Cost-effectiveness of sacituzumab govitecan versus single-agent chemotherapy for metastatic triple-negative breast cancer: a trial-based analysis.

BACKGROUND: Sacituzumab govitecan (SG) has recently been approved in China for the post-line treatment of metastatic triple-negative breast cancer (mTNBC). SG substantially improves progression-free survival and overall survival compared with single-agent chemotherapy for pretreated mTNBC. However, in view of the high price of SG, it is necessary to consider its value in terms of costs and outcomes. This study aimed to estimate the cost-effectiveness of SG versus single-agent treatment of physician's choice (TPC) in the post-line setting for patients with mTNBC from a Chinese healthcare system perspective. METHODS: The cohort characteristics were sourced from the ASCENT randomized clinical trial, which enrolled 468 heavily pretreated patients with mTNBC between November 2017 and September 2019. A partitioned survival model was constructed to assess the long-term costs and effectiveness of SG versus TPC in the post-line treatment of mTNBC. Quality-adjusted life-months (QALMs) and total costs in 2022 US dollars were used to derive incremental cost effectiveness ratio (ICER). QALMs and costs were discounted at 5% annually. The willingness-to-pay (WTP) threshold was defined as $3188 per QALM, three times China's average monthly per capita gross domestic product in 2022. One-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analyses were performed to estimate the robustness of the results. RESULTS: Treatment with SG yielded an incremental 5.17 QALMs at a cost of $44,792 per QALM, much above the WTP threshold of $3188/QALM in China. One-way sensitivity analysis showed that SG price was a crucial factor in the ICER. Probabilistic sensitivity analysis revealed that the cost-effective acceptability of SG was 0% in the current setting. Scenario analyses indicated that the result was robust in all subgroups in ASCENT or under different time horizons. Furthermore, SG must reduce the price to enter the Chinese mainland market. When the monthly cost of SG reduce to $2298, SG has about 50% probability to be a preferred choice than TPC. CONCLUSIONS: SG was estimated to be not cost-effective compared with TPC for post-line treatment for mTNBC in China by the current price in HK under a WTP threshold of $3188 per QALM. A drastic price reduction is necessary to improve its cost-effectiveness.

Clinical benefit of platinum doublet combination therapy in older adults with advanced non-small cell lung cancer: A prospective multicenter study by the National Hospital Organization in Japan.

BACKGROUND: Previous trials suggest that older adults with non-small cell lung cancer (NSCLC) derive benefit from platinum doublet combination therapy, but its superiority is controversial. Although geriatric assessment variables are used to assess the individual risk of severe toxicity and clinical outcomes in older patients, the standard first-line treatment is still debated. Therefore, we aimed to identify the risk factors for clinical outcomes in older patients with NSCLC. METHODS: Patients aged ≥75 years with advanced NSCLC treated at any of 24 National Hospital Organization institutions completed a pre-first-line chemotherapy assessment, including patient characteristics, treatment variables, laboratory test values, and geriatric assessment variables. We evaluated whether these variables were the risk factors for progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 148 patients with advanced NSCLC were treated with combination therapy (n = 90) or monotherapy (n = 58). Median PFS was 5.3 months and OS was 13.6 months. We identified that hypoalbuminemia (hazard ratio [HR] 2.570, 95% confidence interval [CI]: 1.117-5.913, p = 0.0264) was a risk factor for PFS and monotherapy (HR 1.590, 95% CI: 1.070-2.361, p = 0.0217), lactate dehydrogenase (HR 3.682, 95% CI: 1.013-13.39, p = 0.0478), and high C-reactive protein (HR 2.038, 95% CI: 1.141-3.642, p = 0.0161) were risk factors for OS. The median OS was significantly longer in patients treated with combination therapy than in those who received monotherapy (16.5 months vs. 10.3 months; HR 0.684, 95% CI: 0.470-0.995, p = 0.0453). DISCUSSION: Platinum doublet combination therapy may be beneficial in older patients with NSCLC. Identification of risk factors will assist in the development of a personalized treatment strategy.

Resistance to single-agent chemotherapy in low-risk gestational trophoblastic neoplasia.

