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Biomedical subjects

E S Casper

Publications and source records attributed to E S Casper.

At least 37 records · Page 2Linked to original sources
PubMed1995

A phase II trial of doxorubicin HCl Liposome Injection in patients with advanced pancreatic adenocarcinoma.

We conducted a phase II study with doxorubicin encapsulated in a liposomal preparation (Doxorubicin HCl Liposome Injection) at a dose of 75 mg/m2 administered as a one hour infusion once every three weeks. Sixteen patients were entered to the trial and 15 are evaluable for response. Hematologic toxicity was significant. The median white blood count was 1.6 x 10(3)/microliters (range: 0.1-9.5), median absolute neutrophil count 0.6 x 10(3)/microliters (range: 0-5.8) and median platelet count was 142.0 x 10(3)/microliters (range: 20-327). Gastrointestinal toxicity was generally mild. Despite two minor responses in liver metastases with a significant decrease in CEA in one of these patients, no major responses were observed, excluding with 95% confidence, a response rate in excess of 20%.

Adenocarcinoma↗
PubMed1995

Altered patterns of retinoblastoma gene product expression in adult soft-tissue sarcomas.

Altered expression of the retinoblastoma (RB) tumour-suppressor gene product (pRB) has been detected in sporadic bone and soft-tissue sarcomas. Earlier studies, analysing small cohorts of sarcoma patients, have suggested that these alterations are more commonly associated with high-grade tumours, metastatic lesions and poorer survival. This study was designed to re-examine the prevalence and clinical significance of altered pRB expression in a large and selected group of soft-tissue sarcomas from 174 adult patients. Representative tissue sections from these sarcomas were analysed by immunohistochemistry using a well-characterised anti-pRB monoclonal antibody. Tumours were considered to have a positive pRB phenotype only when pure nuclear staining was demonstrated, and cases were segregated into one of three groups. Group 1 (n = 36) were patients whose tumours have minimal or undetectable pRB nuclear staining (< 20% of tumour cells) and were considered pRB negative. Patients with tumours staining in a heterogeneous pattern (20-79% of tumour cells) were classified as group 2 (n = 99). The staining of group 3 (n = 39) was strongly positive with a homogeneous pRB nuclear immunoreactivity (80-100% of tumour cells). pRB alterations were frequently observed in both low- and high-grade lesions. Altered pRB expression did not correlate with known predictors of survival and was not itself an independent predictor of outcome in the long-term follow-up. These findings support earlier observations that alterations of pRB expression are common events in soft-tissue sarcomas; nevertheless, long-term follow-up results indicate that altered patterns of pRB expression do not influence clinical outcome of patients affected with soft-tissue sarcomas. It is postulated that RB alterations are primary events in human sarcomas and may be involved in tumorigenesis or early phases of tumour progression in these neoplasias.

Adult↗
PubMed1995

Hepatic metastases from soft-tissue sarcoma.

OBJECTIVE: Hepatic metastases from soft-tissue sarcoma are evaluated to define treatment and its limitations. METHODS: From 981 adult patients with diagnoses of soft-tissue sarcoma, 65 patients with hepatic metastases were studied. RESULTS: An intra-abdominal primary site was present in 61 of 65 patients, with 85% high-grade leiomyosarcoma. Hepatic resection was performed in 14 patients (22%). All patients have had recurrences after hepatic resection-11 of 14 in the liver--with a median survival of 30 months. Chemotherapy resulted in partial response in three patients and no complete responses. Survival is not influenced by grade, type, primary site, disease-free interval, chemotherapy, or hepatic resection. CONCLUSIONS: The uncommon response to conventional chemotherapy does not support its use in the treatment of hepatic metastases from soft-tissue sarcoma. Extent of disease limits the application and success of hepatic resection for soft-tissue sarcoma, and anything less than complete resection is not indicated.

Adult↗
PubMed1995

Identifying multiple recidivists in a state hospital population.

