Clinical significance of ERCC2 haplotype-tagging single nucleotide polymorphisms in patients with unresectable non-small cell lung cancer treated with first-line platinum-based chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19156-e19156
Author(s):  
Seok-Hyun Kim ◽  
Gyeong-won Lee ◽  
Yi Yeong Jeong ◽  
Ho-Cheol Kim ◽  
Jong Deog Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell ◽  
Rank Test ◽  
Nucleotide Polymorphisms ◽  
Small Cell Lung ◽  
First Line ◽  
Single Nucleotide ◽  
Log Rank Test ◽  
Platinum Based Chemotherapy ◽  
Grade 3

e19156 Background: DNA repair pathway is a crucial molecular mechanism potentially involved in resistance to platinum-based chemotherapy in the unresectable non-small cell lung cancer. Furthermore, single nucleotide polymorphisms (SNPs) and haplotypes in the ERCC2 gene are thought to be associated with the risk of developing lung cancer and clinical outcomes. Methods: We genotyped 8 ERCC2 htSNPs for 129 unresectable NSCLC (stage IIIA, 12; stage III, 36; stage IV, 82) cases treated with first-line platinum-based chemotherapy. Clinical characteristics, treatment outcomes, and predictive value of htSNPs in patient response, survival, and chemotherapy-related adverse events were analyzed according to each ERCC2 htSNP using chi-square test, Kaplan-Meier method, and Cox proportional hazard model. Results: No differences were observed in patient or disease characteristics and response according to ERCC2 htSNPs. In a survival analysis, rs50872 was significantly related to overall survival (OS) (log-rank test, p=0.014). The median survival duration of rs50872 G/G, A/G, and A/A genotypes was 35.75 (95% confidence interval [CI] 21.05-50.45), 36.07 (hazard ratio[HR] 1.02, 95% CI 25.20-46.94), and 16.75 (HR 3.49, 95% CI 5.73-27.77) months, respectively. A significant association was observed between grade 3-4 infections and poor survival: OS in patients with a grade 0-2 infection: 35.75 months (95% CI 28.15-43.35); OS in patients with a grade 3-4 infection: 12.86 months (95% CI 8.99-16.72, HR 3.57) (log-rank test, p<0.001). In a subgroup analysis, rs238405 genotype was significantly related to OS in the taxane-based group. However, rs238416 genotype was significantly associated with OS in the gemcitabine-based group. Conclusions: ERCC2 htSNPs rs50872 (overall), rs238405 (taxane-based group), and rs238416 (gemcitabine-based group) and infection related to first-line chemotherapy were associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy. However, additional large prospective studies focusing on the role of ERCC2 htSNPs in unresectable NSCLC are needed.

Prospective Randomized Trial of Docetaxel Versus Best Supportive Care in Patients With Non–Small-Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy

2000 ◽  
Vol 18 (10) ◽  
pp. 2095-2103 ◽  
Author(s):  
Frances A. Shepherd ◽  
Janet Dancey ◽  
Rodryg Ramlau ◽  
Karin Mattson ◽  
Richard Gralla ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Supportive Care ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Best Supportive Care ◽  
Small Cell ◽  
Rank Test ◽  
Small Cell Lung ◽  
Log Rank Test ◽  
Platinum Based Chemotherapy

