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Results for “multiagent systems”

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PubMed1995

Pharmacokinetics of recombinant human granulocyte-macrophage colony-stimulating factor in children after intravenous and subcutaneous administration.

Despite its widespread use, only limited pharmacokinetic data exist for recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), especially in children. We evaluated the pharmacokinetics of rhGM-CSF in children who had undergone intensive multiagent chemotherapy: 11 children with refractory solid tumors received 500-1500 micrograms/m2 of rhGM-CSF (sargramostim) as a daily 2-h intravenous (iv) infusion, and seven children received subcutaneous (sc) rhGM-CSF at 1500-2000 micrograms/m2/d in two daily injections for 2 weeks. Serum samples obtained before and after rhGM-CSF administration were analyzed for granulocyte-macrophage colony-stimulating factor (GM-CSF) by a bioassay and by ELISA. Concentrations measured by the two methods were highly correlated (r2 = 0.89, p < 0.001). Following 2-h iv infusions, the concentration-time data were best described by a two-compartment, first-order elimination model. The median (range) for rhGM-CSF systemic clearance (CI) was 49 mL/min/m2 (range, 15-118 mL/min/m2), terminal half-life (t1/2) was 1.6 h (range, 0.9-2.5 h), and the time the GM-CSF concentration was > 1 ng/mL was 9 h (range, 6-13 h). The CI was not dose dependent or related to patient age. The absolute neutrophil count day 14 of GM-CSF was significantly related to GM-CSF dosage and platelet count on day 1. There was a weak correlation between AUC and duration of neutropenia (p = 0.05). The sc concentration-time data were best described by a one-compartment model with first-order absorption and elimination. Median apparent clearance was 72 mL/min/m2 (range, 27-231 mL/min/m2) and t1/2 was 2.3 h (range 0.7-3.8 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

PubMed2002

Peripheral T-cell lymphoma arising in the liver.

We report 3 cases of primary hepatic peripheral T-cell lymphoma (PTCL). All patients were men, 50 to 57 years of age, who sought care because of systemic symptoms including fever, fatigue, and weight loss. Physical examination revealed hepatomegaly in 2 patients, associated with jaundice in 1. Two patients had abnormal serum liver enzyme levels and coagulation profiles. Imaging studies demonstrated marked hepatomegaly without focal lesions in 1 patient and multiple discrete tumor masses in 2 patients. Tumor infiltrates in biopsy specimens were heterogeneous with a large cell component in 2 cases. An inflammatory background was present in all cases, complicating the histologic recognition of PTCL Immunohistochemical studies showed that all tumors were of T-cell lineage, and 2 cases had monoclonal T-cell receptor gamma chain gene rearrangements. One patient died of disease shortly after diagnosis, and 2 patients treated with multiagent chemotherapy are in clinical remission with 12 and 84 months of clinicalfollow-up, respectively. PTCL may rarely arise in the liver. These neoplasms respond to chemotherapy, suggesting that this disease is curable if diagnosed at an early stage.

Cell Lineage↗

PubMed1980

Multimodality therapy for medulloblastoma.

Eight patients with recurrent medulloblastoma were treated with a chemotherapy regimen consisting of vincristine, BCNU, dexamethasone and intrathecal and intermediate dose intravenous methotrexate (500 mg/m2). Five also received local low dose radiotherapy (RT). All 8 patients responded to treatment; 6 completely and 2 partially. These latter 2 were in their second and third recurrences. Three remain in remission. The median duration of response was 18.8 months, and median time from start of chemotherapy to death was 32 months using the Kaplan-Meier technique. In addition, 9 other patients with newly diagnosed medulloblastoma were treated with craniospinal radiation and the same adjuvant chemotherapy as above. The first 5 patients also received intraventricular methotrexate and/or intravenous BCNU during radiotherapy. The toxicity in the 5 patients was very severe. There were three toxic deaths, one death from cancer; one patient survives disease-free, but he is demented. With the discontinuance of intraventricular methotrexate and the postponement of myelo-suppressive chemotherapy until after the completion of radiotherapy, the regimen has been well tolerated. All 4 patients treated this way remain alive, well, and disease-free at intervals up to 36 months. We conclude that recurrent medulloblastomas are sensitive to multiagent chemotherapy and that prolonged remissions may occur. With primary adjuvant chemotherapy, extreme caution with myelo-suppressive drugs must be exercised during the period of craniospinal radiotherapy. We also do not recommend the use of intraventricular methotrexate. When these two criteria were followed, the preliminary results with adjuvant chemotherapy appear encouraging.

