Search PubMed⌕ Search

Biomedical subjects

R S Benjamin

Publications and source records attributed to R S Benjamin.

At least 55 records · Page 3Linked to original sources
PubMed1995

Treatment of uveal melanoma metastatic to the liver: a review of the M. D. Anderson Cancer Center experience and prognostic factors.

BACKGROUND: Liver metastasis develops in approximately two-thirds of patients with recurrent uveal melanoma. Despite therapy, the median survival of those with liver metastasis is 5 to 7 months. The recognition of a grave prognosis associated with liver metastasis has led to evaluation of new modalities of therapy, including the use of regional therapies such as intrahepatic arterial chemotherapy and either embolization or chemoembolization of hepatic metastases. In this study, the results of an institutional experience over the past 2 decades are reviewed and prognostic factors that affect survival from the time the liver metastasis is diagnosed are assessed. METHODS: In this study of 201 patients with uveal melanoma involving the liver who were treated at M. D. Anderson Cancer Center between 1968 and 1991, the authors restrospectively reviewed the cases and compared the results of systemic therapies, hepatic intra-arterial chemotherapies, and chemoembolization of liver metastases. Cox's multivariate analysis and stepwise logistic regression were then computed to determine significant prognostic variables. RESULTS: The systemic therapies produced a response rate of less than 1%. Chemoembolization was the most effective treatment, inducing responses in 36% of patients. Survival curves were calculated using the life-table method of Kaplan and Meier. Patient- and tumor-related characteristics were examined and their relation to on survival from the time of diagnosis of liver metastasis was determined. Levels of serum alkaline phosphatase, total bilirubin, and lactic dehydrogenase plus response to treatment showed a strong relation to survival. In contrast, univariate analysis showed that patient age and gender, metastasis free interval, presence of extrahepatic metastasis, and type of therapy for liver metastasis did not influence survival. Multivariate stepwise regression analysis identified serum alkaline phosphatase and metastasis free interval as the main independent prognostic factors for survival after liver metastasis diagnosis. CONCLUSIONS: Of the three modalities of therapy used for choroidal melanoma metastatic to the liver, only chemoembolization using cisplatin-based regimens produced a meaningful response rate. Information from this analysis can be used to predict the outcome of patients with uveal melanoma metastatic to the liver. Patients with metastatic ocular melanoma confined to the liver should be treated with chemoembolization and should not be included in chemotherapy trials designed for cutaneous melanoma.

Adult↗
PubMed1995

A 15-year experience with chemotherapy of patients with paraganglioma.

BACKGROUND: Paraganglioma is a rare tumor thought to arise from the neuroectodermally derived paraganglionic cells that are dispersed widely along the autonomic ganglia. They can metastasize to bones, lymph nodes, and lungs and occasionally present with spinal cord compression. Up to 60% of retroperitoneal paragangliomas can be functional, with symptoms and signs of norepinephrine overproduction. METHOD: A 15-year experience with chemotherapy of patients with paraganglioma was reviewed. The patient population was identified through a search of the data-base maintained by the Departments of Melanoma-Sarcoma Medical Oncology and Pathology at the University of Texas M.D. Anderson Cancer Center (Houston, TX). RESULTS: Thirteen of 84 patients with histologically confirmed diagnosis of paraganglioma were treated with chemotherapy. The median age was 42 years (range, 25-67 years); there were eight males and five females. Primary sites included retroperitoneum (seven patients), head and neck (two patients), pelvis, bladder, mediastinum, and paravertebral (one patient each). Twelve patients received chemotherapy for metastatic disease, and 1 had an unresectable mediastinal primary tumor. Eleven patients received cyclophosphamide, doxorubicin, and DTIC/dacarbazine (CyADIC)/cyclophosphamide, vincristine, doxorubicin and DTIC/dacarbazine (CyVADIC), and 2 received doxorubicin and dacarbazine (ADIC) at standard doses for a median of 4 cycles (range, 2-12 cycles). Six of 13 patients achieved an objective partial remission (response rate = 46%, 95% confidence interval = 19-73%); 6 other patients had stable disease, and one developed progressive disease. At the time of last follow-up, eight patients were alive with disease, four died, and one patient was alive with no evidence of disease. The median follow-up from diagnosis was 45 months (range, 12-300 months). CONCLUSION: Cyclophosphamide, doxorubicin, dacarbazine chemotherapy is active in the treatment of patients with paraganglioma.

