RESUMO
PURPOSE: Chemotherapy with or without radiotherapy is the standard in patients with initially nonmetastatic unresectable pancreatic cancer. Additional surgery is in discussion. The CONKO-007 multicenter randomized trial examines the value of radiotherapy. Our interim analysis showed a significant effect of surgery, which may be relevant to clinical practice. METHODS: One hundred eighty patients received induction chemotherapy (gemcitabine or FOLFIRINOX). Patients without tumor progression were randomized to either chemotherapy alone or to concurrent chemoradiotherapy. At the end of therapy, a panel of five independent pancreatic surgeons judged the resectability of the tumor. RESULTS: Following induction chemotherapy, 126/180 patients (70.0%) were randomized to further treatment. Following study treatment, 36/126 patients (28.5%) underwent surgery; (R0: 25/126 [19.8%]; R1/R2/Rx [nâ¯= 11/126; 6.1%]). Disease-free survival (DFS) and overall survival (OS) were significantly better for patients with R0 resected tumors (median DFS and OS: 16.6 months and 26.5 months, respectively) than for nonoperated patients (median DFS and OS: 11.9 months and 16.5 months, respectively; pâ¯= 0.003). In the 25 patients with R0 resected tumors before treatment, only 6/113 (5.3%) of the recommendations of the panel surgeons recommended R0 resectability, compared with 17/48 (35.4%) after treatment (pâ¯< 0.001). CONCLUSION: Tumor resectability of pancreatic cancer staged as unresectable at primary diagnosis should be reassessed after neoadjuvant treatment. The patient should undergo surgery if a resectability is reached, as this significantly improves their prognosis.
Assuntos
Carcinoma Ductal Pancreático/cirurgia , Quimiorradioterapia , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/terapia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Fluoruracila/administração & dosagem , Humanos , Irinotecano/administração & dosagem , Leucovorina/administração & dosagem , Terapia Neoadjuvante , Oxaliplatina/administração & dosagem , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Complicações Pós-Operatórias , Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Análise de Sobrevida , GencitabinaRESUMO
BACKGROUND: CONKO-006 was designed for patients with pancreatic adenocarcinoma with postsurgical R1 residual status to evaluate the efficacy and safety of the combination of gemcitabine and sorafenib (GemSorafenib) compared with those of gemcitabine + placebo (GemP) for 12 cycles. PATIENTS AND METHODS: This randomised, double-blind, placebo-controlled, multicenter study was planned to detect an improvement in recurrence-free survival (RFS) from 42% to 60% after 18 months. Secondary objectives were overall survival (OS), safety and duration of treatment. RESULTS: 122 patients were included between 02/2008 and 09/2013; 57 were randomised to GemSorafenib and 65 to GemP. Patient characteristics were wellbalanced (GemSorafenib/GemP) in terms of median age (63/63 years), tumour size (T3/T4: 97/97%), and nodal positivity (86/85%). Grade 3/4 toxicities comprised diarrhoea (GemSorafenib: 12%; GemP: 2%), elevated gamma-glutamyl transferase (GGT) (19%; 9%), fatigue (5%; 2%) and hypertension (5%; 2%), as well as neutropenia (18%; 25%) and thrombocytopenia (9%; 2%). By August 2017, 118 (97%) RFS event had occurred. There were no difference in RFS (median GemSorafenib: 8.5 versus GemP: 9.4 months; p = 0.730) nor OS (median GemSorafenib: 17.6 versus GemP: 17.5 months; p = 0.481). Landmark analyses suggest that patients who received more than six cycles of postoperative chemotherapy had significantly longer OS (p = 0.021). CONCLUSION: CONKO-006 is the first randomised clinical trial to include exclusively patients with PDAC with postsurgical R1 status thus far. Sorafenib added to gemcitabine did neither improve RFS nor OS. However, postoperative treatment exceeding six months seemed to prolong survival and should be further investigated in these high-risk patients. CLINICAL TRIAL INFORMATION: German Tumor Study Registry (Deutsches Krebsstudienregister), DRKS00000242.
Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Pancreatectomia , Neoplasias Pancreáticas/terapia , Sorafenibe/administração & dosagem , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Progressão da Doença , Método Duplo-Cego , Esquema de Medicação , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Pancreatectomia/efeitos adversos , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Sorafenibe/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , GencitabinaRESUMO
BACKGROUND: One critical step in the therapy of patients with localized pancreatic cancer is the determination of local resectability. The decision between primary surgery versus upfront local or systemic cancer therapy seems especially to differ between pancreatic cancer centers. In our cohort study, we analyzed the independent judgement of resectability of five experienced high volume pancreatic surgeons in 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer. METHODS: Pretherapeutic CT or MRI scans of 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer were evaluated by 5 independent pancreatic surgeons. Resectability and the degree of abutment of the tumor to the venous and arterial structures adjacent to the pancreas were reported. Interrater reliability and dispersion indices were compared. RESULTS: One hundred ninety-four CT scans and 6 MRI scans were evaluated and all parameters were evaluated by all surgeons in 133 (66.5%) cases. Low agreement was observed for tumor infiltration of venous structures (κ = 0.265 and κ = 0.285) while good agreement was achieved for the abutment of the tumor to arterial structures (interrater reliability celiac trunk κ = 0.708 P < 0.001). In patients with vascular tumor contact indicating locally advanced disease, surgeons highly agreed on unresectability, but in patients with vascular tumor abutment consistent with borderline resectable disease, the judgement of resectability was less uniform (dispersion index locally advanced vs. borderline resectable p < 0.05). CONCLUSION: Excellent agreement between surgeons exists in determining the presence of arterial abutment and locally advanced pancreatic cancer. The determination of resectability in borderline resectable patients is influenced by additional subjective factors. TRIAL REGISTRATION: EudraCT:2009-014476-21 (2013-02-22) and NCT01827553 (2013-04-09).
Assuntos
Carcinoma Ductal Pancreático/cirurgia , Consenso , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Alemanha , Humanos , Imageamento por Ressonância Magnética , Neoplasias Pancreáticas/diagnóstico por imagem , Estudos Prospectivos , Cirurgiões/psicologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: High expression of human equilibrative nucleoside transporter 1 (hENT1) is considered to predict survival in patients treated with adjuvant gemcitabine for pancreatic cancer. A standard evaluation system for immunohistochemical analysis (antibody, scoring system) has not yet been established. METHODS: CONKO-001, a prospective randomised phase III study investigated the role of adjuvant gemcitabine (gem) as compared to observation (obs). Tumour samples of 156 patients were analysed by immunohistochemistry with the rabbit monoclonal antibody SP120 (Ventana Medical Systems) for expression of hENT1. Kaplan-Meier analyses for median disease-free survival (DFS) and overall survival (OS) were performed in dependence of hENT1 expression measured analogously to Farrell et al. 2009 and Poplin et al. 2013. RESULTS: For the 88 gem and 68 obs patients, median DFS/OS was 12.9/22.7 months and 6.2/19.1 months. High hENT1 expression was not associated with improved median DFS (Farrell: no hENT1 22.2 months, low hENT1 13.7 months, high hENT1 12.1 months, p=0.248; Poplin: low hENT1 13.2 months versus high hENT1 11.5 months, p=0.5) or median OS (Farrell: no hENT1 21.7 months, low hENT1 24.7 months, high hENT1 19.5, p=0.571; Poplin: low hENT1 24.4 months versus high hENT1 19.7 months, p=0.92;) in the gem group or in the obs group (median DFS Farrell: no hENT1 5.1 months, low hENT1 6.2 months, high hENT1 7.5 months, p=0.375; Poplin: low hENT1 6.2 months versus high hENT1 5.9 months, p=0.83; median OS Farrell: no hENT1 20.2months, low hENT1 17.7 months, high HENT1 19.1 months, p=0.738; Poplin: low hENT1 17.7 months versus high hENT1 20.4 months, p=0.65) measured by the Farrell or Poplin Score. CONCLUSIONS: We cannot confirm a predictive role of hENT1 measured by the clone SP120 rabbit antibody in our study population. Reproducible standard procedures are urgently needed prior to the implementation or exclusion of hENT1 as a predictive biomarker in the treatment of pancreatic cancer. TRIAL REGISTRATION: ISRCTN34802808.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Desoxicitidina/análogos & derivados , Transportador Equilibrativo 1 de Nucleosídeo/metabolismo , Neoplasias Pancreáticas , Conduta Expectante , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Monoclonais/química , Desoxicitidina/uso terapêutico , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Valor Preditivo dos Testes , Estudos Prospectivos , Coelhos , Análise de Sobrevida , GencitabinaRESUMO