Adolescent↗

PubMed1992

Impact of three methods of treatment intensification on acute lymphoblastic leukemia in children: long-term results of St Jude total therapy study X.

Long-term follow-up observations are reported on 427 patients who received one of three different intensified therapies in total therapy study X for acute lymphoblastic leukemia (ALL). In the trial for 'standard-risk' ALL, 154 of 309 patients in complete remission were randomized to receive high-dose methotrexate (HDMTX, 1 g/m2) periodically during the first 72 of 120 weeks of standard continuation therapy with 6-mercaptopurine and oral MTX; the remaining 155 patients received 1800 cGy cranial irradiation and intrathecal MTX, followed by 6-mercaptopurine/MTX therapy interrupted from week 36-71 for substitution of two other pairs of drugs. At 9 years of follow-up, significantly higher proportions of patients in the HDMTX group have maintained complete remissions (64 +/- 7%, SE, vs. 52 +/- 6%, p = 0.03), hematologic remissions (73 +/- 6% vs. 62 +/- 6%, p = 0.03), and testicular remissions (94 +/- 5% vs. 80 +/- 8%, p = 0.03); however, the proportion continuing in central nervous system remission has been lower (84 +/- 5% vs 93 +/- 4%, p = 0.02). In the evaluation of teniposide/cytarabine and delayed cranial irradiation for 'high-risk' ALL, 36 +/- 9% of 101 patients are predicted to be event-free survivors at 9 years. Altogether, 217 (51%) of the 427 patients are event-free survivors after at least 7 years of follow-up (median, 9 years); an additional 75 patients are alive and free of leukemia for a median of 6.4 years after successful remission retrieval therapy, boosting the total number of long-term survivors to 292 (68%). These results establish the efficacy of HDMTX for patients with standard-risk ALL and indicate the potential of teniposide/cytarabine for use in multiagent regimens for patients with high-risk disease. The overall survival figure, 68%, affords a benchmark for other studies assessing long-term outcome in ALL.

Child↗

PubMed1995

Persistence of circulating blasts after 1 week of multiagent chemotherapy confers a poor prognosis in childhood acute lymphoblastic leukemia.

Early response to therapy, typically assessed by bone marrow status, is predictive of outcome in childhood acute lymphoblastic leukemia (ALL). Less is known about the significance of early clearance of blast cells in peripheral blood. We reviewed medical records of all patients with ALL enrolled on St Jude Total Therapy Study XI (February 1984 to September 1988) to determine the presence of blast cells in peripheral blood at diagnosis and after 1 week of intensive induction therapy. Of the 358 patients, 59 lacked evidence of circulating blast cells at diagnosis, and data were unavailable for 2 patients. The prognostic significance of persistent circulating blast cells in the remaining 297 patients was assessed in a multivariate analysis that included known adverse prognostic factors. Persistent circulating leukemic blasts were present at day 8 in 41 patients (14%). Compared with the "blast-negative" group, these patients had a significantly higher frequency of several adverse clinical features (leukocyte count > 50 x 10(9)/L, mediastinal mass, central nervous system leukemia, T-cell phenotype, lack of CD10 expression, and L2 morphology) and a significantly poorer 5-year event-free survival (34% +/- 8% [SE] v 77% +/- 3%, P < .01). By multivariate analysis, blast cell persistence at week 1 was the most significant adverse feature in the overall cohort (relative risk, 2.9; 95% confidence interval, 1.8 to 4.8) and in an analysis limited to B-lineage cases (relative risk, 3.6; 95% confidence interval, 1.9 to 7.1). Patients identified by this simple, noninvasive measure may benefit from early modification of therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Outcomes in 24 selected patients with stage IVB cervical cancer and excellent performance status treated with radiotherapy and chemotherapy.

