scholarly journals Safety and efficacy of temsirolimus as second-line treatment for patients with recurrent bladder cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 304-304 ◽  
Author(s):  
Nadine Houede ◽  
Guilhem Roubaud ◽  
Hakim Mahammedi ◽  
Lionel Vedrine ◽  
Florence Joly ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Mammalian Target Of Rapamycin ◽  
Signalling Pathway ◽  
Weekly Dose ◽  
Second Line ◽  
Mutational Status ◽  
Urothelial Tumors ◽  
Chemotherapy Efficacy ◽  
Mtor Signalling ◽  
Line Chemotherapy

304 Background: Bladder cancer is the 7th cause of death from cancer in men and 10th in women. For metastatic patients, prognosis is poor with a median overall survival of 15 months that remained unchanged for the past 15 years. No standard second-line chemotherapy is available for patients who relapse. Acquired mutations leading to a deregulation of the PI3K/AKT/mTOR pathway have been reported in more than 40% of bladder cancers suggesting the use of the mTOR (mammalian target of rapamycin) signalling pathway as an attractive target for the treatment of urothelial tumors. Methods: The main objective of this study was to assess the efficacy of temsirolimus, an mTOR inhibitor that is already used for the treatment of renal cancers, in patients with recurrent or metastatic bladder cancer who already received a first line chemotherapy. Efficacy was measured in terms of non-progression of the disease at two months of treatment following the RECIST v1.1 criteria. Based on a two-stage optimal Simon’s design, a total of 15 non-progressions out of 51 eligible and assessable patients were required to claim efficacy. Patients were treated at a weekly dose of 25 mg until progression, unacceptable toxicities or withdrawal. Results: Fifty-four patients were enrolled in the study between November 2009 and July 2014 in seven French centres. At the end of the first stage, six patients out of 17 were progression-free at 2 months leading to the inclusion of additional 37 patients in the second stage of the study. Thirty-six patients were eligible and assessable for the primary efficacy endpoint. A total of 18 (50%) non-progressions were observed at 2 months. Among them, partial response was documented for two patients and stable disease for 16. Twenty-five related adverse events were observed in 19 (35.2%) of the patients. Conclusions: Our study is providing the first clinical evidence of a potential benefit of temsirolimus for the treatment of relapsed bladder cancers. Ancillary study is ongoing to investigate the mutational status of genes which are involved in the PI3K/AKT/mTOR signalling pathway in order to identify a predictive signature of response to temsirolimus in bladder cancer. Clinical trial information: NCT0187943NCT0187943.

Second-Line Chemotherapy in Advanced Bladder Cancer

2000 ◽  
Vol 64 (2) ◽  
pp. 61-69 ◽  
Author(s):  
Michele Pavone-Macaluso ◽  
Cora Sternberg
Keyword(s):  
Bladder Cancer ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
Advanced Bladder Cancer ◽  
Line Chemotherapy

Efficacy and safety of paclitaxel/ramucirumab as the second-line chemotherapy in Japanese patients with advanced gastric cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15540-e15540
Author(s):  
Tetsuya Kusumoto ◽  
Akinori Egashira ◽  
Hideto Sonoda ◽  
Kenkichi Hashimoto ◽  
Hideo Uehara ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Japanese Patients ◽  
Phase Iii ◽  
Weekly Dose ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

e15540 Background: Second-line chemotherapy can now be considered as a proven treatment option for metastatic or locally advanced gastric cancer (AGC). Two global randomized phase III trials (REGARD and RAINBOW) showed that survival benefit was significantly observed in patients treated with ramucirumab (RAM) alone and in combination with weekly doses of PTX, compared with placebo, respectively. The purpose of the study is to evaluate the efficacy and safety of weekly dose of PTX combined with RAM practically as the second-line treatment in Japanese patients with AGC refractory to an S-1-containing chemotherapy regimen. Methods: We conducted a retrospective review of the data of 18 patients with AGC who received more than 2 cycles of PTX/RAM combined chemotherapy as the second-line regimen following S-1-based treatment. The objective response rate (ORR), adverse events, progression-free survival (PFS) and overall survival (OS) were analyzed and compared with PTX monotherapy group. Results: Median number of courses were 5 for the PTX/RAM group and the discontinuation of treatment except for disease progression was found in 2 cases (33.3%). The rates of hematological toxicities of higher than grade 3 were 33.3% in the PTX/RAM group, which were higher than those found in the PTX groups. The tumor responses of the PTX/RAM group were 22% for the ORR and 78% for the DCR, compared with 21% and 48% in the PTX group, respectively. The dose intensities of PTX were 72.4% in the former group. The survival data showed that the MST after second-line exposure was 290 days and the median PFS was 131 days in the PTX/RAM group, compared with 159 days and 90 days in the PTX group, which were not significantly different. Conclusions: PTX/RAM might be one of the best regimens for Japanese patients with AGC as the second-line treatment following S-1-containing chemotherapy.