BACKGROUND: Previous investigations in pancreatic cancer suggest a prognostic role for α-smooth muscle actin (α-SMA) expression and stromal density in the peritumoural stroma. The aim of this study was to further validate the impact of α-SMA expression and stromal density in resectable pancreatic cancer patients treated with adjuvant gemcitabine compared with untreated patients. METHODS: CONKO-001 was a prospective randomised phase III study investigating the role of adjuvant gemcitabine as compared with observation. Tissue samples of 162 patients were available for immunohistochemistry on tissue microarrays to evaluate the impact of α-SMA expression and stromal density impact on patient outcome. RESULTS: High α-SMA expression in tumour stroma was associated with worse patient outcome (DFS: P=0.05, OS: P=0.047). A dense stroma reaction was associated with improved disease-free survival (DFS) and overall survival (OS) in the overall study population (DFS: P=0.001, OS: P=0.001). This positive prognostic impact was restricted to patients with no adjuvant treatment (DFS: P<0.001, OS: P<0.001). In multivariable analysis, α-SMA and stromal density expression were independently predictive factors for survival. CONCLUSIONS: Our data confirm the negative prognostic impact of high α-SMA expression in pancreatic cancer patients after curatively intended resection. In contrast to former investigations, we found a positive prognostic impact for a dense stroma. This significant influence was restricted to patients who received no adjuvant therapy.
Assuntos
Actinas/metabolismo , Adenocarcinoma/metabolismo , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/metabolismo , Células Estromais/metabolismo , Microambiente Tumoral , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante , Desoxicitidina/uso terapêutico , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Prospectivos , Células Estromais/patologia , Taxa de Sobrevida , Análise Serial de Tecidos , GencitabinaRESUMO
BACKGROUND: Previous investigations in pancreatic cancer suggested a prognostic role for secreted protein acidic and rich in cysteine (SPARC) expression in the peritumoral stroma but not for cytoplasmic SPARC expression. The aim of this study was to evaluate the impact of SPARC expression in pancreatic cancer patients treated with gemcitabine compared with untreated patients. PATIENTS AND METHODS: CONKO-001 was a prospective randomized phase III study investigating the role of adjuvant gemcitabine when compared with observation. Tissue samples of 160 patients were available for SPARC immunohistochemistry on tissue microarrays to evaluate its impact on patient outcome. RESULTS: Strong stromal SPARC expression was associated with worse disease-free survival (DFS) and overall survival (OS) in the overall study population (DFS: P = 0.005, OS: P = 0.033). Its negative prognostic impact was restricted to patients treated with gemcitabine (DFS: P = 0.007, OS: P = 0.006). High cytoplasmic SPARC expression also was associated with worse patient outcome (DFS: P = 0.041, OS: P = 0.011). Again the effect was restricted to patients treated with gemcitabine (DFS: P = 0.002, OS: P = 0.003). In multivariable analysis, SPARC expression was independently predictive of patient outcome. CONCLUSIONS: Our data confirm the prognostic significance of SPARC expression after curatively intended resection. The negative prognostic impact was restricted to patients who received adjuvant treatment with gemcitabine, suggesting SPARC as a predictive marker for response to gemcitabine.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Desoxicitidina/análogos & derivados , Osteonectina/metabolismo , Neoplasias Pancreáticas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/terapia , Quimioterapia Adjuvante , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Resultado do Tratamento , GencitabinaRESUMO
BACKGROUND: LY293111 (LY) is a novel oral anticancer agent with leukotriene B4 receptor antagonist and peroxisome proliferator-activated receptor gamma agonist properties, producing promising results alone and in combination with gemcitabine in pancreatic cancer xenograft models. A phase I study proved that the combination (gemcitabine plus LY) is safe and well tolerated. PATIENTS AND METHODS: Chemotherapy-naive patients with histologically confirmed locally advanced or metastatic adenocarcinoma of the pancreas were randomly assigned to gemcitabine 1000 mg/m on days 1, 8, and 15 of a 28-day cycle and continuously administered LY 600 mg twice daily or gemcitabine 1000 mg/m on days 1, 8, and 15 of a 28-day cycle and daily oral placebo. Arms were balanced for Eastern Cooperative Oncology Group performance status and disease stage. The primary end point was 6-month survival; secondary objectives include response rate (RR), progression-free survival, and overall survival. RESULTS: Six-month survival was not different between groups (P>0.2, 1-sided); progression-free survival and RR were not different (P>0.05, 2-sided). RR was also not impacted. LY did not increase grades 3-4 hematologic toxicities, but was associated with a trend toward more, grades 3-4 diarrhea. CONCLUSIONS: These results do not demonstrate any benefit to adding LY to gemcitabine in unpretreated patients with advanced pancreatic carcinoma.