Time Between the First Day of Chemotherapy and the Last Day of Chest Radiation Is the Most Important Predictor of Survival in Limited-Disease Small-Cell Lung Cancer

2006 ◽  
Vol 24 (7) ◽  
pp. 1057-1063 ◽  
Author(s):  
Dirk De Ruysscher ◽  
Madelon Pijls-Johannesma ◽  
Søren M. Bentzen ◽  
André Minken ◽  
Rinus Wanders ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Survival Rate ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Important Predictor ◽  
Phase Iii ◽  
Combined Modality Treatment ◽  
Small Cell Lung ◽  
Limited Disease

Purpose To identify time factors for combined chemotherapy and radiotherapy predictive for long-term survival of patients with limited-disease small-cell lung cancer (LD-SCLC). Methods A systematic overview identified suitable phase III trials. Using meta-analysis methodology to compare results within trials, the influence of the timing of chest radiation and the start of any treatment until the end of radiotherapy (SER) on local tumor control, survival, and esophagitis was analyzed. For comparison between studies, the equivalent radiation dose in 2-Gy fractions, corrected for the overall treatment time of chest radiotherapy, was analyzed. Results The SER was the most important predictor of outcome. There was a significantly higher 5-year survival rate in the shorter SER arms (relative risk [RR] = 0.62; 95% CI, 0.49 to 0.80; P = .0003), which was more than 20% when the SER was less than 30 days (upper bound of 95% CI, 90 days). A low SER was associated with a higher incidence of severe esophagitis (RR = 0.55; 95% CI, 0.42 to 073; P < .0001). Each week of extension of the SER beyond that of the study arm with the shortest SER resulted in an overall absolute decrease in the 5-year survival rate of 1.83% ± 0.18% (95% CI). Conclusion A low time between the first day of chemotherapy and the last day of chest radiotherapy is associated with improved survival in LD-SCLC patients. The novel parameter SER, which takes into account accelerated proliferation of tumor clonogens during both radiotherapy and chemotherapy, may facilitate a more rational design of combined-modality treatment in rapidly proliferating tumors.

Phase II Study of Irinotecan Plus Cisplatin Induction Followed by Concurrent Twice-Daily Thoracic Irradiation With Etoposide Plus Cisplatin Chemotherapy for Limited-Disease Small-Cell Lung Cancer

2005 ◽  
Vol 23 (15) ◽  
pp. 3488-3494 ◽  
Author(s):  
Ji-Youn Han ◽  
Kwan Ho Cho ◽  
Dae Ho Lee ◽  
Hyae Young Kim ◽  
Eun-A Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Induction Chemotherapy ◽  
Cell Lung Cancer ◽  
Group Performance ◽  
Survival Rates ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Limited Disease

Purpose Irinotecan plus cisplatin (IP) chemotherapy demonstrated a promising outcome with a high complete response (CR) rate in chemotherapy-naïve patients with extensive small-cell lung cancer (SCLC). We evaluated the efficacy of induction IP chemotherapy followed by concurrent etoposide plus cisplatin (EP) chemotherapy with twice-daily thoracic radiotherapy (TDTRT) in limited-disease SCLC (LD-SCLC). Patients and Methods Between November 2001 and May 2003, 35 chemotherapy-naïve patients with LD-SCLC were enrolled. Thirty-three patients (94%) were male, and 29 (83%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. The median age was 63 years. Treatment consisted of two 21-day cycles of cisplatin 40 mg/m2 and irinotecan 80 mg/m2 intravenously (IV) on days 1 and 8 followed by two 21-day cycles of cisplatin 60 mg/m2 IV on days 43 and 64, and etoposide 100 mg/m2 IV on days 43 to 45 and 64 to 66, with concurrent TDTRT of total 45 Gy beginning on day 43. Results All 35 patients were assessable for response. The objective response rate was 97% (CR, 3; partial response [PR], 31) after induction chemotherapy and 100% (CR, 15; PR, 20) after concurrent chemoradiotherapy (CCRT). After a median follow-up of 26.5 months, the median survival was 25.0 months (95% CI, 19.0 to 30.9) with 1- and 2-year overall survival rates of 85.7% and 53.9%, respectively. Median progression-free survival (PFS) was 12.9 months with a 1- and 2-year PFS of 58.5% and 36.1%, respectively. The most common toxicities were grade 3 or 4 neutropenia in 68% of patients during induction chemotherapy and 100% during CCRT. Febrile neutropenia occurred in 20% of patients during induction chemotherapy and 60% during CCRT. Conclusion IP induction chemotherapy followed by concurrent TDTRT with EP chemotherapy showed a promising activity with favorable 1- and 2-year survival rates. Based on the favorable outcome in this trial, this regimen should be evaluated in a large phase III trial.