Of 195 patients admitted to a state hospital over a four-month period, 74 were multiple recidivists. Nearly half of the 195 patients could be assigned to one of six profile subgroups of recidivists described in a previous study. Because of the high rate of medication noncompliance in this state hospital sample (65 percent), noncompliance alone was not an adequate predictor of multiple recidivism. The study found that membership in a profile subgroup coupled with factors related to gender, medication noncompliance, homelessness, and arrest history may be a more useful way of predicting multiple recidivism in samples of newly admitted patients.

Adult↗
PubMed1995

Very-high-dose short-term chemotherapy for poor-risk peripheral primitive neuroectodermal tumors, including Ewing's sarcoma, in children and young adults.

PURPOSE: To improve the prognosis of patients with poor-risk peripheral primitive neuroectodermal tumors (pPNETs; including peripheral neuroepithelioma and Ewing's sarcoma), while testing the feasibility of intensive use in adolescents and young adults of high-dose cyclophosphamide, doxorubicin, and vincristine (HD-CAV). PATIENTS AND METHODS: This report concerns previously untreated patients with newly diagnosed pPNET deemed poor-risk because of a tumor volume more than 100 cm3 or metastases to bone or bone marrow. The P6 protocol consists of seven courses of chemotherapy. Courses 1, 2, 3, and 6 include 6-hour infusions of cyclophosphamide on days 1 and 2 for a total of 4,200 mg/m2 per course (140 mg/kg per course for patients < 10 years old), plus 72-hour infusions of doxorubicin 75 mg/m2 and vincristine 2.0 mg/m2 beginning on day 1 (HD-CAV). Courses 4, 5, and 7 consist of 1-hour infusions of ifosfamide 1.8 g/m2/d and etoposide (VP-16) 100 mg/m2/d, for 5 days. Granulocyte colony-stimulating factor (G-CSF) and mesna are used. Courses start after neutrophil counts reach 500/microL and platelet counts reach 100,000/uL. Surgical resection follows course 3 and radiotherapy follows completion of all chemotherapy. RESULTS: Among the first 36 consecutive assessable patients (median age, 17 years), HD-CAV achieved excellent histopathologic or clinical responses in 34 patients and partial responses (PRs) in two patients. For 24 patients with locoregional disease, the 2-year event-free survival rate was 77%; adverse events were two locoregional relapses, one distant relapse, and one secondary leukemia. All six patients with metastatic disease limited to lungs achieved a complete response (CR) and did not relapse; one is in remission 36+ months from diagnosis, but the other patients are not assessable in terms of long-term efficacy of the P6 protocol because of short follow-up time (n = 3), additional systemic therapy (bone marrow transplantation), or septic death (autopsy showed no residual pPNET). All six patients with widespread metastases had major responses, including eradication of extensive bone marrow involvement, but distant relapses ensued. Myelosuppression was severe, but most patients received the first three courses of HD-CAV within 6 to 7 weeks. Major nonhematologic toxicities were mucositis and peripheral neuropathy. CONCLUSION: Excellent antitumor efficacy and manageable toxicity support the dose-intensive use of HD-CAV for pPNET in children, as well as in young adults. Consolidation of remissions of pPNET metastatic to bone and bone marrow remains a therapeutic challenge.

Adolescent↗
PubMed1994

Preoperative and postoperative adjuvant combination chemotherapy for adults with high grade soft tissue sarcoma.

BACKGROUND: Patients with high grade soft tissue sarcoma greater than or equal to 10 cm have a 3-year disease-free survival of approximately 30%. There is no convincing evidence, however, that postoperative adjuvant chemotherapy is beneficial. Preoperative chemotherapy has theoretical advantages over postoperative chemotherapy. METHODS: Twenty-nine evaluable patients with primary or recurrent high grade, nonmetastatic, soft tissue sarcoma were treated with two preoperative cycles of cyclophosphamide 500 mg/m2, doxorubicin 60 mg/m2, and DTIC 1000 mg/m2 before definitive surgery and radiation. Clinical and radiologic assessment of response to chemotherapy was performed preoperatively, and the resected specimen was examined for treatment effects. Patients who did not progress during preoperative therapy were eligible to receive four additional cycles of chemotherapy. Disease-free and overall survival rates of study patients were compared with two cohorts of historic controls. RESULTS: Although subjective changes in the firmness of some tumors were observed, only one patient met the criteria for partial response (3%, 2-sided 95% confidence interval = < 1-17%). Intratumoral hemorrhage, cystic necrosis, and liquefaction were observed regularly, and three tumors were more than 90% necrotic. Toxicity of the chemotherapy was acceptable, but patients were reluctant to receive postoperative therapy. The median time free from distant metastasis was 28 months; median survival was 35 months. These results were not superior to the experience with no chemotherapy, or with postoperative doxorubicin. CONCLUSIONS: Adjuvant chemotherapy for patients with soft tissue sarcoma remains investigational. There is a strong rationale, however, for continued investigation of preoperative chemotherapy for high risk patients using doxorubicin and ifosfamide with colony stimulating factor support. Development of sensitive and specific methods to assess response to preoperative chemotherapy is needed.

