Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in patients with advanced bladder cancer: short-term versus prolonged treatment [German Association of Urological Oncology (AUO) trial AB 20/99]

Albers, Peter; Park, S.-I.; Niegisch, Günter; Fechner, G.; Steiner, U.; Lehmann, Jan; Heimbach, D.; Heidenreich, Axel; Fimmers, Rolf; Siener, Roswitha

doi:10.1093/annonc/mdq398

Cited by 129 publications

(86 citation statements)

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“…Several studies have examined the various prognostic factors of patients. Buti et al identified nine studies (29)(30)(31)(32)(33)(34)(35)(36)(37)) that aimed at evaluate the prognostic factors of 1,273 patients in a second-line treatment setting. In most studies, PS, Hb, and visceral metastasis were identified as the main independent prognostic factors for OS (38).…”

Section: Discussionmentioning

confidence: 99%

The combination of paclitaxel and carboplatin as second-line chemotherapy can be a preferred regimen for patients with urothelial carcinoma after the failure of gemcitabine and cisplatin chemotherapy

et al. 2017

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Abstract. There is no established standard second-line chemotherapy after the failure of the first-line cisplatin-based chemotherapy for patients with advanced or metastatic urothelial carcinoma. With regards to second-line chemotherapy, methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) was used from July 2009 onwards, and paclitaxel and carboplatin (TC) was introduced in April 2014 at the National Kyushu Cancer Center. The present study aimed to assess the prognostic factors for overall survival (OS) in second-line treatment that included best supportive care (BSC), and the tolerability and efficacy of TC chemotherapy. In total, 52 patients who were confirmed to have disease progression with first-line gemcitabine and cisplatin (GC) between June 2009 and November 2016 were enrolled in the current study. In addition, 28 patients selected BSC as second-line treatment, while 24 patients received second-line chemotherapy (MVAC, n=8; TC, n=16). The median OS for BSC, MVAC and TC was 2.8, 5.4, and 12.7 months, respectively. The difference between BSC and MVAC was not statistically significant (P=0.596). However, the difference between BSC and TC was statistically significant after Bonferroni correction (P=0.002). Multivariate analyses revealed that anemia [hazard ratio (HR), 7.047; 95% confidence interval (CI), 1.553-35.636; P= 0.011], the presence of visceral metastasis (HR, 4.174; 95% CI, 1.506-13.429; P= 0.005) and second-line treatment (TC HR, 0.296; 95% CI, 0.124-0.636; P= 0.003) were independent prognostic factors. TC achieved an 18.7% overall response rate and a 56.2% disease control rate. Myelosuppression was the most common grade ≥3 toxicity, but no treatment-associated mortalities occurred during the study period. TC was associated with favorable benefits and safety, and may be considered a preferred regimen after the failure of GC.

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Section: Discussionmentioning

confidence: 99%

The combination of paclitaxel and carboplatin as second-line chemotherapy can be a preferred regimen for patients with urothelial carcinoma after the failure of gemcitabine and cisplatin chemotherapy

et al. 2017

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“…Sternberg et al (24) reported that overall response rate of an every 2 week regimen was 60%, and median overall survival was 14.4 months. Recently in a randomized phase III trial, Albers et al (30) reported on the results of an every 3 weeks GP chemotherapy (short-term arm) versus an every 3 weeks GP chemotherapy until disease progression ( prolonged arm). Overall survival was lower in both arms, with a median survival of 7.8 months for the short-term arm and 8.0 months for the prolonged arm.…”

Section: Discussionmentioning

confidence: 99%

Combination of Gemcitabine and Paclitaxel is a Favorable Option for Patients with Advanced or Metastatic Urothelial Carcinoma Previously Treated with Cisplatin-based Chemotherapy

