Genetic variants related to angiogenesis and apoptosis in patients with glioma / Variantes genéticas relacionadas à angiogênese e apoptose em pacientes com glioma

ABSTRACT Background Glioma, the most common primary malignant brain tumor in adults, is highly aggressive and associated with a poor prognosis. The objectives of this study were to evaluate the association of genetic polymorphisms related to angiogenesis and apoptosis with gliomas, as well as comorbidities, lifestyle, clinical profile, survival and response to treatment (temozolomide [TMZ] and radiotherapy [RT]) in patients with the disease. Methods In a total of 303 individuals, genotypes were performed by real-time PCR, and clinical data, lifestyle and comorbidities were obtained from medical records and questionnaires. The significance level was set at 5%. Results Smoking, alcohol consumption, systemic arterial hypertension, diabetes mellitus and body mass index prevailed among patients, compared to controls (p < 0.05). The heterozygous genotype rs1468727 (T/C) and the homozygous genotype rs2010963 (G/G) (p > 0.05) were observed in both groups. Lifestyle and comorbidities showed independent risk factors for the disease (p < 0.0001, p = 0.0069, p = 0.0394, respectively). Patients with low-grade gliomas had a survival rate of 80.0 ± 1.7% in three years. For the combination of TMZ+RT, survival was 78.7 ± 7.6% in 20 months, compared to TMZ only (21.9 ± 5.1%, p = 0.8711). Conclusions Genetic variants were not associated with gliomas. Specific lifestyle habits and comorbidities stood out as independent risk factors for the disease. Low-grade gliomas showed an increase in patient survival with TMZ+RT treatment.

RESUMO Introdução Glioma, tumor cerebral maligno, é altamente agressivo e associado a mau prognóstico. Os objetivos deste estudo foram avaliar a associação de polimorfismos genéticos relacionados a angiogênese e apoptose em pacientes com glioma, bem como suas comorbidades, hábitos de vida, perfil clínico, sobrevida e resposta ao tratamento (temozolomida [TMZ] e radioterapia [RT]). Métodos 303 indivíduos foram genotipados por PCR em tempo real, e foram coletados dados clínicos, hábitos de vida e comorbidades. Admitiu-se nível de significância para valor p < 0,05. Resultados Tabagismo, elitismo, hipertensão arterial sistêmica, diabetes mellitus e índice de massa corporal prevaleceram entre os pacientes, comprados aos controles (p < 0,05). O genótipo heterozigoto rs1468727 (T/C) e homozigoto rs2010963 (G/G) (p > 0,05) foram observados em ambos os grupos. Tabagismo, elitismo, hipertensão arterial sistêmica, diabetes mellitus e índice de massa corporal apresentaram fatores de risco independentes para a doença (p < 0.0001, p = 0.0069, p = 0.0394, respectivamente). Os pacientes com gliomas de baixo grau apresentaram sobrevida de 80,0 ± 1,7% em três anos. Para a combinação de RT e TMZ, a sobrevida foi de 78,7±7,6% em 20 meses, em comparação com TMZ (21,9 ± 5,1%, p = 0,8711). Conclusões As variantes genéticas não estiveram associadas aos gliomas. Hábitos de vida e comorbidades específicas destacaram-se como fatores de risco independentes para a doença. O tratamento com TMZ + RT mostrou aumento na sobrevida dos pacientes.