PURPOSE: To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non–small-cell lung cancer who had previously been treated with platinum-based chemotherapy. Secondary end points included assessment of response (docetaxel arm only), toxicity, and quality of life. PATIENTS AND METHODS: Patients with performance statuses of 0 to 2 and stage IIIB/IV non–small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters. They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel. Patients were stratified by performance status and best response to cisplatin chemotherapy and were then randomized to treatment with docetaxel 100 mg/m2 (49 patients) or 75 mg/m2 (55 patients) or best supportive care. Patients in both arms were assessed every 3 weeks. RESULTS: One hundred four patients (103 of whom were eligible for entry onto the study) were well balanced for prognostic factors. Of 84 patients with measurable lesions, six (7.1%) achieved partial responses (three patients at each dose level). Time to progression was longer for docetaxel patients than for best supportive care patients (10.6 v 6.7 weeks, respectively; P < .001), as was median survival (7.0 v 4.6 months; log-rank test, P = .047). The difference was more significant for docetaxel 75 mg/m2 patients, compared with corresponding best supportive care patients (7.5 v 4.6 months; log-rank test, P = .010; 1-year survival, 37% v 11%; χ2 test, P = .003). Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m2, three of whom died, and in one patient treated with docetaxel 75 mg/m 2 . Grade 3 or 4 nonhematologic toxicity, with the exception of diarrhea, occurred at a similar rate in both the docetaxel and best supportive care groups. CONCLUSION: Treatment with docetaxel is associated with significant prolongation of survival, and at a dose of 75 mg/m2, the benefits of docetaxel therapy outweigh the risks.

Efficacy and safety of PD-1/PD-L1 antibody combined with chemotherapy as second-line or third-line treatment for metastatic small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20574-e20574
Author(s):  
Jun Wang ◽  
Beibei Yin ◽  
Yaping Guan ◽  
Dongfeng Feng
Keyword(s):  
Lung Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Small Cell ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
First Line ◽  
Platinum Based Chemotherapy ◽  
Extensive Stage ◽  
Grade 3

e20574 Background: For a small subset of patients, immune checkpoint blockade heralds a promising strategy for achieving disease control in small cell lung cancer (SCLC). Nivolumab or pembrolizumab monotherapy has been granted accelerated approval for treatment of patients with extensive-stage SCLC with disease progression after platinum-based chemotherapy and at least one other line of therapy. Moreover, Based on IMpower133 and CASPIAN data, addition of PD-L1 antibody such as atezolizumab or durvalumab to first-line platinum-based chemotherapy prolongs overall survival over chemotherapy alone. However, it remains exclusive that whether PD-1/PD-L1 antibody combined with chemotherapy is effective against extensive-stage SCLC when progressed on previous chemotherapy. Methods: We reviewed patients with extensive-stage SCLC who have failed in first-line or beyond chemotherapy and received PD-1/PD-L1 antibodies with chemotherapy in a single institute. The efficacy and safety were evaluated. The primary end point was the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1. Results: A total of 11 patients were included in this retrospective cohort study. The median age was 46 years (range from 29 to 62). Seven patients were male. Four were current or former smokers. Six received two prior therapies. Nine had previously received radiation therapy. PD-1 and PD-L1 inhibitors were administrated in 5 and 6 patients, respectively. No patient had a complete response. 2 patients had a partial response, and the objective response rate was 18.2%. 5 patients were evaluated as stable disease with a disease control rate of 63.6%. The median overall survival and progression-free survival was 3.0 months and 2.3 months, respectively. A patient with partial response had a long duration of response of 5.2 months. The most common grade 3 or 4 treatment-related were neutropenia, anemia, and decreased neutrophil count. Most immune-related adverse events were grade 1 or 2, with rash, pruritus and hypothyroidism being the most common, and 1 patient had grade 3 pneumonia. Conclusions: Immunotherapy plus chemotherapy could be beneficial for a subgroup of extensive-stage SCLC patients who have progressed after previous chemotherapy. Further prospective, randomized studies are warranted.

Randomized Phase II Trial of Single-Agent Amrubicin or Topotecan as Second-Line Treatment in Patients With Small-Cell Lung Cancer Sensitive to First-Line Platinum-Based Chemotherapy

2011 ◽  
Vol 29 (3) ◽  
pp. 287-293 ◽  
Author(s):  
Robert Jotte ◽  
Paul Conkling ◽  
Craig Reynolds ◽  
Matthew D. Galsky ◽  
Leonard Klein ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Single Agent ◽  
Small Cell ◽  
Line Treatment ◽  
Second Line ◽  
Small Cell Lung ◽  
First Line ◽  
Platinum Based Chemotherapy ◽  
Grade 3