PURPOSE: We sought to review outcomes in patients with stage IVB carcinoma of the cervix treated with irradiation in combination with chemotherapy. MATERIALS AND METHODS: We report outcomes of 24 consecutive patients with good performance status treated from 1998 to 2005. Most of these patients underwent concurrent irradiation with platinum-based chemotherapy. Some patients received subsequent systemic chemotherapy. RESULTS: All patients underwent external beam radiotherapy; 7 patients (29%) had additional high-dose-rate and 12 (50%) low-dose-rate brachytherapy. Two patients (8%) received an IMRT boost instead of brachytherapy. The mean dose to point A was variable (73.9 +/- 19.2 Gy). Twenty patients (83%) received radio-sensitizing platinum-based chemotherapy, and the remaining had radiotherapy alone. Seven patients (29%) had further combination chemotherapy. Therapy was well tolerated. The overall survival was 44% at 36 months and 22% at 5 years. CONCLUSION: Patients with stage IVB cervical cancer have mostly been treated with palliative intent. With the advent of concurrent chemoradiation, we have treated many of these cases with aggressive combination therapy. In this series, the use of radiotherapy and multiagent chemotherapy in patients with stage IVB cervical carcinoma and good performance status was well tolerated and resulted in higher survival rates than previously reported.

Adult↗

PubMed1992

Clinical and biological analysis of peripheral T-cell lymphomas: a single institution study.

Peripheral T-cell lymphoma (PTCL) accounts for 15-20% of non-Hodgkin's lymphoma in the Western World. Clinical, histopathologic, phenotypic and genotypic data were received from 33 cases of PTCL referred to our institution. The median age order was 50 years, 78% were males, and 18% had a history of a preceding disorder of the lymphoid system. 60% had stage 4 at diagnosis and B symptoms were also present in 60%. The most frequent sites of extranodal involvement were bone marrow (54%), liver (45%) and skin (33%). Twenty-eight of 33 cases were histologically classified according to the Working Formulation (most in the diffuse mixed and large-cell subgroups) and the Kiel updated system. Phenotypic and genotypic studies of malignant cells showed a considerable heterogeneity with respect to the expression of either T-cell receptor (TCR) alpha beta and gamma delta and pan-T differentiation molecules. Of the studied cases 63% expressed TCR-alpha beta. All five patients with PTCL of the TCR-gamma delta subtype had a peculiar extra-nodal presentation. The vast majority of cases expressed an abnormal T-cell phenotype with respect to the expression of pan-T antigens, including the lack of expression of the TCR-associated CD3 molecule in 2 cases. Rearrangements of the TCR beta and/or delta-chain genes showed clonality in 21 of the 23 studied cases. Twenty-five patients were treated with a multiagent chemotherapy regimen with curative intent and the remainder received a less intensive palliative regimen. Only 9 patients achieved CR (8 of whom had received an anthracycline-containing regimen) and the 4-year survival rate was 25%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2005

[Case of central nervous system lymphoma metastasized to breast after remission by methotrexate chemotherapy].

We report a case of primary central nervous system lymphoma (PCNSL) who responded well to initial systemic chemotherapy, but subsequently developed breast metastasis with local recurrence in the brain 27 months after complete remission. The 53-year-old female suddenly felt weakness in her left extremity. She was transferred to the emergency ward in our hospital. Neurological examination on admission showed disorientated state and mild hemiparesis. Brain MRI showed a well enhanced round lesion in the right basal ganglia with perifocal edema. A stereotactic biopsy of the tumor made a diagnosis of classic diffuse non-Hodgkin's B-cell type lymphoma. She received chemotherapy with a high-dose methotrexate under a condition of 20% of Karnofsky Performance Status (KPS). She enjoyed a useful life for about 5 years (KPS; 60-70%). Both recurrent and metastatic lesions responded poorly to various aggressive multiagent regimens of chemotherapy. An intensive initial treatment for the primary lesion and closely monitoring of the whole body at regular intervals are necessary for ensuring a long useful life.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Effect of disease and chemotherapy on hemostasis in children with acute lymphoid leukemia.

