Elderly and younger patients with non-small cell lung cancer (NSCLC) derive similar benefit from second-line chemotherapy: A retrospective subset analysis of second-line chemotherapy trials conducted from the Hellenic Cooperative Research Group (HORG).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7564-7564
Author(s):  
Sofia Agelaki ◽  
Dora Hatzidaki ◽  
Lampros Vamvakas ◽  
Athanasios G. Pallis ◽  
Athanasios Karampeazis ◽  
...  

7564 Background: Elderly patients (pts) achieve a similar survival benefit, with acceptable toxicity, from first-line chemotherapy for the treatment of advanced NSCLC compared with their younger counterparts. There have been no second-line trials specifically designed for elderly pts and few data exist on the efficacy and tolerability of second-line therapy in this population. Moreover, little if any information exists on the frequency of administration of second-line chemotherapy in these pts. Methods: The files of 2004 pts with advanced NSCLC enrolled into first-line chemotherapy trials performed by HORG from 1995 to 2007 were reviewed. A total of 600 pts who received second-line chemotherapy within the context of clinical trials were identified. Patients’ data were analysed for efficacy and toxicity according to age. Results: Second-line chemotherapy was administered in 24% and 34% of pts ≥65 and <65 years old after failure of prior therapy (p=0.0001). A total of 219 (24.8%) of 600 pts who received second-line treatment were ≥65 years old (median age 70 yrs, range 65-82). Response rates to second-line therapy were 11.9% for older pts compared to 12.3% for younger pts (p=ns). TTP was 2.8 and 3.1 months for older and younger pts, respectively (p=ns). Elderly pts receiving second-line chemotherapy had a median survival of 7.7 months compared with 8.2 months for younger pts (p=ns). Similar rates of haematological and non-haematological toxicities were encountered between the two groups. Conclusions: The participation of elderly pts to second-line chemotherapy trials was lower compared to younger patients. There was no significant difference in outcome or toxicity between elderly and younger pts. For elderly pts with advanced NSCLC and good performance status, second-line chemotherapy is appropriate. However, specific second-line trials in older pts are required since those included in the current analysis were probably highly selected to fit the inclusion criteria.

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14107-14107
Author(s):  
A. Mancuso ◽  
P. Saletti ◽  
S. Sacchetta ◽  
E. Romagnani ◽  
F. Cavalli ◽  
...  

14107 Background: Recent advances in the treatment of pancreatic cancer might influence the management of locally advanced and metastatic disease, nonetheless prognosis remains dismal (1-year survival rates: 24%). The impact on survival of palliative second-line therapy is hotly debated. Methods: We retrospectively reviewed the clinical records of 103 pancreatic cancer patients admitted to San Camillo/Forlanini Hospital (Rome, Italy) and the Oncology Institute of Southern Switzerland during the period June, 1997 to August, 2005 [60 males, 43 females, median age 65 years (range 43–80); median ECOG performance status (PS): 1]. All patients received Gemcitabine as single agent (90%) or in combination with Oxaliplatin (10%) as upfront therapy. A total of 12 fluoropyrimidine-based salvage regimens were administered to 46 patients in the second line setting. Best supportive care was selected in 57 patients after failing first line therapy. Results: Of 103 evaluable patients, first line chemotherapy produced overall tumor growth control of partial response (PR) and stable disease(SD) by RECIST criteria of 52.4% with a median progression free survival (PFS) of 4.6 months. Multivariate analysis revealed that the most important prognostic factor for PFS was the patient’s PS, as patients with PS of 1–2 at diagnosis had significantly worse results than patients with PS = 0 (First line PFS: 110 days vs 193 days, p<0.05). Baseline CA19–9 and number of metastatic sites were not independent prognostic factors for better first-line PFS. PR was observed in 8/46 patients (17.3%) who received second line chemotherapy, SD in 10 (21.7%), and 28 patients progressed (61%). Median overall second line PFS was 3.2 months. Patients who had responded to first-line Gemcitabine were more likely to respond or attain stable disease with second-line treatment, with a PFS of 5.6 vs 2.85 months (p<0.05). The overall survival for all evaluable patients was 8.4 months. 1-year survival was 52% for patients treated with second line therapy. Conclusions: These results are consistent with historical studies and suggest that fluoropyrimidine-based salvage regimens have marginal but definite activity and should be considered in patients who have responded to first line chemotherapy with an optimal PS. No significant financial relationships to disclose.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 127-127
Author(s):  
Ying Liu ◽  
Feng Wang ◽  
Ning Ma ◽  
Shuning Xu ◽  
Lei Qiao ◽  
...  

