Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours

Sternberg, Cora N.; Mulder, P.H.M. de; Schornagel, J. H.; Théodore, Christine; Fosså, Sophie D.; Oosterom, A.T. van; Witjes, J. Alfred; Spina, Michele; Groeningen, C.J. van; Duclos, B.; Roberts, JT; Balincourt, Christine de; Collette, Laurence

doi:10.1016/j.ejca.2005.08.032

Cited by 479 publications

(251 citation statements)

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“…Patients may have received MVAC in either a standard or dose-dense fashion. 13 Data abstracted for the current analysis included age at the time of neoadjuvant chemotherapy, neoadjuvant chemotherapy regimen, the number of cycles of neoadjuvant chemotherapy, tumor histology at the time of radical cystectomy, Eastern Cooperative Oncology Group performance status, year of diagnosis, clinical tumor classification, race, ethnicity, sex, reason for stopping neoadjuvant chemotherapy, time from last dose of chemotherapy until cystectomy, calculated creatinine clearance using the Cockroft-Gault formula, pathologic response to neoadjuvant chemotherapy, and vital status. Detailed toxicity data are not collected in RISC because of the retrospective nature of the data collection.…”

Section: Study Design and Patient Populationmentioning

confidence: 99%

Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle‐invasive bladder cancer

Galsky

Pal

Chowdhury

et al. 2015

Cancer

167

101

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BACKGROUND: Gemcitabine plus cisplatin (GC) has been adopted as a neoadjuvant regimen for muscle-invasive bladder cancer despite the lack of Level I evidence in this setting. METHODS: Data were collected using an electronic data-capture platform from 28 international centers. Eligible patients had clinical T-classification 2 (cT2) through cT4aN0M0 urothelial cancer of the bladder and received neoadjuvant GC or methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) before undergoing cystectomy. Logistic regression was used to compute propensity scores as the predicted probabilities of patients being assigned to MVAC versus GC given their baseline characteristics. These propensity scores were then included in a new logistic regression model to estimate an adjusted odds ratio comparing the odds of attaining a pathologic complete response (pCR) between patients who received MVAC and those who received GC. RESULTS: In total, 212 patients (146 patients in the GC cohort and 66 patients in the MVAC cohort) met criteria for inclusion in the analysis. The majority of patients in the MVAC cohort (77%) received dose-dense MVAC. The median age of patients was 63 years, they were predominantly men (74%), and they received a median of 3 cycles of neoadjuvant chemotherapy. The pCR rate was 29% in the MVAC cohort and 31% in the GC cohort. There was no significant difference in the pCR rate when adjusted for propensity scores between the 2 regimens (odds ratio, 0.91; 95% confidence interval, 0.48-1.72; P 5.77). In an exploratory analysis evaluating survival, the hazard ratio comparing hazard rates for MVAC versus GC adjusted for propensity scores was not statistically significant (hazard ratio, 0.78; 95% confidence interval, 0.40-1.54; P 5.48). CONCLUSIONS: Patients who received neoadjuvant GC and MVAC achieved comparable pCR rates in the current analysis, providing evidence to support what has become routine practice.

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Section: Study Design and Patient Populationmentioning

confidence: 99%

Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle‐invasive bladder cancer

Galsky

Pal

Chowdhury

et al. 2015

Cancer

167

101

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“…Despite initial high response rates, overall 5-year survival is suboptimal at 5% to 20%. [9][10][11] Several studies have evaluated the clinical and pathological prognostic factors after cystectomy for muscle-invasive UC. Advanced pathologic stage, nodal involvement, tumour size greater than 3 cm, elevated creatinine and lymphovascular invasion are independent risk factors for recurrence, [12][13][14][15] while advanced pathologic stage and nodal involvement are independent prognostic factors for survival.…”

Section: Introductionmentioning

confidence: 99%

Personalized medicine in advanced urothelial cancer: when to treat, how to treat and who to treat

Ehdaie

Smith

Theodorescu

2013

CUAJ

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The past decade has provided an improved understanding of the molecular mechanism of bladder cancer by defining distinct pathways in tumorigenesis and progression. Advances in technologies, such as high-throughput transcript profiling, microarrays and proteomics, offer a systematic approach to identifying targets for bladder cancer diagnostics and drug discovery. This review presents a select outline of the advances in the development of biomarkers and targets for patient prognosis and therapy selection. This paper describes a representative cohort of recent studies that have the potential to significantly impact the management of muscle invasive and metastatic urothelial carcinoma of the bladder. Space constraints do not permit this review to be comprehensive and we apologize to the authors whose work we do not cite.

