Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small cell lung cancer: An analysis of the Spanish Lung Cancer Group pharmacogenomic study of cisplatin and docetaxel combination (PLATAX)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7124-7124
Author(s):  
C. Camps ◽  
R. De Las Peñas ◽  
G. López-Vivanco ◽  
J. Garde ◽  
J. Sanchez ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Dose Intensity ◽  
Small Cell ◽  
Relative Dose Intensity ◽  
Small Cell Lung ◽  
Drug Activity ◽  
Risk Of Death

7124 Background: Chemotherapy is the standard treatment for advanced non-small-cell lung cancer, and myelosuppression is a common side-effect. We aimed to assess whether haematological toxic effects could be a biological measure of drug activity and a marker of efficacy. Methods: We analysed data of 493 patients who received chemotherapy (cisplatin and docetaxel) within the pharmacogenomic, open-label, single-arm, multicentric PLATAX trial. Three subgroups of patients were considered: global population, patients who received at least three cycles of chemotherapy, and those who received at least six cycles. Neutropenia was categorised on the basis of worst WHO grade during chemotherapy: absent (grade 0), mild (grade 1–2), or severe (grade 3–4). Relative dose intensity was analysed for both drugs. The primary endpoint was overall survival. Results: Median overall survival was 9 months (8.2–9.7). Median relative dose intensity was 0.97 for cisplatin and docetaxel. 403 patients received at least three cycles of chemotherapy, and 255 received six or more. Neutropenia appeared in 172 patients (30.8%), 72 of them G3–4 (18.6%). Dose intensity was lower in patients who presented any grade of neutropenia versus those without neutropenia in the three analyzed subgroups, for both drugs (p < 0.05). Factors associated with higher risk of death were ECOG 1–2 (HR 1.8, p = 0.00) and female (HR 1.5, p = 0.02). There were no differences in overall survival between patients with G0 vs G1–2 vs G3–4 neutropenia (8.7 vs 11.6 vs 9.6 m, p = 0.41), however the risk of death was lower in patients with ECOG 0, that presented neutropenia (HR: 0.545, IC 95%: 0.31, 0.96; p = 0.034). Conclusions: Neutropenia during chemotherapy may be associated with increased survival of patients with advanced non-small cell lung cancer and ECOG 0. Its absence is not a result of underdosing. Prospective trials are needed to assess whether neutropenia could be a biological measure of drug activity and a marker of efficacy. No significant financial relationships to disclose.

scholarly journals Relative dose intensity of first-line chemotherapy and overall survival in patients with advanced non-small-cell lung cancer

2019 ◽  
Vol 28 (2) ◽  
pp. 925-932 ◽  
Author(s):  
Jeffrey Crawford ◽  
Neelima Denduluri ◽  
Debra Patt ◽  
Xiaolong Jiao ◽  
Phuong Khanh Morrow ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Dose Intensity ◽  
Small Cell ◽  
Relative Dose Intensity ◽  
Small Cell Lung ◽  
First Line ◽  
Line Chemotherapy

Association between hospital volume and overall survival of patients with metastatic non-small cell lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9044-9044 ◽  
Author(s):  
Gaurav Goyal ◽  
Adam C. Bartley ◽  
Ronald S. Go
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
Small Cell ◽  
Small Cell Lung ◽  
Risk Of Death ◽  
All Cause Mortality ◽  
Lower Volume

9044 Background: Prior studies have shown superior surgical outcomes of stage I-III non-small cell lung cancer (NSCLC) in centers with higher patient volumes. However, there is a lack of such information in stage IV NSCLC. In this study, we aim to determine the association between the number of patients with stage IV NSCLC treated annually at a treatment facility (volume) and all-cause mortality (outcome). Methods: Using the National Cancer Database, we identified patients diagnosed with stage IV NSCLC between 2004 and 2013. We classified the facilities by quartiles (Q; mean patients with NSCLC treated per year): Q1: < 13.8; Q2: 13.8 to 23.6, Q3: 23.6 to 30.3, and Q4: > 30.3. We used sandwich variance estimators to account for clustering of patients within facilities and Cox regression to determine the volume-outcome relationship, adjusting for demographic (sex, age, race), socioeconomic (insurance type), receipt of chemotherapy, and comorbid (Charlson-Deyo score) factors and year of diagnosis. Results: There were 281,654 patients with stage IV NSCLC treated at 1,275 facilities. The median age at diagnosis was 66 years, and 55.7% were men. The median annual facility volume was 23.6 patients per year (range, 1.0 to 301.4). The distribution of patients according to facility volume was: Q1: 6.6%, Q2: 14.9%, Q3: 25.4%, and Q4: 53.1%. The unadjusted median overall survival by facility volume was: Q1: 4.4 months, Q2: 4.5 months, Q3: 4.7 months, and Q4: 5.3 months ( P< .001). Multivariable analysis showed that facility volume was independently associated with all-cause mortality. Compared with patients treated at Q4 facilities, patients treated at lower-quartile facilities had a small but significantly higher risk of death (Q3 hazard ratio [HR], 1.05 [95% CI, 1.03 to 1.07]; Q2 HR, 1.06 [95% CI, 1.03 to 1.09]; Q1 HR, 1.09 [95% CI, 1.06 to 1.13]). Conclusions: Patients who were treated for stage IV NSCLC at lower-volume facilities had a significantly higher risk of all-cause mortality compared with those who were treated at lower-volume facilities. [Table: see text]

