Bempegaldesleukin Plus Nivolumab Versus Sunitinib or Cabozantinib in Previously Untreated Advanced Clear Cell Renal Cell Carcinoma: A Phase III Randomized Study (PIVOT-09).

PURPOSE: Bempegaldesleukin (BEMPEG) is a pegylated interleukin (IL)-2 cytokine prodrug engineered to provide controlled and sustained activation of the clinically validated IL-2 pathway, with the goal of preferentially activating and expanding effector CD8+ T cells and natural killer cells over immunosuppressive regulator T cells in the tumor microenvironment. The open-label, phase III randomized controlled PIVOT-09 trial investigated the efficacy and safety of BEMPEG plus nivolumab (NIVO) as first-line treatment for advanced/metastatic clear cell renal cell carcinoma (ccRCC) with intermediate-/poor-risk disease. METHODS: Patients with previously untreated advanced/metastatic ccRCC were randomly assigned (1:1) to BEMPEG plus NIVO, or investigator's choice of tyrosine kinase inhibitor (TKI; sunitinib or cabozantinib). Coprimary end points were objective response rate (ORR) by blinded independent central review and overall survival (OS) in patients with International Metastatic RCC Database Consortium (IMDC) intermediate-/poor-risk disease. RESULTS: Overall, 623 patients were randomly assigned to BEMPEG plus NIVO (n = 311) or TKI (n = 312; sunitinib n = 225, cabozantinib n = 87), of whom 514 (82.5%) had IMDC intermediate-/poor-risk disease. In patients with IMDC intermediate-/poor-risk disease, ORR with BEMPEG plus NIVO versus TKI was 23.0% (95% CI, 18.0 to 28.7) versus 30.6% (95% CI, 25.1 to 36.6; difference, -7.7 [95% CI, -15.2 to -0.2]; P = .0489), and median OS was 29.0 months versus not estimable (hazard ratio, 0.82 [95% CI, 0.61 to 1.10]; P = .192), respectively. More frequent all-grade treatment-related adverse events (TRAEs) with BEMPEG plus NIVO versus TKI included pyrexia (32.6% v 2.0%) and pruritus (31.3% v 8.8%). Grade 3/4 TRAEs were less frequent with BEMPEG plus NIVO (25.8%) versus TKI (56.5%). CONCLUSION: First-line BEMPEG plus NIVO for advanced/metastatic ccRCC did not improve efficacy in patients with intermediate-/poor-risk disease but led to fewer grade 3/4 TRAEs versus TKI.

A randomised phase II study of chemoradiotherapy with or without nimotuzumab in locally advanced oesophageal cancer: NICE trial.

PURPOSE: Chemoradiotherapy is the standard treatment for patients with inoperable locally advanced oesophageal cancer. We sought to assess the safety and efficacy of chemoradiation combined with nimotuzumab, a humanised antibody directed against epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: Untreated patients with inoperable locally advanced oesophageal cancer and no distant metastases were randomised to chemoradiotherapy (cisplatin and fluorouracil combined with external beam radiation) alone or in combination with nimotuzumab. The primary end-point was the endoscopic complete response (eCR) rate, and secondary end-points comprised quality of life (QoL) and safety. The combined eCR and pathologic complete response (cEPCR) and overall survival (OS) were also evaluated. RESULTS: We enrolled 107 patients with a mean age of 59 years, and 93% had squamous cell carcinoma. Toxicity was manageable in both arms with no important differences in adverse events (AEs). We performed post-treatment endoscopies in 67 patients, including 60 who had a biopsy. In the intent-to-treat population, the eCR rates with and without nimotuzumab were 47.2% and 33.3% (P = 0.17), respectively, and the cEPCR rates were 62.3% and 37.0% (P = 0.02), respectively. With a median follow-up of 14.7 months, the hazard ratio (HR) for OS was 0.68 (95% confidence interval (CI): 0.44-1.07; P = 0.09) with a median OS of 15.9 months for the nimotuzumab arm and 11.5 months for the control arm. Regarding QoL, a significant difference was observed for the physical subscale score (P = 0.03) with lower values for the control arm. CONCLUSION: Combined chemoradiotherapy plus nimotuzumab is safe for patients with locally advanced oesophageal cancer, it appears to increase the cEPCR rate, and without compromising QoL. CLINICAL TRIALS: Identification number: EF024-201; Trial registry: NCT01249352.

