS: A retrospective analysis of 27 patients treated at Rabin Medical Center in Israel is presented, focusing on the treatment details. Data for 40 patients (the authors' 27 patients and an additional 13 patients from the Israeli Cancer Registry), were analyzed for prognostic factors using univariate and multivariate analyses. RESULTS: Univariate analyses revealed regional lymph node involvement and the coexistence of a second primary tumor as unfavorable prognostic factors. On multivariate analysis, only lymph node involvement showed borderline statistical significance. Radiation therapy was highly effective when given as consolidation after surgery or chemotherapy. In 11 patients irradiated effectively, only 1 (9%) in-field recurrence occurred. Radiation therapy yielded responses in 15 of 15 measurable sites (5 complete responses and 10 partial responses). Chemotherapy produced responses in 18 of 26 patients (69%), mostly complete (41%). However, in the absence of radiation therapy, the responses were short lived. CONCLUSIONS: These data support the use of combined treatment with chemotherapy followed by radiation therapy for patients with advanced locoregional Merkel cell carcinoma. In patients with metastatic disease, chemotherapy as well as radiotherapy can provide effective palliation. Further large scale investigations are warranted to confirm this approach.

Adult↗

[Malignant epidural cord compression].

Malignant epidural spinal cord compression (MSCC) may appear in 5-10% of adults and 3-5% of children with active malignant disease. Early diagnosis and treatment are imperative to prevent irreversible neurological damage below the level of cord compression. Unfortunately such procedures are often subjected to patient and/or doctor delay, when the emergency nature of MSCC is not understood. 3 women and 2 men, aged 17-74, are described, who illustrate both the variability of the presentation of MSCC and of its clinical course, and also problems related to imaging studies necessary to reach appropriate therapeutic decisions. These cases should increase physicians' awareness of the necessity for its early diagnosis and treatment. In addition, it is suggested that a multidisciplinary team approach be followed when MSCC is suspected (in accord with flow chart in Hebrew text).

Adolescent↗

Merkel cell carcinoma in Israel.

Merkel cell carcinoma is a rare and highly malignant skin tumor. We present the first report on the clinical and epidemiologic characteristics of Merkel cell carcinoma in Israel. Our findings, including average age of 69 years at diagnosis, equal sex distribution, disease location on sun-exposed skin, and an overall 3 year survival of 58%, are consistent with the data reported in the literature. Unique findings in our study were the predominance of Ashkenazic Jews and the excessive rate of second malignancies. This initial report on Merkel cell carcinoma in Israel emphasizes the need for increased awareness of this aggressive and potentially lethal skin malignancy.

Adult↗

Phase II studies of docetaxel in the treatment of various solid tumours. EORTC Early Clinical Trials Group and the EORTC Soft Tissue and Bone Sarcoma Group.

Docetaxel has been evaluated in six tumour types in a total of 189 patients entered into phase II studies. Treatment consisted of a 1 h intravenous infusion of docetaxel 100 mg/m2 repeated every 3 weeks. No premedication was administered for possible hypersensitivity reactions. Docetaxel was found to be effective as first-line chemotherapy for head and neck cancer (response rate 44%) gastric cancer (23%) and melanoma (14%) and as second-line chemotherapy for soft tissue sarcomas (21%; 95% confidence interval: 7.5%-43.7%). The results in colorectal and renal cancer were disappointing, with response rates of less than 10%. The most frequent adverse effects were alopecia (81%), grade III-IV leukocytopenia of short duration (66%) and skin reactions (52%). Hypersensitivity reactions were mild and occurred in 26% of patients. Docetaxel is an important new drug in the treatment of solid tumours.

Antineoplastic Agents, Phytogenic↗

Allogeneic human liposomal melanoma vaccine with or without IL-2 in metastatic melanoma patients: clinical and immunobiological effects.

The aim of this pilot study was to assess the clinical and immunological effects of human allogeneic liposomal melanoma vaccine alone or combined with Interleukin-2 (IL-2) in patients with metastatic melanoma. Four concurrent treatment arms were included: vaccine alone (A); vaccine combined with systemic IL-2 (B); vaccine combined with low-dose liposomal regional IL-2 (C); and low-dose regional IL-2 as in group C but without vaccine (D). Vaccine was prepared from semisynthetic phospholipids (dimyristol phosphatidylcholine and dimyristol phosphatidylglycerol) and membranes of six human melanoma cell lines. The latter were chosen as expressing MHC class I and II antigens and a "mosaic" of melanoma-associated antigens (MAAs) as detected by MoAbs R24, p97, CF21 and TA99. Nine of the 24 patients had objective clinical responses: of the ten patients treated with liposomal vaccine and low dose regional IL-2 (arm C), three had complete responses (CR) and three had partial responses (PR); of the five patients treated with liposomal, low-dose regional liposomal IL-2 only (arm D), three had PRs. No clinical responses were seen in patients treated by vaccine alone (A) nor in patients treated by vaccine and systemic IL-2 (B). Patients' in vivo and in vitro cellular immune responses were closely monitored. Conversion to positive cutaneous delayed type hypersensitivity (DTH) to membrane vaccine (without liposomes) was induced only in the six clinical responders of arm C. Positive DTH correlated with augmented in vitro proliferative lymphocyte responses stimulated by melanoma cell lines and membrane preparation and with the augmented cytolytic activity against melanoma cell lines.

Adult↗

Docetaxel (Taxotere) in advanced gastric cancer: results of a phase II clinical trial. EORTC Early Clinical Trials Group.

Thirty-seven eligible patients, median age 59 years (range 37-72) and median performance status 1 (0-2), with advanced, untreated, measurable gastric carcinoma were given docetaxel, 100 mg m-2 i.v. over 60 min without premedication, once every 3 weeks. Metastatic sites included the liver in 12 patients and retroperitoneal lymph nodes in 16. Eight of the 33 evaluable patients (24%) achieved a partial remission for a median of 7.5 months (3-11+). An additional 11 patients had stabilisation of disease. The patients received a median of four cycles of docetaxel (range 1-8) for a total of 156 courses. Dose reduction was necessary in 30 cycles; 14 cycles were delayed a mean of 3 days. Haematological toxicity consisted mainly of non-cumulative neutropenia, with a median nadir count of 0.35 x 10(9) l-1 (0.04-1.64) and eight episodes (5%) of leucopenic fever; non-haematological toxicities included alopecia, mild nausea and vomiting and allergic manifestations such as skin rash and pruritus. There were no drug-related deaths. Our data indicate that docetaxel is an active agent in advanced gastric cancer; further clinical investigations seem warranted.

Adult↗