Randomized, double-blind, placebo-controlled phase II study of istiratumab (MM-141) plus nab-paclitaxel and gemcitabine versus nab-paclitaxel and gemcitabine in front-line metastatic pancreatic cancer (CARRIE).

BACKGROUND: Preclinical data suggest that dual blockade of the insulin-like growth factor-1 receptor (IGF-1R) and HER3 pathways has superior activity to IGF-1R blockade alone in pancreatic ductal adenocarcinoma (PDAC). We tested whether istiratumab, an IGF-1R- and ErbB3-bispecific antibody, can enhance the efficacy of standard of care (SOC) chemotherapy in patients with metastatic PDAC selected for high IGF-1 serum levels. PATIENTS AND METHODS: CARRIE was an international, randomized, double-blind, placebo-controlled phase II study for patients with previously untreated metastatic PDAC. In part 1, 10 patients were evaluated for pharmacokinetics and safety. In part 2, patients with high free serum IGF-1 levels were randomized 1 : 1 to receive either istiratumab [2.8 g intravenously (i.v.) every 2 weeks] or placebo combined with gemcitabine/nab-paclitaxel at approved dose schedule. The co-primary endpoints were progression-free survival (PFS) in patients with high IGF-1 levels and PFS in patients with both high serum IGF-1 levels and heregulin (HRG)+ tumors. Key secondary endpoints were overall survival (OS), objective response rate (ORR) by RECIST v.1.1, and adverse events (AEs) rate. RESULTS: A total of 317 patients were screened, with 88 patients randomized in part 2 (experimental arm n = 43; control n = 45). In the high IGF-1 cohort, median PFS was 3.6 and 7.3 months in the experimental versus control arms, respectively [hazard ratio (HR) = 1.88, P = 0.027]. In the high IGF-1/HRG+ subgroup (n = 44), median PFS was 4.1 and 7.3 months, respectively (HR = 1.39, P = 0.42). Median OS and ORR for the overall population were similar between two arms. No significant difference in serious or grade ≥3 AEs was observed, although low-grade AEs leading to early discontinuation were higher in the experimental (39.5%) versus control arm (24.4%). CONCLUSIONS: Istiratumab failed to improve the efficacy of SOC chemotherapy in this patient setting. High serum IGF-1 levels did not appear to be an adverse prognostic factor when compared with non-biomarker-selected historic controls. CLINICAL TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov: NCT02399137; EUDRA CT: 2014-004572-34.

Microbial performance of food safety management systems implemented in the lamb production chain.

The actual microbial status of the lamb production chain at three slaughterhouses, one processing plant, and five butcher shops selling whole or cut lamb carcasses to consumers was assessed with a previously developed microbial assessment scheme. All studied establishments had a food safety management system (FSMS) that was implemented according to legislative requirements. Microbial safety level profiles were constructed for each establishment and provided clear indications of which pathogens, hygiene indicators, or utility parameters required attention to improve the performance of the microbiological control protocols of the implemented FSMS. The highest contamination was found in the slaughterhouses in samples taken from the meat products (aerobic mesophilic plate counts [AMPs] of 3.40 to 6.63 log CFU/cm(2) and Enterobacteriaceae counts of 1.00 to 4.62 log CFU/cm(2)), contact surfaces (AMPs of 2.44 to 8.92 log CFU/cm(2)), and operators' hands and/or gloves (AMPs of 2.84 to 8.09 log CFU/cm(2)), especially after hide removal and evisceration. The microbial assessment scheme is a useful tool for providing insight into the actual microbiological results achieved with an FSMS implemented in establishments at various stages along the lamb production chain.

A phase II study of neoadjuvant gemcitabine plus doxorubicin in stage IIIB breast cancer: a preliminary report.