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/uso terapêutico , Benzoatos/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Desoxicitidina/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores do Leucotrieno B4/antagonistas & inibidores , Resultado do Tratamento , Estados Unidos , GencitabinaRESUMO
This prospective multicentre phase II study characterises the toxicity and activity of first-line capecitabine and oxaliplatin combination therapy (CAPOX) in advanced biliary system adenocarcinomas. Patients received oxaliplatin (130 mg m(-2), day 1) plus capecitabine (1000 mg m(-2) b.i.d., days 1-14) every 3 weeks. Patients were stratified prospectively into two groups based on location of the primary (gallbladder carcinoma (GBC) or extrahepatic cholangiocarcinoma (ECC) versus intrahepatic mass-forming type cholangiocarcinoma (ICC)). Sixty-five patients were evaluable. The response rate in 47 patients with GBC/ECC was 27% (4% complete responses), and in 23 patients (49%) stable disease (SD) was encountered. In 18 patients with ICC, we observed no objective responses, but 6 patients (33%) had SD. Median survival was 12.8 months (95% CI, 10.0-15.6) for patients with GBC or ECC (GBC: 8.2 months; 95% CI, 4.3-11.7; ECC: 16.8 months; 95% CI, 12.7-20.5), and 5.2 months (95% CI, 0.6-9.8) for ICC patients. In both cohorts, therapy was well tolerated. The most common grade 3-4 toxicity was peripheral sensory neuropathy (11 patients). Our data suggest that the CAPOX regimen is a well-tolerated and active treatment option for advanced ECC and GBC but might produce poorer results for ICC.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Compostos Organoplatínicos/administração & dosagem , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Biliar/mortalidade , Neoplasias do Sistema Biliar/patologia , Capecitabina , Quimioterapia Adjuvante , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Progressão da Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Análise de Sobrevida , Resultado do TratamentoAssuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Guias de Prática Clínica como Assunto , Adenocarcinoma/epidemiologia , Medicina Baseada em Evidências , Humanos , Cuidados Paliativos , Neoplasias Pancreáticas/epidemiologia , Fatores de RiscoAssuntos
Adenocarcinoma/terapia , Medicina Baseada em Evidências , Neoplasias Pancreáticas/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/etiologia , Terapia Combinada , Humanos , Cuidados Paliativos , Pâncreas Exócrino/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/etiologia , Fatores de RiscoRESUMO
PURPOSE: To evaluate the feasibility and potential advantages of the radiofrequency ablation of liver tumors using new MRI-compatible semiflexible applicators in a closed-bore high-field MRI scanner. METHODS: We treated 8 patients with 12 malignant liver tumors of different origin (5 colorectal carcinoma, 2 cholangiocellular carcinoma, 1 breast cancer) under MRI guidance. Radiofrequency ablation (RFA) was performed using 5 cm Rita Starburst Semi-Flex applicators (Rita Medical Systems, Milwaukee, WI, USA) which are suitable for MR- and CT-guided interventions and a 150 W RF generator. All interventions were performed in a closed-bore 1.5 T high-field MRI scanner for MRI-guided RFA using fast T1-weighted gradient echo sequences and T2-weighted ultra-turbo spin echo sequences. Control and follow-up MRI examinations were performed on the next day, at 6 weeks, and every 3 months after RFA. Control MRI were performed as double-contrast MRI examinations (enhancement with iron oxide and gadopentetate dimeglumine). All interventions were performed with the patient under local anesthesia and analgo-sedation. RESULTS: The mean diameter of the treated hepatic tumors was 2.4 cm (+/-0.6 cm, range 1.0-3.2 cm). The mean diameter of induced necrosis was 3.1 cm (+/-0.4 cm). We achieved complete ablation in all patients. Follow-up examinations over a duration of 7 months (+/-1.3 months, range 4-9 month) showed a local control rate of 100% in this group of patients. All interventions were performed without major complications; only 2 subcapsular hematomas were documented. CONCLUSION: RFA of liver tumors using semiflexible applicators in closed-bore 1.5 T scanner systems is feasible. These applicators might simplify the RFA of liver tumors under MRI control. The stiff distal part of the applicator facilitates its repositioning.
