Reporting Results From Chemotherapy Trials

Oye, Robert K.

doi:10.1001/jama.1984.03350190024013

Cited by 55 publications

(11 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is expected that greater tumor shrinkage is correlated with outcome, though this link remains highly debated across tumor types (18–21). Other authors have recently described a correlation between change in tumor response by RECIST- taken as a continuous variable - with overall survival in the context of phase I trials (22).…”

Section: Discussionmentioning

confidence: 99%

Tumor Growth Rate Is an Early Indicator of Antitumor Drug Activity in Phase I Clinical Trials

Ferté

Fernandez

Hollebecque

et al. 2014

Clinical Cancer Research

149

141

View full text Add to dashboard Cite

Purpose RECIST evaluation does not take into account the pre-treatment tumor kinetics and may provide incomplete information regarding experimental drug activity. Tumor Growth Rate (TGR) allows for a dynamic and quantitative assessment of the tumor kinetics. How TGR varies along the introduction of experimental therapeutics and is associated with outcome in phase I patients remains unknown. Experimental designs Medical records from all patients (n=253) prospectively treated in 20 phase I trials were analyzed. TGR was computed during the pre-treatment period (REFERENCE) and the EXPERIMENTAL period. Associations between TGR, standard prognostic scores (RMH score) and outcome (PFS, OS) were computed (multivariate analysis). Results We observed a reduction of TGR between the REFERENCE vs. EXPERIMENTAL periods (38% vs. 4.4%, P<.00001). Although most patients were classified as stable disease (65%) or progressive disease (25%) by RECIST at the first evaluation, 82% and 65% of them exhibited a decrease in TGR, respectively. In a multivariate analyses, only the decrease of TGR was associated with PFS (P=.004), whereas the RMH score was the only variable associated with OS (P=.0008). Only the investigated regimens delivered were associated with a decrease of TGR (P<.00001, multivariate analysis). Computing TGR profiles across different clinical trials reveals specific patterns of antitumor activity. Conclusions Exploring TGR in phase I patients is simple and provides clinically relevant information: (i) an early and subtle assessment of signs of antitumor activity; (ii) indpendent association with PFS; and (iii) It reveals drug-specific profiles; suggesting potential utility for guiding the further development of the investigational drugs.

show abstract

Section: Discussionmentioning

confidence: 99%

Tumor Growth Rate Is an Early Indicator of Antitumor Drug Activity in Phase I Clinical Trials

Ferté

Fernandez

Hollebecque

et al. 2014

Clinical Cancer Research

149

141

View full text Add to dashboard Cite

show abstract

“…In our study, we used the objective response rate, overall survival, and event free survival as the primary parameters to assess the association between the expression of TUBB3 and the clinical outcomes of taxane/vinorebine-based chemotherapy. Because a low ORR suggests tumor resistance to the chemotherapy regimen and a short OS/EFS indicates a poor prognosis, it is necessary to include all three parameters in order to make a comprehensive assessment about the treatment response to a chemotherapy regimen [55]. In our analysis, we demonstrated that the high level of TUBB3 expression was associated with a lower ORR, a shorter OS, and a worse EFS, which strongly supported that TUBB3 had a prognostic value in predicting the treatment response to the taxane/vinorebine-based chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

The Prognostic Role of the Class III β-Tubulin in Non-Small Cell Lung Cancer (NSCLC) Patients Receiving the Taxane/Vinorebine-Based Chemotherapy: A Meta-Analysis