Background: Methotrexate (MTX) and actinomycin D (ActD) have been used as first-line chemotherapy agents in the treatment of low-risk gestational trophoblastic neoplasia (GTN). Although low-risk GTN is considered a curable disease, its reported primary remission rates of 49 to 93% reflect the difficulties of treatment and different factors influencing it. Hence, this study aimed to determine the remission rates and related factors of single-agent chemotherapy resistance in low-risk GTN patients. Methods: This retrospective study included patients with diagnosed low-risk GTN who received either MTX once a week (IM, 30mg/m2) or ActD once every two weeks (pulsed IV, 1.25mg/m2). Then, the patients were followed-up until complete remission or single-agent treatment failure to assess resistance rate and related factors. Results: Eighty-four patients were included in the study (18 patients were receiving MTX and 66 patients were receiving ActD). 85.7% of all participants achieved complete remission after first-line chemotherapy (72.2% in MTX vs 89.4% in ActD). There was a significant association for higher tumor size (P=0.046), the occurrence of metastasis (P=0.019), and pretreatment ß-HCG levels (P=0.005) with resistance to treatment. Conclusion: This study demonstrated higher tumor size, the occurrence of metastasis, and pretreatment ß-HCG levels have been associated with increased resistance to first-line chemotherapy agents.

Single-agent chemotherapy in low-risk gestational trophoblastic neoplasia.

Background: Low-risk gestational trophoblastic neoplasia could be cured in the case of appropriate management with single-agent chemotherapy. This study was carried out to compare the efficacy of single-dose methotrexate versus Actinomycin-D in low-risk gestational trophoblastic neoplasia to analyze the most effective agent. Methods: This retrospective cohort study was conducted on the medical record of 170 cases with the diagnosis of low-risk gestational trophoblastic neoplasia from 2012 to 2019 to evaluate the response rate of single-dose weekly-methotrexate versus biweekly-Actinomycin-D. Results: Single agent chemotherapy was required in 170 patients with final risk score of less than 7. Among the 100 cases under weekly-methotrexate therapy, 29 patients were required second-line chemotherapy with Actinomycin-D and combination therapy which means complete remission of 71% with methotrexate, in comparison with 78.5% in the other group. Resistance was mostly seen in patients with documented choriocarcinoma in histology who had not received timely diagnosis and treatment. Conclusion: Individualized decision in the management of low-risk gestational trophoblastic neoplasia cases, based on histology, HCG, and history is the corn stone in successful treatment.

Selection Criteria and Treatment Outcome for Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Unfit for Platinum-Based First-Line Therapy: Results of the MOON-OSS Observational Trial.

Limited evidence is available concerning the selection criteria and the outcomes of platinum unfit newly diagnosed advanced NSCLC patients receiving single-agent chemotherapy. We retrospectively collected data on consecutive, stage IIIB-IV, EGFR/ALK negative and PD-L1 < 50% NSCLC patients treated with first-line single agent chemotherapy. Baseline characteristics, outcome measures and toxicities were recorded, as well as criteria according to which treatment selection was made and what percentage of patients did not receive a first-line platinum-based chemotherapy. Two-hundred and twenty-one patients were included. Median age was 79 (range 56−92) years, M/F 165(74.6%)/56(25.4%), ECOG performance status (PS) 0/1/ ≥ 2 23(10.9%)/94(42.5%)/103(46.6%), with a median of two serious comorbidities. A median of 25% (range 10%-30%) of newly diagnosed NSCLC did not receive a first-line platinum combination. Clinical criteria according to which decision was made were older age (76.5%), comorbidities (72%), poor PS (55.2%) and familiar or social issues (10%). Single-agent treatment consisted of oral metronomic vinorelbine (MetV 78.6%), gemcitabine (Gem 10%), oral standard vinorelbine (Vin 8.2%) and other (O 3.2%). Median progression-free survival (PFS) and overall survival (OS) of single agent treatments ranged from 4.5 to 5 months and from 9 to 10.5 months, respectively. All grade toxicities did not differ among single agents, while grade 3−4 toxicities were less frequent with MetV. Up to 30% of newly diagnosed advanced EGFR/ALK negative and PD-L1 < 50% NSCLC patients do not receive a first-line platinum doublet. Main clinical selection criteria were older age (>70 years), comorbidities and poor PS. An oral treatment was frequently proposed with MetV being the most frequent choice according to its safety profile.

Monotherapy for low-risk gestational trophoblastic neoplasia with score 5-6.