Ikeda

Matsumoto

Tabata

et al. 2011

Japanese Journal of Clinical Oncology

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Objective: To evaluate the efficacy and toxicity of a gemcitabine and paclitaxel regimen for patients with advanced urothelial carcinoma who had previously been treated with methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy, and to determine the prognostic factors for survival in second-line chemotherapy. Patients were evaluated every two cycles by imaging study. Results: Ten of 24 patients (42%) had major response to the gemcitabine and paclitaxel regimen, including 2 patients (8%) who had complete response. Median survival time and median progression-free survival were 12.4 and 6.1 months, respectively. Good performance status and major response to first-line methotrexate, vinblastine, doxorubicin and cisplatin treatment were significant predictors of overall survival and progression-free survival. Grade 3 or 4 neutropenia occurred in 16 patients (67%), but there were no severe infections. There were no treatment-related deaths.Conclusions: Gemcitabine and paclitaxel chemotherapy had favorable benefit and safety profiles, and the regimen is recommended as a potential second-line chemotherapy for advanced or metastatic urothelial carcinoma previously treated with methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy.

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“…Metastatic TCC has a poor prognosis, with a median survival that does not exceed 15 months [2]. Therapeutic options are limited and cisplatinbased chemotherapy is the only treatment that improves survival in the first-line setting; however, resistance occurs rapidly and second-line chemotherapy trials have unfortunately yielded discouraging results, with response rates of~10-30%, progression-free survival (PFS) of between 2 and 3 months and a median survival of only 6-9 months [3][4][5][6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Phase II study of dual phosphoinositol‐3‐kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor BEZ235 in patients with locally advanced or metastatic transitional cell carcinoma

et al. 2016

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ObjectiveTo assess, in a multicentre phase II trial, the safety and efficacy of BEZ235, an oral pan-class I phosphoinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) complex1/2 inhibitor, in locally advanced or metastatic transitional cell carcinoma (TCC) after failure of platinumbased therapy. Patients and MethodsPatients with locally advanced or metastatic TCC progressing after platinum therapy were prospectively stratified by PI3K/ Akt/mTOR pathway alterations, defined as PTEN loss and PIK3CA mutation. All patients received BEZ235 until progressive disease or unacceptable toxicity. The primary endpoint was the progression-free survival (PFS) rate at 16 weeks. This study was, however, closed prematurely because BEZ235 was withdrawn from further development. ResultsA total of 20 patients (18 without and two with PI3K/Akt/ mTOR alterations) were enrolled and received BEZ235. One partial response (5%) and two cases of stable disease (10%) were observed, all in patients without PI3K/mTOR pathway alterations. The PFS rate at 8 and 16 weeks was 15 and 10%, respectively; the median (range) PFS was 62 (38-588) days (95% confidence interval [CI] 53-110); and the median (range) overall survival was 127 (41-734) days (95% CI 58-309). Among the 90% of patients who experienced drugrelated adverse events of any grade, 50% experienced grade 3-4 adverse events, including stomatitis (15%), fatigue (5%), nausea (5%), diarrhoea (5%), renal failure (5%), cutaneous rash (5%), hepatotoxicity (5%) and hypertension (5%). ConclusionBEZ235 showed modest clinical activity and an unfavourable toxicity profile in patients with advanced and pretreated TCC; however, a minority of patients experienced a clinical benefit, suggesting that a complete blockade of the PI3K/mTOR axis could improve outcome in some specific patients. Furthermore, this study showed that molecular stratification of patients for personalized medicine before treatment is feasible.

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Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in patients with advanced bladder cancer: short-term versus prolonged treatment [German Association of Urological Oncology (AUO) trial AB 20/99]

Abstract: Due to rapid tumor progression and toxicity at this dosage and schedule in a multicenter setting, it was not feasible to deliver a prolonged regimen. However, a high response rate of ∼40% makes GP a promising second-line treatment option for patients with metastatic UC.

Cited by 129 publications

References 21 publications

The combination of paclitaxel and carboplatin as second-line chemotherapy can be a preferred regimen for patients with urothelial carcinoma after the failure of gemcitabine and cisplatin chemotherapy

The combination of paclitaxel and carboplatin as second-line chemotherapy can be a preferred regimen for patients with urothelial carcinoma after the failure of gemcitabine and cisplatin chemotherapy

Combination of Gemcitabine and Paclitaxel is a Favorable Option for Patients with Advanced or Metastatic Urothelial Carcinoma Previously Treated with Cisplatin-based Chemotherapy

Phase II study of dual phosphoinositol‐3‐kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor BEZ235 in patients with locally advanced or metastatic transitional cell carcinoma

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