Efficacy and a novel clinicopathologic-genomic nomogram of atezolizumab in advanced non-small cell lung cancer (POPLAR and OAK): A combined analysis of two multicenter, randomized, phase II/III trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2573-2573
Author(s):  
Yunfang Yu ◽  
Yongjian Chen ◽  
Anlin Li ◽  
Qiyun Ou ◽  
Ying Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Group Performance ◽  
Small Cell ◽  
Small Cell Lung ◽  
Combined Analysis ◽  
Risk Of Death ◽  
Previously Treated

2573 Background: Atezolizumab, a programmed death ligand 1 (PD-L1) inhibitor, prolonged overall survival (OS) compared with docetaxel among patients with previously treated advanced non–small-cell lung cancer (NSCLC) in two independent multicentre, randomized trials (POPLAR and OAK). We conducted a combined analysis of the two trials to evaluate its efficacy and genomic biomarkers, and to further developed a novel predictive clinicopathologic-genomic nomogram of immunotherapy in NSCLC. Methods: Patients (N = 1,137) with stage IIIB/IV NSCLC and disease progression after previously platinum-based chemotherapy were randomly assigned (1:1) to receive atezolizumab (1200 mg/kg every 3 weeks) or docetaxel (75 mg/m2 every 3 weeks). The primary endpoint was OS. We applied a two-stage meta-analysis of pooled individual patient data in the intention-to-treat population. In OAK trial, patients treated with atezolizumab were randomly assigned (1:1) to the training group or the validation group to develop a predictive clinicopathologic-genomic nomogram of immunotherapy. POPLAR and OAK were registered with ClinicalTrials.gov, numbers NCT02008227 and NCT01903993. Results: In the pooled analysis, the median overall survival was 13.49 months (95% confidence interval [CI], 11.95 to 15.22) with atezolizumab versus 9.66 months (95% CI, 8.73 to 10.70) with docetaxel. The risk of death was 28% lower with atezolizumab than with docetaxel (hazard ratio [HR], 0.72; 95% CI, 0.62 to 0.83; P < 0.001). The race, sex, tumor histology, eastern cooperative oncology group performance status, PD-L1 expression, and especially pretreatment mutation (TP53, DNMT3A and KEAP1) were significantly associated with OS, and were used for the development of the predictive nomogram. The clinical use of the nomogram showed a closer association with 3-year OS than the blood-based tumor mutational burden (bTMB) or PD-L1 expression alone (nomogram, AUC = 0.818; bTMB, AUC = 0.701; PD-L1, AUC = 0.526) among NSCLC patients who had received atezolizumab. The superior predictability of the nomogram was further confirmed in the validation and entire OAK cohorts. Conclusions: Among patients with advanced, previously treated NSCLC, OS was significantly better with atezolizumab than with docetaxel. Furthermore, we constructed a novel and powerful clinicopathologic-genomic nomogram for personalized immunotherapy options.

scholarly journals Up front chemotherapy dosing and relative dose intensity in extensive stage small cell lung cancer

2017 ◽  
Vol 28 ◽  
pp. ii17-ii18
Author(s):  
A.W. Mølby ◽  
B.E. Laursen ◽  
U. Falkmer ◽  
T. McCulloch ◽  
N.A. Jensen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Dose Intensity ◽  
Small Cell ◽  
Relative Dose Intensity ◽  
Small Cell Lung ◽  
Extensive Stage