Eficacia y seguridad de bevacizumab en eltratamiento del glioblastoma multiforme recurrente, irresecable y terapia previa con temozolamida / Efficacy and safety of bevacizumab in the treatment of recurrent, unresectable glioblastoma multiforme and previous therapy with temozolamide

INTRODUCCIÓN: Antecedentes: El Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) ha recibido la solicitud de evaluar el uso de bevacizumab (BVZ) e irinotecan en pacientes adultos con diagnóstico de glioblastoma multiforme recurrente, irresecable que progresaron a temozolamida dentro del sistema de EsSalud, indicación actualmente no contemplada en el petitorio de medicamentos. Aspectos Generales: Los gliomas son el tipo más común de tumores cerebrales malignos. Ellos se desarrollan a partir de las células gliales que dan apoyo a las células nerviosas del cerebro y medula espinal. Existen cuatro tipos principales de gliomas: astrocitoma, ependimoma, oligliodendroglioma, y tumores mixtos. Los gliomas son clasificados de acuerdo a su 1.) potencial de proliferación ascendente, desde el grado 1 al grado 4. Los gliomas de grado 3 y 4 son conjuntamente referidos con glioblastomas, y son considerados como gliomas de alto grado. El glioma de grado 4 es llamado glioblastoma multiforme. Los síntomas del glioma de alto grado dependen del tamaño, la localización, y el grado de infiltración del tumor. Ellos incluyen dolor de cabeza, náuseas, vómitos, convulsiones, aIteración de la visión, problemas del lenguaje y cambios en las habilidades cognitivas o funcionales. Tecnología Sanitaria de Interés: Bevacizumab (Avastin, Roche) es un anticuerpo monoclonal anti-factor de crecimiento endotelial vascular (VEGF), que inhibe la inducción de la angiogénesis mediada por el VEGF. En consecuencia, se reduce la vascularización de los tumores, y también del crecimiento del mismo. METODOLOGIA: Estratégia de Busqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad del uso de BVZ en comparación con irinotecan, en el tratamiento del GBM con recurrencia o progresión, irresecable durante el tratamiento coadyuvante con TMZ, en las bases de \r\ndatos de MEDLINE, EMBASE, CENTRAL, DARE y TRIPDATABASE. Se hizo una búsqueda adicional en www.clinicaltrials.gov, para poder identificar ensayos clínicos aún en elaboración o que no hayan sido publicados. Adicionalmente, se hizo una búsqueda dentro de la información generada por las principales instituciones internacionales oncológicas y agencias de tecnologías sanitarias que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC).\r\nRESULTADOS: Sinopsis de la Evidencia: Se realizó la búsqueda bibliográfica y de evidencia científica que sustente el uso de BVZ en comparación con irinotecan, en el tratamiento del GBM con recurrencia o progresión, irresecable durante el tratamiento adyuvante con TMZ según la pregunta PICO. Para el \r\npresente documento se seleccionó el siguiente cuerpo de evidencia que es resumido a continuación.Guías Clínicas: Se identificaron cuatro GPC sobre el manejo del glioblastoma recurrente. Evaluaciones de tecnología sanitaria: no se identificaron documentos de ETS para el uso de bevacizumab en el GBM recurrente. Se identificó una evaluación planeada por NICE, la cual fue retirada después de conocer la decisión de la EMA de no aprobar el uso de BVZ para la indicación de GBM recurrente. Revisiones sistemáticas: no se identificó alguna revisión sistemática que haya evaluado el uso de BVZ en comparación con el de irinotecan en pacientes con GBM recurrente. Ensayos clínicos: no se identificó algún ensayo que haya comparado el uso de BVZ con el tratamiento con irinotecan. En su lugar, se identificaron y se han incluido en esta evaluación tres ensayos. Uno de fase II no comparativo que usó BVZ, y otros dos estudios \r\nde fase II aleatorizados que compararon los efectos de BVZ con el régimen de BVZ + irinotecan. Este tipo de evidencia es considerada como indirecta por no responder directamente a la pregunta PICO de esta evaluación. Ensayos Clínicos registrados: no se identificaron ensayos en progreso o aun sin publicar que puedan agregar información a la pregunta PICO de esta evaluación. CONCLUSIONES: Hasta el momento, no se ha identificado evidencia directa para responder si el uso de BVZ es más efectivo y seguro que irinotecan en el tratamiento de los pacientes con GBM recurrente, irresecable y que progresó con el uso de TMZ. Hasta la fecha no se ha identificado algún estudio que haya comparado directamente ambos medicamentos.