Adult↗
PubMed1995

In vivo biologic effects of PIXY321, a synthetic hybrid protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 in cancer patients with normal hematopoiesis: a phase I study.

PIXY321 is a novel fusion protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 that exhibits biologic effects of both its parent cytokines in vitro and in preclinical studies. To evaluate the clinical safety and hematopoietic effects of this hybrid cytokine, PIXY321 was administered by subcutaneous injection twice daily at doses of 25 to 1,000 micrograms/m2/day over 14 days to 24 patients with sarcoma before chemotherapy as part of a phase I trial. The treatment was associated with significant increases in white blood cell, neutrophil, platelet, and reticulocyte counts (all P < .001). The increase in neutrophil count was dose-related and was seen during treatment with the cytokine, whereas the increase in platelet count was gradual and peaked after the cessation of the cytokine treatment and was not clearly dose related. PIXY321 treatment also increased bone marrow (BM) cellularity and the percentage of BM cells in S phase (P < .001). In addition, there was a significant increase in the number of CD34+ cells and committed and multipotential progenitors in the peripheral blood. The ex vivo expansion capacity of peripheral blood and BM progenitor cells was preserved after the in vivo treatment with PIXY321. The treatment was well tolerated, with the most common side-effect being injection site reactions. The results of this study show the biologic and clinical activity of a genetically engineered fusion molecule of two hematopoietic cytokines in humans with normal hematopoietic function.

Agranulocytosis↗
PubMed1995

Efficacy of liposomal muramyl tripeptide (CGP 19835A) in the treatment of relapsed osteosarcoma.

Muramyl tripeptide phosphatidylethanolamine (MTP-PE) is a synthesized lipophilic analogue of muramyl dipeptide. MTP-PE encapsulated in liposomes (L-MTP-PE) allows selective delivery to pulmonary macrophages and circulating monocytes. In vivo administration has resulted in tumor regression in mice with B16 melanoma lung and lymph node metastases and a 40% long-term disease-free survival in dogs with osteosarcoma. Phase I studies have demonstrated that the drug is well tolerated. A Phase II trial using L-MTP-PE was undertaken in relapsed osteosarcoma patients to determine whether L-MTP-PE therapy could improve the progression-free interval in this high-risk group of patients. Patients had histologically proven osteosarcoma and pulmonary metastases that had developed during adjuvant chemotherapy or that were present at diagnosis and had persisted despite chemotherapy. Patients were rendered disease free by surgery. L-MTP-PE, 2 mg/m2, was infused over a 1-hour period twice a week for 12 weeks in 12 patients (Group 1). Sixteen patients (Group 2) received 2 mg/m2 L-MTP-PE twice a week for 12 weeks, then once a week for 12 weeks, for a total of 24 weeks of therapy. Progression-free intervals in each group were calculated from the day of surgery to the day of relapse and compared with the progression-free interval of a historical control group (Group 3) treated postoperatively with chemotherapy at M. D. Anderson Cancer Center between 1980 and 1990. Patients who received 24 weeks of L-MTP-PE therapy had a significant prolongation in time to relapse but those who received 12 weeks of therapy did not. The median time to relapse for group 2 patients was 9.0 months compared with 4.5 months for the control group (Group 3). These data suggest that L-MTP-PE deserves further investigation in a more appropriate adjuvant setting. A nationwide randomized Phase III trial is now underway in newly diagnosed osteosarcoma patients in conjunction with the Children's Cancer Study Group and the Pediatric Oncology Group.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1995

Prolonged disease-free survival following surgical debulking and high-dose cisplatin/doxorubicin in a patient with bulky metastases from giant cell tumor of bone refractory to "standard" chemotherapy.

A 32-year-old man developed multiple pulmonary metastases from a giant cell tumor of bone. His metastases failed to respond to several chemotherapy regimens (high-dose methotrexate with folinic acid plus doxorubicin 90 mg/m2; cyclophosphamide + bleomycin + actinomycin D; mitoxantrone + dacarbazine; and cisplatin 110 mg/m2). He underwent surgical resection (incomplete) of > 1 kg of tumor from his right lung in March 1985, followed by chemotherapy with menogaril (to which he did not respond). In August 1985, he underwent surgical resection (again, incomplete) of > 1 kg of tumor from his left lung. At the time of surgery, the left and right lung tumors differed histopathologically, with giant cell tumor present in the right lung and sarcoma in his left lung. He received carmustine in October 1985 and mitomycin C in December 1985 without response. His multiple bilateral lung metastases had again become quite large by September 1986. At that time, he received doxorubicin 90 mg/m2 plus cisplatin 120 mg/m2, and for the first time experienced tumor reduction (minor response). He underwent a subtotal resection of right lung and chest wall metastases in December 1986, and underwent subtotal resection of left lung metastases in January 1987. Grossly visible residual tumor was left behind on both sides at the time of surgery, although none was apparent on chest radiograph. He received a final chemotherapy treatment with doxorubicin 90 mg/m2 plus cisplatin 120 mg/m2 on February 2, 1987. He remained free of evidence of residual or recurrent tumor at the time of last followup in February, 1994.

