Dataset Information

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

ABSTRACT:

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 patients with solid tumor cancer 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 and 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 I² tests evaluated study heterogeneity.

Results

Overall, 919 articles were reviewed and 22 included; seven were eligible for meta-analysis. Significantly shorter OS at RDI <80% versus ≥80% and <85% versus ≥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-, or 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-, or 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.

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 of patients with solid tumors on nonadjuvant-based chemotherapy regimens, demonstrate a longer overall survival with RDI levels of at least 80% for patients with solid tumors on carboplatin-based and FOLFOX-, FOLFIRI-, or FOLFIRINOX-based chemotherapy regimens, suggesting a protective effect of maintaining RDI ≥80% or ≥ -85%. Although 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.

SUBMITTER: Nielson CM

PROVIDER: S-EPMC8417866 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Recently, it has been reported that the relative dose intensity (RDI) of adjuvant chemotherapy (AC) influences survival in various cancers, but there are very few reports about RDI in pancreatic ductal adenocarcinoma (PDAC). The optimal timing for initiation of AC for PDAC also remains unknown. The aim of this study was to identify the significance of RDI and the time interval between surgery and initiation of AC on survival of patients with PDAC. Clinicopathological factors that affect RDI were also investigated.A total of 311 consecutive PDAC patients who underwent curative resection between May 2005 and January 2015 were enrolled. Patients who underwent neoadjuvant chemoradiation, had UICC stage IV disease, or had early recurrences within 6 months were excluded, and the remaining 168 cases were analyzed.Patients with RDIs ≥80% (n = 79) showed significantly better overall survival (OS) compared to patients with RDIs <80% (n = 55) (median survival time (MST): 45.6 months, 26.0 months, P < 0.001). Patients with no AC (n = 34) showed the worst OS (MST: 20.8 months). Whether the AC was initiated earlier or later than 8 weeks after surgery did not influence survival, either in patients with RDIs ≥80% (P = 0.79) or in those with <80% (P = 0.73). Patients in the S-1 monotherapy group (n = 49) showed significantly better OS than patients in the gemcitabine monotherapy group (n = 51) (MST: 95.0 months, 26.0 months, respectively; P = 0.001). Univariate analysis conducted after adjusting for the chemotherapeutic drug used identified several prognostic factors; male gender (P = 0.01), intraoperative blood transfusion (P = 0.005), lymph node metastasis (P = 0.03), and postoperative WBC count (P = 0.03). Multivariate analysis identified intra-plus postoperative blood transfusion (P = 0.002) and high postoperative platelet-to-lymphocyte ratios (PLR) (P = 0.04) as independent predictors of poor RDI.Efforts to maintain RDI had a greater impact on survival than the struggle to start AC early after surgery. Intra-plus postoperative blood transfusion and a high postoperative PLR could be predictive markers of reduced RDI in AC of PDAC patients. Avoidance of perioperative blood transfusions where possible and nutritional support during the perioperative period could maintain adequate RDI and may lead to improved long-term outcome.

Project description:Background To optimize treatment, choosing the appropriate relative dose intensity (RDI) of nab-paclitaxel is an important way to improve patient tolerance, therapeutic efficacy, and survival. However, few studies have focused on the efficacy of the RDI of nab-paclitaxel in patients with advanced pancreatic cancer, and whether the RDI of nab-paclitaxel could be employed as an index for treatment remains unknown. To explore the relationship between RDI of nab-paclitaxel and chemotherapy efficacy, survival, quality of life (QoL), and adverse effects in patients with advanced pancreatic cancer. Methods In this retrospective study, a total of 32 patients with advanced pancreatic cancer, ECOG score of 0 to 2 were included from January 2017 to March 2020. The patients were treated with nab-paclitaxel combined with gemcitabine as a first-line treatment and divided into high and low RDI groups. Chemotherapy efficacy, survival, QoL, and adverse effects between two groups were compared. Results The disease control rate (DCR) was 20.0% in the low RDI group, compared with 81.8% in the high RDI group (P=0.002). A good correlation between nab-paclitaxel RDI and short-term efficacy was observed in all 32 patients (r=0.728, P<0.01). Furthermore, the high RDI group had significantly better median overall survival (mOS: 12 vs. 8 months, P=0.034) and median progression-free survival (mPFS: 5.5 vs. 3 months, P=0.052) compared to that of low RDI patients. Univariate regression analysis showed that longer overall survival was associated with lower ECOG score [hazard ratio (HR): 10.88; 95% confidence interval (CI): 2.54–46.5, P=0.001], tumors located in the body or tail of pancreases (HR: 3.82; 95% CI: 1.4–10.3, P=0.0081), and higher RDI (HR: 0.21; 95% CI: 0.071–0.6, P=0.004). The high RDI group had a significantly better physical function and emotional function improvement compared to the low RDI group (P<0.05). Moreover, high RDI did not increasing the severity and frequency of the adverse events. Conclusions It is recommended to maintain a sufficient RDI of nab-paclitaxel to ensure that the balance between lerability, therapeutic efficacy, and survival benefits is satisfied in patients with advanced pancreatic cancer.