Adult↗
PubMed1994

The effect of age at diagnosis on outcome in rhabdomyosarcoma.

BACKGROUND: Survival for rhabdomyosarcoma appears to be more favorable in children and adolescents compared with adults. To determine the significance of age at diagnosis as a prognostic indicator in rhabdomyosarcoma, we performed a retrospective analysis of a combined pediatric and adult rhabdomyosarcoma data base. METHODS: Pertinent prognostic variables, including age, TNM stage, histopathologic subtype, anatomic site, resectability, radiation to the primary site, and dose intensity of chemotherapy, were compared in a Cox proportional hazards model with mortality as the outcome variable. RESULTS: Age at diagnosis (P = 0.0001) and local tumor invasiveness (P < 0.0001), distant parenchymal metastases (P < 0.0001), regional lymph node involvement (P = 0.0027), and histopathologic subtype (P = 0.0446) contributed information to the proportional hazards model. CONCLUSIONS: Age at diagnosis is an independent predictor of outcome in patients with rhabdomyosarcoma along with tumor invasiveness, metastases, regional lymph node involvement, and histopathologic subtype.

Adolescent↗
PubMed1994

Phase II trial of gemcitabine (2,2'-difluorodeoxycytidine) in patients with adenocarcinoma of the pancreas.

Gemcitabine is a novel nucleoside analog which demonstrated a broad spectrum of preclinical activity in solid tumor models, and responses in patients with pancreas cancer during phase I evaluation. Patients with measurable adenocarcinoma of the pancreas who had received no previous chemotherapy were eligible for this multicenter phase II clinical trial. Gemcitabine 800 mg/m2 was administered intravenously weekly for 3 consecutive weeks, followed by one week rest, every 4 weeks. Forty-four patients entered the trial; 35 had at least 2 cycles of therapy. Partial response was observed in 5 patients (11%, estimated 95% confidence interval 2-20%), with a median duration of 13 months. All responding patients had stabilization or improvement in performance status. Fourteen patients had stable disease of 4 or more months. The median WBC nadir was 3.8 x 10(3)/microliters (range 1.6-9.3) and the median absolute neutrophil (ANC) nadir was 2.0 x 10(3)/microliters (range 0.4-7.2). Thrombocytopenia - 100.0 x 10(3)/microliters was observed in 15 patients; the median platelet nadir was 123.0 (range 30.0-245.0). All patients experienced a mild to moderate flu-like syndrome. In addition, one patient had a mild hemolytic-uremic syndrome which appeared related to gemcitabine therapy. Gemicitabine demonstrated marginal activity in this resistant neoplasm, without excessive toxicity. Further evaluation, including the use of more intense dosing and/or combination therapy, is warranted.

Adenocarcinoma↗
PubMed1994

Effect of perioperative blood transfusion on recurrence and survival in 232 primary high-grade extremity sarcoma patients.