Adult↗
PubMed1995

Extraskeletal myxoid chondrosarcoma. Long-term experience with chemotherapy.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare low-grade soft tissue sarcoma that has been reported to have an indolent nature history, and relatively good prognosis. The majority of primary tumors are located in the extremities and they tend to be bulky at presentation. Studies with long-term follow-up have revealed the development of distant metastases in virtually all patients, eventually resulting in death. We reviewed our experience with EMC over the last three decades. The patient population was identified through a search of the database maintained by the Departments of Patient Studies, Pathology, and Melanoma-Sarcoma Medical Oncology. Eleven patients with histologically confirmed diagnosis of EMC were identified. The median age was 59 (37-81 years), and there were nine males and two females. Nine patients had an extremity location and the remaining two had a chest wall and abdominal wall primary, respectively. The median size of the primary tumor was 10 cm (range: 4-17 cm) in maximum dimension. Ten of the eleven patients received chemotherapy, mainly with doxorubicin- and dacarbazine-based regimens. One patient is currently on beta-interferon. No objective responses were noted, to a median of 4 (2-6) cycles of chemotherapy. Three patients were treated with ifosfamide as a second-line chemotherapy without any benefit. Three patients have expired, two patients are alive with no evidence of disease, and six patients are alive with disease. The median follow-up is 5 years (range: 1.33-17 years) from diagnosis. Although small numbers preclude adequate assessment, there is no evidence of efficacy of standard soft-tissue sarcoma chemotherapy in patients with EMC.

Adult↗
PubMed1995

Myxoid malignant fibrous histiocytoma: experience with chemotherapy.

Myxoid malignant fibrous histiocytoma (MFH) is an intermediate grade tumor with a definite metastatic potential but a relatively indolent natural history compared to the pleiomorphic variant of MFH. Little is known about its sensitivity to chemotherapy. We reviewed our experience with chemotherapy in myxoid MFH between 1986 and 1992. The patient population was identified through a search of the database maintained by the Departments of Melanoma-Sarcoma Medical Oncology and Pathology: 55 patients with histologically confirmed diagnosis of myxoid MFH were identified. Chemotherapy was administered to 18 of these patients (10 females, 8 males). The median age was 65 (range: 30-76). Ten patients had an extremity primary, seven had a trunk or retroperitoneal primary, and one patient had head and neck as the site of primary tumor. The median size of the primary tumor was 11 cm (range: 5-23 cm) in maximum dimension. Seven patients received chemotherapy in the neoadjuvant setting, eight received it for recurrent or metastatic disease, and three received it postoperatively after complete resection of the tumor. All patients received doxorubicin and dacarbazine with or without cyclophosphamide. Of the 15 patients evaluable for response, 4 achieved an objective response (one CR, 3 PRs, RR = 27%) to a median of 3 cycles (range: 1-7 cycles). At the time of last follow-up, eight patients are alive with no evidence of disease, two patients are alive with disease, and eight patients have expired. The median follow-up is 51 months (range: 26-216 months) from diagnosis. The relatively small sample precludes any definitive conclusions; however, it seems that doxorubicin- and dacarbazine-based chemotherapy has modest activity in myxoid MFH.

Adult↗
PubMed1995

Idarubicin cardiotoxicity: a retrospective study in acute myeloid leukemia and myelodysplasia.