Assuntos
Ablação por Cateter , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética/instrumentação , Idoso , Meios de Contraste , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The majority of pancreatic cancer patients are inoperable at time of diagnosis. For locally inoperable or metastatic disease, the standard therapy remains palliative chemotherapy with Gemcitabine, as so far no other therapy has been shown to be clearly superior. With numerous patients still in a good physical condition at time of progression under Gemcitabine therapy, secondline therapies get into the focus of interest. For the first time, superiority of a secondline therapy compared to best supportive care was demonstrated recently, and more phase III studies are to come. For locally advanced cases, chemoradiation may form another approach and is being discussed. Due to the high percentage of disease recurrence after curative surgery, adjuvant chemotherapy should be offered to all patients. Treatment of pain, malabsorption and maldigestion is an important issue of supportive therapy in pancreatic cancer patients.
Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Adenocarcinoma/cirurgia , Quimioterapia Adjuvante , Humanos , Cuidados Paliativos , Neoplasias Pancreáticas/cirurgia , Radioterapia AdjuvanteRESUMO
AIMS: Several new chemotherapy agents show varying degrees of activity in head and neck cancer. One of them is gemcitabine, which is a new nucleoside analogue with an innovative cytostatic mode of action. Gemcitabine has demonstrated a broad spectrum anti-tumoural effect and a favourable toxicity profile. These attributes prompted us to introduce gemcitabine into the treatment of head-and-neck tumours. MATERIALS AND METHODS: Ten heavily pre-treated patients with recurrent and incurable squamous-cell carcinoma of the head and neck (SCCHN) were treated with Gem. The initial cycle consisted of six administrations of the drug (1250 mg/m2 once weekly intravenously over 30 min) followed by a week without cytotoxic treatment. All following cycles were composed of two infusions once weekly (d1, 8), followed by a week of rest. RESULTS: Toxic effects, length of survival and tumour response was assessable in eight patients owing to one suicide and loss of one patient for follow-up. One complete remission, two partial remissions and three 'no change' situations (stable disease) were observed, yielding a response rate of 37.5%. Median survival was 8 months (range 3-12). The incidence of haematological toxicity was low, with grade 3-4 neutropenia in less than 10%. Flu-like symptoms were reported by one-third of patients. CONCLUSIONS: In this small phase-II study, gemcitabine demonstrated a high anti-tumoural activity in SCCHN, with a favourable toxicity profile. Gemcitabine seems to be a promising new drug without severe burden even for patients who are refractory to other cytostatic drugs. Within recent years, the activity and tolerability of gemcitabine was documented in several phase I and phase II trials, especially in combination with cisplatin, and paclitaxel resp, carboplatin/paclitaxel, cisplatin/ifosfamide, and 5-fluorouracil/paclitaxel. The results of these trials will be outlined in the discussion.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Terapia Combinada , Desoxicitidina/uso terapêutico , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Qualidade de Vida , Radioterapia , Terapia de Salvação , Taxa de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
BACKGROUND: This randomized phase III study compared the overall survival (OS) of pemetrexed plus gemcitabine (PG) versus standard gemcitabine (G) in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Patients with unresectable locally advanced or metastatic pancreatic cancer and no prior systemic therapy (including 5-fluorouracil as a radiosensitizer) were randomized to receive either 1,250 mg/m(2) gemcitabine on days 1 and 8 plus pemetrexed 500 mg/m(2) after gemcitabine on day 8 (PG arm) of each 21-day cycle, or gemcitabine 1,000 mg/m(2) on days 1, 8 and 15 of each 28-day cycle (G arm). RESULTS: Five hundred and sixty-five patients with well-balanced baseline characteristics were randomly assigned (283 PG, 282 G). OS was not improved on the PG arm (6.2 months) compared with the G arm (6.3 months) (P=0.8477). Progression-free survival (3.9 versus 3.3 months; P=0.1109) and time to treatment failure (3 versus 2.2 months; P=0.2680) results were similar. Tumor response rate (14.8% versus 7.1%; P=0.004) was significantly better on the PG arm. Grade 3 or 4 neutropenia (45.1% versus 12.8%), thrombocytopenia (17.9% versus 6.2%), anemia (13.9% versus 2.9%), febrile neutropenia (9.9% versus 0.4%; all P <0.001) and fatigue (15% versus 6.6%; P=0.002) were significantly more common on the PG arm. Four treatment-related deaths occurred on the PG arm and none in the G arm. CONCLUSIONS: Pemetrexed plus gemcitabine therapy did not improve OS. Single-agent gemcitabine remains the standard of care for advanced pancreatic cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Feminino , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neutropenia/induzido quimicamente , Neoplasias Pancreáticas/patologia , Pemetrexede , Análise de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