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“…With contemporary cisplatin-based combination chemotherapy, approximately 50% to 60% of patients will achieve an objective response to treatment and approximately 10% to 20% will achieve a complete response. 1,2 Despite these relatively high response proportions in the context of other solid tumors treated with cytotoxic agents, response durations in metastatic UC are generally short-lived, and median overall survival is only approximately 14 months. 2 Recent attempts to improve contemporary cisplatin-based regimens have proven unsuccessful, with no advances in the efficacy of therapy in the past 30 years.…”

Section: Introductionmentioning

confidence: 99%

Relationship between 6‐ and 9‐month progression‐free survival and overall survival in patients with metastatic urothelial cancer treated with first‐line cisplatin‐based chemotherapy

Galsky

Krege

Lin

et al. 2013

Cancer

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BACKGROUND: Use of progression-free survival (PFS) as a clinical trial endpoint in first-line treatment of patients with metastatic urothelial carcinoma (UC) is attractive, but would be enhanced by establishing a correlation between PFS and overall survival (OS). METHODS: Data was pooled from 7 phase 2 and 3 trials evaluating cisplatin-based chemotherapy in metastatic UC. An independent cohort of patients enrolled on a phase 3 trial was used for external validation. Landmark analyses for progression at 6 and 9 months after treatment initiation were performed to minimize lead-time bias. A proportional hazards model was used to assess the utility of PFS for predicting OS. RESULTS: A total of 364 patients were included in the initial cohort. The median PFS was 8.21 months (95% confidence interval 5 7. 43, 8.39) and the median OS was 13.50 months (95% confidence interval 5 11.80, 15.67). In the landmark analysis, the median OS for patients who progressed at 6 months was 3.87 months compared with 15.06 months for those patients who did not progress (P <.0001) and the median OS for patients who progressed at 9 months was 5.65 months compared with 21.39 months for those patients who did not progress (P <.0001). A Fleischer model demonstrated a statistically significant dependent correlation between PFS and OS. The findings were externally validated in an independent cohort. CONCLUSIONS: PFS at 6 and 9 months predicted OS in this analysis of patients with metastatic UC treated with first-line cisplatin-based chemotherapy and could potentially serve as endpoints in (randomized) phase 2 trials to screen the activity of novel regimens. Cancer 2013;119:3020-6. V C 2013 American Cancer Society.KEYWORDS: urothelial cancer; bladder cancer; chemotherapy; clinical trials; progression-free survival; overall survival; cisplatin. INTRODUCTIONMetastatic urothelial cancer (UC) is a chemosensitive disease. With contemporary cisplatin-based combination chemotherapy, approximately 50% to 60% of patients will achieve an objective response to treatment and approximately 10% to 20% will achieve a complete response. 1,2 Despite these relatively high response proportions in the context of other solid tumors treated with cytotoxic agents, response durations in metastatic UC are generally short-lived, and median overall survival is only approximately 14 months. 2 Recent attempts to improve contemporary cisplatin-based regimens have proven unsuccessful, with no advances in the efficacy of therapy in the past 30 years. 3 The relatively high response rates achieved with first-line cisplatin-based chemotherapy in metastatic UC has created a challenge with regard to appropriate endpoints for phase 2 trials exploring novel therapeutic regimens. A high barrier must be overcome to detect a signal of enhanced antitumor activity (as measured by objective response rate) compared with historical controls. 4 At the same time, tumor response rate has not convincingly proven useful in selecting phase 2 regimens worthy of moving forward to definitive randomiz...

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Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours

Cited by 479 publications

References 14 publications

Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle‐invasive bladder cancer

Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle‐invasive bladder cancer

Personalized medicine in advanced urothelial cancer: when to treat, how to treat and who to treat

Relationship between 6‐ and 9‐month progression‐free survival and overall survival in patients with metastatic urothelial cancer treated with first‐line cisplatin‐based chemotherapy

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