Docetaxel dose-intensity effect on overall survival in patients with metastatic castrate-sensitive prostate cancer

Kushnir, Igal; Mallick, Ranjeeta; Ong, Michael; Canil, Christina; Bossé, Dominick; Koczka, Kim; Reaume, N.

doi:10.1007/s00280-020-04063-7

Cited by 5 publications

(4 citation statements)

References 23 publications

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“…RDI cutoffs ranged from 63.6% [30] to 90% [27]. Kushnir et al reported significantly improved OS of patients with metastatic castrate‐sensitive prostate cancer per 10% increase in RDI of docetaxel [31]. Low RDI levels were associated with decreased OS and PFS in three studies [16, 32], whereas no significant associations between RDI and OS and/or PFS were identified in four studies [17, 19, 27, 30].…”

Section: Resultsmentioning

confidence: 99%

“…Eight studies reported median OS [16][17][18][19][20][21] and PFS [16-19, 22, 23] but not HR. RDI cutoffs ranged from 0% (vs. 100%) for 5-fluorouracil bolus [22] to 80%, 85%, or 90% in several studies describing FOLFIRI-, FOLFOX-, or FOLFIRINOX-based regimens [28][29][30][31], including one with RDI cutoff of 77% [17] and one with RDI 79% [29]. The differences in OS between RDI categories were up to approximately 14 months [16,17,18,19,29,32,33].…”

Section: Outcomes Of the Systematic Literature Reviewmentioning

confidence: 99%

“…RDI cutoffs ranged from 63.6% [30] to 90% [27]. Kushnir [31]. Low RDI levels were associated with decreased OS and PFS in three studies [16,32], whereas no significant associations between RDI and OS and/or PFS were identified in four studies [17,19,27,30].…”

Section: Outcomes Of the Systematic Literature Reviewmentioning

confidence: 99%

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Relative Dose Intensity of Chemotherapy and Survival in Patients with Advanced Stage Solid Tumor Cancer: A Systematic Review and Meta-Analysis

et al. 2021

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Background. Chemotherapy-induced toxicities lead to therapy dose reduction or delay affecting patient outcomes. This systematic review and meta-analysis evaluated the impact of relative dose intensity (RDI) on survival in adult solid-tumor cancer patients on nonadjuvant-based chemotherapy regimens. Methods. PubMed, Embase, and Web of Science databases were searched for peer-reviewed English journal articles or congress abstracts evaluating association between RDI and survival; observational studies, case series of ≥20 patients, and clinical trials published between 2013─2020 were eligible. Meta-analyses were conducted to quantify the association between RDI levels and overall survival (OS) among studies reporting a hazard ratio (HR) for OS by similar tumor types, regimens, and RDI. Forest plots represented summary HR and 95% confidence interval (CI); Cochran's Q and I 2 tests evaluated study heterogeneity.Results. Overall, 914 articles were reviewed and 37 included; seven were eligible for meta-analysis. Significantly shorter OS at RDI <80 vs ≥80% and <85% vs ≥85% was observed upon meta-analysis of four carboplatin-based studies for breast, non-small cell lung, or ovarian cancer (HR 1.17; 95% CI: 1.07-1.27), and three FOLFOX-/FOLFIRI/ FOLFIRINOX-based studies for colorectal or pancreatic cancer (HR 1.39; 95% CI: 1.03-1.89). Grade 3 or higher hematologic toxicities were higher for carboplatin-based regimens (thrombocytopenia: 14-22%; anemia: 15-19%; neutropenia: 24-58%) than FOLFOX-/FOLFIRI/FOLFIRINOX-based regimens (thrombocytopenia: 1-4%; anemia: 5-19%; neutropenia: 19-47%). Conclusion.The results suggested longer OS with RDI ≥80 or ≥85% for both regimens, indicating that management of toxicities across treatment modalities may contribute to maintenance of higher RDI and benefit survival for patients with advanced solid tumors. The Oncologist ;9999:• • Implications for Practice: Chemotherapy-induced toxicities lead to dose reduction and/or treatment delay , thus affecting patient outcomes. Results of this systematic review and meta-analysis, evaluating the impact of relative dose intensity (RDI) on survival in solid tumor cancer patients on nonadjuvant-based chemotherapy regimens, demonstrate a longer overall survival with RDI levels of at least 80% for solid tumor cancer patients on carboplatin-based and FOLFOX-/FOLFIRI/FOLFIRINOXbased chemotherapy regimens, suggesting a protective effect of maintaining RDI ≥80 or ≥85%. While grade 3 or higher hematologic toxicities occurred more in carboplatin-based studies, managing toxicities across treatment regimens may contribute to maintenance of higher RDI and ultimately benefit overall survival.

