Effectiveness Of First-line Treatment Research Articles

Comparison of First-Line Chemotherapeutics and Validation of the EORTC Prognostic Index in Malignant Pleural Mesothelioma: Retrospective Single-Centre Experience.

To evaluate the efficiency of pemetrexed cisplatin in comparison with gemcitabine cisplatin and to validate the EORTC (European Organisation for Research and Treatment of Cancer) prognostic score in combination chemotherapy treatment for malignant pleural mesothelioma. An observational study. Place and Duration of the Study:Department of Oncology, Dicle University Hospital, Diyarbakir, Turkiye, from October 2000 to November 2017. Malignant pleural mesothelioma (MPM) patients with EORTC score 0- were recruited. Factors affecting the prognosis of the disease and the effectiveness of first-line treatment were retrospectively analysed. EORTC prognostic score was calculated with a cut-off and survival analyses were used by the Kaplan-Meier method. Log-rank and univariable Cox regression tests were used to search for prognostic factors' impact on survival. Patients who received gemcitabine cisplatin treatment had a median progression-free survival (PFS) of 9 months, while those who received pemetrexed cisplatin therapy had a median PFS of 7 months. Median overall survival (OS) was 17 months in the gemcitabine cisplatin group and 18 months in the pemetrexed cisplatin group (p = 0.051). When the low-risk group was compared with the high-risk group, the median OS was found to be statistically significant (p = 0.009). The EORTC prognostic score, which is used for prognostic prediction in the period when pemetrexed is not utilised in the treatment of MPM, accurately predicts prognosis subsequent to the administration of pemetrexed in treatment. In the context of first-line treatment, cisplatin in combination with gemcitabine and cisplatin in combination with pemetrexed demonstrated comparable efficacy with respect to both overall survival and progression-free survival. Chemotherapy, Mesothelioma, Prognosis, Gemcitabine, Progression-free survival.

Possible hampered effectiveness of second-line treatment with rituximab-containing chemotherapy without signs of rituximab resistance: a population-based study among patients with chronic lymphocytic leukemia.

Rituximab-containing chemotherapy remains a viable frontline treatment option for patients with chronic lymphocytic leukemia (CLL) in the era of novel agents. However, its effectiveness in the second-line setting-in relation to previous rituximab exposure in first-line-has hardly been evaluated in a population-based setting. Therefore, in this comprehensive, population-based study, we assessed the impact of first-line treatment with rituximab-containing chemotherapy on the effectiveness of second-line treatment with rituximab-containing chemotherapy. We selected all 1735 patients diagnosed with CLL between 2004 and 2010 from the Dutch Population-based HAematological Registry for Observational Studies (PHAROS). The primary endpoint was treatment-free survival (TFS). First- and second-line treatment was instituted in 663 (38%) and 284 (43%) patients, respectively. In first line, the median TFS was 19.7 and 67.1months for chemotherapy without (n = 445; 67%) and with rituximab (n = 218; 33%), respectively (adjusted hazard ratio [HRadjusted], 0.83; P= 0.031). The median TFS among recipients of second-line chemotherapy without (n = 165; 57%) and with rituximab (n = 121; 42%) was 15.0 and 15.3months, respectively (HRadjusted, 0.93; P= 0.614). Of the 121 patients who received rituximab-containing chemotherapy in second-line, 89 (74%) and 32 (26%) received first-line chemotherapy without and with rituximab, respectively. Median TFS in these two treatment groups was 18.3 and 12.1months, respectively (HRadjusted, 1.71; P= 0.060). Collectively, in this population-based study, the effectiveness of first-line treatment with rituximab-containing chemotherapy was less pronounced in second-line treatment. The hampered effectiveness of rituximab-containing chemotherapy in second-line could not be explained by previous rituximab exposure.