scholarly journals Multicenter, Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Pravastatin Added to First-Line Standard Chemotherapy in Small-Cell Lung Cancer (LUNGSTAR)

2017 ◽  
Vol 35 (14) ◽  
pp. 1506-1514 ◽  
Author(s):  
Michael J. Seckl ◽  
Christian H. Ottensmeier ◽  
Michael Cullen ◽  
Peter Schmid ◽  
Yenting Ngai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Limited Disease ◽  
Extensive Disease ◽  
Double Blind ◽  
Patients With Cancer

Purpose Treating small-cell lung cancer (SCLC) remains a therapeutic challenge. Experimental studies show that statins exert additive effects with agents, such as cisplatin, to impair tumor growth, and observational studies suggest that statins combined with anticancer therapies delay relapse and prolong life in several cancer types. To our knowledge, we report the first large, randomized, placebo-controlled, double-blind trial of a statin with standard-of-care for patients with cancer, specifically SCLC. Patients and Methods Patients with confirmed SCLC (limited or extensive disease) and performance status 0 to 3 were randomly assigned to receive daily pravastatin 40 mg or placebo, combined with up to six cycles of etoposide plus cisplatin or carboplatin every 3 weeks, until disease progression or intolerable toxicity. Primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), response rate, and toxicity. Results Eight hundred forty-six patients from 91 United Kingdom hospitals were recruited. The median age of recruited patients was 64 years of age, 43% had limited disease, and 57% had extensive disease. There were 758 deaths and 787 PFS events. No benefit was found for pravastatin, either in all patients or in several subgroups. For pravastatin versus placebo, the 2-year OS rate was 13.2% (95% CI, 10.0 to 16.7) versus 14.1% (95% CI, 10.9 to 17.7), respectively, with a hazard ratio of 1.01 (95% CI, 0.88 to 1.16; P = .90. The median OS was 10.7 months v 10.6 months, respectively. The median PFS was 7.7 months v 7.3 months, respectively. The median OS (pravastatin v placebo) was 14.6 months in both groups for limited disease and 9.1 months versus 8.8 months, respectively, for extensive disease. Adverse events were similar between groups. Conclusion Pravastatin 40 mg combined with standard SCLC therapy, although safe, does not benefit patients. Our conclusions are the same as those found in all four much smaller, randomized, placebo-controlled trials specifically designed to evaluate statin therapy in patients with cancer.

Early Compared With Late Radiotherapy in Combined Modality Treatment for Limited Disease Small-Cell Lung Cancer: A London Lung Cancer Group Multicenter Randomized Clinical Trial and Meta-Analysis

2006 ◽  
Vol 24 (24) ◽  
pp. 3823-3830 ◽  
Author(s):  
Stephen G. Spiro ◽  
Lindsay E. James ◽  
Robin M. Rudd ◽  
Colin W. Trask ◽  
Jeffrey S. Tobias ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Meta Analysis ◽  
Small Cell ◽  
Combined Modality Treatment ◽  
Small Cell Lung ◽  
Limited Disease ◽  
Cancer Group ◽  
Survival Difference