Phase II study of combination chemotherapy with docetaxel and carboplatin for elderly patients with advanced non-small cell lung cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19073-e19073
Author(s):  
B. Kim ◽  
H. Kim ◽  
T. Kim ◽  
H. Lee ◽  
B. Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Elderly Patients ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Combination Chemotherapy ◽  
Dose Intensity ◽  
Small Cell ◽  
Time To Progression ◽  
Small Cell Lung

e19073 Background: More than 50% of advanced non-small cell lung cancer (NSCLC) are diagnosed in patients older than age 65 years. Cisplatin-based chemotherapy has been used in patients with advanced NSCLC as standard treatment, and we investigated the efficacy and safety of combination chemotherapy with docetaxel and carboplatin for elderly patients with advanced non- small cell lung cancer. Methods: Chemotherapy-naïve patients (age ≥ 65 years) with stage IIIB or IV NSCLC were enrolled. Patients received docetaxel (75 mg/m2 on D1) and carboplatin (AUC of 5 mg/ml/min on D1) every 3 weeks. End points included response, time to progression, overall survival, and toxicity. Results: Total 37 patients were enrolled between March 2005 and August 2008. Median age was 75 years old (range, 65 to 84 years), and 33 patients (89.2%) had ECOG PS 0 or 1. Twenty two patients (59.5%) had increased Charlson comorbidity index score (CCI ≥1). The median number of treatment cycles was five (range, 1–8), and relative dose intensity was 95.6% in docetaxel and 95.8% in carboplatin. Overall response rate was 51.3% (95% CI 34.9–67.1) with one complete response, and 18 partial responses. The median time to progression was 6.7 months and median overall survival was 12.3 months. In 164 cycles, grade 3 or 4 hematologic toxicities included neutropenia (10.4%), anemia (1.8%), and thrombocytopenia (1.2%). Non-hematologic toxicities were tolerable. Conclusions: The combination chemotherapy with docetaxel and carboplatin was effective with tolerable toxicities in elderly patients with advanced non-small cell lung cancer. No significant financial relationships to disclose.

scholarly journals The Factors Reducing Relative Dose Intensity of Cisplatin and Vinorelbine as Adjuvant Chemotherapy in Patients with Non-Small Cell Lung Cancer

Oncomedicine ◽  
2018 ◽  
Vol 3 ◽  
pp. 9-14
Author(s):  
Ryo Inose ◽  
Katsuyuki Takahashi ◽  
Naruo Yoshimura ◽  
Tomoya Kawaguchi ◽  
Mitsutaka Takada ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Dose Intensity ◽  
Small Cell ◽  
Relative Dose Intensity ◽  
Small Cell Lung

scholarly journals Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: a pooled analysis of 6 randomized trials

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Piera Gargiulo ◽  
Laura Arenare ◽  
Cesare Gridelli ◽  
Alessandro Morabito ◽  
Fortunato Ciardiello ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Value ◽  
Pooled Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Risk Of Death ◽  
Chemotherapy Induced Neutropenia

Abstract Background Chemotherapy-induced neutropenia (CIN) has been demonstrated to be a prognostic factor in several cancer conditions. We previously found a significant prognostic value of CIN on overall survival (OS), in a pooled dataset of patients with advanced non-small-cell lung cancer (NSCLC) receiving first line chemotherapy from 1996 to 2001. However, the prognostic role of CIN in NSCLC is still debated. Methods We performed a post hoc analysis pooling data prospectively collected in six randomized phase 3 trials in NSCLC conducted from 2002 to 2016. Patients who never started chemotherapy and those for whom toxicity data were missing were excluded. Neutropenia was categorized on the basis of worst grade during chemotherapy: absent (grade 0), mild (grade 1–2), or severe (grade 3–4). The primary endpoint was OS. Multivariable Cox model was applied for statistical analyses. In the primary analysis, a minimum time (landmark) at 180 days from randomization was applied in order to minimize the time-dependent bias. Results Overall, 1529 patients, who received chemotherapy, were eligible; 572 of them (who received 6 cycles of treatment) represented the landmark population. Severe CIN was reported in 143 (25.0%) patients and mild CIN in 135 (23.6%). At multivariable OS analysis, CIN was significantly predictive of prognosis although its prognostic value was entirely driven by severe CIN (hazard ratio [HR] of death 0.71; 95%CI: 0.53–0.95) while it was not evident with mild CIN (HR 1.21; 95%CI: 0.92–1.58). Consistent results were observed in the out-of-landmark group (including 957 patients), where both severe and mild CIN were significantly associated with a reduced risk of death. Conclusion The pooled analysis of six large trials of NSCLC treatment shows that CIN occurrence is significantly associated with a longer overall survival, particularly in patients developing severe CIN, confirming our previous findings.

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