Validation of the Effectiveness and Safety of Temozolomide during and after Radiotherapy for Newly Diagnosed Glioblastomas: 10-year Experience of a Single Institution

This study was performed to validate the effectiveness and safety of concurrent chemoradiotherapy and adjuvant therapy with temozolomide for newly diagnosed glioblastoma multiforme as a standard treatment protocol. Between 2004 and 2011, patients newly diagnosed with glioblastoma who were treated with temozolomide during concurrent chemoradiotherapy and adjuvant chemotherapy were included from a single institution and analyzed retrospectively. The primary endpoint was overall survival, and the secondary endpoints were progression-free survival, response, and safety. A total of 71 patients were enrolled in this study. The response rate was 41% (29/71), and the tumor control rate was 80% (57/71). In the 67 patients who completed the concurrent chemoradiotherapy with temozolomide, the median overall survival was 19 months and the 1- and 2-yr overall survival rates were 78.3% and 41.7%, respectively. The median progression free survival was 9 months, and the 1- and 2-yr progression free survival rates were 33.8% and 14.3%, respectively. The mean duration of survival after progression of disease in salvage treatment group was 11.9 (1.3-53.2) months. Concurrent chemoradiotherapy with temozolomide resulted in grade 3 or 4 hematologic toxic effects in 2.8% of the patients. The current protocol of temozolomide during and after radiation therapy is both effective and safe and is still appropriate as the standard protocol for treatment of glioblastoma. An active salvage treatment might be required for a better prognosis.

Quimioterapia neoadjuvante e resposta patológica: coorte retrospectiva / Neoadjuvant chemotherapy and pathologic response: a retrospective cohort

OBJETIVO: Avaliar a taxa de resposta patológica completa atingida pelas pacientes com diagnóstico de câncer de mama localmente avançado submetidas à quimioterapia neoadjuvante baseada no esquema doxorrubicina/ciclofosfamida seguido de paclitaxel. MÉTODOS: Coorte retrospectiva de pacientes admitidas no Hospital de Câncer de Barretos com câncer de mama localmente avançado entre 2006 e 2008 submetidas ao protocolo de doxorrubicina/ciclofosfamida seguido de paclitaxel (4 ciclos de doxorrubicina 60mg/m² e ciclofosfamida 600mg/m² a cada 21 dias; 4 ciclos de paclitaxel 175mg/m² a cada 21 dias). As seguintes variáveis foram avaliadas: idade, menopausa, performance status, estadiamento clínico inicial, dados antropométricos, quimioterapia (dose - duração), perfil de toxicidade, estadiamento clínico pós-tratamento, cirurgia, resposta patológica completa, sobrevida livre de doença e características anatomopatológicas (tipo e grau histológico, perfil hormonal e comprometimento linfonodal). A análise estatística foi realizada considerando-se o nível de significância de 5%. RESULTADOS: Das 434 pacientes avaliadas, 136 foram excluídas por erro no estadiamento ou por terem recebido outro tipo de quimioterapia. A mediana de idade foi 50 anos, todas com performance status 0-1. A mediana do tamanho clínico inicial do tumor foi 65mm e a mediana do tamanho clínico final do tumor foi 22mm. Apresentaram resposta patológica completa 51 (17,1%) pacientes. Aquelas que apresentavam perfil hormonal negativo ou que eram triplo-negativas (Her-2 e perfil hormonal negativos) tiveram impacto favorável na resposta patológica completa. CONCLUSÃO: Quimioterapia neoadjuvante com doxorrubicina/ciclofosfamida seguidas de paclitaxel ofereceu taxa de resposta patológica completa na população estudada de acordo com a literatura. Pacientes triplo-negativas tiveram maior chance de atingir essa resposta.