Perfil clínico e tumoral de pacientes submetidas a tratamento neoadjuvante de câncer de mama no Hospital Erasto Gaertner / Clinical and tumor profile of patients undergoing neoadjuvant treatment of breast cancer at Erasto Gaertner Hospital

Objetivo: Avaliar o perfil clínico e tumoral das pacientes submetidas a tratamento neoadjuvante de câncer de mama, no ano de 2011, no Hospital Erasto Gaertner, em Curitiba, Paraná. Métodos: Realizado um estudo retrospectivo, com levantamento e análise de dados quantitativos de 135 pacientes com câncer de mama que estavam em quimioterapia neoadjuvante, no ano de 2011, no Hospital Erasto Gaertner. As variáveis estudadas foram: idade, status menopausal, Índice de Massa Corporal (IMC) na ocasião do diagnóstico, subtipo histológico, TNM ao diagnóstico, perfil imuno-histoquímico, esquema de quimioterapia realizado, datas de início e de término da quimioterapia, data da cirurgia, e tipo de cirurgia. Resultados: A idade mediana foi 51 anos; 48,88% das pacientes estavam na pós-menopausa; 65,91% apresentavam excesso de peso ou obesidade grau I ou II; 43,70% das pacientes tinham câncer de mama em estádio clínico IIB e 37,86% em estádio III; mais de 92,59% dos tumores era carcinoma ductal invasor. O receptor de estrogênio era positivo em 65,18% das pacientes e o de progesterona em 50,37%. A proteína HER2 (Human Epidermal growth factor Receptor-type 2) era superexpressa em 25,92% das pacientes. O esquema de quimioterapia neoadjuvante mais utilizado era composto por doxorrubicina, ciclofosfamida e paclitaxel semanal. A quadrantectomia foi realizada em 71 pacientes e a mastectomia em 52. O esvaziamento axilar foi realizado em 119 pacientes. Conclusão: As características clínicas e tumorais das pacientes do Hospital Erasto Gaertner se assemelham às descritas na literatura, exceto pelo estádio clínico ser menos avançado.

Objective: To evaluate the clinical and tumor profile of patients undergoing neoadjuvant treatment of breast cancer in 2011, at Erasto Gaertner Hospital, in Curitiba, Paraná. Methods: A retrospective study was done, with quantitative data survey and analysis of 135 patients with breast cancer who were on neoadjuvant chemotherapy, in 2011, at Erasto Gaertner Hospital. The variables studied were age, menopausal status, Body Mass Index (BMI) at diagnosis, histological subtype, TNM diagnosis, immunohistochemical profile, chemotherapy regimen, dates of start and end of chemotherapy, date of surgery, and type of surgery. Results: The median age was 51 years; 48.88% of patients were postmenopausal; 65.91% were overweight or obese grade I or II; 43.70% of patients had breast cancer with clinical stage IIB and 37.86% in stage III; 92.59% of the tumors were invasive ductal carcinoma. The estrogen receptor was positive in 65.18% of patients and the progesterone receptor was positive in 50.37% of them. Human Epidermal growth factor Receptor-type 2 (HER2) was overexpressed in 25,92% of patients. The neoadjuvant chemotherapy regimen most used consisted of doxorubicin, cyclophosphamide and weekly paclitaxel. Quadrantectomy was performed in 71 patients and mastectomy in 52. Axillary dissection was performed in 119 patients. Conclusion: The clinical and tumor characteristics of the patients in Erasto Gaertner Hospital are similar to those described in the literature, except for clinical stage being less advanced.

Phase II multicenter trial of docetaxel, epirubicin, and 5-fluorouracil (DEF) in the treatment of advanced gastric cancer: a novel, safe, and active regimen.

BACKGROUND: This study evaluated the efficacy and safety of docetaxel, epirubicin, and 5-fluorouracil (5-FU) [DEF] as treatment for locally advanced unresectable or metastatic gastric cancer. METHODS: Thirty-seven patients participated in the study (median age, 56 years; range, 22-73 years); Eastern Cooperative Oncology Group performance status [PS], 0-2). Docetaxel 75 mg/m2 IV (day 1), 5-FU 500 mg/m2 IV (days 1-3), and epirubicin 50 mg/m2 IV (day 1) were administered every 3 weeks for six cycles. RESULTS: In total, 20/37 patients (54%) completed six treatment cycles. Thirteen patients (35%; 95% confidence intervals [CI], 20% to 51%) had an objective response; 1 patient (3%) achieved a complete response and 12 patients (32%) achieved partial responses. Stable disease was observed in 7 patients (19%) and progressive disease in 5 patients (14%). Twelve patients (32%) were unevaluable. Clinical benefit (based on PS, weight gain, and analgesic consumption) was observed in 11 patients (30%). Median follow-up was 41 months (range, 26-53 months), median time to progression was 6.6 months (range, 0.5-29.2 months), median overall survival was 10.7 months (range, 7.0-14.6 months), and 1-year survival was 40%. The regimen was well tolerated. Grade 3-4 febrile neutropenia occurred in 8 patients (22%; 6% of cycles) and grade 3-4 neutropenia in 1 patient (1% of cycles). The most frequent grade 3-4 toxicities were alopecia (11% of cycles), diarrhea (4% of cycles) and vomiting (2% of cycles); grade 1-2 asthenia and fatigue occurred in 43% of cycles. CONCLUSION: DEF is effective in the treatment of advanced gastric cancer, and has a good safety profile.