Objective: To investigate the monotherapy for gestational trophoblastic neoplasia (GTN) patients with FIGO/WHO prognostic score of 5-6. Methods: The low-risk GTN patients from 2012 to 2019 were enrolled. The study is a retrospective report to analyze the efficacy and safety of single-agent chemotherapy and combination chemotherapy in patients with a high FIGO/WHO prognostic score of 5-6. Results: 75 cases (33.5%) were included. Complete remission was in all patients. Among the 29 cases taking single-agent chemotherapy, 22 cases (75.9%) developed drug resistance. Among the 46 cases taking combination chemotherapy, 7 patients (15.2%) developed drug resistance. There was a statistically significant difference in the drug resistance rate between these two subgroups (P < 0.05), but there was not statistically significant difference in the total number of chemotherapy courses (<2mIU/ml) (P < 0.05). Conclusion: Monotherapy showed remarkable advantages in GTN patients with FIGO/WHO prognostic score of 5-6.

Evaluation and simplification of risk factors in FIGO 2000 scoring system for gestational trophoblastic neoplasia: a 19-year retrospective analysis.

OBJECTIVES: The International Federation of Gynecology and Obstetrics (FIGO) 2000 scoring system classifies gestational trophoblastic neoplasia (GTN) patients into low- and high-risk groups, so that single- or multi-agent chemotherapy can be administered accordingly. However, a number of FIGO-defined low-risk patients still exhibit resistance to single-agent regimens, and the risk factors currently adopted in the FIGO scoring system possess inequable values for predicting single-agent chemoresistance. The purpose of this study is therefore to evaluate the efficacy of risk factors in predicting single-agent chemoresistance and explore the feasibility of simplifying the FIGO 2000 scoring system for GTN. METHODS: The clinical data of 578 GTN patients who received chemotherapy between January 2000 and December 2018 were retrospectively reviewed. Univariate and multivariate logistic regression analyses were carried out to identify risk factors associated with single-agent chemoresistance in low-risk GTN patients. Then, simplified models were built and compared with the original FIGO 2000 scoring system. RESULTS: Among the eight FIGO risk factors, the univariate and multivariate analyses identified that pretreatment serum human chorionic gonadotropin (hCG) level and interval from antecedent pregnancy were consistently independent predictors for both first-line and subsequent single-agent chemoresistance. The simplified model with two independent factors showed a better performance in predicting single-agent chemoresistance than the model with the other four non-independent factors. However, the addition of other co-factors did improve the efficiency. Overall, simplified models can achieve favorable performance, but the original FIGO 2000 prognostic system still features the highest discrimination. CONCLUSIONS: Pretreatment serum hCG level and interval from antecedent pregnancy were independent predictors for both first-line and subsequent single-agent chemoresistance, and they had greater weight than other non-independent factors in predicting single-agent chemoresistance. The simplified model composed of certain selected factors is a promising alternative to the original FIGO 2000 prognostic system, and it shows comparable performance.

Efficacy of platinum agents for stage III non-small-cell lung cancer following platinum-based chemoradiotherapy: a retrospective study.

BACKGROUND: Platinum-based chemoradiotherapy is the standard treatment for unresectable stage III non-small-cell lung cancer (NSCLC). However, few studies have evaluated the efficacy of subsequent chemotherapy for relapsed NSCLC following platinum-based chemoradiotherapy. This study aimed to evaluate the efficacy of platinum-doublet chemotherapy as a second-line treatment for patients with unresectable stage III NSCLC. METHODS: We retrospectively evaluated patients with unresectable stage III NSCLC treated with cytotoxic chemotherapy following platinum-based chemoradiotherapy who were registered in a nationwide registry NSCLC database. Patients were divided into the platinum-doublet chemotherapy (platinum) group and single-agent chemotherapy (non-platinum) group based on the type of second-line chemotherapy. RESULTS: The platinum group (n = 119) showed significantly better overall survival (OS) than the non-platinum group (n = 201) (median OS: 21.5 vs. 10.5 months, hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.40-0.73, p < 0.001). OS from the beginning of chemoradiotherapy was also significantly better in the platinum group than in the non-platinum group (median OS: 34.9 vs. 21.8 months, HR: 0.58, 95% CI: 0.43-0.79, p = 0.001). In the multivariate analysis, platinum-doublet chemotherapy as second-line therapy, female sex, clinical stage IIIA, and duration of ≥ 8.6 months from the beginning of first-line therapy to the beginning of second-line therapy were associated with significantly better OS. CONCLUSION: Platinum-doublet chemotherapy as a second-line therapy may prolong survival in unresectable stage III NSCLC patients following platinum-based chemoradiotherapy. Thus, re-administration of platinum agents may be a promising treatment for unresectable stage III NSCLC treated with platinum-based chemoradiotherapy.