OBJECTIVE: To evaluate the complete pathologic response attained by patients diagnosed with locally advanced breast cancer submitted to neoadjuvant chemotherapy based on the doxorubicin/cyclophosphamide regimen followed by paclitaxel. METHODS: A retrospective cohort of patients with locally advanced breast cancer, admitted to the Hospital de Câncer de Barretos between 2006 and 2008 submitted to the doxorubicin/cyclophosphamide protocol followed by paclitaxel (4 cycles of doxorubicin 60mg/m² and cyclophosphamide 600mg/m² every 21 days; 4 cycles of paclitaxel 175mg/m² every 21 days). The following variables were assessed: age, menopause, performance status, initial clinical staging, anthropometric data, chemotherapy (dose - duration), toxicity profile, post-treatment staging, surgery, pathologic complete response rate, disease-free survival, and pathological characteristics (type and histological degree, hormonal profile and lymph node involvement). Statistical analysis was performed using a 5% level of significance. RESULTS: Of the 434 patients evaluated, 136 were excluded due to error in staging or because they had received another type of chemotherapy. Median age was 50 years, all with performance status 0-1. Median initial clinical size of tumor was 65mm and the median final clinical size of the tumor was 22mm. Fifty-one (17.1%) patients experienced a pathologic complete response. Those with a negative hormonal profile or who were triple-negative (negative Her-2 and hormonal profile) experienced a favorable impact on the pathologic complete response. CONCLUSION: Neoadjuvant chemotherapy with doxorubicin/cyclophosphamide followed by paclitaxel provided a pathologic complete response in the population studied in accordance with that observed in the literature. Triple-negative patients had a greater chance of attaining this response.

Isolated limb perfusion with hyperthermia and chemotherapy: predictive factors for regional toxicity

OBJECTIVE: Isolated limb perfusion combined with melphalan is an accepted treatment for obtaining locoregional control in advanced melanoma of the extremities and other malignant neoplasias restricted to the limb. This study aims to examine the factors associated with toxicity caused by the regional method. We considered the technical aspects of severe complications associated with the procedure in an attempt to diminish the patient morbidity that occurs during the learning curve. METHODS: We conducted a retrospective analysis of the records of patients who underwent perfusion at the AC Camargo Hospital in São Paulo, Brazil between January 2000 and January 2009. The Wieberdink scale was applied to classify local toxicity and its relation to clinical and laboratory variables. RESULTS: Fifty-eight perfusions were performed in 55 patients. Most patients (86.2%) presented a toxicity level between I and III. Grade V toxicity was seen in five cases (8.6%), four of which occurred in the first 2 years. Creatine phosphokinase, an important predictive factor for toxicity, had an average value of 231.8 for toxicity grades I-III and 1286.2 for toxicity grades IV-V (p = 0.001). There was a relationship between the melphalan dose and toxicity, which was 77 mg (25 to 130 mg) for toxicity grades I-II and 93.5 mg (45 to 120 mg) for toxicity grades IV-V (p = 0.0204). CONCLUSION: It is possible to prevent the toxicity associated with melphalan by adjusting the dose according to the patient's body weight (especially for women and obese patients) and the creatine phosphokinase values in the postoperative period.

Is the Low-Thalidomide Dose MPT Regimen Beneficial?

No abstract available.

Treatment of recurrent glioblastoma with intra-arterial BCNU [1, 3-bis (2-chloroethyl)-1-nitrosourea] / Tratamento do glioblastoma recorrente com BCNU [1, 3-bis (2-chloroethyl)-1-nitrosourea] intra arterial

