Emma Chen Sasse

Optimal duration of first-line chemotherapy for advanced non-small cell lung cancer: a systematic review with meta-analysis

BACKGROUND The optimal duration of first-line chemotherapy for advanced non-small cell lung cancer (NSCLC) has been a matter for debate for nearly 20 years. In order to elucidate this issue, a meta-analysis comparing the different durations of same treatments was performed. METHODS We searched for all published randomised controlled trials (RCTs) comparing different durations of first-line treatment of advanced NSCLC. The MEDLINE, EMBASE, LILACS and CENTRAL databases were searched for RCTs comparing a defined number of cycles of chemotherapy versus continuing treatment until disease progression, or a defined number of cycles versus a higher number of cycles of the same chemotherapy. Trials including biological agents were excluded. RESULTS Seven trials that included 1559 patients were analysed. Treatment for more than 4 cycles was associated with a non-statistically significant decrease in the hazard of mortality relative to shorter treatment (hazard ratio (HR)=0.97; 95% confidence interval (CI)=0.84-1.11; P=.65). In those treated with third-generation chemotherapy through the whole study time, treatment for more than 4 cycles was associated with a non-statistically significant increase in mortality (HR=1.08; 95% CI=0.90-1.28; P=.28). Patients receiving more chemotherapy had significant longer progression-free survival (HR=.75; 95% CI=0.60-0.85; P<0.0001) than the group with shorter duration of treatment. In an intent-to-treat analysis, there was no difference in the overall response rate between the groups (odds ratio (OR)=0.78; 95% CI=0.60-1.01; P=.96). Longer treatment was associated with more severe leucopaenia but with no significant increase in non-haematological toxicities. CONCLUSIONS In patients with advanced NSCLC the use of more than 4 cycles of first-line chemotherapy with third-generation regimens significantly increases progression-free survival but not overall survival and is associated with higher incidence of adverse events. There is no evidence to support continuous chemotherapy until progression in patients with lung cancer.

Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

BackgroundMany adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting.MethodsRandomized controlled trials were searched comparing adjuvant therapy (chemotherapy, vaccine, immunotherapy, biochemotherapy) versus no active treatment after surgery among renal cell cancer patients. Outcomes were overall survival (OS), disease-free survival (DFS), and severe toxicities. Risk ratios (RR), hazard ratios (HR) and 95% confidence intervals were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by I2. Different strategies of adjuvant treatment were evaluated separately.ResultsTen studies (2,609 patients) were included. Adjuvant therapy provided no benefits in terms of OS (HR 1.07; 95%CI 0.89 to 1.28; P = 0.48 I2 = 0%) or DFS (HR 1.03; 95%CI 0.87 to 1.21; P = 0.77 I2 = 15%) when compared to no treatment. No subgroup analysis (immunotherapy, vaccines, biochemotherapy and hormone therapy) had relevant results. Toxicity evaluation depicted a significantly higher frequency of serious adverse events in the adjuvant group.ConclusionsThis analysis provided no support for the hypothesis that the agents studied provide any clinical benefit for renal cancer patients although they increase the risk of toxic effects. Randomized trials are underway to test targeted therapies, which might open a new therapeutic frontier. Until these trials yield results, no adjuvant therapy can be recommended for patients who undergo surgical resection for renal cell cancer.

Camptothecins Compared with Etoposide in Combination with Platinum Analog in Extensive Stage Small Cell Lung Cancer: Systematic Review with Meta-Analysis

Introduction: Superiority of camptothecin regimens over etoposide—both combined with platinum analogs—in extensive disease small cell lung cancer has been a matter of debate with contradictory findings in randomized trials. A systematic review was sought to elucidate this issue. Methods: Randomized controlled trials comparing first-line camptothecin-platinum doublets versus etoposide-platinum doublets in patients with extensive disease small cell lung cancer were searched in MEDLINE, EMBASE, LILACS, and CENTRAL databases, European Society of Medical Oncology, American Society of Clinical Oncology, and International Association for the Study of Lung Cancer meeting sites. Meta-analyses were performed using fixed-effects model. Subgroup analyses were undertaken comparing each type of camptothecin to etoposide-based regimens. The outcomes of interest were overall survival (OS), progression-free survival (PFS), response rate (RR), and toxicities. Results: Eight studies (3086 patients) were included. The meta-analysis of topotecan regimens (TP) was not reliable due to impending heterogeneity. Meta-analysis of trials testing irinotecan combinations (IP) versus etoposide regimens (EP; 1561 patients) stated an OS improvement in favor of IP arm, though with considerable heterogeneity, whose origin seemed to be a Japanese trial. In the analyses without that study (1407 patients left), IP brought a significant improvement in OS (hazard ratio = 0.87; 95% confidence interval 0.78–0.97; p = 0.02; I2 = 0). IP also increased PFS (hazard ratio = 0.83; 95% confidence interval 0.73–0.95; p = 0.006; I2 = 0%). There was no impact in RR (absolute RR 56% with IP; 53% with EP; p = 0.17). IP caused more diarrhea (p < 0.0001) but less hematological toxicities (p < 0.001) than EP. Conclusions: The present meta-analysis demonstrates statistically significant OS and PFS benefits of IP over EP regimens in western and eastern patients. Specific characteristics of safety profile should be taken into account when administrating IP chemotherapy.

