Early mortality and overall survival in oncology phase I trial participants: can we improve patient selection?

Chau, Nicole G.; Florescu, Ana; Chan, Kelvin K.; Wang, Lisa; Chen, Eric X.; Bedard, Philippe L.; Oza, Amit M.; Siu, Lillian L.

doi:10.1186/1471-2407-11-426

Cited by 30 publications

(39 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Three patients (right three columns on Figure 5) showed best objective response of stable disease according to RECIST 1.1 guidelines during the trial period but survived only 7–10 weeks. Although a goal of the inclusion criteria was to select patients with anticipated 180 days survival, retrospective reviews of large phase I groups have demonstrated that up to 20% of patients die within the first 90 days of oncology phase I trials (Arkenau et al , 2008; Penel et al , 2010; Chau et al , 2011), as was the case with this trial.…”

Section: Resultsmentioning

confidence: 97%

A first-in-class, first-in-human, phase I trial of p28, a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in patients with advanced solid tumours

et al. 2013

View full text Add to dashboard Cite

Background:This first-in-human, phase I clinical trial of p28 (NSC745104), a 28-amino-acid fragment of the cupredoxin azurin, investigated the safety, tolerability, pharmacokinetics and preliminary activity of p28 in patients with p53+ metastatic solid tumours.Methods:A total of 15 patients were administered p28 i.v. as a short infusion three times per week for 4 weeks followed by a 2-week rest under an accelerated titration 3+3 dose escalation design until either a grade 3-related adverse event occurred or the maximum tolerated dose (MTD) was reached. Single-dose and steady-state serum pharmacokinetics were characterised. Assessments included toxicity, best objective response by RECIST 1.1 Criteria, and overall survival.Results:No patients exhibited any dose-limiting toxicities (DLTs), significant adverse events or exhibited an immune response (IgG) to the peptide. The No Observed Adverse Effect Level (NOAEL) and MTD were not reached. Seven patients demonstrated stable disease for 7–61 weeks, three a partial response for 44–125 weeks, and one a complete response for 139 weeks. Three patients are still alive at 158, 140, and 110 weeks post therapy completion.Conclusion:p28 was tolerated with no significant adverse events. An MTD was not reached. Evidence of anti-tumour activity indicates a highly favourable therapeutic index and demonstrates proof of concept for this new class of non-HDM2-mediated peptide inhibitors of p53 ubiquitination.

show abstract

Section: Resultsmentioning

confidence: 97%

A first-in-class, first-in-human, phase I trial of p28, a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in patients with advanced solid tumours

et al. 2013

View full text Add to dashboard Cite

show abstract

“…3,[27][28][29] The effectiveness of these markers of inflammation in prognostication of survival is well established across numerous malignancies in various settings. Similar to other validated prognostic scores used to assess patient suitability for phase 1 trials, such as the RMH score, the Hammersmith score, the Princes Margaret Hospital Index, and the Nijmegen score (which have been effective at predicting survival differences between high-risk and low-risk groups), we believe that NLR, MLR, or PLR could provide a more relevant patient-selection factor in this era of cancer IO.…”

Section: Discussionmentioning

confidence: 99%

“…Similar to other validated prognostic scores used to assess patient suitability for phase 1 trials, such as the RMH score, the Hammersmith score, the Princes Margaret Hospital Index, and the Nijmegen score (which have been effective at predicting survival differences between high-risk and low-risk groups), we believe that NLR, MLR, or PLR could provide a more relevant patient-selection factor in this era of cancer IO. 3,[27][28][29] The effectiveness of these markers of inflammation in prognostication of survival is well established across numerous malignancies in various settings. One potential explanation for the impact of these markers is that an increase in NLR, MLR, and PLR values on Abbreviations: CI, confidence interval; MLR, monocyte-to-lymphocyte ratio; NA, not applicable; NLR, neutrophil-to-lymphocyte ratio; OC, optimal cutoff; PLR, platelet-to-lymphocyte ratio.…”

Section: Discussionmentioning

confidence: 99%

The prognostic and predictive impact of inflammatory biomarkers in patients who have advanced‐stage cancer treated with immunotherapy