Contemporary therapies for patients with glioblastomas remain marginally efficient, and recurrence following surgery, radiation therapy and adjuvant chemotherapy is practically universal. The major obstacles to the successful use of chemotherapy for CNS tumors are the drug delivery to the tumor site and the infusion of chemotherapeutic agents directly into the arterial supply of a tumor. The latter could provide a pharmacokinetic advantage by enhancing drug delivery to the tumor. Sixteen patients with recurrent unilateral glioblastomas treated with intra-arterial BCNU were evaluated retrospectively. During the infusion, eleven patients referred pain in the ipsilateral eye, five patients were nauseated, three reported headache, one patient presented mental confusion, while two presented focal signs. There were two deaths during the course of therapy. Four patients achieved temporary clinical improvement, seven showed disease stability, and three presented clinical deterioration. The median total survival time was 87.9 weeks. Unilateral vision loss and focal signs were observed as delayed complications of this treatment. This study has confirmed previous reports indicating that arterial chemotherapy is clearly not curative, and presents serious toxicity. Only through a randomized prospective study performed in a large series of patients can the questions concerning survival period increment be answered properly.

Os tratamentos atuais para pacientes com glioblastoma permanecem pouco eficientes e a recorrência, acompanhando cirurgia, radioterapia e quimioterapia, é a regra geral. O maior obstáculo para o sucesso da quimioterapia para os tumores do SNC é a disponibilização da droga no sitio do tumor sendo que a infusão do agente quimioterápico diretamente na trama arterial da lesão pode proporcionar vantagens por maior liberação da substância diretamente no tumor. Estudamos retrospectivamente dezesseis pacientes com glioblastomas recorrentes, unilaterais, que foram tratados com BCNU intra-arterial; durante a infusão, onze pacientes sentiram dor no olho ipsilateral, cinco ficaram nauseados, três queixaram-se de cefaléia, um apresentou confusão mental e dois apresentaram sinais focais. Ocorreram duas mortes durante a terapia. Quatro pacientes apresentaram melhora clinica temporária, sete apresentaram estabilização e três apresentaram deterioração. A média de sobrevida total foi de 87,9 semanas. Perda da visão unilateral e sinais focais foram complicações tardias. Este estudo confirmou trabalhos anteriores indicando que a quimioterapia intra-arterial claramente não é curativa, séria toxicidade pode ocorrer e somente um estudo prospectivo e randomizado, realizado em uma serie maior de pacientes, poderá responder questões sobre o aumento do tempo de sobrevida de forma adequada.

Visual Prognosis of Retinoblastoma in the Posterior Pole Treated with Primary Chemotherapy Plus Local Treatments

PURPOSE: To evaluate the visual outcomes of retinoblastoma in the posterior pole (RBPP) treated with chemotherapy plus local treatments and to address the prognostic factors that influence such outcomes. METHODS: The medical records of patients with RBPP diagnosed at the Department of Pediatric Ophthalmology, Seoul National University Children's Hospital between August 1987 and September 2007 were reviewed retrospectively. Only those patients treated via primary chemotherapy plus local treatments were included. The presence of foveal involvement and tumors in the posterior pole before and after treatment, the type of regression pattern and the best corrected visual acuity (BCVA) of each patient were evaluated. RESULTS: A total of 13 eyes in 12 patients were included. The mean final BCVA for treated RBPP was 20/210 (range, hand motion to 20/16). However, eight eyes (61.5%) had an acuity of 20/200 or better and seven eyes (53.8%) had an acuity of 20/50 or better. The mean final BCVA was significantly better in cases with negative foveal involvement; however, four eyes (37.5%) with positive foveal involvement had an acuity of 20/200 or better. Tumors area in the posterior pole and the type of regression pattern were not significantly related to final BCVA. CONCLUSIONS: Over one half of the studied RBPP patients had working vision. Although the eyes had RBPP with positive foveal involvement, about one-third of the patients had working vision. Vision preservation should be considered when deciding on RBPP treatment.

Paraneoplastic leukocytoclastic vasculitis in chronic lymphoid leukemia.

A 50-year-old female who was a known case of chronic lymphoid leukemia (CLL) developed ecchymoses, purpuric spots with papules, some nodules (1-3 mm) and crusts all over the body associated with severe burning and itching along with exaggeration of CLL. The lesions were more prominent on lower limbs and face. Skin biopsy was reported as leukocytoclastic vasculitis. These lesions regressed after treatment with leukeran and glucocorticoids.