Is there a role for consolidative radiotherapy in the treatment of aggressive and localized Non-Hodgkin Lymphoma? A systematic review with meta-analysis

BackgroundChemotherapy is the mainstay of non-Hodgkin lymphoma (NHL) treatment. Based on expert opinion, the use of radiotherapy (RT) is currently preferred in some institutions as consolidative treatment for patients with localized disease. The lack of conclusive data coming from conflicting studies about the impact of treatment demands a systematic review, which could provide the most reliable assessment for clinical decision-making. We evaluate the addition of RT post-CT, for aggressive and localized NHL (ALNHL).MethodsRandomized controlled trials (RCT) that evaluated chemotherapy alone versus chemotherapy plus RT were searched in databases. The outcomes were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicity. Risk ratio (RR) and hazard ratio (HR) with their respective 95% confidence intervals (CI) were calculated using a fized-effect model.ResultsFour trials (1,796 patients) met the inclusion criteria. All trials tested the use of RT after systemic therapy comprising anthracycline-based chemotherapy. This systematic review showed that RT enhances PFS after chemotherapy (hazard ratio [HR] 0.81; 95% CI 0.67-0.98; p = 0.03), with no impact on ORR and OS. Some heterogeneity between trials could limit the conclusions about OS. Toxicity data could not be pooled due to differences in reporting adverse events.ConclusionsThis systematic review with meta-analysis shows no improvement in survival when adding RT to systemic therapy for ALNHL. Our conclusions are limited by the available data. Further evaluations of new RT technologies and its association with biologic agents are needed.

Duration of Chemotherapy for Metastatic Non–Small-Cell Lung Cancer: More May Be Not Better

pared to best supportive care alone. 2 Trials fully published presented no gain in OS (hazard ratio [HR], 0.98; 95% CI, 0.90 to 1.07) while those presented in abstract format stated relevant gain in OS (HR, 0.79; 95% CI 0.69 to 0.91). The difference among these two groups (fully and partially published trials) cannot be overlooked (interaction P .01). Nevertheless, the main source of concern in this meta-analysis is the assumption that different therapeutic approaches were similar and could be polled. Seven trials continued all drugs used in first-line therapy, three maintained a single drug already used in first-line therapy (maintenance therapies) and three switched to a new single drug before progression (sequential therapy) in the longer therapy arms. Even though there was no relevant statistical heterogeneity, pooling all these types of trials caused an inconsistency beyond numbers. Is the use of docetaxel or pemetrexed after four cycles of platinum-based chemotherapy similar to maintaining a platinum-doublet up to six cycles? Can continuing vinorelbine after platinum doublet be considered equal to docetaxel after platinum doublets? Are six or more courses of platinum doublets better than four cycles? It is hardly believable that such specifics question could be answered by a single broad meta-analysis. Ideally, a systematic review must point to a specific direction, and this was not the case with the Soon et al metaanalysis. An appropriated answer to the optimal duration of first-line chemotherapy must be better defined. The meta-analysis presented by Soon et al 1 did not perform a straightforward comparison of duration of first-line therapy alone, it is confounded by major differences in treatment. The OS benefit identified (HR, 0.92; 95% CI 0.86 to 0.99) when all types of trials were combined merits a deeper discussion. We could speculate that not all therapeutic approaches (maintenance and sequential) contribute equally to this result. In fact, the inclusion of one large sequential trial 3 seemed to be capital for achieving this survival gain as the robust analysis pointed out. These consideration were all taken into account in other systematic review recently published. 4 This review had more restricts inclusion criteria: trials comparing early introduction of a different drug (sequential trials) were excluded to avoid confounding bias. These narrow inclusion criteria of the meta-analysis diminished the number of included trials and patients but provided an interesting clinical uniformity among trials. Prolonged use of third-generation doublets increased progressionfree survival (HR, 0.75; 95% CI, 0.65 to 0.85) but not OS (HR, 1.08; 95% CI 0.90 to 1.28). The conclusion was that three to four cycles of platinum-based doublets would provide similar benefit of longer platinum-doublets therapies with less toxicity.