Analysis of the characteristics of second primary malignancy affecting the survival of lymphoma patients

Objective: To analyze the characteristics of the second primary tumor affecting the survival of patients with lymphoma, and to explore the risk factors of death from the second primary tumor. Methods: The medical records and related death information of 1 173 lymphoma patients who had already died with known causes were collected. The basic causes of death and the characteristics of patients who died of the second primary tumor were analyzed. Cox regression model was used to analyze the risk factors of lymphoma patients who died of the second primary tumor. Results: Among the 1 173 patients who had died, 94 (8.0%) died of the second primary tumor, 935 (79.7%) died of the primary lymphoma and 144 (12.3%) died of other diseases. The second primary tumor accounted for 17.5% (38/217) of all causes of death in patients with the survival period of more than 5 years, and the second primary tumor accounted for 28.3% (17/60) of all causes of death in patients with the survival period of more than 10 years. Among 94 cases who died of second primary tumors, 31 died of lung cancer, 15 died of gastric cancer, 13 died of liver cancer, 9 died of pancreatic cancer, 6 died of colorectal cancer, 6 died of second primary lymphoma and 14 died of other types of tumors. Univariate Cox regression analysis showed that age, first-line treatment effect, and chest or mediastinal radiotherapy were associated with the death from second primary tumors for lymphoma patients (all P<0.05). Multivariate Cox regression analysis showed that the effect of first-line treatment (P=0.030) and the chest or mediastinal radiotherapy (P=0.039) were independent factors for the death of lymphoma patients from the second primary tumor. Conclusions: The second primary tumor is an important factor affecting the survival of lymphoma patients, and the risk of death from second primary tumors increases significantly over time. The effect of first-line treatment and radiotherapy in the chest or mediastinum are independent factors for the death of lymphoma patients from the second primary tumor.

Effectiveness of first-line treatments in metastatic squamous non-small-cell lung cancer.

Commonly used first-line (1L) chemotherapies for patients with advanced squamous-cell lung cancer (scc) include gemcitabine-platinum (gp), nab-paclitaxel-carboplatin (nabpc), and sb-paclitaxel-carboplatin (sbpc) regimens. However, no head-to-head trials have compared those treatments. In the present study, we compared the efficacy of 1L gp, nabpc, and sbpc in patients with scc and in patients with scc who subsequently received second-line (2L) immunotherapy. Medical records of patients who initiated the 1L treatments of interest between June 2014 and October 2015 were reviewed by 132 participating physicians. Kaplan-Meier curves were used to evaluate overall survival (os), progression-free survival (pfs), and treatment discontinuation (td), and then Cox proportional hazards regression was used to compare the results between the cohorts. Medical records of 458 patients with scc receiving gp (n = 139), nabpc (n = 159), or sbpc (n = 160) as 1L therapy were reviewed. Median os was longer with nabpc (23.9 months) than with gp (16.9 months; adjusted hazard ratio vs. nabpc: 1.55; p < 0.05) and with sbpc (18.3 months; adjusted hazard ratio: 1.42; p = 0.10). No differences were observed in pfs (median pfs: 8.8, 8.0, and 7.6 months for gp, nabpc, and sbpc respectively; log-rank p = 0.76) or in td (median td: 5.5, 5.7, and 4.6 months respectively; p = 0.65). For patients who subsequently received 2L immunotherapy, no differences in os were observed (median os: 27.3, 25.0, and 23.0 months respectively; p = 0.59). In a nationwide sample of scc patients, longer median os was associated with 1L nabpc than with gp and sbpc. Median os for all 1L agents considered was similar in the subgroup of patients who sequenced to a 2L immunotherapy.

Monitoring the effect of first line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma

BackgroundPrecision medicine calls for an early indicator of treatment efficiency. Circulating tumor DNA (ctDNA) is a promising marker in this setting. Our prospective study explored the association between disease development and change of ctDNA during first line chemotherapy in patients with RAS/RAF mutated metastatic colorectal cancer (mCRC).MethodsThe study included 138 patients with mCRC receiving standard first line treatment. In patients with RAS/RAF mutated tumor DNA the same mutation was quantified in the plasma using droplet digital PCR. The fractional abundance of ctDNA was assessed in plasma before treatment start and at every treatment cycle until radiologically defined progressive disease.ResultsRAS/RAF mutations were detected in the plasma from 77 patients. Twenty patients progressed on treatment and 57 stopped treatment without progression. The presence of mutated DNA in plasma was correlated with poor overall survival. A low level of ctDNA after the first cycle of chemotherapy was associated with a low risk of progression. On the other hand, a significant increase of ctDNA at any time during the treatment course was associated with a high risk of progression on continuous treatment. The first increase in ctDNA level occurred at a median of 51 days before radiologically confirmed progression.ConclusionsThe results indicate that the ctDNA level holds potential as a clinically valuable marker in first line treatment of mCRC. A rapid decrease was associated with a prolonged progression free interval, whereas a significant increase gave notice of early progression with a relevant lead time.