Evaluation and simplification of risk factors in FIGO 2000 scoring system for gestational trophoblastic neoplasia: a 19-year retrospective analysis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVES@#The International Federation of Gynecology and Obstetrics (FIGO) 2000 scoring system classifies gestational trophoblastic neoplasia (GTN) patients into low- and high-risk groups, so that single- or multi-agent chemotherapy can be administered accordingly. However, a number of FIGO-defined low-risk patients still exhibit resistance to single-agent regimens, and the risk factors currently adopted in the FIGO scoring system possess inequable values for predicting single-agent chemoresistance. The purpose of this study is therefore to evaluate the efficacy of risk factors in predicting single-agent chemoresistance and explore the feasibility of simplifying the FIGO 2000 scoring system for GTN.@*METHODS@#The clinical data of 578 GTN patients who received chemotherapy between January 2000 and December 2018 were retrospectively reviewed. Univariate and multivariate logistic regression analyses were carried out to identify risk factors associated with single-agent chemoresistance in low-risk GTN patients. Then, simplified models were built and compared with the original FIGO 2000 scoring system.@*RESULTS@#Among the eight FIGO risk factors, the univariate and multivariate analyses identified that pretreatment serum human chorionic gonadotropin (hCG) level and interval from antecedent pregnancy were consistently independent predictors for both first-line and subsequent single-agent chemoresistance. The simplified model with two independent factors showed a better performance in predicting single-agent chemoresistance than the model with the other four non-independent factors. However, the addition of other co-factors did improve the efficiency. Overall, simplified models can achieve favorable performance, but the original FIGO 2000 prognostic system still features the highest discrimination.@*CONCLUSIONS@#Pretreatment serum hCG level and interval from antecedent pregnancy were independent predictors for both first-line and subsequent single-agent chemoresistance, and they had greater weight than other non-independent factors in predicting single-agent chemoresistance. The simplified model composed of certain selected factors is a promising alternative to the original FIGO 2000 prognostic system, and it shows comparable performance.

Immune Checkpoint Inhibitors Plus Single-Agent Chemotherapy for Advanced Non-Small-Cell Lung Cancer After Resistance to EGFR-TKI.

PURPOSE: Platinum-based chemotherapy remains the classic treatment option for patients with advanced non-small-cell lung cancer (NSCLC) who progress while receiving treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). In this study, we analyzed real-world outcomes of treatment with immune checkpoint inhibitors (ICIs) combined with platinum-free chemotherapy in patients with NSCLC after developing resistance to EGFR-TKIs. METHODS: This retrospective study included patients with mutation-positive NSCLC after developing resistance to EGFR-TKIs. Patients who received chemotherapy alone plus ICIs with or without anti-angiogenic drugs (cohort A) or platinum-based chemotherapy (cohort B) between February 2019 and August 2020 were enrolled. Clinical characteristics, EGFR mutation status, response to therapy, and adverse events (AEs) were retrospectively analyzed. RESULTS: Seventeen patients were eligible and included in the analysis, including 8 in cohort A and 9 in cohort B. After a median follow-up of 7.6 months, the median progression-free survival was 6.5 months [95% confidence interval (CI), 6.1 to 7.0] in cohort A and 3.6 months (95% CI, 1.3-5.8) in cohort B (hazard ratios, 0.22; 95% CI, 0.05-0.93; P = 0.039). The overall response and disease control rates were 50% and 100% in cohort A, and 22% and 89% in cohort B, respectively. Adverse events of grade 3 or higher occurred in 25% of the patients in cohort A and in 33.3% of the patients in cohort B. CONCLUSION: ICIs plus platinum-free, single-agent chemotherapy provides promising progression-free survival and overall response rate benefit, along with a low rate of severe AEs in patients with EGFR-TKI-resistant advanced NSCLC.

Personalizing First-Line Systemic Therapy in Metastatic Colorectal Cancer: Is There a Role for Initial Low-Intensity Therapy in 2021 and Beyond? A Perspective From Members of the Australasian Gastrointestinal Trials Group.