2014

View full text Add to dashboard Cite

BackgroundA number of studies have examined the relationship between the expression of the class III β-tubulin (TUBB3) and the treatment responses to the taxane/vinorebine-based chemotherapy in patients with non-small cell lung cancer (NSCLC). However, the results of these studies were inconsistent and inconclusive. Therefore, we conducted an up-to-date meta-analysis to evaluate the prognostic role of TUBB3 in the taxane/vinorebine-based chemotherapy.MethodsA literature search for relevant studies was conducted in PubMed, Embase, and CNKI. The inclusion criteria were the taxane/vinorebine-based chemotherapy in patients with NSCLC and the evaluation of the clinical outcomes in relation to the expression of TUBB3. The clinical outcomes analyzed in this study included the overall response rate (ORR), overall survival (OS), and event-free survival (EFS). Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were calculated to assess the risk associated with the TUBB3 expression in the taxane/vinorebine-based chemotherapy.ResultsA total of 28 studies with 2401 NSCLC patients were qualified for this meta-analysis. We found that the positive or high level of TUBB3 expression was associated with a poorer ORR (OR = 0.24, 95% CI = 0.16–0.36, p<0.001), an unfavorable OS (HR = 1.52, 95% CI = 1.27–1.82, p<0.001), and a worse EFS (HR = 1.47, 95% CI = 1.24–1.74, p<0.001) compared to the negative or low level of TUBB3 expression. The statistically significant associations between TUBB3 and chemotherapy responses were also observed in the stratified subgroup analysis, which included the analysis by ethnic subgroup (Asian and Caucasian), chemotherapy regimen (taxane-based and vinorebine-based), TUBB3 detection method (IHC and PCR), and treatment strategy (surgery plus adjuvant chemotherapy and palliative chemotherapy).ConclusionsThe expression level of TUBB3 may be a useful biomarker to predict the clinical outcomes of the taxane/vinorebine-based chemotherapy in patients with NSCLC.

show abstract

“…Possible explanations for why OS could be lower in patients carrying the UGT1A1*28 allele include suboptimal treatment due to the severity of adverse effects and the decreased dose intensity resulting from frequent dose reduction or treatment delay [13], [59]. These two parameters are intrinsically correlated but not necessarily consistent with one another [61]. OS is defined as the time from randomization to death caused by any reason and represents the gold standard metric for establishing efficacy.…”

Section: Discussionmentioning

confidence: 99%

Association between UGT1A1*28 Polymorphisms and Clinical Outcomes of Irinotecan-Based Chemotherapies in Colorectal Cancer: A Meta-Analysis in Caucasians

et al. 2013

View full text Add to dashboard Cite

BackgroundWhether UGT1A1*28 genotype is associated with clinical outcomes of irinotecan (IRI)-based chemotherapy in Colorectal cancer (CRC) is an important gap in existing knowledge to inform clinical utility. Published data on the association between UGT1A1*28 gene polymorphisms and clinical outcomes of IRI-based chemotherapy in CRC were inconsistent.Methodology/Principal FindingsLiterature retrieval, trials selection and assessment, data collection, and statistical analysis were performed according to the PRISMA guidelines. Primary outcomes included therapeutic response (TR), progression-free survival (PFS) and overall survival (OS). We calculated odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI). Twelve clinical trials were included. No statistical heterogeneity was detected in analyses of all studies and for each subgroup. Differences in TR, PFS and OS for any genotype comparison, UGT1A1*28/*28 versus (vs) UGT1A1*1/*1 (homozygous model), UGT1A1*1/*28 vs UGT1A1*1/*1 (heterozygous model), and UGT1A1*28/*28 vs all others (recessive model, only for TR) were not statistically significant. IRI dose also did not impact upon TR and PFS differences between UGT1A1 genotype groups. A statistically significant increase in the hazard of death was found in Low IRI subgroup of the homozygous model (HR = 1.48, 95% CI = 1.06–2.07; P = 0.02). The UGT1A1*28 allele was associated with a trend of increase in the hazard of death in two models (homozygous model: HR = 1.22, 95% CI = 0.99–1.51; heterozygous model: HR = 1.13, 95% CI = 0.96–1.32). These latter findings were driven primarily by one single large study (Shulman et al. 2011).Conclusions/SignificanceUGT1A1*28 polymorphism cannot be considered as a reliable predictor of TR and PFS in CRC patients treated with IRI-based chemotherapy. The OS relationship with UGT1A1*28 in the patients with lower-dose IRI chemotherapy requires further validation.

show abstract

Reporting Results From Chemotherapy Trials

Cited by 55 publications

References 33 publications

Tumor Growth Rate Is an Early Indicator of Antitumor Drug Activity in Phase I Clinical Trials

Tumor Growth Rate Is an Early Indicator of Antitumor Drug Activity in Phase I Clinical Trials

The Prognostic Role of the Class III β-Tubulin in Non-Small Cell Lung Cancer (NSCLC) Patients Receiving the Taxane/Vinorebine-Based Chemotherapy: A Meta-Analysis

Association between UGT1A1*28 Polymorphisms and Clinical Outcomes of Irinotecan-Based Chemotherapies in Colorectal Cancer: A Meta-Analysis in Caucasians

Contact Info

Product

Resources

About