Tratamento conservador do câncer de mama / Conservative treatment of cancer of the breast

Ha muito tempo vem-se tantando encontrar uma alternativa para o tratamento do cancer de mama diferente da cirurgia radical proposta por Halsted em 1890. Muitas formas de cirurgia conservadora foram desenvolvidas com esta finalidade. A eficacia de seu emprego ainda tem sido muito discutida,porem ha estudos que demonstram inexistir diferenca de sobrevida entre as pacientes com tratamento conservador e radical. Parece haver, contudo, maior incidencia de recidiva local nas pacientes tratadas conservadoramente

Estudo prospectivo randomizado do tratamento do carcinoma avançado de cabeça e pescoço, com ou sem quimioterapia neoadjuvante / Prospective and randomized study on the treatment of advanced head and neck cancer with and without neoadjuvant chemotherapy

A radioterapia (RT) é o tratamento "standard" para carcinoma avançado e inoperável de cabeça e pescoço. Em estudo piloto (SBOC V,p.99) realizado em nosso hospital com quimioterapia (QT) neoadjuvante com cisplatina (CDDP) e 5- fluorouracil (5Fu) obtivemos índice de resposta objetiva de 73,3 por cento. Considerando que säo poucos os estudos randomizados com combinaçöes contendo CDDP que avaliem o efeito da quimioterapia neoadjuvante na sobrevida (SV), iniciamos em fevereiro de 1987 um estudo fase III, randomizado com a finalidade de analisar o seu valor na sobrevida. Os pacientes (pts) deveriam ser portadores de carcinoma epidermóide localmente avançado e mensurável, sem tratamento prévio, inoperável., sem metástases a distância e em bom estado geral (Zubrod 0-II) e eram aleatoriamente divididos em dois grupos: A) submetido a RT isolada com 5.000 rads./5 sem. e complementaçäo com 2.000 rads./2 sem. e B) tratado com 2-3 ciclos de CDDP 120 mg/m2 D1 e 5Fu 1.000 mg/m2 D1-5 seguido de RT. Até março de 1989 foram incluídos 110 pts (55 no grupo A e 55 no grupo B). Cavidade bucal 58 pts (52,79 por cento), orofaringe 27 (24,55 por cento), hipofaringe 13 (11,82 por cento) e laringe 12 (10,91 por cento) com distribuiçäo homogênea entre os grupos (p > 0,283). A maioria dos pts eram estádios (EC) IV (grupo A 81,82 por cento e grupo B 80 por cento). Os grupos foram semelhantes quanto aos demais fatores prognósticos: sexo, idade, índice de Zubrod, tumor, nódulos (presença, tamanho, lateralidade, fixaçäo, ulceraçäo), grau de diferenciaçäo. Dos pts submetidos a QT, 22 receberam 3 ciclos, 21, 2 ciclos e 12 apenas 1 ciclo (por abandono, recusa ou morte precoce). Onze (20 por cento) tiveram resposta completa e 26 (47,28 por cento) resposta parcial totalizando 67,28 por cento de resposta objetiva. A toxicidade da QT foi principalmente náuseas e vômitos (grau I/6 pts e grau II/30 pts), anemia (grau I/14 pts e grau II/2 pts) e aumento da creatinina sérica (grau I/11 pts e grau II/1 pts). A SV mediana no grupo A foi de 400 dias e no grupo B de 639 dias. Na análise de sobrevida utilizando curvas de Kaplan-Meier até o presente momento, os grupos näo se mostraram significativamente diferentes quando utilizados os métodos de Cox-Mantel (log-rank) (p=0,14964) e Wilcoxon Breslow) (p=0,09596). Em nossa instituiçäo até o presente momento a QT neoadjuvante näo alterou a SV e nossos métodos de tratamento, tais como, intensificaçäo da QT ou RT + QT simultaneamente, deveräo ser...