127 Background: Cetuximab plus chemotherapy is a first-line treatment option for metastatic RAS wild type colorectal cancer patients. Currently, no data are available on continuing cetuximab or changing bevacizumab as second-line therapy beyond first-line cetuximab-based chemotherapy. Methods: Patients (aged ≥18 years) with metastatic, histologically and genetically confirmed wild-type KRAS, NRAS and BRAF colorectal cancer progressing after first-line cetuximab plus chemotherapy were randomly assigned (1:1 ratio) to second-line chemotherapy with cetuximab (arm A) or with bevacizumab (arm B) 2·5 mg/kg per week equivalently. The choice between oxaliplatin-based or irinotecan-based second-line chemotherapy depended on the first-line regimen (switch of chemotherapy). The primary endpoints were progression-free survival (PFS) and objective response rate (ORR). The second endpoint was overall survival (OS). Results: 77 Patients (from July 1, 2016 to Sept 20, 2019, 77) were randomized (41 in arm A and 36 in arm B). ORR was 29.3% and 19.4% in Arm A and Arm B ( p= 0.31). PFS was 7.2 months (95% CI 5.2–9.2) for Arm A and 5.9 months (95% CI 5.1–6.7) for Arm B ( p= 0.677). OS was 18.5 months (95% CI 15.1–21.8) for Arm A and 17.5 months (95% CI 15.4–19·7) for Arm B ( p= 0.444). Patients with ECOG PS 0 had significantly longer PFS and OS than ECOG PS 1 in second-line therapy whether cetuximab or bevacizumab combined with chemotherapy. ECOG 0 group vs ECOG 1 group, PFS was 8.7 months vs 4.6 months (p = 0.00) and OS was 21.2 months vs 12.3 months (p = 0.00). Moreover, ETS may predict efficacy of second-line continued cetuximab. The most frequently grade 3–4 adverse events in both arms were neutropenia (19.4% VS 16.7%), diarrhea (7.5% vs 11.1%), and nausea(10% vs 13.9%). Conclusions: Continuing cetuximab or changing bevacizumab plus standard second-line chemotherapy in patients with metastatic wild-type KRAS, NRAS and BRAF colorectal cancer after first-line cetuximab plus chemotherapy have similar clinical benefits. ECOG score is an independent predictor of prognosis and second-line treatment efficacy for colorectal cancer.


2019 ◽  
Vol 26 (1) ◽  
Author(s):  
S. Bazarbashi ◽  
A. M. Hakoun ◽  
A. M. Gad ◽  
M. A. Elshenawy ◽  
A. Aljubran ◽  
...  

Background Exposing patients with metastatic colorectal cancer (mcrc) to all three active chemotherapeutic agents (oxaliplatin, irinotecan, fluorouracil) has improved survival. The benefit of second-line chemotherapy after a first-line triplet is not clearly defined. We evaluated the efficacy of second-line chemotherapy in patients who had received first-line triplet therapy.Methods The medical records of patients treated on a prospective trial of first-line triplet therapy were reviewed for second-line treatment. Univariate and multivariate analyses were performed to establish factors of prognostic significance.Results Of the 53 patients who received first-line triplet therapy, 28 (53%) received second-line chemotherapy [13 men; 8 with a colon primary; mutant KRAS in 10, wild-type in 15, and unknown status in 3; Eastern Cooperative Oncology Group performance status (ps) of 1 in 16 patients, ps 2 in 3, ps 3 in 2, and unknown in 7; involved organs: liver in 17 patients, lung in 16, and peritoneum in 8]. Second-line chemotherapy consisted of xelox or folfox in 13 patients, xeliri or folfiri in 12, and single-agent irinotecan in 3. Concurrent bevacizumab was given in 16 patients (57%), and cetuximab, in 2 (7%). Median survival was 28.0 months [95% confidence interval (ci): 22.8 months to 33.2 months] for patients receiving second-line therapy and 23.0 months (95% ci: 13.2 months to 32.8 months) for those not receiving it. Best response was partial in 6 patients (21%), stable disease in 11 (39%), and progressive disease in 11 (39%). Median progression-free survival was 4.8 months (95% ci: 2.4 months to 9.6 months), and overall survival was 15 months (95% ci: 9.6 months to 20.4 months).Conclusions Second-line chemotherapy after first-line triplet therapy in mcrc is feasible and suggests efficacy comparable to that reported for second-line therapy after a doublet, regardless of the agent used.by research evidence.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14588-14588
Author(s):  
F. Dane ◽  
M. Gumus ◽  
A. Ozturk ◽  
F. Yumuk ◽  
S. Iyikesici ◽  
...  