BACKGROUND: Allogeneic blood transfusion (BT) has been implicated as an unfavorable factor influencing cancer recurrence and overall survival. METHODS: To investigate this, 232 consecutive localized, high-grade extremity soft tissue sarcoma (STS) patients admitted between January 1, 1983, and December 31, 1989, were analyzed from our prospective database by univariable and Cox multivariable statistical methods. RESULTS: Twenty-eight patients developed a local recurrence (LR). Factors found significantly unfavorable for the rate of developing an LR by uni- and multivariable tests were age > 60 years and positive microscopic margin. Eighty-nine patients developed a distant metastasis (DM) and 72 patients died of their tumor. Median follow-up of survivors was 48 months. Unfavorable factors for DM and tumor mortality (TM) by univariable analysis included large size, deep tumor (that involved or was below the superficial fascia), positive microscopic margin, invasion of a vital structure, operative blood loss, duration of operation, and perioperative BT (whole blood or packed cells -24 to +48 h of curative operation). Multivariable analysis found large size, deep tumor, and positive margin significant independent unfavorable factors for DM and TM. The effect of BT was not a significant independent prognosticator for LR, DM, or TM by multivariable analysis (p = 0.26, 0.56, 0.08, respectively). The only factor that was found to be significant in a multivariable analysis of factors contributing to postmetastasis survival was time < 6 months until metastasis (p = 0.008). BT had no significant impact on postmetastasis survival (p = 0.42). There was a significant association between BT and deep, large tumors. As the size of deep tumors increased from < 5, > or = 5 < 10, > or = 10 < 15, or > or = 15 cm, the amount transfused was 15, 16, 49, and 68% (p < 0.00001). Also, BT was significantly (p < 0.005) associated with low hematocrit at initial diagnosis, blood loss during surgery, and the length of the surgical procedure. CONCLUSIONS: These data emphasize the importance of size, depth, and margin on distant recurrence and death for localized high-grade extremity STS. In the absence of a randomized trial, the impact of allogeneic blood transfusion would appear to be due to its strong association with large size and deep tumor invasion. This study also highlights the importance of a multivariable analysis and long-term follow-up to better define this controversial question.

Blood Transfusion↗
PubMed1994

Biological study of R24 mouse monoclonal antibody in patients undergoing thoracotomy for pulmonary metastases from soft tissue sarcoma.

The disialoganglioside GD3 is expressed on the surface of soft tissue sarcoma, malignant melanoma, and other malignant cells and is, therefore, a potential target for therapeutic monoclonal antibodies. Intravenously administered R24, a murine IgG3 monoclonal antibody to GD3, induces inflammation and tumor regression at sites of metastatic malignant melanoma. R24 5 mg/m2 was given intravenously every other day for six doses to 10 patients with pulmonary metastases from a primary soft tissue sarcoma of the extremity for whom thoracotomy was planned. Resected tissue was available from 7 patients. All metastases expressed GD3; however, expression was heterogeneous within tumors, and in no tumor were more than 80% of the cells GD3 positive. A mild to moderate infiltrate consisting of mononuclear cells with T-cell markers was identified around or within pulmonary metastases in 6 patients. Tolerable acute allergic reactions occurred in all patients, but 3 patients had severe chest tightness and bronchospasm that limited the planned therapy. The setting of thoracotomy for metastatic disease provides an ideal system for studies on the pharmacology and biological effects of monoclonal antibodies that target soft tissue sarcoma antigens.

Adult↗
PubMed1993

Edatrexate in patients with soft tissue sarcoma. Activity in malignant fibrous histiocytoma.

BACKGROUND: Chemotherapy has had little impact on the natural history of soft tissue sarcoma, and often is associated with serious toxicity. Edatrexate, an investigational antifolate, is active in patients with lung cancer, and has cytotoxic activity in human sarcoma cell lines. METHODS: Edatrexate was administered to 36 patients with measurable, advanced soft tissue sarcoma who had not previously received chemotherapy. The drug was given weekly for 5 weeks, then every other week. The initial dose, 80 mg/m2, was escalated by 10 mg/m2 every 2 weeks in the absence of toxicity. Eleven patients had leiomyosarcoma, 7 had malignant fibrous histiocytoma (MFH), and 5 had liposarcoma; the remainder of cell types included hemangiopericytoma (4), angiosarcoma (3), synovial (2), spindle cell (2), extraosseous chondrosarcoma (1), and fibrosarcoma (1). RESULTS: Thirty-five patients are evaluable. Partial response (PR) was seen in five of the seven patients with MFH; no other major responses occurred. Overall, the response frequency was 14% (two-sided 95% confidence interval, 3% to 26%). Median duration of PR was 6 months (range, 4-18 months). One patient had a minor tumor regression, and six had stable disease. Myelosuppression was generally mild; only three patients had grade 3 hematologic toxicity. Modification of dose or schedule was required in 50% of patients for mucositis. Fatigue was a common toxicity, seen in 66% of patients, but was tolerable in the majority. A rash was seen in 46% of patients; one patient had hepatic toxicity. CONCLUSIONS: Overall, the activity of edatrexate in this study, dominated by patients with either visceral or vascular sarcoma, was poor. However, the responses observed in patients with metastatic MFH suggests that further evaluation of edatrexate in patients with soft tissue sarcoma is warranted.