Palliative chemotherapy is the cornerstone of treatment for the majority of patients with metastatic colorectal cancer, with the aim of increasing length and quality of life. Although guidelines outline the available treatment options in the first line, they provide limited guidance on choice and intensity of the chemotherapy backbone. Data from the TRIBE and TRIBE2 studies confirm a survival benefit with triplet FOLFOXIRI and bevacizumab, and this is a preferred option for younger patients with good performance status able to tolerate it. However, the relative benefit of a fluoropyrimidine doublet with oxaliplatin or irinotecan over single-agent fluoropyrimidine with or without a biologic is less certain; the available data demonstrate that single-agent fluoropyrimidine plus a biologic with planned sequencing of subsequent agents can produce similar overall survival outcomes with reduced toxicity. Our analysis of local real-world registry data suggests that this is an underutilized approach, particularly in younger and fitter patients. Established prognostic factors, including patient age, performance status, tumor sidedness, and biomarkers such as RAS/BRAF, are key in treatment selection; patients with left-sided RAS/BRAF wild-type disease or patients with low tumor bulk may be ideal for a less intensive regimen. Further studies are required to confirm the value of less-intensive regimens in the modern era, where the incorporation of biologic therapies has become routine and where non-chemotherapy options are emerging as viable options for molecularly defined patient subsets.

Feasibility and efficiency of double-agent versus single-agent concurrent chemoradiotherapy in patients with nasopharyngeal carcinoma.

PURPOSE: Concurrent chemoradiotherapy (CCRT) is the mainstay of treatment for nasopharyngeal carcinoma (NPC) patients. It remains unclear whether double-agent CCRT (d-CCRT) is more effective than single-agent CCRT (s-CCRT). In this study, we compared the treatment efficiency and toxicity of d-CCRT with s-CCRT in NPC patients. METHODS AND MATERIALS: Patients with stage II-IV NPC treated with d-CCRT or s-CCRT were retrospectively reviewed. The d-CCRT group patients were compared with s-CCRT group patients for overall survival (OS), locoregional relapse-free survival (LRRFS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and toxicity. Differences in baseline characteristics were adjusted using the pair-matching method. RESULTS: In this study, 933 patients who received CCRT for NPC between 2011 and 2014 were pair-matched at a 1:2 ratio (n = 311 for d-CCRT; n = 622 for s-CCRT). The d-CCRT treated patients showed no significant advantages in terms of 4-year OS (87.2% vs. 85.5%), DFS (84.1% vs. 79.5%), LRRFS (94.6% vs. 91.8%), DMFS (87.5% vs. 85.5%) compared with s-CCRT treated patients (P = 0.450, 0.106, 0.203, 0.366, respectively). Multivariate analysis showed that CCRT regimen had no significant effects on survival. In the d-CCRT group, the incidence of grade 3-4 hematological toxicities was significantly higher. CONCLUSIONS: The d-CCRT regimen did not confer significant survival benefits compared with the s-CCRT regimen in the treatment of stage II-IV NPC patients. Furthermore, patients treated with the d-CCRT regimen experienced greater hematological toxicity.

Comparison of the clinical efficacy between single-agent and dual-agent concurrent chemoradiotherapy in the treatment of unresectable esophageal squamous cell carcinoma: a multicenter retrospective analysis.