Purpose This phase II study evaluated the safety and efficacy of single-agent amrubicin versus topotecan in patients with small-cell lung cancer (SCLC) sensitive to first-line platinum-based chemotherapy. Patients and Methods Patients were randomly assigned 2:1 to amrubicin (40 mg/m2/d in a 5-minute intravenous [IV] infusion, days 1 through 3, every 21 days) or topotecan (1.5 mg/m2/d in a 30-minute IV infusion, days 1 through 5, every 21 days). The primary efficacy end point was overall response rate (ORR) for amrubicin. Secondary end points included time to progression, median progression-free survival (PFS), and median overall survival (OS). Results Of 76 patients enrolled, 50 patients were randomly assigned to amrubicin, and 26 patients were randomly assigned to topotecan. Amrubicin treatment resulted in a significantly higher ORR than topotecan (44% v 15%; P = .021). Median PFS and median OS were 4.5 months and 9.2 months with amrubicin and 3.3 months and 7.6 months with topotecan, respectively. Tolerability was similar with both agents. However, grade 3 or worse neutropenia and thrombocytopenia seemed to be more frequent in the topotecan group as compared with the amrubicin group (78% and 61% v 61% and 39%, respectively). Conclusion Amrubicin shows promising activity, with an ORR of 44% compared with an ORR of 15% for topotecan as second-line treatment in patients with SCLC sensitive to first-line platinum-based chemotherapy. In addition, the safety profiles were comparable; however, a trend was noted for more frequent grade 3 or worse neutropenia and thrombocytopenia in the topotecan group as compared with the amrubicin group. Additional studies are ongoing.

scholarly journals Single Nucleotide Polymorphism at rs1982073:T869C of the TGFβ1 Gene Is Associated With the Risk of Radiation Pneumonitis in Patients With Non–Small-Cell Lung Cancer Treated With Definitive Radiotherapy

2009 ◽  
Vol 27 (20) ◽  
pp. 3370-3378 ◽  
Author(s):  
Xianglin Yuan ◽  
Zhongxing Liao ◽  
Zhensheng Liu ◽  
Li-E Wang ◽  
Susan L. Tucker ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Lower Risk ◽  
Radiation Pneumonitis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Single Nucleotide ◽  
Platinum Based Chemotherapy ◽  
Grade 3

Purpose In search of reliable biologic markers to predict the risk of normal tissue damage by radio(chemo)therapy before treatment, we investigated the association between single nucleotide polymorphisms (SNPs) in the transforming growth factor 1 (TGFβ1) gene and risk of radiation pneumonitis (RP) in patients with non–small-cell lung cancer (NSCLC). Patients and Methods Using 164 available genomic DNA samples from patients with NSCLC treated with definitive radio(chemo)therapy, we genotyped three SNPs of the TGFβ1 gene (rs1800469:C-509T, rs1800471:G915C, and rs1982073:T869C) by polymerase chain reaction restriction fragment length polymorphism method. We used Kaplan-Meier cumulative probability to assess the risk of grade ≥ 3 RP and Cox proportional hazards analyses to evaluate the effect of TGFβ1 genotypes on such risk. Results There were 90 men and 74 women in the study, with median age of 63 years. Radiation doses ranging from 60 to 70 Gy (median = 63 Gy) in 30 to 58 fractions were given to 158 patients (96.3%) and platinum-based chemotherapy to 147 (89.6%). Grade ≥ 2 and grade ≥ 3 RP were observed in 74 (45.1%) and 36 patients (22.0%), respectively. Multivariate analysis found CT/CC genotypes of TGFβ1 rs1982073:T869C to be associated with a statistically significantly lower risk of RP grades ≥ 2 (hazard ratio [HR] = 0.489; 95% CI, 0.227 to 0.861; P = .013) and grades ≥ 3 (HR = 0.390; 95% CI, 0.197 to .774; P = 0.007), respectively, compared with the TT genotype, after adjustment for Karnofsky performance status, smoking status, pulmonary function, and dosimetric parameters. Conclusion Our results showed that CT/CC genotypes of TGFβ1 rs1982073:T869C gene were associated with lower risk of RP in patients with NSCLC treated with definitive radio(chemo)therapy and thus may serve as a reliable predictor of RP.

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