A possible linkage between AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway

2003 ◽  
Vol 8 (1) ◽  
pp. 65-79 ◽  
Author(s):  
Naoki Kimura ◽  
Chiharu Tokunaga ◽  
Sushila Dalal ◽  
Christine Richardson ◽  
Ken-ichi Yoshino ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mammalian Target Of Rapamycin ◽  
Signalling Pathway ◽  
Target Of Rapamycin ◽  
Amp Activated Protein Kinase ◽  
Mtor Signalling ◽  
Mtor Signalling Pathway

scholarly journals LKB1 mutations are not associated with the efficacy of first-line and second-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC): a post hoc analysis of the TAILOR trial

ESMO Open ◽  
2020 ◽  
Vol 5 (3) ◽  
pp. e000748
Author(s):  
Claudio Vernieri ◽  
Monica Ganzinelli ◽  
Eliana Rulli ◽  
Gabriella Farina ◽  
Anna Cecilia Bettini ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Cytotoxic Chemotherapy ◽  
Second Line ◽  
Small Cell Lung ◽  
First Line ◽  
Mutational Status ◽  
Platinum Based Chemotherapy ◽  
Nsclc Patients ◽  
The Impact ◽  
Chemotherapy Efficacy

PurposeIn patients with advanced lung adenocarcinoma, the impact of LKB1 mutations on cytotoxic chemotherapy efficacy remains poorly explored. Here, we aimed at investigating the potential impact of LKB1 mutational status on chemotherapy efficacy in advanced non-small-cell lung cancer (NSCLC) patients enrolled in the TArceva Italian Lung Optimisation tRial (TAILOR) trial.MethodsThe multicenter TAILOR trial randomised patients with EGFR-wild type (wt) advanced NSCLC progressing on/after previous platinum-based chemotherapy to receive docetaxel or erlotinib. Here, we evaluated the impact of LKB1 mutational status on progression-free survival (PFS) and overall survival (OS) in patients treated with second-line docetaxel/erlotinib or during prior platinum-based chemotherapy.ResultsOut of 222 patients randomised in the TAILOR trial, left-over tumour tissues were available for 188 patients, and 120 patients with evaluable LKB1 status were included. Of them, 17 (14.17%) patients had LKB1-mutated tumours, while 103 (85.83%) had LKB1-wt disease. During second-line treatment, PFS and OS were not statistically significantly different in patients with LKB1-mutated when compared with LKB1-wt NSCLC (adjusted HR (aHR)=1.29, 95% CI 0.75 to 2.21; p=0.364 and aHR=1.41, 95% CI 0.82 to 2.44; p=0.218, respectively). Similarly, we found no significant association between LKB1 mutations and patient PFS or OS during prior first-line platinum-based chemotherapy (aHR=1.04, 95% CI 0.55 to 1.97; p=0.910 and aHR=0.83, 95% CI 0.42 to 1.65; p=0.602, respectively).ConclusionAmong advanced NSCLC patients receiving two lines of systemic therapy, LKB1 mutations were not associated with PFS or OS during second-line docetaxel or prior first-line platinum-based chemotherapy. While larger prospective trials are needed to confirm our findings, cytotoxic chemotherapy remains the backbone of investigational combination strategies in this patient population.

Responsiveness of Skin Metastases to CMF in A Patient with Urothelial Carcinoma of the Bladder: A Case Report

2003 ◽  
Vol 89 (1) ◽  
pp. 85-87 ◽  
Author(s):  
Gerardo Rosati ◽  
Antonio Rossi ◽  
Domenico Germano ◽  
Angelo Piccirillo ◽  
Domenico De Sanctis ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Case Report ◽  
Urothelial Carcinoma ◽  
Bladder Cancer Patient ◽  
Second Line ◽  
Cutaneous Lesions ◽  
Present Case Report ◽  
Skin Metastases ◽  
Carcinoma Of The Bladder ◽  
Line Chemotherapy

Skin metastases from urothelial carcinoma of the bladder are uncommon, and there are few cases reported in literature. The present case report describes the results of a combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) administered as second-line chemotherapy in a cisplatin-resistant metastatic bladder cancer patient. The improvement in cutaneous lesions and pain reduction obtained prompt further exploration of the activity of this regimen in a second-line approach.

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