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Biomedical subjects

A Sulkes

Publications and source records attributed to A Sulkes.

At least 19 recordsLinked to original sources
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

Gemcitabine in patients with advanced malignant melanoma or gastric cancer: phase II studies of the EORTC Early Clinical Trials Group.

BACKGROUND: Gemcitabine is a water-soluble analogue of deoxycytidine which has shown significant antitumour activity in a broad panel of slow-growing murine and human carcinomas. Objective responses have been reported in early clinical studies in breast, head and neck, non-small cell lung cancer patients. The weekly schedule was selected for disease-oriented phase II studies because of its better tolerability as compared to daily or twice-weekly schemes. PATIENTS AND METHODS: Gemcitabine (1000 mg/m2) was given as a 30 min. infusion, weekly for three consecutive weeks, followed by one-week rest, every 4 weeks. Twenty-nine patients with locally advanced/metastatic gastric cancer and 39 patients with metastatic malignant melanoma entered the study. No prior chemotherapy for advanced disease had been given in all cases. RESULTS: Among 26 evaluable patients with gastric cancer, 1 partial response (PR) of 9 months (4%), 11 no change (NC) and 14 tumour progression (PD) were observed. Of 33 evaluable patients with malignant melanoma, 1 patient achieved a PR for 10 months (3%), 2 had NC and 30 PD. Toxicity was similar in the two groups with moderate myelosuppression, mainly neutropenia, mild to moderate nausea and vomiting in 70% of patients and fatigue grade 1-2 in 50%. CONCLUSIONS: At the tested schedule gemcitabine has no relevant antitumour activity in previously untreated patients with advanced malignant melanoma or gastric cancer.

Adenocarcinoma↗
PubMed1994

Taxol: initial Israeli experience with a novel anticancer agent.

Taxol is a novel taxane derivative obtained from the bark of the Pacific yew, Taxus brevifolia, which has demonstrated substantial antitumor activity in early clinical trials. Intensive research efforts were necessary to overcome both supply problems and hypersensitivity reactions to the drug and thus assure its widespread use. Taxol is active in a variety of neoplasias, including advanced breast and ovarian tumors resistant to drugs such as doxorubicin and cisplatin, respectively. We report here the initial experience with taxol in these two disease entities in Israel, at three institutions within the framework of large multinational trials. These studies compared a) the use of two dose levels of taxol, and b) short, 3-h administration vs. a longer 24-h infusion of the drug. A total of 107 Israeli patients, 38 with ovarian cancer and 69 with breast cancer, were given 706 courses of taxol. Our results show that the administration of taxol at doses ranging between 135 and 175 mg/m2 is indeed feasible and that 3-h infusions are as well tolerated as longer administration. The main hematological toxicity was leukopenia, which was promptly reversible and was more pronounced both at the higher dose level and with the more prolonged infusion. Of the nonhematological side effects, the most prominent were alopecia, mild nausea and vomiting, limb paresthesias, fatigue and myalgia. Allergic reactions following routine premedication were mild and infrequent, never necessitating discontinuation of the drug. Clinically significant cardiac events did not occur. Taxol is an important addition to the anticancer chemotherapy armamentarium.

Adult↗
PubMed1993

Second-line chemotherapy with mitoxantrone as a single agent in metastatic breast cancer.

Ninety-three evaluable patients with metastatic breast cancer previously treated with chemotherapy, received mitoxantrone as a single agent (14 mg/m2, by rapid intravenous infusion, once every 3 weeks). Patients received a median of 7 courses (range 2 to 18), with a mean cumulative total dose of 133 mg (range 36 to 342). A complete response (CR) was achieved in 2 patients (2%). Partial response (PR) was observed in 23 patients (25%). The overall response rate (CR+PR) was thus 27%, with a median duration of 9 months (range 3 to 18). Responses were observed in all metastatic sites, except for brain and peritoneum. Stabilization (S) occurred in 26 patients (28%). The remaining 42 patients (45%) showed clear progression of their metastatic disease while on therapy. The actuarial 24-month survival for the whole group was 13%, increasing to 29% in responders (CR+PR), as compared with only 10% for non-responders (S+P; P < 0.0001). Mitoxantrone was generally well tolerated; nausea, vomiting and hair loss were mild. Nine out of 625 treatment cycles resulted in leukopenic fever with uneventful recovery. All patients had serial MUGA scans; 3 patients (cumulative total doses of 200, 250 and 342 mg, respectively) developed a significant drop in the left ventricular ejection fraction. Clinical evidence of congestive heart failure was observed in one patient who had received prior doxorubicin-based adjuvant chemotherapy. Mitoxantrone seems to be as effective as other drugs given singly or in combination as second-line chemotherapy in patients with metastatic breast cancer. Its low morbidity makes its use attractive in this setting.