The purpose of this ongoing study is to determine the response and safety of a combination of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) plus doxorubicin as neoadjuvant therapy for stage IIIB breast cancer. Thirty-nine chemotherapy-naive patients were enrolled in the study. The median age was 54 years (range, 32 to 74 years), and the median Karnofsky performance status was 100. Gemcitabine 1,200 mg/m(2) was given on days 1 and 8, and doxorubicin 60 mg/m(2) on day 1, followed by surgery or radiotherapy. Ninety-seven of 117 cycles (83%) were administered at full dose. An overall response rate of 95% was obtained, with a complete response in 18% (seven patients) and a partial response in 77% (30 patients). Twenty-eight patients (72%) underwent breast surgery after a maximum of three cycles of neoadjuvant therapy. World Health Organization grade 3/4 toxicities included leukopenia in nine cycles (8%), neutropenia in 16 cycles (14%), febrile neutropenia in 11 cycles (9%), and anemia in two cycles (2%). The most important nonhematologic toxicity was grade 2/4 mucositis in 16 cycles (14%), and/or grade 2/3 diarrhea in 10 cycles (9%). Neoadjuvant therapy with gemcitabine plus doxorubicin results in a high tumor response rate with moderate oral and hematologic toxicity. Semin Oncol 28 (suppl 10):57-61.

Treatment of newly diagnosed and relapsed acute promyelocytic leukemia with intravenous liposomal all-trans retinoic acid.

A novel intravenous liposomal formulation of all-trans retinoic acid (ATRA) was evaluated in 69 patients with acute promyelocytic leukemia (APL): 32 new diagnoses, 35 relapses, and 2 oral ATRA failures. Liposomal ATRA (90 mg/m(2)) was administered every other day until complete remission (CR) or a maximum of 56 days. Treatment following CR was liposomal ATRA with or without chemotherapy. In an intent-to-treat (ITT) analysis of all patients, CR rates were 62%, 70%, and 20% in newly diagnosed, group 1 first relapses (ATRA naive or off oral ATRA more than or equal to 1 year), or group 2 relapses (second or subsequent relapse or first relapses off oral ATRA less than 1 year), respectively. In 56 evaluable patients (receiving 4 or more doses), CR rates for the same groups were 87% (20 of 23), 78% (14 of 18), and 23% (3 of 13). Remission failure in newly diagnosed patients was not from resistant disease. Several patients in CR became polymerase chain reaction (PCR) negative for promyelocytic leukemia/retinoic acid receptor-alpha (PML/RARalpha) after liposomal ATRA alone. Toxicity was generally mild, most commonly headaches (67. 5%). Eighteen patients (26%) had ATRA syndrome develop during induction. One-year survival of ITT patients was 62%, 56%, and 20% for newly diagnosed, group 1, and group 2, respectively. The medium duration of CR has not yet been reached and was 18 and 5.5 months in the same groups. These results demonstrate that liposomal ATRA is effective in inducing CR in newly diagnosed or group 1 APL patients. It provides a reliable dosage of ATRA for patients with APL unable to swallow or absorb medications and can induce molecular remissions without chemotherapy.

Elderly patients with aggressive non-Hodgkin's lymphoma treated with CHOP chemotherapy plus granulocyte-macrophage colony-stimulating factor: identification of two age subgroups with differing hematologic toxicity.