Purpose To replicate an earlier National Cancer Institute of Canada (NCIC) trial that examined the effect on survival of the timing of thoracic radiotherapy (TRT) in patients with limited disease small-cell lung cancer (SCLC). Patients and Methods Patients received three cycles of cyclophosphamide, doxorubicin, and vincristine alternating with three cycles of etoposide and cisplatin. Three hundred twenty five chemotherapy- and radiotherapy-naïve patients were randomly assigned to either early TRT administered concurrently in the second cycle or late TRT administered concurrently with the sixth cycle; the dose was 40 Gy in 15 fractions over 3 weeks. Results TRT was received by 92% and 82% of patients in the early and late arms, respectively (P = .01). Sixty-nine percent of patients in the early arm received all six courses of chemotherapy compared with 80% in the late arm (P = .003). There was no evidence of a survival difference; median overall survival time was 13.7 and 15.1 months in the early and late arms, respectively (P = .23). In a meta-analysis of all eight trials that compared early and late TRT, there were three in which the proportion of patients who completed their planned chemotherapy was similar between the TRT arms (hazard ratio [HR] = 0.73; 95% CI, 0.62 to 0.86) and five in which proportionally fewer patients in the early TRT arm completed their chemotherapy (HR = 1.06; 95% CI, 0.97 to 1.17). Conclusion This study failed to show a survival advantage for early TRT with chemotherapy in limited-stage SCLC, unlike the NCIC trial. However, the results of a meta-analysis suggest that it is essential to ensure that the delivery of chemotherapy is optimal when administered with early TRT.

Low SER versus high SER thoracic radiotherapy in the management of limited-stage small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18170-18170
Author(s):  
K. Lee ◽  
S. Lee ◽  
S. Lee ◽  
J. Kim ◽  
C. Shin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Rational Design ◽  
Cox Model ◽  
Small Cell ◽  
Combined Modality Treatment ◽  
Thoracic Radiotherapy ◽  
Small Cell Lung ◽  
Limited Disease

18170 Background: Patients with small-cell lung cancer account for about 20% of all lung cancer patients, with only one third of the patients presenting with limited disease. Although the combinations of chemo and radiation therapy have improved the prognosis substantially, the optimal chemoradiotherapy remains controversial in LD-SCLC. There are many reports that the overall duration of the chemoradiotherapy package is the most relevant predictor of the outcome. Therefore we tested SER beginning with the start of any treatment until the end of radiotherapy in patients with LD-SCLC. Methods: We enrolled the patients who were diagnosed as SCLC histologically in Korea University Medical Center from 2003 to 2006. All of them presented with limited disease. We divided them into two groups; the low SER (within 60 days of SER) and the high SER group (over 60 days). The patients were treated with thoracic radiotherapy and platinum based topoisomerase inhibitor. Overall survival was analyzed with a Cox model adjusted for performance and the chemotherapy regimen. Results: Of 29 patients, 16 patients were in low SER and 13 patients were in high SER. Low SER, as compared with high SER, significantly prolonged survival rate (p=0.028). We evaluated the radiation effect by the time between the start of chemotherapy and the start of radiotherapy, below 30 days and above 30 days, but there were no statistically comparable difference in there survival time between the two groups (p=0.176). The survival times of the patients were increased by 3.094 times in the low SER (95% C.I, 1.083 to 8.840, p=0.028) and by 6.901 times in ECOG groups 0 or 1 compared with group 2 (95% C.I, 1.563 to 30.468, p=0.018). There were no statistically significant increases in the side effects: pneumonitis, esophagitis, and BM suppressions. Conclusions: The cumulative survival of the patients in the low SER group is higher than for patients in the high SER group. The SER may facilitate a more rational design of combined-modality treatment in rapidly proliferating tumors. [Table: see text] No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document