14588 Background: With the development of oxaliplatin and irinotecan, multiple effective regimens are now available in advanced colorectal cancer (CRC), both as first- and second-line treatment options. Exposure to all of the active drugs is effective in prolonging overall survival (OS) and time to progression (TTP). There are limited studies, if any, analyzing the outcome of second line chemotherapy in metastatic CRC in Turkey. Thus, we aimed to evaluate the outcome of second-line treatments in metastatic CRC patients. Methods: Among 173 patients with metastatic CRC who were given first line chemotherapy 106 (47 female, 59 male) were administered second line treatment after progression. All patients histologically confirmed colorectal adenocarcinoma with ECOG performance score of 2 or lower, and received second line therapy for metastatic CRC after experienced disease progression during or following treatment with first-line therapy were entered the study. The patients were evaluated clinically and radiologically after each three-cycle period, and chemotherapy was changed or stopped if the cancer has progressed. Age, gender, grade, chemotherapy type (combination vs single agent), lymphatic, vascular, and perineural invasion, were analyzed as prognostic factors. Results: At a median follow up of 10 (range 1–40) months from the start of second line chemotherapy median TTP and OS time were 5 and 16 months respectively. Median age was 62 years (range 27–89). After second line therapy 16% of the patient had objective response rate (0.9% complete responses plus 15.1% partial responses), 37.7% had stable disease resulting in a tumor control rate of 53.7%, and 46.2% had progressive disease. One-year progression free survival and OS rates were 15 % and 53.5%, respectively. No difference was seen in the survival of patients received combination or single agent second line chemotherapy (p=0.14). Overall, over 12% of the patients suffered from grade 3 or 4 adverse effects. In multivariate analysis histological grade (p=0.015) was the only independent prognostic factor for survival. Conclusion: The survival outcome and adverse effects of second line treatments in Turkish patients in our department with metastatic CRC is consistent with the worlds’ literature. No significant financial relationships to disclose.


2019 ◽  
Vol 21 (10) ◽  
pp. 718-724 ◽  
Author(s):  
Wen-Cong Ruan ◽  
Yue-Ping Che ◽  
Li Ding ◽  
Hai-Feng Li

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy. Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S680-S681
Author(s):  
Carly Heck ◽  
Judith Martin ◽  
Marcia Kurs-Lasky

