RESUMEN
BACKGROUND: Aromatase inhibitors have been used empirically to treat a subset of patients with hormone receptor positive uterine leiomyosarcomas(LMS) and carcinosarcomas (UCS) mainly supported by retrospective data. We evaluated the activity of anastrozole in two rare cohorts; patients with recurrent/metastatic LMS and UCS enrolled in PARAGON, a basket trial of anastrozole in estrogen receptor (ER+)/progesterone receptor positive (PR+) gynecological cancers. METHOD: An investigator-initiated, single-arm, prospective open-label trial of anastrozole 1 mg/day in patients with ER &/or PR + ve LMS or UCS with measurable disease, treated until progression or unacceptable toxicity. Primary endpoint was clinical benefit (complete/partial response + stable disease) rate (CBR) at 3 months. Secondary endpoints include progression-free survival (PFS), quality of life and toxicity. RESULTS: 39 eligible patients were enrolled, 32 with LMS and 7 with UCS. For the LMS cohort CBR at 3 months was 35% (95% CI: 21-53%) with a median duration of clinical benefit of 5.8 months. Best response was a partial response in one patient. Two patients remained on treatment for more than one year. The median progression-free survival was 2.8 months (95% CI: 2.6-4.9). For the UCS cohort CBR at 3 months was 43% (95% CI: 16-75%) with a median duration of clinical benefit of 5.6 months. Stable disease was seen in 3 patients but no objective responses were seen. The median progression-free survival was 2.7 months (95% CI, 1.1-8.2). Safety was acceptable with 5/39 evaluable patients showing grade 3 toxicities. CONCLUSION: Whilst objective response rates with anastrozole are low, the clinical benefit rate and good tolerance suggests that aromatase inhibitor therapy may have a role in a subset of patients with metastatic LMS and UCS.
Asunto(s)
Anastrozol/uso terapéutico , Carcinosarcoma/tratamiento farmacológico , Leiomiosarcoma/tratamiento farmacológico , Neoplasias Uterinas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anastrozol/efectos adversos , Inhibidores de la Aromatasa/efectos adversos , Inhibidores de la Aromatasa/uso terapéutico , Carcinosarcoma/metabolismo , Carcinosarcoma/patología , Femenino , Humanos , Leiomiosarcoma/metabolismo , Leiomiosarcoma/patología , Persona de Mediana Edad , Metástasis de la Neoplasia , Estudios Prospectivos , Calidad de Vida , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologíaRESUMEN
PURPOSE: The phase II TACTIC trial prospectively selected patients with KRAS wild-type advanced biliary tract cancer for first-line treatment with panitumumab and combination chemotherapy. METHODS: Of 78 patients screened, 85 % had KRAS wild-type tumours and 48 were enrolled. Participants received cisplatin 25 mg/m(2) and gemcitabine 1000 mg/m(2) on day 1 and day 8 of each 21-day cycle and panitumumab 9 mg/kg on day 1 of each cycle. Treatment was continued until disease progression, unacceptable toxicity, or request to discontinue. The primary endpoint was the clinical benefit rate (CBR) at 12 weeks (complete response, partial response, or stable disease). CBR of 70 % was considered to be of clinical interest. Secondary outcomes were progression-free survival, time to treatment failure, overall survival, CA19.9 response and safety. RESULTS: Thirty-four patients had a clinical benefit at 12 weeks, an actuarial rate of 80 % (95 % CI 65-89 %). 46 % had a complete or partial response. Median progression-free survival was 8.0 months (95 % CI 5.1-9.9) and median overall survival 11.9 months (95 % CI 7.4-15.8). Infection accounted for 27 % of the grade 3 or 4 toxicity, with rash (13 %), fatigue (13 %), and hypomagnesemia (10 %) among the more common grade 3 or 4 non-haematological toxicities. CONCLUSION: A marker-driven approach to patient selection was feasible in advanced biliary tract cancer in an Australian population. The combination of panitumumab, gemcitabine, and cisplatin in KRAS wild-type cancers was generally well tolerated and showed promising clinical efficacy. Further exploration of anti-EGFR therapy in a more selected population is warranted.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Sistema Biliar/tratamiento farmacológico , Selección de Paciente , Proteínas Proto-Oncogénicas p21(ras)/genética , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Australia , Neoplasias del Sistema Biliar/genética , Neoplasias del Sistema Biliar/patología , Antígeno CA-19-9/sangre , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Panitumumab , Estudios Prospectivos , Tasa de Supervivencia , Resultado del Tratamiento , GemcitabinaRESUMEN
The patterns of fingertip prints (dermatoglyphics) in Swedish series of sexual offenders of law compared with common offenders of law and normal individuals were analysed. The dermatoglyphic patterns in common offenders of law did not differ from those in normal individuals. The group of sexual offenders of law showed statistically significant differences (p < 0.001) in the dermatoglyphic patterns compared to the samples of common criminals and normals.