Relative dose intensity as a proxy measure of quality and prognosis in adjuvant chemotherapy for breast cancer in daily clinical practice

Schraa, Suzanna J.; Frerichs, Kirsten; Agterof, Mariette J; Hunting, Jarmo C B; Los, Maartje; Jong, P.C. de

doi:10.1016/j.ejca.2017.04.001

Cited by 20 publications

(17 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Results of retrospective analysis evaluating the effect of chemotherapy dose reduction have been mixed due to a heterogeneity in regimen selection, lack of adjustment for confounding variables, and inadequate follow-up to determine effect. 18,19 Evaluation of docetaxel dose reductions have also yielded conflicting results. 20,21 Currently, a paucity of data exists for dose adjustments affecting survival for third-generation anthracycline/taxane-based regimens.…”

Section: Introductionmentioning

confidence: 99%

Impact of Cumulative Chemotherapy Dose on Survival With Adjuvant FEC-D Chemotherapy for Breast Cancer

Veitch

Khan

Tilley

et al. 2019

Journal of the National Comprehensive Cancer Network

View full text Add to dashboard Cite

Background: Reductions in adjuvant chemotherapy dose <85% for historical regimens (ie, cyclophosphamide/methotrexate/fluorouracil) are known to affect breast cancer survival. This threshold, in addition to early versus late dose reductions, are poorly defined for third-generation anthracycline/taxane-based chemotherapy. In patients with breast cancer receiving adjuvant 5-fluorouracil/epirubicin/cyclophosphamide followed by docetaxel (FEC-D), we evaluated the impact of chemotherapy total cumulative dose (TCD), and early (FEC) versus late (D only) dose reductions, on survival outcomes. Patients and Methods: Women with stage I–III, hormone receptor–positive/negative, HER2-negative breast cancer treated with adjuvant FEC-D chemotherapy from 2007 through 2014 in Alberta, Canada, were included. TCD for cycles 1 to 6 of <85% or ≥85% was calculated. Average cumulative dose was also calculated for early (cycles 1–3) and late (cycles 4–6) chemotherapy. Survival outcomes (disease-free survival [DFS] and overall survival [OS]) were estimated using Kaplan-Meier and multivariate analysis. Cohorts were evaluated for uniformity. Results: Characteristics were reasonably balanced for all cohorts. Overall, 1,302 patients were evaluated for dose reductions, with 16% being reduced <85% (n=202) relative to ≥85% (n=1,100; 84%). Patients who received TCD ≥85% relative to <85% had superior 5-year DFS (P=.025) and OS (P<.001) according to Kaplan-Meier analysis, which remained significant on univariate and multivariate analyses. In stratified late and early dose reduction cohorts, DFS and OS showed a significant inferior survival trend for dose reduction early in treatment administration in 5-year Kaplan-Meier (P=.002 and P<.001, respectively) and multivariate analyses (hazard ratio [HR], 1.46; P=.073, and HR, 1.77; P=.011, respectively). Dose delays of <14 or ≥14 days and granulocyte colony-stimulating factor use did not affect outcomes. Conclusions: Chemotherapy TCD <85% for adjuvant FEC-D affects breast cancer survival. Late reductions (D only) were not shown to adversely affect DFS or OS. Conversely, early reductions (FEC±D) negatively affected patient outcomes.

show abstract

Section: Introductionmentioning

confidence: 99%

Impact of Cumulative Chemotherapy Dose on Survival With Adjuvant FEC-D Chemotherapy for Breast Cancer

Veitch

Khan

Tilley

et al. 2019

Journal of the National Comprehensive Cancer Network

View full text Add to dashboard Cite

show abstract

“…The practicality of relative dose intensity (RDI), calculated as the percentage of the delivered DI divided by the standard DI, has been shown to be an indicator of the treatment intensity of anticancer drugs [7]. The correlations between RDI and therapeutic efficacy were reported in various types of cancers, including breast cancer [8], pancreatic ductal adenocarcinoma [9], renal cell carcinoma [10], malignant lymphoma [11], and HCC [12]. However, since lenvatinib is the first oral MTA that is dosed by the patient's weight (8 mg once a day for patients weighing <60 kg or 12 mg once a day for those weighing ≥60 kg), RDI may not accurately reflect the actual treatment intensity, as is demonstrated in the following examples.Case 1: A 170 cm tall patient weighing 60 kg.…”

mentioning

confidence: 99%

Dose Intensity/Body Surface Area Ratio is a Novel Marker Useful for Predicting Response to Lenvatinib against Hepatocellular Carcinoma

