Dose-dense Cisplatin Research Articles

Comparison of outcomes and side effects for neoadjuvant chemotherapy with weekly cisplatin and paclitaxel followed by chemoradiation vs. chemoradiation alone in stage IIB\u2013IVA cervical cancer: study protocol for a randomized controlled trial

BackgroundCurrently, the standard treatment for locally advanced cervical cancer is concurrent chemoradiation (CCRT). The effect of neoadjuvant chemotherapy in advanced cervical cancer is controversial. Studies have shown that the addition of a weekly regimen of neoadjuvant chemotherapy (NACT) followed by CCRT may be superior to a thrice-weekly regimen of NACT and CCRT. Among patients who had not received prior cisplatin, a cisplatin and paclitaxel (TP) regimen resulted in longer overall survival than other regimens. This study aims to investigate the feasibility, safety, and efficacy of NACT with weekly TP followed by CCRT.MethodsThis is a prospective, randomized, open-labeled, multicentered phase III study. Based on a 65% of 2-year disease-free survival (DFS) rate in the CCRT group and 80% of that in NACT followed by CCRT group, and on prerequisite conditions including an 8% loss to follow-up, a two-sided 5% of type I error probability, and an 80% of power, a total of 300 cases were required for enrollment. Patients with IIB–IVA cervical cancer will be randomly allocated in a 1:1 ratio to one of two intervention arms. In the study arm, patients will receive dose-dense cisplatin (40 mg/m2) and paclitaxel (60 mg/m2) weekly for 4 cycles followed by CCRT (45 Gy in 5 weeks concurrent with cisplatin 40 mg/m2 weekly) plus image-guided adaptive brachytherapy (IGBRT). In the control arm, patients will undergo CCRT treatment. The primary endpoint of the study is 2-year disease-free survival (DFS); the secondary endpoints are 5-year overall survival (OS) and disease-free survival (DFS), the response rate 3 months after treatment completion, grade III/IV adverse effects, and quality of life, and potential biomarkers for predicting treatment response will also be studied.DiscussionThe data gathered from the study will be used to determine whether NACT with weekly TP followed by CCRT may become an optimized treatment for locally advanced cervical cancer.Trial registrationChinese Clinical Trial Registry ChiCTR1900025327. Registered on 24 August 2019. medresman.org.cn ChiCTR1900025326

Dose-Dense Cisplatin-Based Neoadjuvant Chemotherapy Increases Survival in Advanced Cervical Cancer: A Meta-Analysis

Background: The benefit of neoadjuvant chemotherapy remains unclear for the treatment of locally-advanced cervical cancer. With this meta-analysis, we set out to demonstrate the benefit of using dose-dense cisplatin-based neoadjuvant chemotherapy in terms of overall survival. Methods: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) method was applied for this meta-analysis (PROSPERO study’s registration number CRD42021245170). We searched through MEDLINE and Cochrane library databases up to December 2020 to identify randomized clinical trials. Randomized clinical trials were eligible if they intended to compare the survival benefit of using cisplatin-based neoadjuvant chemotherapy followed by local treatment versus local treatment alone for the treatment of locally-advanced cervical cancer. The primary outcome was overall survival as the time interval between the date of randomization and the date of death from any cause or the last follow-up. We used the risk-ratios (RRs) and their 95% Confidence Interval (95%CI) for the effects of neoadjuvant chemotherapy on overall survival and subgroup interactions in a forest plot using fixed or random effect. Findings: Twenty eligible randomized clinical trials were retrieved between 1991 and 2019, corresponding to 3,125 women with FIGO stages IB2-IVA cervical cancer. Median follow-up ranged from 16 to 108 months, 1584 patients were randomly assigned to receive neoadjuvant chemotherapy followed by local treatment and 1541 patients to local treatment alone. More than 50% of the randomized clinical trials were assessed as low risk of bias. There was no benefit of neoadjuvant chemotherapy in overall survival, but with significant heterogeneity across studies (I2= 49%, P < 0.01). In contrast, dose-dense cisplatin ≥ 72.5 mg/m2/3-weeks was significantly associated with increased overall survival (RR for fixed effect = 0.84, 95% CI = 0.76-0.93) with no heterogeneity across the pooled studies (I2= 39%, P= 0.10). The survival benefit was even greater when cisplatin was administered at a dose over 105 mg/m2/3-weeks (RR = 0.75, 95% CI =0.65-0.87). Interpretation This meta-analysis demonstrated the survival benefit of using dose-dense cisplatin-based neoadjuvant chemotherapy for the treatment of women with locally-advanced cervical cancer, and thus opens perspectives for designing new clinical trials in this setting. Funding: INSERM, University of Paris Declaration of Interest: These authors have no conflict of interest to report.

Dose-dense cisplatin with gemcitabine for relapsed platinum-resistant ovarian cancer.

Standard of care treatment for women who develop relapsed ovarian cancer includes sequential platinum- and/or paclitaxel-based chemotherapy, with reducing disease-free intervals. Once platinum resistance develops, treatment options become limited and dose-dense regimens may be offered. We report the efficacy and safety of dose-dense cisplatin with gemcitabine chemotherapy for relapsed platinum-resistant ovarian cancer. A retrospective analysis of all patients with relapsed, platinum-resistant ovarian, primary peritoneal or fallopian tube cancer treated with cisplatin 35 mg/m2 of body surface area by intravenous infusion with gemcitabine 1000 mg/m2 of body surface area by intravenous infusion on days 1 and 8 of every 21-day treatment cycle between 1 January 2009 and 1 June 2017. Ninety-four eligible patients had received a median of three (range one-eight) prior lines of cytotoxic therapy for relapsed ovarian cancer. Sixty patients (64%) had received ≥ 1 prior dose-dense chemotherapy regimen. Dose-dense cisplatin with gemcitabine was associated with a median progression-free survival (PFS) of 4.4 months (95% CI 3.6 to 5.3) and overall survival of 7.6 months (95% CI 5.6 to 9.6). The median PFS for dose-dense cisplatin with gemcitabine as first- (n = 34), second- (n = 42), and third-line or later (n = 18) dose-dense therapy was 4.2 (95% CI 3.2 to 5.2), 5.0 (95% CI 3.5 to 6.5), and 4.2 (95% CI 3.3 to 5.1) months respectively. The RECIST objective response rate for first-, second-, and third-line dose-dense cisplatin with gemcitabine was 23%, 14 %, and 7 % respectively. The most common grade 3 - 4 adverse events were thrombocytopenia (20%), anemia (18%), and neutropenia (14%). Dose-dense cisplatin with gemcitabine provides modest efficacy whether it is used as a first- or subsequent line of dose-dense chemotherapy to treat relapsed platinum-resistant ovarian cancer and the toxicity is manageable with supportive measures.

P2.07-046 Nivolumab Exerts Remarkable Antitumor Activity in NSCLC After an Immune-Modulating Biochemotherapy Regimen

Dose-dense cisplatin and daily oral etoposide +/- bevacizumab, mAb to the vascular endothelial-growth factor is a safe and active treatment for un-resectable NSCLC patients. It elicited remarkable Immunological effects, including rise in central-memory-T-cells and activated-dendritic cells and decline in regulatory-T-cells, potentially additive to anti-PD-1/PDL-1 immune-checkpoint inhibition. We therefore, performed a retrospective analysis aimed to evaluate both overall survival (OS) and progression free survival (PFS) in patients receiving treatment with Nivolumab, a mAb to PD-1, after they had received different first line chemotherapy regimens.