Publicado en The Lancet Oncology 17 March 2015 .
Dr Akira Kawai, MDcorrespondenceemail, Nobuhito Araki, MD, Hideshi Sugiura, MD, Takafumi Ueda, MD, Tsukasa Yonemoto, PhD, Mitsuru Takahashi, PhD, Hideo Morioka, MD, Hiroaki Hiraga, MD, Toru Hiruma, PhD, Toshiyuki Kunisada, MD, Akihiko Matsumine, MD, Takanori Tanase, MSc, Tadashi Hasegawa, MD, Shunji Takahashi, MD .
Background
Trabectedin binds to the minor groove of DNA and blocks DNA repair machinery. Preclinical data have shown that trabectedin also modulates the transcription of the oncogenic fusion proteins of translocation-related sarcomas. We aimed to assess the efficacy and safety of trabectedin as second-line therapy or later for patients with advanced translocation-related sarcoma.
Methods
We did a multicentre randomised open-label study in Japan. Eligible patients had pathological diagnosis of translocation-related sarcoma, were aged 19 years or older, were unresponsive or intolerant to standard chemotherapy regimens, no more than four previous chemotherapy regimens, Eastern Cooperative Oncology Group performance status 0 or 1, adequate bone marrow reserve, renal and liver functions, and had measurable lesions. Patients were randomly assigned (1:1) by the minimisation method to receive either trabectedin (1·2 mg/m2 given via a central venous line over 24 h on day 1 of a 21 day treatment cycle) or best supportive care, which was adjusted centrally by pathological subtype. Investigators, patients, and the sponsor were unmasked to the treatment assignment. Progression-free survival and objective responses were assessed by a masked central radiology imaging review. Efficacy was assessed by masked central radiology imaging review. The primary endpoint was progression-free survival for the full analysis set population. Follow-up is ongoing for the patients under study treatment. The study is registered with Japan Pharmaceutical Information Center, number JapicCTI-121850.
Findings
Between July 11, 2012, and Jan 20, 2014, 76 patients were enrolled and allocated to receive either trabectedin (n=39) or best supportive care (n=37). After central review to confirm pathological subtypes, 73 patients (37 in the trabectedin group and 36 in the best supportive care group) were included in the primary efficacy analysis. Median progression-free survival of the trabectedin group was 5·6 months (95% CI 4·1–7·5) and the best supportive care group was 0·9 months (0·7–1·0). The hazard ratio (HR) for progression-free survival of trabectedin versus best supportive care was 0·07 (90% CI 0·03–0·14 and 95% CI 0·03–0·16) by a Cox proportional hazards model (p 0·0001). The most common drug-related adverse events for patients treated with trabectedin were nausea (32 [89%] of 36), decreased appetite (21 [58%]), decreased neutrophil count (30 [83%]), increased alanine aminotransferase (24 [67%]), and decreased white blood cell count (20 [56%]).
Interpretation
Trabectedin significantly reduced the risk of disease progression and death in patients with advanced translocation-related sarcoma after standard chemotherapy such as doxorubicin, and should be considered as a new therapeutic treatment option for this patient population.
Funding
Taiho Pharmaceutical Co., Ltd.
Diagn Pathol. 2016 Apr .
Sugita S, Asanuma H, Hasegawa T.
Department of Surgical Pathology, Sapporo Medical University, School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.
Abstract
BACKGROUND:
Fluorescence in situ hybridization (FISH) is one of the most powerful genetic analysis tools for pathological diagnoses. FISH can detect various genetic abnormalities including gene translocation that was specifically found in translocation-related sarcomas (TRSs). Here, we report the use of FISH in expert review in a phase 2 study of trabectedin monotherapy for patients with advanced TRS.
METHODS:
TRS patients (n = 76) were enrolled in the trial at 12 study sites after pathological diagnoses were made, including morphological examination with or without evidence of translocation by genetic testing. Following histological reviews of the representative specimens at the study sites, we performed immunohistochemistry using the appropriate antibodies and FISH for genetic confirmation of the tumor types in the expert review.