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Section: Resultsmentioning

confidence: 99%

Section: Outcomes Of the Systematic Literature Reviewmentioning

confidence: 99%

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Relative Dose Intensity of Chemotherapy and Survival in Patients with Advanced Stage Solid Tumor Cancer: A Systematic Review and Meta-Analysis

et al. 2021

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“…By 2004, a landmark series of studies showed that docetaxel-based therapy for the first time demonstrated improved survival for men with metastaticcastration-resistant prostate adenocarcinoma (17, 18, 31). Newer studies refined our knowledge and documented benefits dependent upon dose intensity (32) and that taxane analogues may prolong benefits (21). Such progress led investigators to consider moving docetaxel chemotherapy into initial treatment strategies for newly diagnosed hormone-sensitive metastatic prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Chemotherapy for the initial treatment of metastatic prostate adenocarcinoma and neuroendocrine carcinoma at diagnosis: real world application and impact in the SEER database (2004 –2018)

et al. 2023

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BackgroundRandomized controlled phase III trials have reported significant improvements in disease response and survival with the addition of chemotherapy to androgen deprivation therapy for men presenting with metastatic prostate cancer. We examined the implementation of such knowledge and its impact within the Surveillance, Epidemiology, and End Results (SEER) database.MethodThe administration of chemotherapy for men with an initial presentation of metastatic prostate cancer from 2004 to 2018 in the SEER database and its association with survival outcomes was examined. Kaplan–Meier estimates were applied to compare survival curves. Cox proportion hazard survival models were used to analyze the association of chemotherapy and other variables with both cancer- specific and overall survival.ResultA total of 727,804 patients were identified with 99.9% presenting with adenocarcinoma and 0.1% with neuroendocrine histopathology. Chemotherapy as initial treatment for men with de novo distant metastatic adenocarcinoma increased from 5.8% during 2004–2013 to 21.4% during 2014–2018. Chemotherapy was associated with a poorer prognosis during 2004–2013 but was associated with improved cancer-specific (hazard ratio (HR) = 0.85, 95% confidence interval (CI): 0.78–0.93, p=0.0004) and overall survival (HR= 0.78, 95% CI: 0.71–0.85, p < 0.0001) during 2014–2018. The improved prognosis during 2014–2018 was observed in patients with visceral or bone metastasis and most impactful for patients aged 71–80 years. These findings were confirmed by subsequent propensity score matching analyses. Furthermore, chemotherapy was consistently provided to 54% of patients with neuroendocrine carcinoma at diagnosis from 2004 to 2018. Treatment was associated with improved cancer-specific survival (HR= 0.62, 95% CI: 0.45–0.87, p=0.0055) and overall survival (HR= 0.69, 95% CI: 0.51–0. 94, p=0.0176) during 2014–2018 but not significant in earlier years.ConclusionChemotherapy at initial diagnosis was increasingly employed in men with metastatic adenocarcinoma after 2014 and consistent with the evolution of National Comprehensive Cancer Network (NCCN) guidelines. Benefits for chemotherapy are suggested after 2014 in the treatment of men with metastatic adenocarcinoma. The use of chemotherapy for neuroendocrine carcinoma at diagnosis has remained stable, and outcomes have improved in more recent years. Further development and optimization of chemotherapy continues to evolve for men with de novo diagnosis of metastatic prostate cancer.

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A sub-pharmacological test dose does not predict individual docetaxel exposure in prostate cancer patients

Heerma van Voss,

Notohardjo,

van Dodewaard-de Jong

et al. 2024

Cancer Chemother Pharmacol

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Purpose Docetaxel is a cytotoxic drug used for first-line treatment of various malignancies. It has a narrow therapeutic index and shows wide interpatient variability in clearance and toxicity. Tools for individual dose optimization are needed to maximize efficacy and avoid toxicity. Methods We performed a proof-of-concept study (EudraCT 2016-003785-77) to evaluate whether pharmacokinetics after a sub-pharmacological test dose of 1000 µg docetaxel (millidose) could be used to predict therapeutic dose exposure. Thirty prostate cancer patients eligible for treatment with docetaxel as part of routine clinical care were included. An intravenous docetaxel millidose was administered 1–7 days prior to therapeutic docetaxel. After both doses plasma docetaxel concentrations were measured by ultra- high performance liquid chromatography-tandem mass spectrometry. The docetaxel clearance was estimated with non-linear mixed effects modeling. Results Geometric mean docetaxel clearance was 57.9 L/h (GCV 78.6%) after admission of a millidose and 40.3 L/h (GCV 60.7%) after admission of a therapeutic dose. The millidose and therapeutic dose in a single patient were not significantly correlated (Spearman’s rho R = 0.02, P = 0.92). Conclusion Docetaxel pharmacokinetics at milli- and therapeutic dose level showed insufficient correlation for individual dose optimization. However, the clearance of a docetaxel millidose and full dose are within the same order of magnitude. Therefore, docetaxel millidose pharmacokinetics could potentially facilitate prediction of docetaxel pharmacokinetics at a population level in situations where therapeutic dose levels are impractical, such as pharmacokinetic drug-drug interaction studies or pediatric studies.

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Docetaxel dose-intensity effect on overall survival in patients with metastatic castrate-sensitive prostate cancer

Cited by 5 publications

References 23 publications

Relative Dose Intensity of Chemotherapy and Survival in Patients with Advanced Stage Solid Tumor Cancer: A Systematic Review and Meta-Analysis

Relative Dose Intensity of Chemotherapy and Survival in Patients with Advanced Stage Solid Tumor Cancer: A Systematic Review and Meta-Analysis

Chemotherapy for the initial treatment of metastatic prostate adenocarcinoma and neuroendocrine carcinoma at diagnosis: real world application and impact in the SEER database (2004 –2018)

A sub-pharmacological test dose does not predict individual docetaxel exposure in prostate cancer patients

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