PURPOSE: Standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy repeated at 3-week intervals is difficult to deliver in elderly patients with non-Hodgkin's lymphoma (NHL). The use of hemopoietic growth factors may decrease the hematologic toxicity of chemotherapy and allow the delivery of full-dose CHOP. PATIENTS AND METHODS: We conducted a phase II trial with the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) to CHOP chemotherapy in NHL patients older than 60 years of age. Twenty-six previously untreated patients were assessable; median age was 67 years (range, 61 to 84 years). CHOP included cyclophosphamide 750 mg/m2 intravenously day 1; doxorubicin 50 mg/m2 intravenously day 1; vincristine 1.4 mg/m2 (2 mg total dose) intravenously day 1; and prednisone 100 mg orally days 1 through 5. GM-CSF 5 microg/kg was administered subcutaneously on days 4 through 13. Cycles were repeated every 21 days for six cycles. Results were analyzed for the total group and for two age subgroups: 61 to 69 years (n = 15) and 70 years or older (n = 11). RESULTS: Sixteen patients (62%) achieved a complete response (CR), four patients (15%) achieved a partial response (PR), and six patients (23%) did not respond to therapy. After a median follow-up of 41 months, the median progression-free and overall survival were 19 and 30 months, respectively. Twenty patients completed six cycles. One hundred thirty-eight of the 156 planned cycles were delivered (88%). The relative dose-intensity was 95%. The chemotherapy-induced toxicity was important. Absolute neutrophil count was less than 500/mL in 43% of the cycles, platelet nadir was less than 20,000/mL in 19%, and febrile neutropenia occurred in 21%. There were no grades 3 to 4 mucositis. Treatment-related death occurred in two patients, and was associated with neutropenic septic shock. The toxicity related to GM-CSF was mild hypotension after the cytokine was administered in 7% of cycles. When the results of the study were analyzed by age subgroups, we observed that whereas response and median survival were similar in patients aged 61 to 69 years or 70 years or older, there were significant differences in dose delivery and toxicity. Chemotherapy was delivered in 86 of 90 planned cycles in patients aged 61 to 69 years, but in only 52 of 72 planned cycles in patients aged 70 to 84 years (P = .00008). Absolute neutrophil count was less than 500/mL in 24% of cycles in patients aged 61 to 69 years and 73% of cycles in patients aged 70 years or older (P = .00001). The platelet nadir of less than 20,000/mL occurred in 5% of patients aged 61 to 69 years and in 42% of patients aged 70 years or older (P < .0001). Fever and neutropenia occurred in 8% of patients aged 61 to 69 years and in 42% of patients aged 70 years or older (P < .0001). Mucositis (grades 1 to 2) occurred in 21% of patients aged 61 to 69 years and in 42% of patients aged 70 years or older (P = .006). CONCLUSION: CHOP chemotherapy plus GM-CSF is an active regimen in elderly patients with NHL. Despite cytokine support, the toxicity of the regimen is elevated. We have identified two age subgroups (61 to 69 and > or = 70 years) that do not differ in treatment efficacy but show large differences in treatment-related toxicity.

Situación socioeconómica de pacientes con neoplasias hematológicas - INEN, 1991 / Socioeconomical status of patients with hematologic neoplams - INEN, 1991

En 1991 se evaluaron en forma prospectiva 405 casos nuevos de pacientes adultos portadores de neoplasias hematológicas (candidatos a recibir quimioterapia sistémica), para determinar la situación socioeconómica de pacientes con cáncer, admitidos al Instituto Nacional de Enfermedades Neoplásicas del Perú. Fueron incluidos en este estudio 203 mujeres (50.2 por ciento) y 202 hombres (49.8 por ciento) siendo los diagnósticos: linfoma no Hodgkin en 261 pacientes (64.4 por ciento), leucemias agudas en 94 (23.2 por ciento), mieloma múltiple en 20 (5 por ciento) y otros diagnósticos en 30 (7.4 por ciento). Sólo el 33.5 por ciento (141) se encontraban adecuadamente empleados. El 39.2 por ciento (158) eran amas de casa y 52 (12.8 por ciento) eran estudiantes. Los resultados muestran que el 78.2 por ciento (317) vivían en estado de extrema pobreza, mientras que sólo el 7.5 por ciento (33) de los pacientes asumían directamente los costos de sus tratamientos. Se analiza el impacto de esta situación en el cumplimiento de los diversos tratamientos quimioterápicos y se discuten alternativas para mejorar la disponibilidad de estos tratamientos, para los pacientes con cáncer en el Perú.

Tratamiento de linfomas intestinales con régimen CHOP en el Perú: análisis de factores pronósticos / Treatment of intestinal lymphoma with a combination of CHOP in Perú. analysis of pronostic factors