RESULTS:
Among the 76 TRS cases, no split signal for SS18 probe was detected by FISH in three synovial sarcoma cases that were diagnosed at the study sites. Malignant peripheral nerve sheath tumor (MPNST) was diagnosed in two cases and sarcomatoid carcinoma in one. One of the cases was a small round cell variant of MPNST. After excluding these three cases, we assessed the other 73. There were no split signals detected in 7 of the 73 cases by FISH analysis, due to decalcification and hyperfixation procedures. Excluding these seven cases, FISH detected translocations in 95 % (63/66) of the study cases with a high sensitivity.
CONCLUSIONS:
The diagnosis of TRS by FISH was highly sensitive and enabled genetic confirmation of the pathological diagnoses. We strongly recommend FISH as a confirmatory diagnostic test for TRS, which would enable the selection of patients with TRS in whom trabectedin is expected to be effective. This study was done in part that registered with Japan Pharmaceutical Information Center, number JapicCTI-121850.
KEYWORDS:
Fluorescence in situ hybridization; Immunohistochemistry; Malignant peripheral nerve sheath tumor; Sarcomatoid carcinoma; Synovial sarcoma; Translocation-related sarcoma
En una reunión del Fondo Monetario Internacional, el ministro de Finanzas británico alertó sobre las consecuencias que tendrá la resistencia a los antibióticos de las infecciones comunes.
Publicado: 14 abr 2016 .
La resistencia de las bacterias a los antibióticos se convertirá en "una amenaza aún mayor que el cáncer para la humanidad" si no se toma una acción global, advirtió este jueves el ministro de Finanzas británico, George Osborne, durante una reunión del Fondo Monetario Internacional en Washington D.C., EE.UU., informa el diario 'The Independent'.
Según Osborne, la evidencia más reciente sugiere que anualmente 10 millones de personas en todo el mundo podrían morir para el año 2050, como consecuencia de la falta de efectividad de los antibióticos contra las infecciones comunes. Una cifra que supera el actual número de víctimas anuales de cáncer.
"No es solo un problema sanitario sino también económico. El costo de no hacer nada, tanto en términos de vidas perdidas y dinero perdido, es demasiado grande, y el mundo necesita unirse para acordar un enfoque común", dijo Osborne durante su intervención.
De acuerdo con los datos presentados por el ministro británico, para el 2050 la resistencia antimicrobiana podría reducir el PIB mundial hasta en un 3,5%, equivalente a unos 100 billones de dólares, por lo que instó a los gobiernos a cambiar radicalmente los incentivos para la industria farmacéutica y crear nuevos sistemas de recompensa financiados a nivel mundial para apoyar el desarrollo de nuevos antibióticos y garantizar el acceso de los países en desarrollo a esos antibióticos.
Un estudio en cuatro hospitales españoles detecta el doble de las reapariciones esperadas .
ANA MACPHERSON 14/04/2016 .
Los medicamentos que eliminan en más de un 95% de casos el virus de la hepatitis C tienen una secuela inesperada: aumentan el riesgo de reaparición del cáncer de hígado en personas curadas y que posteriormente toman la medicación para erradicar el virus, que seguramente estuvo en el origen de su cáncer previo. Los autores del hallazgo, publicado en el Journal of Hepatology, la principal publicación mundial en enfermedades del hígado, plantean actuar con cautela ante este incremento de riesgo detectado, más del doble en seis meses después del tratamiento.
La Agencia Europea de Medicamentos (EMA) anunciará hoy la información que requerirá a los laboratorios fabricantes de estos medicamentos así como las acciones que se han de poner en marcha para afrontar los interrogantes que surgen.
¿Se ha de evitar el tratamiento en personas que hayan superado un cáncer?
¿Y en el caso de trasplantes?
¿Hay aumento de riesgo para quienes hayan tenido otro tipo de cáncer?
...