Adult↗
PubMed1993

The use of cyclophosphamide, methotrexate, and 5-fluorouracil in the treatment of Merkel cell carcinoma.

Five patients with advanced Merkel cell carcinoma (MCC) are described. Four patients with regional lymph node involvement and one with disseminated skin metastases were treated with systemic chemotherapy, including cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). The patients received a median of six cycles of CMF (range: 2 to 6), and chemotherapy was well tolerated. Four complete and one partial response were noted. Three patients are alive and are disease-free at 5, 12, and 37 months from the onset of CMF chemotherapy. Two patients died from disseminated metastatic disease at 3 and 24 months from the onset of chemotherapy. CMF chemotherapy appears to be an active regimen in the treatment of locally advanced MCC. Further experience with this combination is warranted.

Adult↗
PubMed1993

The treatment of advanced Merkel cell carcinoma. A multimodality chemotherapy and radiation therapy treatment approach.

BACKGROUND: The optimal management of Merkel cell carcinoma has not been clearly defined. OBJECTIVE: To describe the treatment of eight patients who presented with Merkel cell carcinoma. METHODS: Eight patients with advanced locoregional Merkel cell carcinoma were seen in our institute over a 7-year period. Four patients were successfully treated by induction chemotherapy after excisional biopsy, followed by radiotherapy. Three patients died from widespread metastases and one from neutropenic sepsis induced by chemotherapy. RESULTS: These cases demonstrate the potential lethality and aggressive nature of this rare skin tumor despite its chemosensitive and radioresponsive character. In all four patients who are alive and disease-free, chemotherapy was given first and radiotherapy was given as consolidation. CONCLUSION: We suggest that a multimodality treatment approach--chemotherapy followed by radiotherapy--is indicated in patients with advanced Merkel cell carcinoma.

Adult↗
PubMed1993

Current developments in breast cancer.

Interest in the prevention and early detection of breast cancer (BC) is increasing. Prevention studies are under way, and new data from mass screening trials are being evaluated. Improvement of the quality of mammography films and their proper interpretation are regarded as essential for effective early detection. With screening encompassing an increasing number of women, the rising proportion of suspicious breast findings had led to renewed efforts to improve the accuracy of cytologic diagnosis. Basic research continues to contribute to a better understanding of BC biology. Improved discrimination between subsets of patients with different prognosis is expected to optimize results of therapy in operable BC. Reports on taxol and suramin, new types of antitumoral drugs, as well as progress in monoclonal antibody therapy, may constitute preliminary steps towards novel therapeutic strategies.

Breast Neoplasms↗
PubMed1992

Breast metastases to bones of the extremities: simultaneous involvement of all four limbs.

Metastases to bones of the hands and feet are unusual, and simultaneous metastases to the bones of more than one extremity in a given patient is an extremely rare occurrence with only five previous case reports. In each of these cases the bones of two extremities were affected. A case is presented where the bones of both hands and both feet exhibited bone metastases. A second case with foot bone metastases is recorded. In both cases the primary tumour was a breast carcinoma. Theories of causation of such metastases are discussed.

Arm↗
PubMed1991

The infrequent association of systemic lupus erythematosus and solid tumors.

The authors describe the clinical course of two patients with long-standing, indolent systemic lupus erythematous (SLE) who developed, respectively, a breast carcinoma and a malignant melanoma 8 and 15 years after the diagnosis of lupus; both patients died with evidence of widespread, rapidly progressive metastatic disease at a time when the SLE was minimally active and did not require immunosuppressive therapy. The association of SLE and solid tumors in the same patient is reviewed. The frequency of this association appears to be low and the most often described tumors are of uterine and bladder origin. The clinical course of the solid malignancy in these patients is not always described in detail. Careful epidemiologic studies on the true incidence of solid tumors in patients with SLE are required to better understand this association.

Adult↗
PubMed1991

Phase I and clinical pharmacological evaluation of aphidicolin glycinate.