Ameliorating effects of Andrographis paniculata extract against cyclophosphamide-induced toxicity in mice.

Major drawbacks of chemotherapeutic agents are their toxic side effects and lack of tumor specificity. Immunological and biochemical studies were here carried out to investigate protective effects of ethanolic extract of Andrographis paniculata against cyclophosphamide (CTX) induced toxicity in vivo. Intraperitoneal administration of the extract significantly increased the total WBC account (3256.5+/-196 cells/cm(2)), bone marrow cellularity (17.1+/-10.4x10(6) cells/femur) and betaesterase positive cells (849+/-23.2 cells/4000 cells) in CTX treated animals, when compared to CTX alone treated control mice. Weights of lymphoid organs such as a spleen and thymus, reduced by CTX administration, were also increased by A paniculata treatment. Reduction of GSH in liver (4.8+/-0.21nmol/mg protein) and in intestinal mucosa (13+/-0.67 nmol/mg protein) of CTX-treated controls was significantly reversed by A paniculata administration (liver: 6.4+/-0.13, intestinal mucosa: 17.11+/-0.06), with amelioration of changes in serum and liver ALP, GPT, LPO (lipid peroxidation). Histopathological analysis of small intestine also suggests that extract could reduce the CTX induced intestinal damage. The level of proinflammatory cytokine TNF-alpha, which was elevated during CTX administration, was significantly reduced by the A paniculata extract administration. The lowered levels of other cytokines like IFN-gamma, IL-2, GM-CSF, after CTX treatment were also found to be increased by extract administration.

Temozolomide Chemotherapy in Patients with Recurrent Malignant Gliomas

Numerous studies have demonstrated the clinical activity of temozolomide, a second-generation alkylating agent, against malignant brain tumors, however, its activity has not been reported in an Asian population. This study analyzed the efficacy and toxicity of temozolomide in 25 adult patients with recurrent or progressive malignant gliomas after surgery and standard radiation therapy with or without chemotherapy, enrolled in our institution since July 2000. Sixteen patients had glioblastoma multiforme (GBM), six with anaplastic astrocytoma, and three with anaplastic oligodendroglioma. Of the 25 patients, 3 (12%) achieved a complete response (CR), 8 (32%) achieved a partial response (PR), 6 (24%) had stable disease (SD), and 8 (32%) had progressive disease (PD). Two patients achieved a CR, 4 patients achieved a PR, 3 patients had SD and 7 patients had PD in GBM, and 1 patient achieved a CR, 4 patients achieved a PR, 3 patients had SD, 1 patient had PD in the non-GBM patients. Median progression free survival was 8 weeks in GBM and 22 weeks in the non-GBM patients. The median overall survival of each group was 17 weeks and 28 weeks. Temozolomide demonstrated moderate activity in recurrent and progressive malignant gliomas without serious toxicity.

Histamine combined with melphalan in isolated limb perfusion for the treatment of locally advanced soft tissue sarcomas: preclinical studies in rats

OBJETIVO: Avaliar o potencial benéfico da histamina combinada ao melfalano, na perfusão de membro isolado (PMI), como alternativa à combinacão TNF-alfa mais melfalano, no tratamento de sarcomas de partes moles irressecaveis em extremidades, em ratos de linhagem Brown Norway (BN). MÉTODOS: 20 ratos BN foram submetidos a implantacão de fragmentos de fibrosarcoma singênico BN-175 na pata traseira direita. Em cerca de 7-10 dias o tumor atingiu um diâmetro médio de 12-15 mm e foram aleatóriamente divididos em quatro grupos (controle, melfalano,histamina em doses progessivas combinada ao melfalano e histamina) sendo submetidos a PMI experimental por 30 minutos. Os tumores foram então medidos diariamente com o uso de paquímetro e o volume tumoral calculado. RESULTADOS: As curvas de resposta mostram um efeito significativo da combinacão de Histamina na concentracão de 200 mg/mL ao melfalano, com 66% de resposta global incluindo 33% de respostas completas (p < 0.01). Não houve efeitos colaterais sistêmicos e localmente apenas edema leve e transitório nos animais tratados com histamine. CONCLUSAO: A histamina em combinacão com o melfalano apresenta um efeito promissor na PMI garantindo maiores investigacões do seu mecanismo de acão e do seu potencial uso na perfusão de órgãos.