Adult↗
PubMed1993

Gastrointestinal autonomic nerve tumors. A clinicopathological, immunohistochemical, and ultrastructural study of 12 cases.

The gastrointestinal autonomic nerve tumor (GAN tumor) is an uncommon stromal tumor of the intestinal tract and retroperitoneum first described by Herrera and associates in 1984. Distinction of GAN tumors from other gastrointestinal stromal tumors is based on electron microscopic findings. Thus far there have been 12 reported cases. We present an additional 12 GAN tumors, identified by us during 4 years. There were seven male and five female patients and they ranged in age from 10 to 85 years (mean: 58 years). Sites of the tumors were stomach (three), jejunum (two), ileum (four), mesentery (one), and retroperitoneum (two). Eight of the tumors measured > 10 cm in greatest dimension. Usually well circumscribed, the neoplasms were tan to light pink, sometimes hemorrhagic, and soft. There was a variety of histologic patterns including fascicles, palisades, and whorls. Mitotic activity varied from 0 to 23 mitosis per 10 high-power fields (HPF). Using a panel of 10 immunohistochemical stains, only vimentin was consistently positive. There was neuron-specific enolase reactivity in six and S-100 protein reactivity in two cases. All muscle markers were negative. Ultrastructural studies showed neuron-like cells with long axonic cytoplasmic processes ending in bulbous synapse-like structures containing dense-core neurosecretory granules and clear vesicles. Basement membrane was absent. These features are reminiscent of ganglia of the intestinal autonomic nervous system. The patients were followed for 5-125 months (mean of 26 months). Tumor recurred or metastasized to the liver in seven patients (58%) and four patients died with tumor. There were correlations between tumor size (> 10 cm), mitotic count (at least five per 10 HPF), and aggressive behavior.

Adolescent↗
PubMed1993

Development and treatment of pulmonary metastases in adult patients with extremity soft tissue sarcoma.

OBJECTIVE: The authors reviewed a series of adult patients with extremity soft tissue sarcoma to determine the incidence of pulmonary metastases and outcome after treatment. METHODS: Of 716 patients admitted between January 1983 and December 1990, 135 (19%) had isolated pulmonary metastases as the initial site of distant recurrence. Fifty-eight percent (78 of 135) of the patients were treated surgically, and 83% of them had their tumors completely resected. RESULTS: The median survival after complete resection was 19 months; incomplete resection, 10 months; and no operation, 8 months (p = 0.005). The 3-year survival rate after complete resection was 23%, compared with a 2% rate (1 of 57) in those treated nonsurgically (p < 0.001). Factors associated with an increased risk of pulmonary metastases included high tumor grade, tumor size greater than 5 cm, lower extremity site, and histologic type (spindle cell, tendosynovial, and extraskeletal osteosarcoma). Factors associated with complete resectability were the histologic types of spindle cell and extraskeletal osteosarcoma. CONCLUSIONS: Complete surgical resection remains the only possibility for cure from pulmonary metastases in soft tissue sarcoma; however, only 11% of the 19% of patients with an extremity sarcoma whose first distant recurrence is in the lung will be alive at 3 years, despite therapy. Complete resection and the development of more effective adjuvant treatments are imperative to improve outcome for this group of patients.

Adolescent↗
PubMed1993

Reasons for admission among six profile subgroups of recidivists of inpatient services.

