Phase II California Cancer Consortium Trial of Gemcitabine-Eribulin Combination in Cisplatin-Ineligible Patients With Metastatic Urothelial Carcinoma: Final Report (NCI-9653).

PURPOSE: Patients with metastatic urothelial carcinoma are often ineligible for cisplatin-based treatments. A National Cancer Institute Cancer Therapy Evaluation Program-sponsored trial assessed the tolerability and efficacy of a gemcitabine-eribulin combination in this population. METHODS: Patients with treatment-naïve advanced or recurrent metastatic urothelial carcinoma of the bladder, ureter, or urethra not amenable to curative surgery and not candidates for cisplatin-based therapy were eligible. Cisplatin ineligibility was defined as creatinine clearance less than 60 mL/min (but ≥ 30 mL/min), grade 2 neuropathy, or grade 2 hearing loss. Treatment was gemcitabine 1,000 mg/m2 intravenously followed by eribulin 1.4 mg/m2, both on days 1 and 8, repeated in 21-day cycles until progression or unacceptable toxicity. A Simon two-stage phase II trial design was used to distinguish between Response Evaluation Criteria in Solid Tumors, version 1.1 objective response rates of 20% versus 50%. RESULTS: Between June 2015 and March 2017, 24 eligible patients with a median age of 73 years (range, 62 to 88 years) underwent therapy. Performance status of 0, 1, or 2 was seen in 11, 11, and two patients, respectively. Sites of disease included: lymph nodes, 16; lungs, nine; liver, seven; bladder, five; bones, two. Median number of cycles received was four (range, one to 16). Of 24 patients, 12 were confirmed responders; the observed objective response rate was 50% (95% CI, 29% to 71%). Median overall survival was 11.9 months (95% CI, 5.6 to 20.4 months), and median progression-free survival was 5.3 months (95% CI, 4.5 to 6.7 months). The most common treatment-related any-grade toxicities were fatigue (83% of patients), neutropenia (79%), anemia (63%), alopecia (50%), elevated AST (50%), and constipation, nausea, and thrombocytopenia (42% each). CONCLUSION: Gemcitabine-eribulin treatment response and survival for cisplatin-ineligible patients compare favorably to other regimens. Additional research is needed.

[Two cases of urothelial cancer responsive to high-dose-intensity methotrexate vinblastine doxorubicin and cisplatin (M-VAC) therapy].

We report two cases of metastatic urothelial cancer treated with high-dose-intensity (HD) methotrexate vinblastine, doxorubicin and cisplatin (MVAC). After HD-MVAC, the size of primary and lymph node tumors decreased by 57-67% as compared with the standard M-VAC therapy. By shortening the dose interval, HD-MVAC may increase the anti-tumor effect without increasing side effects.

[A study of post-operative chemotherapy for renal pelvic and ureteral tumors].

A study was made of the relationship between post-operative chemotherapy and metastasis and recurrence of bladder tumor in 9 patients with renal pelvic and ureteral tumors. Within 6 months on average, post-operative metastasis was found in 33.3% (3 out of 9 cases). Differentiating according to the type of chemotherapy, the rate of occurrence of metastasis was 50% (2 out of 4) in the case of treatment with either a combination of FT-207, chromomycin A3 and cytosine arabinoside, or with FT-207 alone, while it was 100% (2 out of 2) in stage pT2 and pT3 patients. For combined administration of CDDP, FT-207 and cytosine arabinoside, or for that of CDDP and neocarzinostatin, on the other hand, the rate of occurrence of metastasis was only 20% (1 out of 5) in stage pT2 and pT3 patients, while CDDP administration was found to be effective for preventing post-operative metastasis. However, while recurrence of bladder tumor was found in a total of 3 out of 9 cases (33.3%), recurrence occurred in 40% (2 out of 5) of the cases treated with CDDP. The administration of CDDP was therefore not found to be effective for preventing recurrence of bladder tumor.

Chronic kidney disease after nephroureterectomy for upper tract urothelial carcinoma and implications for the administration of perioperative chemotherapy.