Early occurrence of acute myeloid leukemia following adjuvant radiotherapy and higher cumulative dose of cyclophosphamide in carcinoma breast.

We report a case of cancer breast developing acute myeloid leukemia (AML) within a relatively short interval of two and a half years of her primary treatment. This could be attributed to post operative radiotherapy and a higher cumulative dose of cyclophosphamide (14.4 gm) which had to be given as a part of her combination chemotherapy regimen, initially as adjuvant and then later as salvage chemotherapy. The successful salvage therapy for secondary AML instituted in this case is also discussed.

Complete axillary conversion after neoadjuvant chemotherapy in locally advanced breast cancer: a step towards conserving axilla?

OBJECTIVES: This study was designed to assess the clinical, sonographic and histopathological response of axillary lymph node metastasis to neoadjuvant chemotherapy in patients with locally advanced breast cancer. MATERIAL AND METHODS: Forty patients with locally advanced breast cancer (LABC) with clinically palpable or sonographically detectable axillary nodes were studied. FNAC of the primary tumor and axillary nodes was done and patients were started on neoadjuvant chemotherapy. Axillary nodes were assessed clinically and sonographically for response after 3 cycles of chemotherapy. All patients underwent total mastectomy with axillary clearance and the lymph nodes in the specimen were examined for metastasis. RESULTS: 47% patients had complete clinical nodal response, while 19% showed complete sonographic response. Complete pathological nodal response was documented in 22% of patients. Ultrasonography was found to be more sensitive than clinical examination in assessing complete nodal response. 10% of the patients had complete pathological response of both primary tumor and axillary nodes. There was significant correlation between pathological response of primary tumor and lymph nodes (P=0.004). Patients with complete sonographic or clinical response were found to have no or minimal residual disease in axilla and hence axillary dissection may be avoided in them.

Trasplante de células hematopoyéticas de sangre periférica utilizando quimioterapia inmunosupresora sin destrucción de la médula ósea: "minitrasplante" / Peripheral blood hematopoietic cell transplant using immunosuppressive chemotherapy without bone marrow destruction: minitransplant

Using a nonmyeloablative, immunosuppressive, fludarabine (FLU)-base conditioning regimen, we have performed allogeneic peripheral blood stem cell transplants in 17 patients (six with chronic granulocytic leukemia, four with acute myelogenous leukemia, five with acute lymphoblastic leukemia, one with myelodysplasia and one, with thalassemia major). Conditioning regimen consisted of FLU/busulfan/cyclophosphamide or FLU melphalan. To avoid graft vs. host disease (GVHD), cyclosporine and methotrexate were used. Median granulocyte recovery time to 0.5 x 10(9) was 11 days, whereas median platelet recovery time to 20 x 10(9) was 12 days. Seven patients did not need red blood cell transfusions and four did not need platelet transfusions. In thirteen individuals (76), the procedure could be completed fully on an outpatient basis. Follow-up times range between 1 and 14 months. Five of 17 patients developed acute GVHD whereas 4/10 developed chronic GVHD. The 14-month survival (SV) is 70 and median SV is not reached. Five patients (29) have died, three due to relapse of the disease and two due to GVHD. The transplant-related mortality was 5.8. This procedure is substantially less costly than its counterpart, using in-hospital myeloablative conditioning regimens, and may represent another approach in management of patients requiring allogeneic stem cell transplant.