Monitoring the effect of first-line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma.

3593 Background: Personalized medicine calls for an early indicator of treatment failure. Circulating tumor DNA (ctDNA) is a promising marker in this setting and our prospective study explored the association between disease control and change of ctDNA during first line chemotherapy in patients with RAS/RAF mutated metastatic colorectal cancer (mCRC). Methods: The present study included 138 mCRC patients receiving standard first line combination chemotherapy. In patients with a RAS/RAF mutated tumor the same mutation was quantified in the plasma using droplet digital PCR (ddPCR). The fractional abundance of ctDNA (ctDNA level) was assessed in plasma before treatment start and at every treatment cycle until radiologically defined progressive disease (PD). Results: RAS/RAF mutations were detected in the plasma from 77 patients (94% of patients with a tumor mutation). Twenty patients progressed on treatment and 57 stopped treatment without progression. The presence of a RAS/RAF mutation in plasma correlated to overall survival (OS) with a median of 24.2 months for patients with a wild-type tumor compared to 12.7 months for patients with a mution in plasma. A substantial increase in ctDNA level was highly associated with progression on treatment (risk ratio = 4.58, 95%CI = 1.99-10.51, p &lt; 0.0001). Furthermore, with a stable ctDNA level the chance of non-progression was 88.2% (range 76.1-95.6%). The first substantial increase in ctDNA level occurred at a median of 51 days (range 14-133 days) before radiologically confirmed PD. Conclusions: The results indicate that ctDNA level may be predictive of treatment effect in patients with mCRC. An increase was observed to correlate with high risk of progression with a relevant lead time, whereas an unchanging ctDNA level related to stable disease.

High-dose chemotherapy as salvage treatment in germ-cell cancer: when, in whom and how.

Over the past two decades, the use of well-validated, guideline-based strategies resulted in high cure rates in patients with germ-cell cancer (GCC) often despite widespread metastatic disease at initial presentation. Yet, about 30% of patients diagnosed with metastatic disease corresponding to about 5-10% of GCC patients overall will experience disease progression or recurrence at some time point of their disease with the need for salvage treatment. Salvage treatment is more complex and less well validated than first-line treatment: Its rare patient cohorts are more heterogeneous and prognostic factors impact more compared to other treatment scenarios. In patients with metastatic GCC, there are several scenarios in which first-line treatment strategies can fail (Fig.1). Prior to initiation of any salvage treatment, several considerations have to be made, which will be addressed in this review: verification that first-line treatment has indeed failed, estimation of the adequacy and the effectiveness of first-line treatment, search for metastatic sites and extent of disease recurrence, assessment of known prognostic factors and finally the choice of the optimal salvage strategy taking into account the aforementioned variables. High-dose chemotherapy will be a rational choice for many patients in need of salvage treatment, but careful patient selection will be required to avoid overtreatment and unnecessary long-term toxicity.

Effect of First-Line Treatment on Myeloid-Derived Suppressor Cells’ Subpopulations in the Peripheral Blood of Patients with Non–Small Cell Lung Cancer

IntroductionMyeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature cells of myeloid origin whose expression is induced by, among others things, vascular endothelial growth factor. We have previously identified two monocytic and one granulocytic MDSC subpopulations associated with the clinical outcome in patients with non–small cell lung cancer (NSCLC). The aim of the present study was to evaluate the effect of chemotherapy on these MDSC subpopulations. MethodsCirculating immune cells from 46 patients with unresectable NSCLC were analyzed by flow cytometry before the initiation of chemotherapy and after three cycles. Changes in the frequencies of the MDSC subpopulations were correlated with clinical outcome. ResultsChemotherapy had no uniform effect on either the number or the functionality of monocytic and granulocytic MDSCs. However, three cycles of bevacizumab-containing regimens significantly reduced the percentage of the granulocytic-MDSCs compared with non–bevacizumab-based regimens (p = 0.0086). At the time of evaluation of response, disease progression was associated with significantly higher levels of all three MDSC subpopulations compared with in patients with disease control. Ιn patients with disease progression after three cycles of chemotherapy, the percentage of CD15-positive monocytic MDSCs was significantly increased compared with baseline. ConclusionsIn the peripheral blood of patients with NSCLC, bevacizumab-based chemotherapy significantly reduced the levels of granulocytic MDSCs. An increase in the levels of CD15-positive monocytic MDSCs was associated with poor response to treatment and disease progression, providing evidence of their clinical relevance in patients with NSCLC.

First-line treatment in the management of advanced renal cell carcinoma: systematic review and network meta-analysis

Objectives: To conduct a systematic review and network meta-analysis (NMA) to assess effectiveness of first-line treatments for advanced renal cell carcinoma (RCC).Methods: Database searches were conducted to identify randomized controlled trials (RCTs) reporting results for eligible treatments. A fixed-effect Bayesian NMA was conducted to assess the relative effectiveness of treatments, with progression-free survival (PFS) reported as hazard ratios (HRs) and 95% credible intervals (CrIs).Results: Eleven unique RCTs were suitable for inclusion in the NMA. In the base case, in terms of PFS, sunitinib was superior compared with bevacizumab + IFN-α (HR = 0.79, 95% CrI: 0.64 – 0.96), everolimus (HR = 0.70, 95% CrI: 0.56 – 0.87), sorafenib (HR = 0.56, 95% CrI: 0.40 – 0.77) and temsirolimus + bevacizumab (HR = 0.74, 95% CrI: 0.56 – 0.96). Although, the point values for the mean and median HRs were < 1.0, there was no significant difference in PFS between sunitinib and axitinib, pazopanib or tivozanib. Although sensitivity analyses impacted the results of the NMA, no treatment was significantly more efficacious than sunitinib.Conclusion: Results from this analysis suggest that there is no treatment superior to the current benchmark treatment, sunitinib, in the management of advanced RCC in the first-line setting.

The frequency of tetracycline resistance genes co-detected with respiratory pathogens: a database mining study uncovering descriptive trends throughout the United States.

BackgroundThe Center for Disease Control and Prevention (CDC) indicates that one of the largest problems threatening healthcare includes antibiotic resistance. Tetracycline, an effective antibiotic that has been in use for many years, is becoming less successful in treating certain pathogens. To better understand the temporal patterns in the growth of antibiotic resistance, patient diagnostic test records can be analyzed.MethodsData mining methods including frequent item set mining and association rules via the Apriori algorithm were used to analyze results from 80,241 Target Enriched Multiplex-PCR (TEM-PCR) reference laboratory tests. From the data mining results, five common respiratory pathogens and their co-detection rates with tetracycline resistance genes (TRG) were further analyzed and organized according to year, patient age, and geography.ResultsFrom 2010, all five pathogens were associated with at least a 24% rise in co-detection rate for TRGs. Patients from 0–2 years old exhibited the lowest rate of TRG co-detection, while patients between 13–50 years old displayed the highest frequency of TRG co-detection. The Northeastern region of the United States recorded the highest rate of patients co-detected with a TRG and a respiratory pathogen. Along the East–west gradient, the relative frequency of co-detection between TRGs and respiratory pathogens decreased dramatically.ConclusionsSignificant trends were uncovered regarding the co-detection frequencies of TRGs and respiratory pathogens over time. It is valuable for the field of public health to monitor trends regarding the spread of resistant infectious disease, especially since tetracycline continues to be utilized a treatment for various microbial infections. Analyzing large datasets containing TEM-PCR results for co-detections provides valuable insights into trends of antibiotic resistance gene expression so that the effectiveness of first-line treatments can be continuously monitored.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-460) contains supplementary material, which is available to authorized users.