PURPOSE: We sought to determine the effect of disease and combination chemotherapy on the hemostatic system in children with acute lymphoid leukemia (ALL). PATIENTS AND METHODS: We conducted a prospective study of children newly diagnosed with ALL. Plasma samples were obtained at four time points: at diagnosis before therapy, 5 days after administration of L-asparaginase alone, after the remission induction program, and at completion of the consolidation phase. Plasma levels of 21 hemostatic proteins were measured. The amount of thrombin generated following activation with an APTT reagent was quantitated. RESULTS: At diagnosis there were significant elevations in factors VIII, IX, von Willebrand, alpha 2-macroglobulin and protein S. In contrast, there were significant reductions in protein C, prekallikrein, and factors XIIIA and XIIIS. L-asparaginase treatment alone decreased concentrations of 11 proteins, with antithrombin III being affected to the greatest extent. After multiagent chemotherapy, not including L-asparaginase, concentrations of most proteins increased to or above baseline. At completion of consolidation therapy, which included weekly L-asparaginase administration, concentrations of most proteins were decreased compared with baseline values. The amount of thrombin generated following activation with an APTT reagent was similar to adults. CONCLUSION: Plasma concentrations of coagulation proteins are affected by disease (ALL) alone and by combination chemotherapy with or without L-asparaginase. There is no impairment of in vitro capacity to generate thrombin. L-asparaginase alone caused a decrease in almost all proteins; however, ATIII was affected to the greatest extent.

Adolescent↗

PubMed2003

Overview of cutaneous T-cell lymphoma: prognostic factors and novel therapeutic approaches.

The cutaneous T-cell lymphomas (CTCL) comprise a heterogeneous group of entities. The WHO classification distinguishes indolent low-risk entities, including mycosis fungoides/Sézary syndrome (MF/SS), from aggressive entities, including peripheral T-cell lymphoma and its variants and HTLV-1 associated acute T-cell leukemia/lymphoma. Mycosis fungoides represents the most benign of the cutaneous T-cell lymphomas, with 10-year relative survival ranging from 100% to 41%, depending on the degree of skin involvement. Probability of progression to extracutaneous disease within 20 years of diagnosis can be up to 40%, depending on stage. Treatment strategies for early stage CTCL include topical therapies with or without interferon-alpha or oral agents, while advanced stage patients often progress and are treated with chemotherapy and novel agents. Multiagent cytotoxic regimens are palliative with no demonstrated survival benefit. Among the novel therapies for CTCL is bexarotene, a retinoid X-receptor (RXR)-selective agonist, which has demonstrated efficacy in advanced refractory CTCL. Other novel agents include the interleukin (IL)-2 fusion toxin (ONTAK), pentostatin (a potent adenosine deaminase inhibitor), histone deacetylase inhibitors such as depsipeptide, NF-kappaB inhibitors, cytokine receptor antagonists, immunomodulatory therapies and allogeneic stem cell therapy. The value of new therapeutic approaches to CTCL urgently needs to be assessed.

Antineoplastic Agents↗

PubMed1983

Modern management of gestational trophoblastic disease.

Gestational trophoblastic disease is a disorder of pregnancy which may present in a very benign or malignant fashion. Hydatidiform mole complicates approximately 1 in 2000 pregnancies in the United States. The diagnosis may be made prior to evacuation if the signs and symptoms are kept in mind. When the patient presents with spontaneous expulsion of typical molar tissue, a complete evaluation is carried out, including physical examination, uterine curettage for histologic study, and initiation of weekly beta subunit of HCG determinations. At 8 weeks' post-evacuation, about 50% of patients continue to have detectable serum HCG levels. Of these patients, about half may develop chorioadenoma destruens (invasive mole) or choriocarcinoma and require chemotherapy (6, 16). Patient stratification in a clinical classification system based on anatomical extent of disease and certain risk factors is essential for proper management. Review of results obtained at gestational trophoblastic disease treatment centers has shown that with exception of the high-risk patient, virtually 100 per cent cure is possible with early diagnosis and appropriate treatment. Treatment of the high-risk patient with initial triple-drug chemotherapy and simultaneous irradiation of liver or brain metastases may be expected to yield a 90 per cent complete remission. If complete remission in the high-risk patient is maintained for 3 months after cessation of treatment, there appears to be a 98 per cent chance of remaining free of disease (47). The information accumulated in the 25 years since methotrexate was introduced into the treatment of gestational trophoblastic disease has made these excellent results possible. Aggressive multiagent chemotherapy, proper patient classification, radiation, surgery, and utilization of the beta subunit of HCG to monitor therapy are all pivotal in achieving these successes of modern management.