Amifostine (WR-2721), a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin's lymphomas: a phase II study

Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY) (7 g/m2), used to mobilize peripheral blood progenitor cells (PBPC) and to reduce tumor burden. We enrolled 29 patients, 22 (75.9 percent) affected by aggressive and 7 (24.1 percent) by indolent non-Hodgkin's lymphoma (NHL), who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients) affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0.04). None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage) colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively). Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.

Adjuvant therapy in invasive thymoma: an audit of cases treated over an 8 year period.

Invasive thymomas comprise 0.1%-0.2% of all malignancies in India. This report is an audit of 11 cases (10 males and 1 female) at a mean age of 36.6 years (range 25-52 years) of invasive thymoma accrued over an eight year period treated by combined modality treatment. Nine of these presented with myaesthenia gravis. All patients underwent initial surgery (3 partial and 8 total resections) and postoperative radiotherapy. Two of the three partially resected patients received one course of chemotherapy prior to radiotherapy consisting of cyclophosphamide, vincristine, procarbazine and prednisolone. At a median follow up of 28 months (range 2-87) there have been no local relapses, one distant metastasis and one death due to uncontrolled myaesthenia. The treatment strategies with invasive thymomas would depend upon the extent of resection. Postoperative radiotherapy appears to be indicated in all cases, however the role of chemotherapy may be limited to those with partial resection.

Role of bio-metal Fe(III) in anticancer effect of dacarbazine.

Physicochemical, Microbial and Pharmacological studies on Fe(III)-Dacarbazine complex have been done in solid and aqueous phase. On the basis of elemental analysis, polarographic studies, amperometric titrations and IR spectral studies the probable formula for the complex has been worked out to be 1:1, Fe(III)-Dacarbazine. The metal ligand interaction has been studied using polarographic method at 25 +/- 1 degrees C and at ionic strength of mu = 1.0 (KCl). Microbial studies on the complex was done against various pathogenic bacteria viz. Pseudomonas mangiferae, Staphylococcus aureus, Salmonella typhi and Vibrio cholarae and fungi i.e. Trichothecium and Chrysosporium sp. using Raper's method. Mouse sarcoma cell line 180 and Balb/C mice were used for the anticancer screening of solid complex in vitro and in vivo respectively. The observed polarographic data, on lingane treatment revealed the formation of single (1:1) (M:L) complex with Fe(III) and dacarbazine ligands. The results of amperometric titrations of Fe(III) with dacarbazine in IM KCl supporting electrolyte pH 7.0 +/- 0.1 supported the above findings the IR data speaks of the complex formation between the metal and the dacarbazine ligand through the two nitrogen one each of primary amide and trizo groups. The results of microbial and pharmacological studies with the M:Drug complex revealed that the anticancer activity of the drug metal complex is nearly doubled as compared to the pure drug. As such Fe(III) dacarbazine complex may be recommended to the therapeutic experts for its possible use as more potent anticancer drug.

Epithelial ovarian cancer treated by platinum or platinum analogue with cyclophosphamide: experience in Ramathibodi Hospital.

This study presented the outcome of 92 EOC patients treated by platinum or platinum analogue with cyclophosphamide from January 1, 1993 to December 31, 1995. There were 77 evaluable patients. The follow-up ranged from 4-42 months (median 14 months). The over all 3-year survival was 64 per cent and the median progression-free interval was 16 months for the whole group. There was no significant difference in survival between patients who received cisplatin and those who received carboplatin (P = 0.093). Patients who underwent optimal debulking surgery had significantly longer progression-free interval (P = 0.001) than those who had sub-optimal surgery. Fifty four per cent of patients with clear cell carcinoma died of the disease. Patients who received cisplatin had a drop out rate while on therapy more often (24% vs 5.3%) than that of carboplatin. Toxicities from chemotherapy were moderate but manageable.