PURPOSE: To estimate the incidence of idarubicin (IDA)-related cardiomyopathy in acute myeloid leukemia (AML) and myelodysplasia (MDS). PATIENTS AND METHODS: We analyzed a group of 127 AML/MDS patients who received IDA-based induction and postremission or salvage therapy and achieved a complete remission (CR) that lasted > or = 12 weeks for the development of IDA-related congestive heart failure (CHF). CHF was defined as definite if a resting left ventricular ejection fraction (LVEF) of < or = 45% measured by radionuclide ventriculogram (RV) accompanied the clinical diagnosis of CHF, which had to be made during or within 6 months of receiving IDA and for which no other cause was apparent; without RV confirmation, the diagnosis was considered probable. Patients who had RVs performed were evaluated for decreasing LVEF. Older age (> or = 70 years), prior/sequential anthracycline/mitoxantrone (anthraquinone) therapy, and cardiac disease/hypertension were evaluated as risk factors for the development of CHF. RESULTS: One hundred fifteen patients were assessable (median age, 40 years; median dose, 96 mg/m2). Sixty-five had RVs performed during therapy; 43 had risk factors. The probability of IDA-related cardiomyopathy was 5% at a cumulative IDA dose of 150 to 290 mg/m2, with 18 patients receiving doses greater than 150 mg/m2. At a cumulative IDA dose of 150 mg/m2, the probability of a mild or greater asymptomatic decrease probability of a mild or greater asymptomatic decrease in LVEF (> or = 10% to a level < or = 50%) was 18%, whereas the probability of a moderate or greater asymptomatic decrease in LVEF (> or = 15% to a level < or = 45%) was 7%. No patient with asymptomatic LVEF decreases developed CHF. CHF was more frequent in patients with prior/sequential exposure to anthracyclines/mitoxantrone (P = .01). CONCLUSION: In this patient group, IDA-related cardiomyopathy was uncommon with cumulative IDA doses of up to 290 mg/m2. Asymptomatic LVEF decreases were more frequent, but their predictive value for the development of CHF is unclear.

Adolescent↗
PubMed1995

Role of computed tomography in the staging of patients with local-regional metastases of melanoma.

PURPOSE: To determine the value of computed tomographic (CT) scans in the staging of asymptomatic melanoma patients who presented with or developed local-regional disease as the first site of recurrence and had both a normal chest radiograph and serum lactate dehydrogenase (LDH) level. PATIENTS AND METHODS: The records of 99 patients with local-regional disease were reviewed. Of these, 89 met the study criteria and are the subjects of this analysis. Radiologic findings were categorized into the following four groups: (1) true-positive (TP), when the scan identified either regional or distant disease that was not appreciated on physical examination; (2) false-positive (FP), when the scan showed a radiologic abnormality that either did not change for at least 6 months or was proven to be histologically benign; (3) false-negative (FN), when a patient had symptoms suggestive of or suspicious for metastases and was subsequently found to have metastases, but all imaging studies were nondiagnostic; and (4) true-negative (TN), when all imaging studies were negative for metastases in an asymptomatic patient. RESULTS: Findings on CT scan were TP for six patients (7%), FP for 20 (22%), and TN for 63 (71%). Of the six patients with TP findings, CT of the chest identified disease that was not visible on chest radiograph in only one and CT of the abdomen or pelvis showed metastases in five. CT or magnetic resonance imaging (MRI) of the brain showed no evidence of brain metastases in any patient, although it showed asymptomatic skull metastases in one patient. The most common FP findings were hypodense hepatic lesions and noncalcified lung nodules. CONCLUSION: TP findings are observed in approximately 7% of patients with local-regional disease, which indicates a low yield but definite usefulness of CT scans in this subset of patients. Because FP are more common than TP findings, histologic diagnosis of recurrence is advisable. CT scan or MRI of the brain is not necessary in asymptomatic patients. CT of the chest adds little to a chest radiograph. In light of today's more cost-conscious health-care environment, our results are of practical importance.

Adult↗
PubMed1995

Prognostic value of size of lymph node metastases in patients with cutaneous melanoma.

PURPOSE: To determine the prognostic significance of the size of the lymph node mass as measured by physical examination (PE) and of the size of the largest node measured by pathologic analysis (path) in patients with cutaneous melanoma and nodal metastases. PATIENTS AND METHODS: The medical records of all patients with nodal metastases seen at The University of Texas M.D. Anderson Cancer Center from January 1, 1973 to December 31, 1989 were reviewed. Patient eligibility criteria included the following: (1) availability of data describing the nodal size either by PE or by path and the number of positive nodes; (2) no history of preoperative chemotherapy or radiotherapy; and (3) no history or presence of in-transit, satellite, local, or distant metastases. Eleven variables, including largest diameter of the nodal mass by PE and diameter of the largest node by path, were examined as potential prognostic factors for disease-free survival (DFS) and overall survival (OS). RESULTS: Of 800 patients evaluated, 442 met the eligibility criteria and are the subjects of this study. In the univariate analysis, size of the nodal mass by PE was marginally significant for survival as a continuous variable (P = .045), but not as a categorical variable using a cutoff size of < or = 3 or more than 3 cm as indicated by the American Joint Committee on Cancer (AJCC) staging system (P = .61). Size of the largest node by path was not significant for survival. In the multivariate analysis, only the number of positive nodes (P < .001), age (P < .001), and tumor thickness (P < .001) were significant for survival. CONCLUSION: Size of the nodal mass by PE and size of the largest node by path are not useful prognostic factors for survival and should be eliminated from the current staging system. More powerful and well-established prognostic factors, such as the number of positive nodes, should be considered for inclusion in staging.