Abstract Background Background: Antibiotic resistance is a major public health concern. A modifiable intervention is outpatient antibiotic stewardship. The goal of this study was to review the electronic health records (EHR) of children diagnosed with community acquired pneumonia (CAP) to compare patients who received non-guideline concordant therapy with those prescribed recommended therapy. Methods Methods: This was a retrospective chart review of 300 children (6 months to 6 years old) with an outpatient diagnosis of CAP between July 2017 and June 2019. 45 Children’s Hospital of Pittsburgh (CHP) and UPMC Children’s Community Pediatrics (CCP) practices were included. CHP practices are academic-based with trainees involved in visits, while CCP practices do not include trainees. First-line recommended therapy was defined as amoxicillin, second-line therapy as azithromycin or amoxicillin-clavulanate, and all other prescriptions were defined as other. Patients prescribed first-line therapy were compared to patients with second-line therapy or other. If first-line therapy was not prescribed, the EHR was manually reviewed for justification. If drug allergy was listed, the medication allergy and type of reaction were recorded. Results Results: In this study the minority of children (43%) were prescribed first-line therapy. This group was younger (57 vs. 63 months of age), more likely to be Non-white (80%), and seen at the CHP locations than those prescribed non-guideline concordant therapy. The average symptom duration was shorter, heart rate and respiratory rate were higher and the presence of fever was more common in the first-line therapy group. Justification for non-guideline therapy was most often reported as to provide coverage for atypical organisms. The most common drug allergy recorded was amoxicillin, and urticaria with unknown timing was the most common type of reaction. Demographics Comparison Results Justification for Second-line / Other Therapy and Drug Allergy Results Conclusion This project observed a high proportion of children being prescribed non-guideline concordant therapy for a diagnosis of CAP. Age, race, practice location, and severity of illness measures showed a statistically significant difference between groups. This study highlights the importance of education which reviews the current guidelines and the most likely pathogens for children with CAP. Disclosures All Authors: No reported disclosures


2012 ◽  
Vol 6 (1) ◽  
pp. 3 ◽  
Author(s):  
Emmad E. Habib ◽  
Amr T. El-Kashef ◽  
Ezzat S. Fahmy

Neuroblastoma is a high-grade malignancy of childhood. It is chemo- and radio-sensitive but prone to relapse after initial remission. The aim of the current study was to study the results of the first- and second-line chemotherapy on the short-term response and long-term survival of children, and to further describe the side effects of treatment. Ninety-five children with advanced neuroblastoma were included in the study, divided into two groups according to the treatment strategy: 65 were treated by first-line chemotherapy alone, and 30 children who were not responding or relapsed after first-line chemotherapy were treated by second-line chemotherapy. External beam radiotherapy was given to bone and brain secondary cancers when detected. Staging workup was performed before, during and after management. Response was documented after surgery for the primary tumor. Median follow up was 32 months (range 24-60 months). Chemothe rapy was continued until toxicity or disease progression occurred, indicating interruption of chemotherapy. Patients received a maximum of 8 cycles. Toxicity was mainly myelo-suppression, with grade II-III severity in 60% of the firstline and 70% of the second-line chemotherapy patients. Median total actuarial survival was nearly 51 months for the first-line chemotherapy group and 30 months for the second-line line group, with a statistically significant difference between the two groups (P&lt;0.01).


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4851-4851
Author(s):  
Vittorio Ruggero Zilioli ◽  
Chiara Rusconi ◽  
Cristina Gabutti ◽  
Giovanni Grillo ◽  
Elisa Zucchetti ◽  
...  