BACKGROUND: Some Chinese patients with esophageal squamous cell carcinomaare often treated with single-agent concurrent chemoradiotherapy. However, no results have been reported from randomized controlled clinical trials comparing single-agent with double-agent concurrent chemoradiotherapy. It therefore remains unclear whether these regimens are equally clinically effective. In this study, we retrospectively analyzed and compared the therapeutic effects of single-agent and double-agent concurrent chemoradiotherapy in patients with unresectable esophageal squamous cell carcinoma. METHODS: This study enrolled 168 patients who received definitive concurrent chemoradiotherapy for locally advanced unresectable esophageal squamous carcinoma at 10 hospitals between 2010 and 2015. We evaluated survival time and toxicity. The Kaplan-Meier method was used to estimate survival data. The log-rank test was used in univariate analysis A Cox proportional hazards regression model was used to conduct a multivariate analysis of the effects of prognostic factors on survival. RESULTS: In this study, 100 (59.5%) and 68 patients (40.5%) received single-agent and dual-agent combination chemoradiotherapy, respectively. The estimate 5-year progression-free survival (PFS) rate and overall survival (OS) rate of dual-agent therapy was higher than that of single-agent therapy (52.5% and 40.9%, 78.2% and 60.7%, respectively), but there were no significant differences (P = 0.367 and 0.161, respectively). Multivariate analysis showed that sex, age,and radiotherapy dose had no significant effects on OS or PFS. Only disease stage was associated with OS and PFS in the multivariable analysis (P = 0.006 and 0.003, respectively). In dual-agent group, the incidence of acute toxicity and the incidence of 3 and4 grade toxicity were higher than single-agent group. CONCLUSION: The 5-year PFS and OS rates of dual-agent therapy were higher than those of single-agent concurrent chemoradiotherapy for patients with unresectable esophageal squamous cell carcinoma; however, there were no significant differences in univariate analysis and multivariable analysis. Single-agent concurrent chemotherapy had less toxicity than a double-drug regimen. Therefore, we suggest that single therapis not inferior to dual therapy y. In the future, we aim to confirm our hypothesis through a prospective randomized study.

Trastuzumab combined with doublet or single-agent chemotherapy as first-line therapy for HER2-positive metastatic breast cancer.

PURPOSE: To investigate the efficacy and safety of doublet versus single-agent chemotherapy (CT) plus trastuzumab (H) as first-line therapy for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer (MBC). METHODS: We searched for randomized clinical trials (RCTs) that evaluated the treatment effects of single-agent or doublet CT+H as first-line therapies for HER2-positive MBC. The main outcomes measured for this study included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). A meta-analysis and trial sequential analysis (TSA) were performed, and the study quality was evaluated using the GRADE framework. The PROSPERO registry number of our analysis is CRD42016043766. RESULTS: The results from four RCTs including 1044 participants were pooled. Moderate-quality evidence indicated that compared with single-agent CT+H, doublet CT+H correlated better with prolonged PFS (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.63-0.75, P < 0.0001) and OS (HR = 0.90, 95% CI 0.88-0.92, P < 0.0001). However, moderate-quality evidence revealed no significant difference between the two regimens regarding the ORR (relative risk [RR] = 1.07, 95% CI 0.98-1.17, P = 0.157), which was confirmed by TSA, indicating that the cumulative Z-curve entered the futility area. Moderate-quality evidence indicated that treatment-related grade 3 or 4 toxicities of thrombocytopenia (RR = 4.08, P = 0.000), nausea/vomiting (RR = 4.26, P = 0.002), diarrhea (RR = 2.81, P = 0.002), and stomatitis (RR = 5.02, P = 0.003) were observed more frequently with doublet CT+H than with single-agent CT+H. CONCLUSIONS: Compared with single-agent CT, the combination of doublet CT with trastuzumab as first-line therapy for HER2-positive MBC is associated with longer PFS and OS, but more treatment-related grade 3 or 4 toxicities. Therefore, doublet CT appears to be an appropriate regimen for HER2-positive MBC with a good performance status.

Effectiveness and safety of Kang′ai injection combined with single agent chemotherapy in treatment of el-derly patients with advanced NSCLC / 实用医学杂志

Objective To observe the effectiveness and safety of Kang′ai injection combined with docetaxel or gemcitabine chemotherapy in treatment of elderly patients with advanced non-small cell lung cancer(NSCLC). Methods A multi-center,randomized and parallel control study was carried out in 150 elderly patients with ad-vanced NSCLC treated in 3 hospitals during the period from June 2013 to August 2014.The patients were randomly divided into platinum-based group(platinum-based doublet chemotherapy)and Kang′ai group(Kang′ai injection combined with single agent chemotherapy). The clinical efficacy,quality of life and adverse reactions were ob-served and compared between the two groups. Results There was no significant difference in the disease control rate between the two groups group(79.66% vs 81.82%)(χ2=0.101,P=0.751)while the effective rate of Kang′ai group was significantly higher than that of platinum-based group(30.51% vs 14.29%)(χ2=5.240,P=0.022). The effective rate of clinical symptom relief in Kang′ai group after treatment was significantly higher than that in platinum-based group(69.49% vs 48.05%)(χ2=6.278,P=0.012),and the increase rate of PS score in Kang′ai group after the treatment was also significantly higher than that in platinum-based group(18.64% vs 3.90%)(χ2=7.868,P=0.005).There was no significant difference in quality of life between two groups(P>0.05).The quali-ty of life score of Kang′ai group was significantly higher than that of platinum-based group at the second course of treatment(P<0.05).The incidence of adverse reactions in Kang′ai group was significantly lower than that in the platinum-based group(47.46% vs 71.42%)(χ2= 8.070,P < 0.05). Conclusion Kang′ai injection combined with single agent chemotherapy can effectively relieve clinical symptoms and reduce the tumor size in elderly patients with advanced NSCLC,with high safety.

