Effectiveness Of Second-line Chemotherapy Research Articles

Impact of nab-paclitaxel-based second-line chemotherapy on the outcomes of pancreatic cancer.

483 Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with no standard second line chemotherapies. We conducted a retrospective study with the primary aim to examine the effect of second line chemotherapy with nab-paclitaxel-based regimen on the overall survival (OS) and progression-free survival (PFS) of locally advanced and metastatic PDAC patients. Methods: Indiana University Simon Cancer Center (IUSCC) Cancer Registry was used to identify patients with locally advanced or metastatic PDAC between 2009 and 2015. Only patients who received second line chemotherapies were included in the study. These patients were divided in to two groups: a) nab-paclitaxel-based treatment and, b) non-nab-paclitaxel-based treatment. Demographic (age, race, gender, year of diagnosis, family history, comorbidity), clinical (histology, CA 19-9, bilirubin, tumor location, performance status, metastatic sites, chemotherapy, surgery or radiation) and outcome (OS, PFS) characteristics were obtained. OS and PFS were estimate by using Kaplan-Meier method and 95% CI. Cox proportional-hazard model was used for multivariate analysis. Results: Forty-seven (39%) and seventy-three (61%) patients received nab-paclitaxel-based and non-nab-paclitaxel-based second line chemotherapy, respectively. In the univariate analyses, nab-paclitaxel-based treatment was only associated with younger age (60.4 vs. 64 years; P = 0.02). The median PFS was 2.8 and 2.1 months (HR 0.62; 95% CI 0.38-1.02; P = 0.06), and the median OS was 7.5 and 4.7 months (HR 0.67; 95% CI 0.45-1.00; P = 0.05) in patients who received nab-paclitaxel based second line treatment versus not, respectively. Multivariate analyses adjusted for age showed a significantly improved PFS (adjusted HR 0.60, 95% CI 0.36-0.98; P = 0.04) and a suggestion of improved OS (adjusted HR 0.67; 95% CI 0.44-1.01, P = 0.05) in the nab-paclitaxel based second line treatment group versus not, respectively. Conclusions: In a single institution retrospective study, we report significant improvement in the PFS and a suggestion of improvement in the OS with nab-paclitaxel based treatment as compared with non-nab-paclitaxel based treatment in the second line setting.

Effect of Second-Line Chemotherapy in Elderly Patients with Non-Small Cell Lung Cancer

Background: The effect of second-line chemotherapy in patients with non-small cell lung cancer (NSCLC) who received first-line chemotherapy at the age of ≥ 75 years is unclear. Methods: Sixty-five elderly patients with NSCLC who received first-line chemotherapy at the age of ≥ 75 years and treated with second-line chemotherapy at Shizuoka Cancer Center between January 2005 and December 2014 were retrospectively reviewed. Results: The overall response rate of the second-line chemotherapy was 9.2% [95% confidence interval (CI) 4-19]. The median progression-free survival at the second-line chemotherapy was 2.2 months. The median overall survival at the second-line chemotherapy was 7.5 months. Multivariate analysis of prognostic factors showed that an Eastern Cooperative Oncology Group performance-status score (PS 0–1/PS 2; HR, 0.396; 95% CI, 0.192–0.899; p=0.03) and histology (squamous/non-squamous; HR, 0.465; 95% CI, 0.228–0.884; p=0.02) were significantly independent prognostic factors. On the other hand, the number of treatment-related deaths was 2 (3.1%) due to pneumonitis. Moreover, the proportion of patients who received third-line chemotherapy was only 35.9%. Conclusion: Our study suggests that elderly patients have difficulty moving on to the next line of chemotherapy; however, selected elderly patients well tolerated the adverse effects of second-line chemotherapy, and second-line chemotherapy might be effective for elderly patients with NSCLC who received first-line chemotherapy at the age of ≥ 75 years. Therefore, prospective study should be planned in order to demonstrate the efficacy of second-line chemotherapy for elderly patients with NSCLC.

Chemotherapy versus best supportive care for extensive small cell lung cancer.

