Development and validation of a model that predicts early death among cancer patients participating in phase I clinical trials investigating cytotoxics

Penel, Nicolas; Delord, Jean‐Pierre; Bonneterre, Marie-Edith; Bachelot, Thomas; Ray‐Coquard, Isabelle; Blay, Jean‐Yves; Pascal, Laurent; Borel, Cécile; Filleron, Thomas; Adenis, Antoine; Bonneterre, Jacques

doi:10.1007/s10637-009-9224-x

Cited by 28 publications

(23 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…could modify clinical practice and thereby permit to use lymphopenia for decision making in routine practice. Currently, we plan to evaluate this prognostic factor in other solid tumors (ovarian carcinoma, lung cancer)51 and also to explore the mechanisms of such lymphopenia.…”

Section: Discussionmentioning

confidence: 99%

Lymphopenia as a Prognostic Factor for Overall Survival in Advanced Carcinomas, Sarcomas, and Lymphomas

Ray‐Coquard

Cropet²,

Glabbeke³

et al. 2009

Cancer Research

Self Cite

666

481

View full text Add to dashboard Cite

Lymphopenia is frequent in advanced cancers and predicts the toxicity of chemotherapy. Its effect on relapse and survival is uncertain. Its prognostic value for survival was analyzed in three databases of previously reported prospective multicenter studies: (a) FEC chemotherapy in metastatic breast carcinoma; (b) CYVADIC in advanced soft tissue sarcoma (European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group 62791); and (c) prospective, consecutive phase III studies of aggressive diffuse large-cell non-Hodgkin's lymphomas conducted at Centre Léon Bérard between 1987 and 1993. Univariate and multivariate analyses of prognostic factors for survival were performed. The incidence of lymphopenia of <1,000/ML before treatment was constant among the series: 25%, 24%, and 27%, respectively. Lymphopenia was significantly more frequent (P < 0.05) in metastatic breast cancer patients with performance status (PS) of >1, non-Hodgkin's lymphoma patients with international prognostic index (IPI) of > 0, and advanced soft tissue sarcoma and metastatic breast cancer patients with bone metastases. In univariate analysis, lymphopenia of <1,000/ML significantly correlated to overall survival in patients with metastatic breast cancer (median, 10 versus 14 mo; P < 0.0001), advanced soft tissue sarcoma (median, 5 versus 10 months; P < 0.01), and nonHodgkin lymphoma (median, 11 versus 94 months; P < 0.0001). In multivariate analysis (Cox model), lymphopenia was an independent prognostic factor for overall survival in metastatic breast cancer [RR (relative risk), 1.8; 95% CI (confidence interval), 1.3-2.4] along with liver metastases and PS; in advanced soft tissue sarcoma (RR, 1.46; 95% CI, 1.0-2.1) along with liver metastases, lung metastases, and PS; and in nonHodgkin's lymphoma (RR, 1.48; 95% CI, 1.03-2.1) along with IPI. Our findings show that lymphopenia is an independent prognostic factor for overall and progression-free survival in several cancers. [Cancer Res 2009;69(13):5383-91]

show abstract

Section: Discussionmentioning

confidence: 99%

Lymphopenia as a Prognostic Factor for Overall Survival in Advanced Carcinomas, Sarcomas, and Lymphomas

Ray‐Coquard

Cropet²,

Glabbeke³

et al. 2009

Cancer Research

Self Cite

666

481

View full text Add to dashboard Cite

show abstract

“…and additionally CTC count as a 4th factor (hereafter called the RMH 2010 prognostic score). In addition, we applied to our series 5 previously reported phase I prognostic scores (Supplementary Table S1): Chicago (8), Oxford (5), Lyon (4), Lille (9,24), and MD Anderson (10). We compared the RMH 2008 and RMH 2010 prognostic scores with the other scores, and evaluated their performance in predicting 90-day mortality using receiver operating characteristic (ROC) curves and comparing their areas under the curves (AUCs) using a nonparametric statistical method based on the Mann-Whitney Ustatistic (25,26).…”

Section: Translational Relevancementioning

confidence: 99%

Baseline Circulating Tumor Cell Counts Significantly Enhance a Prognostic Score for Patients Participating in Phase I Oncology Trials