BACKGROUND: The prevalence of chronic kidney disease (CKD) in patients with upper tract urothelial carcinoma (UTUC) is poorly defined, both before and after nephrouretectomy. Although multimodal treatment paradigms for UTUC are under-developed, this has important implications on patients' ability to receive cisplatin-based combination chemotherapy (CBCC). METHODS: Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula in 336 patients with UTUC, who were treated at the Cleveland Clinic by nephroureterectomy since 1992. An eGFR cutoff of 60 mL/min/1.73 m(2) was used to determine the presence of CKD and eligibility for CBCC. RESULTS: Median age was 72 years and median preoperative eGFR was 59 mL/min/1.73m(2). Before nephroureterectomy, only 48% of patients were eligible to receive CBCC and this decreased to 22% postoperatively (P < .001). In the 144 patients with pT2-pT4 and/or pN1-pN3 disease who are suitable to receive CBCC, these proportions were 40% and 24%, respectively (P = .009). Although 50 patients overall received some form of perioperative chemotherapy, only 3 and 11 patients received neoadjuvant and adjuvant CBCC, respectively. CONCLUSIONS: CKD is prevalent in the UTUC population and a minority of patients has an optimal eGFR to receive neoadjuvant CBCC. Nephrouretectomy may eliminate CBCC as a therapeutic option in 49% of high-risk patients if it is deferred to the adjuvant setting. Multimodal treatment strategies for UTUC should focus on neoadjuvant chemotherapy, as few patients are eligible for adjuvant CBCC because of the substantial decline in eGFR caused by nephroureterectomy.

Efeitos da sondagem nasogástrica em pacientes com acidente cerebrovascular e disfagia / Effects of nasogastric catheterization in patients with stroke and dysphagia / Efectos de la cateterización nasogástrica en pacientes con accidente cerebrovascular y disfagia

O estudo teve por objetivo analisar os efeitos da sondagem gástrica em pacientes com acidente vascular cerebral e disfagia. Revisão sistemática da literatura, realizada em seis bases de dados, com os descritores stroke e intubation, gastrointestinal. Foram encontrados 120 estudos e selecionados três ensaios clínicos. Os resultados apontaram diferentes desfechos, entre os quais: aumento do nível sérico de albumina (gastrostomia), prognóstico ruim e risco de morte (gastrostomia), aumento das falhas no tratamento devido a bloqueio, deslocamento e reinserção da sonda nasogástrica, e aumento da incidência de hemorragia gastrointestinal (sonda nasogástrica). A partir dos resultados obtidos nesta revisão sistemática, ressaltam-se as seguintes evidências: a sondagem nasogástrica deve ser adotada precocemente como um método de alimentação enteral; as falhas do tratamento são mais comuns naqueles que utilizam a sonda nasogástrica como método de alimentação; os resultados relacionados à melhora do estado funcional dos pacientes foram semelhantes, independente do método de terapia nutricional empregado.

This study aimed to analyze the effects of gastric intubation in patients with stroke and dysphagia. A systematic literature review was performed in six databases, using the keywords stroke and intubation, gastrointestinal. One hundred and twenty studies were found, from which three clinical trials were selected. The results showed different outcomes, including: increased serum albumin level (gastrostomy), poor prognosis and risk of death (gastrostomy), increased treatment failures because of blocking, displacement and reinsertion need of the nasogastric tube, and increased incidence of gastrointestinal bleeding (nasogastric tube). From the results obtained in this systematic review, we emphasize the following evidences: a nasogastric catheter should be adopted as a method of early enteral feeding; treatment failures are more common in those who use nasogastric tube-feeding; outcomes related to improved functional status of patients were similar, regardless of the method of nutritional therapy used.

El objetivo del estudio fue analizar los efectos de la intubación gástrica en pacientes con accidente cerebrovascular y disfagia. Se llevó a cabo una revisión sistemática de la literatura en seis bases de datos, utilizando-se las palabras clave accidente cerebrovascular y intubación, gastrointestinal. Entre 120 estudios identificados, fueran seleccionados tres ensayos clínicos. Los resultados mostraron diferentes desfechos, incluyendo: aumento del nivel de albúmina sérica (gastrostomía); mal pronóstico y riesgo de muerte (gastrostomía); aumento de los fracasos del tratamiento debido a obstrucción, desplazamiento y necesidad de reinserción de la sonda nasogástrica; y aumento de la incidencia de hemorragia gastrointestinal (sonda nasogástrica). A partir de los resultados obtenidos, destacamos las siguientes evidencias: se deben adoptar catéteres nasogástricas como método de alimentación enteral temprana; fracasos del tratamiento son más comunes en aquellos que utilizan la alimentación con sonda nasogástrica; los resultados relacionados con la mejora del estado funcional de los pacientes fueron similares, independientemente del método de terapia nutricional utilizado.