Phase I trial of nedaplatin chemotherapy concurrent with radiotherapy for untreated locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: In this phase I study, single-agent chemotherapy was conducted in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) using nedaplatin (NDP) and concomitant radiotherapy. The study sought to determine the maximum tolerated dose (MTD), recommended dose (RD) and the clinical efficacy of this treatment in locoregionally advanced NPC patients. EXPERIMENTAL DESIGN: Twenty patients were enrolled. The eligibility criteria included local advanced NPC (stage III or IVa) without any previous treatment and an expected survival of ≥ 3 months. The regimen consisted of 1.8-2.0 Gy daily radiation for 5 days a week and NDP with dose escalation of 70-100 mg/m(2) on day 1. The cycles were repeated every 21 days (day 1, day 22 and day 43) until the completion of chemoradiation. Dose-limiting toxicities (DLTs) included: grade 4 anemia; grade 4 neutropenia lasting for ≥ 5 days; grades 3 and 4 febrile neutropenia; grade 4 thrombocytopenia; grades 3-4 non-hematological toxicity (with the exception of alopecia, nausea) and any of the grade 5 responses. RESULTS: Ninety-five percent of the assessed patients experienced a treatment response. The median time to progression among all patients was 41.9 months. Two-year overall survival was 95%, while the progression-free survival was 85%. DLT included febrile neutropenia of grade 3. The RD of NDP was 90 mg/m(2) during cycles 1-3. CONCLUSION: NDP combined with radiotherapy and administered every 21 days for three cycles was active in patients with locoregionally advanced NPC. The regimen resulted in mild adverse effects and good patient compliance. Based on the findings from the study, the RD of NDP for phase II trial was found to be 90 mg/m(2).

Second-line single-agent versus doublet chemotherapy as salvage therapy for metastatic urothelial cancer: a systematic review and meta-analysis.

BACKGROUND: The efficacy and safety of a combination of chemotherapeutic agent compared with single-agent chemotherapy in the second-line setting of advanced urothelial carcinoma (UC) are unclear. We aimed to study the survival impact of single-agent compared with doublet chemotherapy as second-line chemotherapy of advanced UC. PATIENTS AND METHODS: Literature was searched for studies including single-agent or doublet chemotherapy in the second-line setting after platinum-based chemotherapy. Random-effects models were used to pool trial-level data according to treatment arm, including median progression-free survival (PFS), overall survival (OS), objective response rate (ORR) probability, and grade 3-4 toxicity. Univariable and multivariable analyses, including sensitivity analyses, were carried out, adjusting for the percent of patients with ECOG performance status ≥1 and hepatic metastases. RESULTS: Forty-six arms of trials including 1910 patients were selected: 22 arms with single agent (n = 1202) and 24 arms with doublets (n = 708). The pooled ORR with single agents was 14.2% [95% confidence interval (CI) 11.1-17.9] versus 31.9% [95% CI 27.3-36.9] with doublet chemotherapy. Pooled median PFS was 2.69 and 4.05 months, respectively. The pooled median OS was 6.98 and 8.50 months, respectively. Multivariably, the odds ratio for ORR and the pooled median difference of PFS were statistically significant (P < 0.001 and P = 0.002) whereas the median difference in OS was not (P = 0.284). When including single-agent vinflunine or taxanes only, differences were significant only for ORR (P < 0.001) favoring doublet chemotherapy. No statistically significant differences in grade 3-4 toxicity were seen between the two groups. CONCLUSIONS: Despite significant improvements in ORR and PFS, doublet regimens did not extend OS compared with single agents for the second-line chemotherapy of UC. Prospective trials are necessary to elucidate the role of combination chemotherapy, with or without targeted agents, in the salvage setting. Currently, improvements in this field should be pursued considering single-agent chemotherapy as the foundation for new more active combinations.