Eso

Nakano

Mishima

et al. 2019

Cancers

View full text Add to dashboard Cite

Lenvatinib was recently approved as a novel first-line molecular targeted agent (MTA) for treating hepatocellular carcinoma (HCC). The importance of relative dose intensity (RDI) has been shown in the treatment of various types of cancers. However, RDI may not accurately reflect the treatment intensity of lenvatinib, as it is the first oral MTA where the dose is based on the patient's weight. We aimed to evaluate the utility of 2M-DBR (the delivered dose intensity/body surface area ratio at 60 days) by comparing the relationship between 2M-DBR, 2M-RDI (RDI at 60 days), and the therapeutic response. The therapeutic response to lenvatinib was evaluated in 45 patients who underwent computed tomography 8-12 weeks after treatment initiation. We also investigated the clinical factors associated with high 2M-DBR. The area under the receiver operating characteristic of 2M-DBR that predicts the response to lenvatinib was higher than that of 2M-RDI (0.8004 vs. 0.7778). Patients with high 2M-DBR achieved significantly better objective responses and disease control rates than those with low 2M-DBR (p < 0.0001 and 0.0008). Patients with high 2M-DBR experienced significantly longer progression-free survival (PFS) than those with low 2M-DBR (p = 0.0001), while there was no significant correlation between 2M-RDI levels and PFS (p = 0.2198). Patients who achieved higher levels of 2M-DBR had a significantly better modified ALBI grade (p = 0.0437), better CONUT score (p = 0.0222), and higher BTR (p = 0.0281). Multivariate analysis revealed that high 2M-DBR was the only significant factor associated with longer PFS. In conclusion, 2M-DBR could be an important factor that reflects treatment intensity and useful for predicting the response to lenvatinib against HCC, instead of 2M-RDI.Cancers 2020, 12, 49 2 of 12 based on the two Phase III studies [4,5]. However, due to its various adverse events (AEs) and limited efficacy, identification of novel MTA compounds has been required. Recently, lenvatinib (Lenvima ® , Eisai Co., Ltd., Tokyo, Japan) was approved as a novel first-line MTA for unresectable HCC in the EU, USA, and Asia, including Japan, China, Korea, and Taiwan, based on the Phase III REFLECT trial [6].In order to optimize and maximize the therapeutic effects of pharmacotherapy, especially in the case of anticancer drug treatment, it is essential to appropriately evaluate the patient's condition before administration, sufficiently manage AEs after initiation, and keep the dose intensity (DI) high. The practicality of relative dose intensity (RDI), calculated as the percentage of the delivered DI divided by the standard DI, has been shown to be an indicator of the treatment intensity of anticancer drugs [7]. The correlations between RDI and therapeutic efficacy were reported in various types of cancers, including breast cancer [8], pancreatic ductal adenocarcinoma [9], renal cell carcinoma [10], malignant lymphoma [11], and HCC [12]. However, since lenvatinib is the first oral MTA that is dosed by the patient's weight (8 mg once...

show abstract

“…Docetaxel trihydrate (DCT) is a second generation taxane derived from a compound found in the European yew tree Taxus baccata [31]. The drug is practically insoluble in water and is being currently used in chemotherapy of gastro/esophageal [32,33,34,35,36] and breast [37,38,39,40] cancers. It binds precisely to the β-tubulin subunit of microtubules and antagonizes the disassembly of this key cytoskeletal protein, with the result that bundles of microtubules and aberrant structures, derived from the microtubules, appear in the mitotic phase of the cell cycle.…”

Section: Introductionmentioning

confidence: 99%

Transferrin-Conjugated Docetaxel–PLGA Nanoparticles for Tumor Targeting: Influence on MCF-7 Cell Cycle

Jose

Cinu²,

Sebastian

et al. 2019

Polymers

View full text Add to dashboard Cite

Targeted drug delivery systems are commonly used to improve the therapeutic index of anti-cancer drugs by increasing their selectivity and reducing systemic distribution and toxicity. Ligand-conjugated nanoparticles (NPs) can be effectively applied for active chemotherapeutic targeting to overexpressed receptors of tumor cells. In this study, transferrin (Tf) was successfully conjugated with poly-l-lactic-co-glycolic acid (PLGA) using ethylene diamine confirmed by NMR, for the loading of docetaxel trihydrate (DCT) into PLGA nanoparticles (NPs). The DCT-loaded Tf-conjugated PLGA NPs were produced by an emulsion-solvent evaporation technique, and a 32 full factorial design was used to optimize the nanoparticle formulations. The DCT-loaded Tf-conjugated PLGA NPs were characterized by FTIR spectroscopy, differential scanning calorimetry, powder X-ray diffraction (PXRD), TEM, particle size, and zeta potential analysis. In vitro release kinetics confirmed that release of DCT from the designed formulations followed a zero-order kinetics and a diffusion controlled non-Fickian release profile. The DCT-loaded Tf-conjugated PLGA NPs were evaluated in vitro in MCF-7 cells for bioactivity assessment. Cytotoxicity studies confirmed that the Tf-conjugated PLGA NPs were more active than the non-conjugated counterparts. Cell uptake studies re-confirmed the ligand-mediated active targeting of the formulated NPs. From the cell cycle analysis, the anti-cancer activity of DCT-loaded Tf-conjugated PLGA NPs was shown to occur by arresting the G2/M phase.

show abstract

Relative dose intensity as a proxy measure of quality and prognosis in adjuvant chemotherapy for breast cancer in daily clinical practice

Cited by 20 publications

References 9 publications

Impact of Cumulative Chemotherapy Dose on Survival With Adjuvant FEC-D Chemotherapy for Breast Cancer

Impact of Cumulative Chemotherapy Dose on Survival With Adjuvant FEC-D Chemotherapy for Breast Cancer

Dose Intensity/Body Surface Area Ratio is a Novel Marker Useful for Predicting Response to Lenvatinib against Hepatocellular Carcinoma

Transferrin-Conjugated Docetaxel–PLGA Nanoparticles for Tumor Targeting: Influence on MCF-7 Cell Cycle

Contact Info

Product

Resources

About