Adult↗

PubMed1990

Clinical and biological heterogeneity of childhood B cell acute lymphocytic leukemia: implications for clinical trials.

Thirty-two children or adolescents had B cell acute lymphocytic leukemia (ALL) diagnosed by demonstration of surface immunoglobulin expression on greater than 10% of their bone marrow blasts. All patients had greater than 25% bone marrow lymphoblasts. Only five of 32 patients (16%) presented with an abdominal mass; however, 24 cases (75%) had FAB L3 morphology. By comparison with findings in common ALL, these 32 children were older (median age, 8 years) and had a higher incidence of central nervous system disease at presentation (22%); all but one were white, and 24 were males. Blast cells from individual cases expressed mu kappa (n = 13), mu lambda (n = 9), gamma kappa (n = 1), alpha kappa (n = 1), or mu with an undetermined light chain (n = 8). The most frequently identified cytogenetic abnormality was the classic B cell-associated t(8;14)(q23;q24) (n = 4); the t(1;19)(q23;p13.3), t(9;22)(q23;q11), and t(1;22) were observed in single cases. Twenty patients were treated uniformly on a single protocol designed for children with advanced B cell malignancy; therapy for the other 12 children varied. Nine children (28%) are surviving event-free; all but one for 3 years or more. We conclude that approximately 25% of children with B cell ALL are curable with intensive multiagent chemotherapy and that classification by immunophenotyping is superior to use of clinical and/or lymphoblast morphologic features.

Adolescent↗

PubMed2004

MAGMA: a multiagent architecture for metaheuristics.

In this work, we introduce a multiagent architecture called the MultiAGent Metaheuristic Architecture (MAGMA) conceived as a conceptual and practical framework for metaheuristic algorithms. Metaheuristics can be seen as the result of the interaction among different kinds of agents: The basic architecture contains three levels, each hosting one or more agents. Level-0 agents build solutions, level-1 agents improve solutions, and level-2 agents provide the high level strategy. In this framework, classical metaheuristic algorithms can be smoothly accommodated and extended. The basic three level architecture can be enhanced with the introduction of a fourth level of agents (level-3 agents) coordinating lower level agents. With this additional level, MAGMA can also describe, in a uniform way, cooperative search and, in general, any combination of metaheuristics. We describe the entire architecture, the structure of agents in each level in terms of tuples, and the structure of their coordination as a labeled transition system. We propose this perspective with the aim to achieve a better and clearer understanding of metaheuristics, obtain hybrid algorithms, suggest guidelines for a software engineering-oriented implementation and for didactic purposes. Some specializations of the general architecture will be provided in order to show that existing metaheuristics [e.g., greedy randomized adaptive procedure (GRASP), ant colony optimization (ACO), iterated local search (ILS), memetic algorithms (MAs)] can be easily described in our framework. We describe cooperative search and large neighborhood search (LNS) in the proposed framework exploiting level-3 agents. We show also that a simple hybrid algorithm, called guided restart ILS, can be easily conceived as a combination of existing components in our framework.

Journal Article↗

PubMed1994

Global information infrastructure.

The High Performance Computing and Communications Program (HPCC) is a multiagency federal initiative under the leadership of the White House Office of Science and Technology Policy, established by the High Performance Computing Act of 1991. It has been assigned a critical role in supporting the international collaboration essential to science and to health care. Goals of the HPCC are to extend USA leadership in high performance computing and networking technologies; to improve technology transfer for economic competitiveness, education, and national security; and to provide a key part of the foundation for the National Information Infrastructure. The first component of the National Institutes of Health to participate in the HPCC, the National Library of Medicine (NLM), recently issued a solicitation for proposals to address a range of issues, from privacy to 'testbed' networks, 'virtual reality,' and more. These efforts will build upon the NLM's extensive outreach program and other initiatives, including the Unified Medical Language System (UMLS), MEDLARS, and Grateful Med. New Internet search tools are emerging, such as Gopher and 'Knowbots'. Medicine will succeed in developing future intelligent agents to assist in utilizing computer networks. Our ability to serve patients is so often restricted by lack of information and knowledge at the time and place of medical decision-making. The new technologies, properly employed, will also greatly enhance our ability to serve the patient.