The toxicity profile and the pharmacokinetics of aphidicolin glycinate, a water-soluble analogue of aphidicolin, have been evaluated in two consecutive phase I clinical studies. In the first study, aphidicolin glycinate was given by 1-hour infusion for 5 consecutive days, every 3 weeks (daily x 5 study); in the second study, which was planned on the basis of the pharmacokinetic information obtained in the previous study, the drug was given by 24-hour continuous infusion. Treatment was repeated every 3 weeks. In the daily x 5 study, the daily dose was escalated from 12 mg/m2 to the maximum tolerated dose of 2250 mg/m2. Local toxicity was dose limiting. Elimination half-life was 2 +/- 0.2 hours (mean +/- SE) with aphidicolin being undetectable 6-8 hours after the end of the infusion. In the 24-hour continuous-infusion study, the dose was escalated from 435 mg/m2 to the maximum tolerated dose of 4500 mg/m2. Local toxicity was dose limiting, while other toxic effects were absent. The experimentally determined concentrations at the steady state were in agreement with those predicted on the basis of the available pharmacokinetic data. The targeted concentration at the steady state of 3 micrograms/mL was achieved at doses greater than or equal to 3000 mg/m2. Twenty-four-hour continuous infusion is the recommended schedule for clinical evaluations of aphidicolin glycinate as the synchronizing agent or in combination with cisplatin.

Adult↗
PubMed1991

Pharmacokinetic and imaging studies in patients receiving a formulation of liposome-associated adriamycin.

Pharmacokinetic and imaging studies in 19 patients receiving liposome-entrapped adriamycin (L-ADM) were carried out within the framework of a Phase I clinical trial (Gabizon et al., 1989a). The formulation of L-ADM tested consisted of 0.2 microM-extruded multilamellar vesicles composed of egg phosphatidylcholine, egg-derived phosphatidyl-glycerol (PG), cholesterol, and ADM intercalated in the fluid lipid bilayer. Plasma clearance of total drug extracted from the plasma after L-ADM infusion followed a biexponential curve with a pattern similar to that reported for free ADM. The plasma concentration of drug circulating in liposome-associated from was also measured in a subgroup of seven patients. Liposome-associated drug was found to be rapidly cleared from plasma. Its ratio to non-liposome-associated drug appeared to correlate with liver reserve, with highest ratios in patients with normal liver function. Liposome clearance, as measured by the plasma concentration of PG in three patients was slower than the clearance of liposome-associated ADM, suggesting that liposomes lose part of their drug payload during circulation. To learn about the liposome organ distribution, imaging studies were carried out with 111Indium-deferoxamine labelled liposomes of the same composition. Liposomes were cleared predominantly by liver and spleen and to a lesser extent by bone marrow in seven out of nine patients. In two patients with active hepatitis and severe liver dysfunction, there was minimal liver uptake and increased spleen and bone marrow uptake. Except for one hepatoma patient, intrahepatic and extrahepatic tumours were not imaged by liposomes, suggesting that liposome uptake is restricted to cells of the reticulo-endothelial system (RES).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Radiation therapy for locally advanced breast cancer: prognostic factors and complication rate.

A retrospective analysis was carried out in 100 patients with locally advanced breast cancer without distant metastases treated by radiotherapy between 1960 and 1979. The primary tumor was irradiated to a total dose of 60 Gy in 76 patients and to doses ranging between 60 and 80 Gy in 24 patients. The regional lymphatics were treated with doses between 50 and 60 Gy. Following radiotherapy, chemotherapy was administered to 58 patients and hormonal therapy to 29, while 13 patients received no further therapy. Locoregional recurrences were documented in 29% and distant metastases in 49% of patients. The actuarial survival was 56% at 5 years, 21% at 10 years and 14% at 15 years. At 10 years 90% of the surviving patients had some degree of radiation damage.

Adult↗
PubMed1989

Cisplatin, bleomycin, and methotrexate (PBM) chemotherapy in locally advanced and metastatic head and neck cancer.

Twenty-two patients with locally advanced or metastatic head and neck tumors received a total of 84 courses of a combination of cisplatin, bleomycin, and Methotrexate (PBM) for a median of four courses per patient (range, 1-7). Among these 22 patients there were four patients (18%) who achieved complete remission (CR) and 13 patients (60%) who had a partial remission (PR). The overall remission rate (CR + PR) thus reached 78%; five patients (22%) progressed while on therapy. The mean duration of objective response (CR + PR) was 8 months; CR lasted a median of 18 months (range, 2-48). Survival was not influenced by tumor histology or by previous surgery. The presence of locoregional disease did adversely affect survival from the onset of chemotherapy (P = 0.1). The rate of survival was also affected by primary tumor site; patients with nasopharyngeal primaries survived longer than all other patients (22 vs. 11 months, P = 0.06). Toxicity to chemotherapy consisted mainly of nausea and vomiting and stomatitis. Three patients developed fever while leukopenic. One patient experienced irreversible renal damage, and another suffered from bleomycin-induced pulmonary fibrosis. The high response rate obtained in our group of patients did not have a substantial impact on overall survival. Aggressive, multimodality approaches should be considered in the treatment of these patients when possible.

Antineoplastic Combined Chemotherapy Protocols↗