Olmos

Baird

Yap

et al. 2011

Clinical Cancer Research

View full text Add to dashboard Cite

Background: High circulating tumor cell (CTC) counts are associated with poor prognosis in several cancers. Enrollment of patients on phase I oncology trials requires a careful assessment of the potential risks and benefits. Many patients enrolled on such trials using established eligibility criteria have a short life expectancy and are less likely to benefit from trial participation. We hypothesized that the incorporation of CTC counts might improve patient selection for phase I trials.Methods: This retrospective analysis evaluated patients who had baseline CTCs enumerated prior to their starting on a phase I trial. CTCs were enumerated using the CellSearch System.Results: Between January 2006 and December 2009 a total of 128 patients enrolled in phase I trials had CTC counts evaluated. Higher CTC counts as a continuous variable independently correlated with risk of death in this patient population (P ¼ 0.006). A multivariate point-based risk model was generated using CTCs as a dichotomous variable (!3 or <3), and incorporated other established prognostic factors, including albumin <35 g/L, lactate dehydrogenase greater than upper limit of normal, and >2 metastatic sites. Comparison of receiver operating characteristic curves demonstrated that the addition of baseline CTC counts improved the performance of the prospectively validated Royal Marsden Hospital phase I prognostic score, which now identifies three risk groups (P < 0.0001): good prognosis [score 0-1, median overall survival (OS) 63.7 weeks], intermediate prognosis (score 2-3, median OS 37.3 weeks), and poor prognosis (score 4, median OS 13.4 weeks).Conclusion: CTC enumeration improved the performance of a validated prognostic score to help select patients for phase I oncology trials. Clin Cancer Res; 17(15); 5188-96. Ó2011 AACR.

show abstract

“…Penel et al [9] analyzed 148 patients who were screened for phase I trial entry from 1997 to 2002 and identified albumin < 38 g/L and lymphocyte count < 700/mm 3 to be independent predictors of 90DM. The same authors validated these predictors in a cohort of 128 patients treated with cytotoxic agents from 1986 to 1993 at a separate center [5]. To date, no risk index has been prospectively validated to predict 90DM.…”

Section: Discussionmentioning

confidence: 99%

“…Retrospective reviews by large phase I groups have demonstrated that approximately 25% to 33% of patients do not meet the necessary eligibility criteria at screening [1,2]. In addition, up to 20% of patients die within the first 90 days of PIT entry [3-5]. These early deaths on study are usually attributed to disease progression, as contemporary PIT are safe with a toxic death rate of around 0.5% [3,6-9].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

View full text Add to dashboard Cite

BackgroundPatient selection for phase I trials (PIT) in oncology is challenging. A typical inclusion criterion for PIT is 'life expectancy > 3 months', however the 90 day mortality (90DM) and overall survival (OS) of patients with advanced solid malignancies are difficult to predict.MethodsWe analyzed 233 patients who were enrolled in PIT at Princess Margaret Hospital. We assessed the relationship between 17 clinical characteristics and 90DM using univariate and multivariate logistic regression analyses to create a risk score (PMHI). We also applied the Royal Marsden Hospital risk score (RMI), which consists of 3 markers (albumin < 35g/L, > 2 metastatic sites, LDH > ULN).ResultsMedian age was 57 years (range 21-88). The 90DM rate was 14%; median OS was 320 days. Predictors of 90DM were albumin < 35g/L (OR = 8.2, p = 0.01), > 2 metastatic sites (OR = 2.6, p = 0.02), and ECOG > 0 (OR = 6.3, p = 0.001); all 3 factors constitute the PMHI. To predict 90DM, the PMHI performed better than the RMI (AUC = 0.78 vs 0.69). To predict OS, the RMI performed slightly better (RMI ≥ 2, HR = 2.2, p = 0.002 vs PMHI ≥ 2, HR = 1.6, p = 0.05).ConclusionsTo predict 90DM, the PMHI is helpful. To predict OS, risk models should include ECOG > 0, > 2 metastatic sites, and LDH > ULN. Prospective validation of the PMHI is warranted.

show abstract

Development and validation of a model that predicts early death among cancer patients participating in phase I clinical trials investigating cytotoxics

Abstract: We do not recommend the enrolment of patients with albumin level below 38g/l and lymphocytes count below 700/mm(3), in phase 1 trial investigating cytotoxics. Our model is helpful to discriminate "patients with reasonable life expectancy" as defined in most phase 1 protocols.

Cited by 28 publications

References 35 publications

Lymphopenia as a Prognostic Factor for Overall Survival in Advanced Carcinomas, Sarcomas, and Lymphomas

Lymphopenia as a Prognostic Factor for Overall Survival in Advanced Carcinomas, Sarcomas, and Lymphomas

Baseline Circulating Tumor Cell Counts Significantly Enhance a Prognostic Score for Patients Participating in Phase I Oncology Trials

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

Contact Info

Product

Resources

About