Entre enero de 1980 y diciembre de 1992, fueron tratados 52 pacientes portadores de linfoma intestinal, con el régimen CHOP (ciclofosfamida, adriablastina, vincristina y prednisona) por 6 cursos. La relación hombre/mujer fue de 1:1.3 con una edad media de 40 años (16-72). La histología más frecuente fue WF:G en 60 por ciento y WF:E en 14.5 por ciento. La localización primaria fue intestino delgado difuso en 34 por ciento de casos y primarios ileocecales en 36 por ciento siendo linfomas mediterráneos el 67 por ciento y el tipo occidental en 23 por ciento. De acuerdo a la clasificación TNM el 68 por ciento eran T-3 o T-4 y el 80 por ciento tenían compromiso ganglionar siendo estadío clínico IV el 58 por ciento. La tasa de respuestas totales fue de 72. 8 por ciento con 47.6 por ciento de respuestas completas. Con un seguimiento medio de 20 meses la sobrevida media es de 19.0 meses; la sobrevida actuaría a 12 meses fue de 58 por ciento y 7 por ciento a los 60 meses. Se identificó el compromiso ganglionar, el estadío clínico TNM y el obtener respuesta completa luego del CHOP como factores pronósticos independiente para sobrevida. El enfoque multidisciplinario en éstos pacientes potencialmente curables puede mejorar los resultados obtenidos.

Hipercalcemia de la malignidad / Malignancy hypercalcemia

La hipercalcemia de la malignidad constituye la emergencia metabólica más frecuente en el área oncológica, pudiendo afectar hasta un 10-20 por ciento de los pacientes. La hipercalcemia afecta profundamente la calidad de vida del paciente con cáncer y compromete multiples sistemas orgánicos provocando alteraciones potencialmente letales a nivel neuromuscular, gastrointestinal, renal y cardiovascular. En la presente revisión se enfocan aspectois epidemiológicos, se analizan los mecanismos de producción de hipercalcemia en las diferentes neoplasias, se discuten las dificultades en el diagnóstico preciso de esta entidad y las causas desencadenantes del mismo y finalmente se plantean los diferentes tratamientos actuales así como los temas de controversia e investigación en el cuidado de los pacientes con cáncer.

[Lymphomas of the gastrointestinal tract: a neoplastic disease of underdevelopment]. / Linfomas del tracto gastrointestinal: una enfermedad neoplásica del subdesarrollo.

458/3,495 malignant lymphomas seen at the Instituto de Enfermedades Neoplásicas between 1965-1992, had primary extranodal disease in the GI tract. This is one of the largest institutional series reported, which would suggest that this is a relatively frequent malignancy in Peruvian population. Fifty per cent of cases had a primary in the small bowel and 38.9 per cent in the stomach. The age at presentation, the clinical picture and the location at the intestine show similarities with the so called Mediterranean lymphoma. Cases were classified according to the TNM system, and patients in stages I-II were surgically resected; 80 per cent of them were alive and free of disease at 5 years. Gastric lymphomas with inoperable disease were treated with chemotherapy with a 5-year survival of 50 per cent.

Plasmocitoma extramedular de pulmón: presentación de un caso y discusión del problema / Medular plasmocitoma of the lung

Los plasmocitomas extramedulares (PEM) de partes blandas son condiciones raras, pero que tienen preferente localización en las vías aéreas superiores. Representan aproximadamente el 4 por ciento de las neoplasias de las células plasmáticas. Los PEM del pulmón son extremadamente raros; el primer caso fue publicado por Gordon y Walker en 1944 y desde entonces han aparecido esporádicos casos en la literatura internacional. Hasta donde hemos podido investigar, no hay casos publicados en las revistas especializadas del país. El caso que presentamos corresponde a un varón de 68 años de edad procedente de Piura, que refería historia de 2 años de astenia y adelgazamiento y 4 meses de tos y disnea progresiva. La radiografía de torax mostraba la imagen de un proceso tumoral sólido de 10x9x8 cm del lóbulo inferior izquierdo. El paciente tenía anemia y globulinas en 4.8 por ciento; el proteinograma electroforético mostró gammapatía monoclonal IgG a cadena ligera lambda; el dosaje de inmunoglobulinas estableció una cifra 4218 mg/dl de IgG y la beta-2-microglobulina en 31.7 mg/dl. La biopsia percutanea de la masa pulmonar izquierda mostró la presencia de células plasmáticas maduras e inmaduras en relación con Plasmocitoma. La gammagrafía ósea fue normal; el estudio radiológico del esqueleto reveló osteoporosis generalizada. En el aspirado de médula ósea y biopsia de hueso la celularidad era normal sin presencia de proliferación de células plasmáticas. El paciente recibe quimioterapia con régimen BVCMP