Adult↗
PubMed1995

Chemotherapy in osteosarcoma. Basis for application and antagonism to implementation; early controversies surrounding its implementation.

Chemotherapy in osteosarcoma has had a major impact in attaining metastasis-free survival, and the cure rates with the use of modern regimens range from 65% to 75%. Preoperative chemotherapy has facilitated surgical resection of the primary tumor, rendering increased numbers of candidates for limb salvage. The effects on the primary tumor may be used as a predictive factor in determining outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Effects of in vivo treatment with PIXY321 (GM-CSF/IL-3 fusion protein) on proliferation kinetics of bone marrow and blood myeloid progenitor cells in patients with sarcoma.

PIXY321, a stimulator of multipotent colony-forming units (CFU-GEMM), burst-forming unit-erythroid (BFU-E), and colony-forming units granulocyte/macrophage (CFU-GM) progenitor cell proliferation in vitro, is currently being assessed in phase-I/-II clinical trials. We evaluated kinetics of CFU-GEMM, BFU-E, and CFU-GM proliferation in bone marrow (BM), blood, and granulocyte (CFU-G) and macrophage (CFU-M) progenitors in BM of chemotherapy-naive patients with sarcoma-administered PIXY321 (25 to 1000 micrograms/m2/day subcutaneously for 14 days). BM and/or blood cells from three to four patients at each dosage were assessed before, during, 1 to 2 days, and 7 days following treatment with PIXY321. Cells were pulse-treated in vitro with or without high-specific activity tritiated thymidine (3H-dThr) (to assess the percentage of progenitors in S-phase of cell cycle) and cultured for immature and more mature subsets of CFU-GEMM, BFU-E, CFU-GM, and for CFU-G and CFU-M. Despite heterogeneity in baseline cycling status of progenitors in BM, administration of 125 to 500 micrograms PIXY321 to patients at least doubled (p < 0.001) cycling rates of all BM progenitors. The cycling rates of blood progenitors increased from a slow or non-cycling state to > 38% cells in cycle. Within 1 to 2 days after cessation of PIXY321 infusion, all progenitors were in a slow or noncycling phase below that of many of the pre-BM samples (immature and mature CFU-GM and mature BFU-E) or were back to background levels (CFU-G, CFU-M, CFU-GEMM, and immature BFU-E). These cycling effects were similar to those previously noted for BM CFU-GM and BFU-E in patients on clinical trial with GM-CSF. In contrast, higher dosages of PIXY321, especially 1000 micrograms, increased cycling of BM and blood progenitor cells early during treatment, but cycling rates decreased while patients were still being administered PIXY321; decreased cycling was maintained after cessation of PIXY321. PIXY321 is thus highly active in vivo as a stimulator of multipotential and more lineage-restricted progenitors. The kinetics of progenitor cell proliferation noted in this study highlight differences seen with GM-CSF and G-CSF. The effects described here could be of relevance in design of future clinical trials using PIXY321 as an adjunct treatment in patients undergoing cytoreductive therapy.

Blood Cells↗
PubMed1995

Soft-tissue sarcoma of the extremities. MR appearance of post-treatment changes and local recurrences.

MR imaging has the potential to provide valuable insights into intratumoral changes following preoperative therapy and has proven beneficial in the diagnosis of recurrent soft-tissue sarcoma of the extremities and differentiation of recurrence from postsurgical/postradiation changes. As advances occur in surgical and adjuvant treatment programs, further refinements of qualitative and quantitative MR imaging parameters should continue to enhance the role of MR imaging in the post-treatment evaluation of patients with soft-tissue sarcoma of the extremities.

Chemotherapy, Adjuvant↗