Bilen

Martini

Liu

et al. 2018

Cancer

133

View full text Add to dashboard Cite

BACKGROUND: Optimal prognostic and predictive biomarkers for patients with advanced-stage cancer patients who received immunotherapy (IO) are lacking. Inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), and the platelet-to-lymphocyte ratio (PLR), are readily available. The authors investigated the association between these markers and clinical outcomes of patients with advanced-stage cancer who received IO. METHODS: A retrospective review was conducted of 90 patients with advanced cancer who received treatment on phase 1 clinical trials of IO-based treatment regimens. NLR, MLR, and PLR values were log-transformed and treated as continuous variables for each patient. Overall survival (OS), progression-free survival (PFS), and clinical benefit were used to measure clinical outcomes. For univariate associations and multivariable analyses, Cox proportional-hazards models or logistic regression models were used. RESULTS: The median patient age was 63 years, and most were men (59%). The most common histologies were melanoma (33%) and gastrointestinal cancers (22%). High baseline NLR, MLR, and PLR values were associated significantly with worse OS and PFS (P < .05) and a lower chance of benefit (NLR and PLR; P < .05). Increased NLR, MLR, and PLR values 6 weeks after baseline were associated with shorter OS and PFS (P ≤ .052). CONCLUSIONS: Baseline and early changes in NLR, MLR, and PLR values were strongly associated with clinical outcomes in patients who received IO-based treatment regimens on phase 1 trials. Confirmation in a homogenous patient population treated on late-stage trials or outside of trial settings is warranted. These values may warrant consideration for inclusion when risk stratifying patients enrolled onto phase 1 clinical trials of IO agents. Cancer 2019;125:127-134.

show abstract

“…The OS in our group of patients who started participation was 8.18 months. Earlier reports of OS in phase‐I clinical trials showed OS rates varying between 9.9 (Arkenau et al, ) and 10.5 (Chau et al, ) months. Variations in research modalities, group size, heterogeneity of tumour types, or baseline condition may explain these variations in survival.…”

Section: Discussionmentioning

confidence: 97%

Self-reported quality of life and hope in phase-I trial participants: An observational prospective cohort study

et al. 2018

View full text Add to dashboard Cite

For advanced cancer patients deliberating early clinical trial participation, adequate information about expected effect on quality of life (HRQoL) and hope, may support decision making. The aim was to assess the potential relation of HRQoL to eligibility for phase-I trial participation, and to observe the variations in patient-reported outcomes. Patients completed questionnaires at preconsent (n = 124), baseline (n = 96), and after first evaluation of a phase-I trial (n = 76). The Mann-Whitney U test was used to test differences between eligible and ineligible patients. Univariate logistic regression was performed for eligibility. Factorial repeated-measures ANOVA compared the outcomes of patients continuing vs. stopping participation after first evaluation over time. Eligibility is associated with significant better global health OR = 0.946, 95% CI [0.918, 0.975], p = 0.001, physical functioning OR = 0.959, 95% CI [0.933, 0.985], p = 0.002, role functioning OR = 0.974, 95% CI [0.957, 0.991] and better appetite OR = 1.114 95% CI [1.035, 1.192]. HRQoL outcomes like global health, social functioning and appetite decline in all patients and differ between patients continuing or having to end participation. Over time, hope and tenacity decline in all patients and coping strategies alter in patients stopping participation. Trial participation influences patient-reported outcomes. Global health may predict for eligibility and trial continuation. Informing patients could affect patients' decision making.

show abstract

Early mortality and overall survival in oncology phase I trial participants: can we improve patient selection?

Cited by 30 publications

References 21 publications

A first-in-class, first-in-human, phase I trial of p28, a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in patients with advanced solid tumours

A first-in-class, first-in-human, phase I trial of p28, a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in patients with advanced solid tumours

The prognostic and predictive impact of inflammatory biomarkers in patients who have advanced‐stage cancer treated with immunotherapy

Self-reported quality of life and hope in phase-I trial participants: An observational prospective cohort study

Contact Info

Product

Resources

About