PURPOSE: To present first results of radiofrequency ablation of liver tumors using a new MR compatible applicator. MATERIALS AND METHODS: We performed 37 interventions in 20 patients (mean age 58.6 years) with primary intrahepatic malignancies or metastases: colorectal carcinoma n = 6, hepatocellular carcinoma n = 3, pancreatic carcinoma n = 4, sarcoma n = 2, cholangiocellular carcinoma n = 1, carcinoma of the tonsil n = 1, breast carcinoma n = 1, gastric carcinoma n = 1, and gastrointestinal stroma tumor n = 1. Interventions were performed under CT-guidance with CT fluoroscopy (n = 32) and under MR-guidance (n = 5) using fast T1-weighted sequences in breath-hold technique. RFA was performed with the RF-generator (150 W) under local anesthesia and sedation using MR compatible applicators (Starburst XL, Rita Medical Systems, USA) together with the appropriate Soft Tissue Introducer System. Intra-interventional control was performed with intrahepatically or intralesionally placed introducer system or applicator. MRI was performed with plain breath-triggered T2-weighted turbo spin echo sequences (TSE T2) with fat saturation. RESULTS: All interventions were performed without major events. The mean diameter of induced coagulation was 4.0 (+/- 0.7) cm. Repositioning was necessary in 8 interventions (21 %) after detection of residual tumor on an intra-interventional MRI. After a mean follow-up of 6.5 (+/- 1.2) months, the local tumor control rate was 92 %. CONCLUSION: MR-compatible RF applicators offer the opportunity for intra-interventional detection of residual tumor during RF ablations by use of sensitive MRI sequences. These procedures may lead to a higher confidence in tumour ablation and may reduce the number of re-interventions and local recurrences of intrahepatic tumors.
Assuntos
Ablação por Cateter , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , Ablação por Cateter/métodos , Fluoroscopia , Seguimentos , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Reoperação , Sensibilidade e Especificidade , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
In the present study, we combined the PCR-clamping approach with melting curve analysis using mutant specific hybridisation probes and wild-type specific peptide nucleic acids (PNAs) to determine the genotypes of the most frequent point mutation in codon 12 of the proto-oncogene Ki-ras in tissue and plasma samples of patients with pancreatic cancer. The sensitivity of our assay was 1-5 x 10(-5). The melting curve analysis of tissue samples of four patients revealed two valine mutations, one none-valine mutation and one wild-type sequence. Ki-ras alterations were found in 28% of DNAs (18 out of 64) of nonrelated plasma samples of 10 patients with ductal adenocarcinoma of the pancreas. The valine mutation was the predominantly detected gene alteration (83%). Out of ten patients investigated, four patients (40%) became positive during clinical observation with respect to Ki-ras mutation. All four patients exhibited progressive disease and high levels of tumour marker CA 19-9. In conclusion, the one-step procedure discribed may be a useful clinical tool for analysing Ki-ras point mutations in tissue and plasmas samples. In addition, this method can be adapted for simultanous detection of multiple mutations and quantitation.
Assuntos
Carcinoma Ductal Pancreático/genética , Genes ras , Neoplasias Pancreáticas/genética , Mutação Puntual , Reação em Cadeia da Polimerase/métodos , Carcinoma Ductal Pancreático/sangue , Feminino , Humanos , Hibridização In Situ , Masculino , Neoplasias Pancreáticas/sangue , Ácidos Nucleicos Peptídicos , Proto-Oncogene Mas , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Aggressive fibromatosis is the name for uncommon soft-tissue neoplasms arising within musculoaponeurotic tissue. They show benign histologic features but have an aggressive local behaviour and frequently recur after surgery or radiation. A 48-year-old black woman presented with recurrent aggressive fibromatosis after primary radiotherapy in the left temporal fossa involving the base of the skull. The patient received interferon alpha2a subcutaneously for 6 months. A slow but steady reduction of the tumour was observed, and pre-existing symptoms disappeared.