Combination chemotherapy has been the mainstay of treatment for extensive stage small celI lung cancer (SCLC) over the last 30 years, even though it only gives a short prolongation in median survival time. The main goal for these patients should be palliation with the aim of improving their quality of life. To determine the effectiveness of first-line chemotherapy versus placebo or best supportive care (BSC) in prolonging survival in patients with extensive SCLC at diagnosis and the effectiveness of second-line chemotherapy at relapse or progression after first-line chemotherapy compared with BSC or placebo in prolonging survival in patients with extensive SCLC; as well as to evaluate the adverse events of treatment and the quality of life of patients. This is the second update of the review. MEDLINE (1966 to October 2013), EMBASE (1974 to October 2013), and the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 3) were searched. Experts in the field were contacted. Phase III randomised controlled trials in which any chemotherapy treatment was compared with placebo or BSC in patients with extensive SCLC, as first-line or second-line therapy at relapse. Two authors independently extracted data and assessed study quality. We resolved disagreements by discussion. Additional information was obtained from one study author. Two studies of unclear risk of bias were included for first-line chemotherapy. A total of 88 men under 70 years with good performance status were randomised to receive either supportive care, placebo infusion or ifosfamide. Ifosfamide gave an extra mean survival of 78.5 days compared with supportive care or placebo infusion. Partial tumour response was greater with the active treatment. Toxicity was only seen in the chemotherapy group and quality of life was only assessed at the beginning of treatment. The quality of the evidence for overall survival and adverse effects was very low.Three studies of moderate risk of bias were included for second-line chemotherapy at relapse (one identified in the last search). A total of 932 men and women under 75 years and any performance status were randomised to receive either methotrexate-doxorubicin, topotecan, or picoplatin versus symptomatic treatment or BSC. The methotrexate-doxorubicin treatment gave a median survival of 63 days longer than in the symptomatic-treatment group for patients allocated to receive four cycles of first-line chemotherapy, and 21 days longer for patients allocated to receive eight cycles of first-line chemotherapy.Treatment with topotecan gave a median survival of 84 days longer than in the BSC group (log-rank P = 0.01). The adjusted hazard ratio (HR) for overall survival was 0.61 (95% CI 0.43 to 0.87). Treatment with picoplatin gave a median survival time of six days longer than BSC (HR 0.817, 95% CI 0.65 to 1.03, P = 0.0895). A meta-analysis of topotecan and picoplatin gave a HR of 0.73 (95% CI 0.55 to 0.96, P = 0.03; low-quality evidence).Partial or complete response in the methotrexate-doxorubicin group was 22.3%. Five patients (7%, 95% CI 2.33 to 15.67) showed a partial response with topotecan. No data were provided about tumour response in the picoplatin study. Toxicity was worst in the chemotherapy group (moderate-quality evidence). Quality of life was better in the topotecan group and was not measured in the methotrexate-doxorubicin and picoplatin studies (low-quality evidence). Two small RCTs from the 1970s suggest that first-line chemotherapeutic treatment (based on ifosfamide) may provide a small survival benefit (less than three months) in comparison with supportive care or placebo infusion in patients with advanced SCLC. However platinum-based combination chemotherapy regimens have been shown to increase complete response rates when compared to non-platinum chemotherapy regimens with no significant difference in survival, and so these are currently the standard first-line treatment for patients with SCLC.Second-line chemotherapy at relapse or progression may prolong survival for some weeks in relation to BSC. Nevertheless, the impact of first-line chemotherapy on quality of life, older patients, women and patients with poor prognosis is unknown and the benefits of second-line chemotherapy are also unclear for older people. Globally, the evidence on which these conclusions are based is very scarce and of uncertain or low quality, which calls for well-designed, controlled trials to further evaluate the trade-offs between benefits and risks of different chemotherapeutic schedules in patients with advanced SCLC.

Clinical features of unresectable high-grade lung neuroendocrine carcinoma diagnosed using biopsy specimens

BackgroundThe overall clinicopathological features or the optimal therapy for large cell neuroendocrine carcinoma (LCNEC) have yet to be defined, because LCNEC has not been studied in the same depth as had small cell lung carcinoma (SCLC) in both clinical and biological standpoints. The aim of this study was to elucidate the clinical features of high-grade neuroendocrine carcinoma (HGNEC)-probable LCNEC diagnosed by biopsy, and compare therapeutic efficacy with patients with SCLC. MethodsWe retrospectively examined the chart of total of 25 patients who underwent chemotherapy or chemoradiotherapy as initial therapy for a histologic diagnosis of HGNEC-probable LCNEC, using biopsy samples and compared their data with those of 180 patients with SCLC. We analyzed their responses to chemotherapy and/or radiation therapy and survival outcomes. ResultsIn 25 patients with HGNEC-probable LCNEC, 18 patients initially received chemotherapy (17 (94%) of whom received platinum-based chemotherapy) with an overall response rate (ORR) of 61%. The remaining 7 patients received chemoradiotherapy with an ORR of 86%, and 12 of the 25 patients who received second-line chemotherapy had an ORR of 17%. A total of 101 patients with SCLC who initially received chemotherapy had an ORR of 63%, and 79 patients who initially received chemoradiotherapy had an ORR of 98%, and 102 of the 180 patients who received second-line chemotherapy had an ORR of 45%. The 1-year overall survival rate for patients with stage IV HGNEC-probable LCNEC (n=13) and those with ED-SCLC (n=80) was 34% and 49%, respectively (p=0.84). ConclusionThe overall response rate to initial treatment and the survival outcomes of HGNEC-probable LCNEC were comparable to those of SCLC, but the effectiveness of second-line chemotherapy appeared to differ between the 2 groups.

Primary chemotherapy-associated effect of second-line chemotherapy on survival of patients with advanced ovarian cancer

The current treatment of patients with recurrent ovarian cancer who have received initial platinum- or taxane-based chemotherapy depends on the results of the initial chemotherapy. The purpose of this study was to evaluate how to make the selection of second-line agents for patients with recurrent ovarian carcinoma initially diagnosed as stage II to IV. We conducted a retrospective crossover study in patients who received second-line chemotherapy at Jikei University School of Medicine. We evaluated the responses, progression-free survivals, survivals of second-line chemotherapy, and overall survivals after primary surgery for 51 patients. The treatment cohorts were defined as follows: TC1, patients who were given paclitaxel and carboplatin as first-line chemotherapy and who, upon recurrence, were treated with a platinum-based combination as second-line; and TC2, patients who were given a non-taxane-based platinum combination as first-line chemotherapy, followed, at the time of recurrence, with paclitaxel and carboplatin. The response rates of the second-line chemotherapy for the TC1 and TC2 groups were 44% and 25% (P=0.09). The median progression-free survivals of TC1 and TC2 were 12.9 and 6.4 months (P=0.018; hazard ratio [HR], 2.42; 95% confidence interval [CI], 1.16-5.04). The median survivals after second-line chemotherapy for the two groups were 16.8 and 10.4 months (P=0.007; HR, 2.78; 95% CI, 1.33-5.84) and overall survivals after primary surgery were 36.6 and 27.9 months (P=0.007; HR, 2.36; 95% CI, 1.07-5.21). The TC1 group demonstrated a significantly better response and extension of progression-free survival, as well as significantly better survival after crossover and overall survival after primary surgery. As this was a retrospective analysis, this effect should be considered as hypothesis-generating and assessed prospectively in other trials comparing these two chemotherapy schedules.