The incidence pattern of medication and program non compliance, violent acts, suicide attempts and chemical abuse defined as reasons for hospital admission was evaluated in a total sample (n = 416) of recidivists and their six constituent profile subgroups (n = 272). The total sample was drawn from two different state-operated hospitals and two different time periods. The incidence pattern observed for the total sample in order of descending priority was medication non compliance, program non compliance, chemical abuse, violent acts and suicide attempts. The incidence pattern ordering and the relevant percentages of occurrence were observed for both hospitals. There were time period differences in the ordering and percentages of the reasons for admission which revealed an increase in both medication and program non compliance as well as chemical abuse in the more recent sample. There were also specific subgroup differences in the incidence pattern concerning some reasons for admission. These subgroup differences are discussed in detail.

Adult↗
PubMed1992

Tendosynovial sarcoma. Clinicopathologic features, treatment, and prognosis.

BACKGROUND: Clinicopathologic features, treatment, and results are reported for 95 tendosynovial sarcomas identified from a prospective sarcoma data base established at Memorial Sloan-Kettering Cancer Center (MSKCC) in 1982. METHODS: Eighty-five patients had definitive treatment of the primary tumor at MSKCC: Epithelial sarcomas were excluded. RESULTS: The local recurrence rate was 18%. Survival rates were not influenced by either the method of local treatment or the use of chemotherapy. The overall actuarial survival rate was 59% at 5 years (median, 92 months). For 25 patients who had resection of pulmonary metastases, the 5-year actuarial survival rate was 43% (median, 22 months) from the time of first thoracotomy. Sex, age, tumor site, and histologic subtype (monophasic versus biphasic) were not significant predictors of survival rates. Regional lymph node metastasis occurred in 3%. The incidence of distant metastasis was 49%, with an associated 5-year survival rate of 31% (median, 33 months). Tumor size was a highly significant prognostic feature, with 5-year survival rates of 86% for patients with tumors smaller than 5 cm and 22% for those with tumors larger than 10 cm (P less than 0.00001). CONCLUSIONS: Improvement of treatment results for tendosynovial sarcoma will require effective new systemic adjuvant therapeutic strategies.

Actuarial Analysis↗
PubMed1992

Management of small soft-tissue sarcoma of the extremity in adults.

To determine the significance of small (< or = 5 cm in diameter) soft-tissue sarcoma of the extremity, 174 adult patients were identified from information that had been entered prospectively into a database of 1742 patients between July 1982 and December 1990. Median follow-up was 48 months. The majority of tumors were high grade (n = 114; 66%). Local recurrence (n = 17) was seen in patients with both high-grade (11%) and low-grade tumors (7%). Distant metastases were seen in 7% of high-grade tumors and in no low-grade tumors. The overall 5-year survival rate was 94% for all patients. Grade, depth, location, type of operation, and sex did not affect 5-year survival or local recurrence-free survival. Neither postoperative adjuvant chemotherapy nor radiation therapy resulted in superior 5-year survival or local recurrence-free survival when compared with no postoperative treatment. The prognosis of these lesions is favorable, and no additional prognostic factors were identified. Inclusion of these patients into adjuvant therapy trials examining survival is inappropriate.

Adolescent↗
PubMed1992

Phase II trial of fazarabine (arabinofuranosyl-5-azacytidine) in patients with advanced pancreatic adenocarcinoma.

We conducted a phase II evaluation of fazarabine 1.75-2.0 mg/m2/hr over 72 hours every 28 days in 14 previously untreated patients with advanced adenocarcinoma of the pancreas. The initial dose was 1.75 mg/m2/hr in 10 patients, and 2.0 mg/m2/hr in 4 patients. The dose was escalated in 8 patients, including all 4 who started at the higher dose level. Toxicity was unexpectedly mild. The median WBC nadir was 4.4 (range: 2.4-15.8) x 10(3)/microliters, the median absolute neutrophil nadir was 3.2 (range: 0.9-13.0) x 10(3)/microliters, and the median platelet count was 134.0 (range: 48.0-291.0) x 10(3)/microliters. Gastrointestinal toxicity was generally mild. No major responses were seen, excluding, with 95% confidence, a response rate in excess of 20%.

Adenocarcinoma↗