Computer Communication Networks↗

PubMed1985

Multiagent chemotherapy, prophylactic neuraxis irradiation, and consolidative irradiation for small cell carcinoma of the lung.

Between 6/81 and 6/83, 73 patients with small cell carcinoma of the lung were treated according to a prospective protocol in which cyclophosphamide, doxorubicin, and vincristine (CAV) were given concurrently with prophylactic craniocervical irradiation to the level of C5. Both limited and extensive disease patients with normal computed tomography of the brain received 25 Gy in 10 fractions in 2 weeks. Complete responders to CAV received consolidative thoracic irradiation (CTI) to the local-regional primary (37.5 Gy in 15 fractions in 3 weeks), the first 25 Gy in 10 fractions serving as prophylaxis of the C6 to T12 spinal cord. The neuraxis from L1 to S2 then received 25 Gy in 10 fractions in 2 weeks. Consolidative irradiation of localizable metastatic sites was given in extensive disease patients. Partial and nonresponders to CAV received 50-60 Gy in 5-6 weeks to local-regional disease. With a median followup of 29 months, survival was significantly better (p less than .01) in patients receiving CTI to the chest after complete response to CAV (both limited disease and extensive disease) than without CTI. Of 41 patients completing the protocol and without central nervous system (CNS) involvement at presentation, four (9%) failed initially in the CNS (two brain, two spinal axis); CNS failure was the cause of death in all four patients with no other sites of metastases at death in two of these. Failure to complete protocol treatment was due to disease progression during chemotherapy in 25/73 (34%) and chemotherapy related complications (three sepsis, one gastrointestinal bleed) in four of 73 (5.5%) patients. CTI and prophylactic neuraxis irradiation did not increase morbidity or result in mortality in the sequence utilized; prophylactic neuraxis irradiation appears to reduce the CNS relapse rate, and CTI benefits survival.

Actuarial Analysis↗

PubMed2001

Adult medulloblastoma: multiagent chemotherapy.

In this study, the records of 17 adult patients with medulloblastoma treated with craniospinal radiation and 1 of 2 multiagent chemotherapy protocols were reviewed for progression-free survival, overall survival, and toxicity, and the patients were compared with each other and with similarly treated children and adults. Records of patients treated at 3 institutions were reviewed. Seventeen medulloblastoma patients (11 female, 6 male) with a median age of 23 years (range, 18-47 years) were treated with surgery, craniospinal radiation (CSRT) plus local boost, and 1 of 2 adjuvant chemotherapy regimens. All tumors were infratentorial (10 in 4th ventricle and 7 in left or right hemisphere). Ten patients presented with hydrocephalus, and 7 of them were shunted. Eight patients had gross total resection, 7 had subtotal resection (>50% removed), and 2 had partial resection (<50% removed). Postoperatively, 3 patients had positive cytology and 3 had positive spinal MRI. Five patients were classified as good risk and 12 were classified as poor risk (Chang staging system). Ten patients were treated with the "Packer protocol," consisting of CSRT plus weekly vincristine followed by 8 cycles of cisplatin, lomustine, and vincristine. Seven patients were treated with the Pediatric Oncology Group (POG) protocol, consisting of alternating courses of cisplatin/etoposide and cyclophosphamide/vincristine, followed by CSRT. Eight of 17 patients relapsed, with all 8 relapsing at the primary site. Other relapse sites included the leptomeninges (5), bone (1), and brain (1). The estimated median relapse-free survival (Kaplan-Meier) for all patients was 48 months (95% confidence interval, >26 months to infinity). Median relapse-free survival for patients on the Packer protocol was 26 months, and for those on the POG regimen was 48 months (P = 0.410). Five of 10 on the Packer protocol were relapse-free, while 4 of 7 were relapse-free on the POG regimen. Two patients relapsed during chemotherapy and 6 relapsed after completing all therapy at 18, 18, 26, 30, 40, and 48 months. The estimated median survival of all patients was 56 months (95% confidence interval, 27 to infinity) with 11 patients alive; for the Packer protocol, median survival was 36 months, and for the POG protocol, it was 57 months (P = 0.058). The hazard ratio was 0 (95% confidence interval, 0 to infinity). Toxicity during the Packer protocol was moderately severe, with only 1 of 10 patients able to complete all therapy. Two patients had severe abdominal pain during CSRT + vincristine, and 5 had peripheral neuropathy during vincristine therapy. Hearing loss (>20 dB) occurred in 7, neutropenia (<500 microl) in 6, thrombocytopenia (<50,000 microl) in 6, nephrotoxicity (>25% decrease by creatinine clearance) in 2, and decreased pulmonary function (diffusing capacity for carbon monoxide decrease >40%) in 1. On the POG protocol, only 1 patient had persistent nausea and vomiting, 2 had peripheral neuropathy, and 3 had hearing deficit (>20 dB) or tinnitus. The POG and Packer protocols did not have a statistically significant difference in relapse-free or overall survival because of the small sample size. The POG protocol seemed to have less nonhematologic toxicity. Adults on the Packer protocol appeared to have shorter median survival and greater toxicity than did children. To know whether adding adjuvant chemotherapy to craniospinal radiation in adult therapy increases relapse-free and overall survival, we must await the results of a larger randomized controlled clinical trial.