Cost Effectiveness of First-Line Treatment with Doxorubicin/Ifosfamide Compared to Trabectedin Monotherapy in the Management of Advanced Soft Tissue Sarcoma in Italy, Spain, and Sweden

Background. Doxorubicin/ifosfamide is a first-line systemic chemotherapy for the majority of advanced soft tissue sarcoma (ASTS) subtypes. Trabectedin is indicated for the treatment of ASTS after failure of anthracyclines and/or ifosfamide; however it is being increasingly used off-label as a first-line treatment. This study estimated the cost effectiveness of these two treatments in the first-line management of ASTS in Italy, Spain, and Sweden. Methods. A Markov model was constructed to estimate the cost effectiveness of doxorubicin/ifosfamide compared to trabectedin monotherapy, defined as the cost per QALY gained, in each country. Results. First-line treatment with doxorubicin/ifosfamide resulted in lower two-year healthcare costs and more QALYs than first-line treatment with trabectedin monotherapy in all three countries. Probabilistic sensitivity analysis showed that at a cost per QALY threshold of €35,000, >90% of a cohort would be cost effectively treated with doxorubicin/ifosfamide compared to trabectedin monotherapy in all three countries. Conclusion. Within the model's limitations, first-line treatment of patients with ASTS with doxorubicin/ifosfamide instead of trabectedin monotherapy affords a cost-effective use of publicly funded healthcare resources in Italy, Spain, and Sweden and is therefore the preferred treatment in all three countries. These findings support the recommendation that trabectedin should remain a second-line treatment.

Effectiveness of first line treatment with bortezomib prior to autologous stem cell transplantation for multiple myeloma

Background: In this retrospective study we evaluated effectiveness and safety of first- line treatment with bortezomib and dexamethasone in multiple myeloma patients, comparing our results with already published clinical studies. Methods: Patients received bortezomib as part of everyday clinical practice and according to the latest guidelines of the Združenje hematologov Slovenije . Patients who were previously treated with first-line VAD (vincristine, doxorubicin modified with farmarubicine, dexamethasone), but due to uneffectiveness changed the treatment to bortezomib, were also included in the study. In 30 patients effectiveness was evaluated after average 3–4 cycles of bortezomib and dexamethasone according to the modified Southwest Oncology Group criteria. Treatment effectiveness was evaluated according to the previous VAD treatment, renal function and cytogenetic analysis. Side effects and reasons for early treatment discontinuation were described. Results: Patients received 2 to 8 cycles (median 4 cycles) of bortezomib and dexamethasone treatment. After average 3–4 cycles, 80 % of patients acheived good treatment response (56.7 % very good partial response, 23.3 % partial response). We observed that the treatment effectiveness was not influenced by previous VAD treatment, renal insufficiency and negative cytogenetic analisys, since we observed similar rates of very good partial response and partial response in patients without previous VAD treatment (82.3 % vs. 76.9 %), normal renal function (85.7 % vs. 75 % ) and normal cytogenetics (77.8 % vs. 80 %), although statistical evaluation was not possible due to small number of patients. The most common side effect was neuropathy (40 %) and in 5 patients (16.6 %), due to grade 3 or more, the treatment was discontinued. Other side effects were: anemia (26.6 %), infection (166 %), thrombocytopenia (10 %), neutropenia (6.6 %), gastrointestinal problems (23.3 %) and herpes zooster (6.6 %). Conclusions: Bortezomib (Velcade) in combination with dexamethasone is an effective and safe first-line multiple myeloma treatment and is not influenced by renal insuficience, unfavourable cytogenetic analysis or previous uneffective VAD treatment.

Effect of first-line treatment and CHFR and 14–3-3σ methylation status on survival to second-line chemotherapy or EGFR tyrosine kinase inhibitors (TKIs) in stage IV non-small-cell lung cancer (NSCLC)

8068 Background: We analyzed the outcome of second-line chemotherapy vs EGFR TKIs in 179 of 366 patients (p) who had been included in an ERCC1-based customized cisplatin trial and correlated the re...