Abstract Abstract 4851 Background: Primary Mediastinal B-Cell Lymphoma (PMBL) is an uncommon disease, characterized by aggressive and invasive course but with a good prognosis after anthracycline-based chemotherapy. In the PET era the role of consolidation radiotherapy is under debate and, despite CD20 expression, the efficacy of Rituximab is still unclear. We retrospectively analyzed the outcome of 36 consecutive patients (pts) affected by PMBL treated in the last 10 years at our institution. We focused on anti-CD20 antibody efficacy when added to chemotherapy and on the role of autologous stem cell transplantation (ASCT) in PET positive pts after first-line treatment. Patients and methods: From June 2000 to March 2011 36 pts with biopsy proven PMBL referred to our institution. Median age was 35 years (range: 18–68); 21 pts (58%) were female and a mediastinal bulk at diagnosis was documented in 33 pts (92%). B-symptoms were reported in 16 cases (44%) and an extra-nodal involvement in 19 cases (53%). Age-adjusted IPI score was ≥ 2 in 12 pts (33%). For all patients first line treatment consisted in a third generation anthracycline-based chemotherapy (VACOP-B), with the addiction of 6 Rituximab doses in 15 pts (42%). Pts obtaining complete remission (CR) with negative PET after (R)-VACOP-B were consolidated by radiotherapy (RT), while pts in partial remission (PR) with residual FDG uptake underwent a second-line chemotherapy with 3 DHAP cycles followed by autologous stem cell transplantation (ASCT). Results: In the whole cohort, after first-line therapy overall response rate (ORR) was 97%, with a CR rate of 39%. RT was therefore performed in 14 PET-negative pts. 2/14 pts experienced early relapse and only one of them obtained a second CR after salvage therapy, while the non-responding patient died because of progressive disease. Twenty-one pts (58%) showed a residual FDG uptake after (R)-VACOP-B and underwent second-line therapy. Nineteen pts responding to second-line therapy achieved ASCT, while 2 pts progressed and died after salvage therapy. ORR after ASCT was 86% with a CR rate of 71%. Post-ASCT RT was performed in 10 pts, 7 CR and 3 PR; two PR pts converted to CR after RT. With a median follow-up of 66 months (range: 13–142) 2-year overall survival (OS) and progression free survival (PFS) were respectively 94% and 89%. Among the 15 pts receiving first-line chemotherapy containing Rituximab, ORR after R-VACOP-B was 93% with a CR rate of 40%. RT was therefore performed in 6 PET-negative pts. 1/6 pts experienced early relapse and died of progressive disease. One patient showed progressive disease after R-VACOP-B and underwent second-line therapy with ASCT, obtaining CR. Eight pts (53%) showed a residual FDG-uptake after R-VACOP-B and underwent second-line therapy and ASCT. ORR and CR rate after ASCT were 100% and 75% respectively. Two pts in PR after ASCT converted to CR after RT. Among the 21 pts receiving chemotherapy without Rituximab, ORR after VACOP-B was 100% and CR rate was 38%. RT was therefore performed in 8 PET-negative pts; one of them experienced early relapse and obtained a second CR after salvage therapy. Thirteen pts (62%) showed a residual FDG-uptake after VACOP-B and underwent second-line therapy. Eleven pts responding to second-line therapy achieved ASCT, while 2 pts progressed and died after salvage therapy. ORR and CR rate after ASCT were 77% and 69% respectively. No statistically significant difference in ORR, CR rate, OS and PFS (Figure 1) was found between pts treated with Rituximab plus chemotherapy and pts treated with chemotherapy alone. Conclusions: These data substantially confirm the satisfactory outcome of PMBL, with a 2-year OS and PFS of 94% and 89% for the entire cohort. We registered a residual FDG uptake after first line chemotherapy in a proportion of pts higher than expected (58%). This subgroup of pts clearly take advantage from second line chemotherapy followed by ASCT, obtaining a CR rate of 71%. The addiction of Rituximab to first line chemotherapy instead does not seem to improve PMBL pts outcome in this small and retrospectively analyzed population. The role of immunotherapy in this rare lymphoma subtype and the chance to safely avoid RT consolidation in PET negative pts need to be further investigated in wider prospective trial. Disclosures: No relevant conflicts of interest to declare.


2012 ◽  
pp. e3
Author(s):  
Emmad E. Habib ◽  
Amr T. El-Kashef ◽  
Ezzat S. Fahmy

Neuroblastoma is a high-grade malignancy of childhood. It is chemo- and radio-sensitive but prone to relapse after initial remission. The aim of the current study was to study the results of the first- and second-line chemotherapy on the short-term response and long-term survival of children, and to further describe the side effects of treatment. Ninety-five children with advanced neuroblastoma were included in the study, divided into two groups according to the treatment strategy: 65 were treated by first-line chemotherapy alone, and 30 children who were not responding or relapsed after first-line chemotherapy were treated by second-line chemotherapy. External beam radiotherapy was given to bone and brain secondary cancers when detected. Staging workup was performed before, during and after management. Response was documented after surgery for the primary tumor. Median follow up was 32 months (range 24-60 months). Chemothe rapy was continued until toxicity or disease progression occurred, indicating interruption of chemotherapy. Patients received a maximum of 8 cycles. Toxicity was mainly myelo-suppression, with grade II-III severity in 60% of the firstline and 70% of the second-line chemotherapy patients. Median total actuarial survival was nearly 51 months for the first-line chemotherapy group and 30 months for the second-line line group, with a statistically significant difference between the two groups (P<0.01).


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