Abdominal Pain↗

PubMed2003

Use of tamoxifen in the treatment of malignant melanoma.

BACKGROUND: Tamoxifen has been used in the treatment of patients with metastatic malignant melanoma either as a single agent or, more commonly, in combination with other chemotherapeutic agents. The aim of the current study was to summarize the available clinical evidence on the role of the tamoxifen in different combination chemotherapy regimens because clinical studies including tamoxifen have produced inconclusive results. METHODS: The authors designed a systematic review and metaanalysis of published randomized controlled trials to assess the benefit of tamoxifen added to various single-agent or multiagent chemotherapy or biochemotherapy regimens. RESULTS: Six randomized trials met the inclusion criteria and were analyzed. These 6 trials involved a combined total of 912 patients. Of this number, 455 patients were randomized to receive tamoxifen added to chemotherapy or biochemotherapy regimens and 457 were randomized to receive chemotherapy or biochemotherapy without tamoxifen. The overall response rate was not improved significantly by the addition of tamoxifen to the chemotherapy regimen (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.75-1.82; test for overall effect: P = 0.14). The results were not statistically significant for complete response (OR, 0.64; 95% CI, 0.33-1.25; test for overall effect: P = 0.19). CONCLUSIONS: The current metaanalysis demonstrated that tamoxifen does not improve the overall response rate, complete response rate, or survival rate when administered along with combined chemotherapy regimens. Currently, the strength of evidence does not support the use of tamoxifen in combination with other systemic chemotherapy for the treatment of metastatic melanoma.

Adult↗

PubMed1979

Response of 9L tumor cells in vitro to spirohydantoin mustard.

The effects of spirohydantoin mustard (SHM), a potential antitumor agent for central nervous system tumors, in the in vitro 9L rat brain tumor model were studied. In cell culture medium at 37 degrees, the drug was totally detoxified within 30 min. Dose-response curves for exponentially growing and plateau-phase cells were similar and indicated that a small fraction of cells were resistant to SHM. When exponentially growing cells were treated with SHM (5 microgram/ml for 1 hr), recovery from potentially lethal damage occurred within 28 hr. When cells were perturbed by SHM, the S, G2, and M phases were prolonged, there was a G2 block, some cells entered mitosis, but few divided, and cells tended to accumulate in mid-S, then moved synchronously to G2-M. The rate at which cells moved was concentration dependent and was much slower at high concentrations. The ability of SHM to both synchronize cells and block DNA synthesis may be useful in multiagent therapy regimens.

Animals↗