Concurrent Thoracic Radiotherapy Research Articles

Randomized phase II trial of S-1 plus cisplatin or docetaxel plus cisplatin with concurrent thoracic radiotherapy for inoperable stage III non-small cell lung cancer (TORG1018).

8534 Background: Concurrent chemoradiotherapy (CCRT) is standard of care in patients with inoperable stage III non-small cell lung cancer (NSCLC), however the best chemotherapy regimen has not been identified. The study was conducted to evaluate cisplatin plus S-1 (SP) or cisplatin plus docetaxel (DP) both with concurrent thoracic radiotherapy in patients with inoperable stage III NSCLC. Methods: Patients with inoperable stage III NSCLC were randomized to SP (S-1 40 mg/m2 twice a day on days 1-14 and 29-42 plus cisplatin 60 mg/m2 on days 1 and 29) or DP (docetaxel 50 mg/m2 and cisplatin 80 mg/m2 on days 1 and 29), stratified by institution, gender, histology, and stage. In both arms, concurrent radiotherapy began on day 1 (60 Gy/30 fr). After CCRT, patients in each group received two additional cycles of the consolidation chemotherapy. Primary endpoint was 2-year overall survival (OS), and secondary endpoints were OS, progression-free survival (PFS), toxicity profile, dose intensity and objective response rate (ORR). Results: From May 2011 to August 2014, 110 patients were enrolled from 19 institutions. Four patients (one in SP and 3 in DP) were ineligible, and 106 patients (53 in each arm) were evaluable for efficacy and safety. Patient characteristics were: male/female 83/23; median age 65 (range 42-74); performance status 0/1 59/47; IIIA/IIIB 59/47. With a median follow-up of 39.3 months, 2-year survival and median OS were 79% (95% CI: 66-88%) and 55.2 months in the SP arm and 69% (95% CI: 55-80%) and 50.8 months in the DP arm, respectively. ORR and median PFS in SP arm were 71.7% and 11.6 months, and ones in the DP arm were 67.9% and 19.9 months. Grade 3/4 leukopenia (62.3/34.0%) and neutropenia (56.6/28.3%) were significantly more frequent in DP arm than SP arm. Incidences of non-hematological toxicities including febrile neutropenia, anorexia, nausea, diarrhea, radiation pneumonitis and esophagitis tended to be higher in DP arm. No treatment-related death occurred. Conclusions: The 2-year OS favored for SP arm with less toxicity. We choose SP with concurrent thoracic radiotherapy as a future reference regimen. Clinical trial information: UMIN000005993.

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial

The optimal chemotherapy regimen administered currently with radiation in patients with stage III non-small cell lung cancer (NSCLC) remains unclear. A multicenter phase III trial was conducted to compare the efficacy of concurrent thoracic radiation therapy with either etoposide/cisplatin (EP) or carboplatin/paclitaxel (PC) in patients with stage III NSCLC. Patients were randomly received 60-66 Gy of thoracic radiation therapy concurrent with either etoposide 50 mg/m2 on days 1-5 and cisplatin 50 mg/m2 on days 1 and 8 every 4 weeks for two cycles (EP arm), or paclitaxel 45 mg/m2 and carboplatin (AUC 2) on day 1 weekly (PC arm). The primary end point was overall survival (OS). The study was designed with 80% power to detect a 17% superiority in 3-year OS with a type I error rate of 0.05. A total of 200 patients were randomized and 191 patients were treated (95 in the EP arm and 96 in the PC arm). With a median follow-up time of 73 months, the 3-year OS was significantly higher in the EP arm than that of the PC arm. The estimated difference was 15.0% (95% CI 2.0%-28.0%) and P value of 0.024. Median survival times were 23.3 months in the EP arm and 20.7 months in the PC arm (log-rank test P = 0.095, HR 0.76, 95%CI 0.55-1.05). The incidence of Grade ≥2 radiation pneumonitis was higher in the PC arm (33.3% versus 18.9%, P = 0.036), while the incidence of Grade ≥3 esophagitis was higher in the EP arm (20.0% versus 6.3%, P = 0.009). EP might be superior to weekly PC in terms of OS in the setting of concurrent chemoradiation for unresectable stage III NSCLC. NCT01494558.

Radiation Therapy in the Treatment of Small Cell Lung Cancer

Small cell lung cancer (SCLC) represents between 13-15% of all lung cancers; however is the fifth leading cause of cancer death worldwide. SCLC prognosis remains poor despite improvements in diagnosis and treatment over the last 30 years. Patients with SCLC are typically divided into those with limited stage (LS) versus extensive stage (ES). LS disease is treated with concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI). For patients with ES-SCLC current approach is using combination chemotherapy with a platinum-based regimen.

Thoracic irradiation in 3 weeks for limited-stage small cell lung cancer: Is twice a day fractionation really needed?

PurposeMany Canadian institutions treat limited-disease small cell lung cancer with 40Gy in 15 fractions delivered once-a-day in 3weeks concomitantly with chemotherapy. This regimen is convenient and seems to be effective. Here, we report and compare with a literature review the outcomes of patients with limited-stage small cell lung cancer treated in our institution with this hypofractionated regimen. Patients and methodsFrom January 2004 to December 2012, patients with limited-stage small cell lung cancer treated curatively with platinum-based chemotherapy and concurrent thoracic radiotherapy at a dose of 40Gy in 16 fractions once-a-day were eligible for this review. ResultsSixty-eight patients fit the analysis criteria, including ten patients with small pleural effusion. The median age was 66years old. After a median follow-up of 77months for those alive, the median survival was 28months. At 3 and 5years respectively, the locoregional control rates were 67 and 64%, while the overall survival rates were 40 and 35%. Prophylaxis cranial irradiation was delivered to 68% of the patients. Grade 2 and 3 acute esophagitis occurred in respectively 49 and 9% of the patients. There was no grade 4 radiation-induced toxicity. All patients, except for one, completed their thoracic irradiation course without interruption. ConclusionOnce-a-day hypofractionated radiation with concurrent chemotherapy followed by prophylactic cranial irradiation is a practical regimen. Based on our experience and the published literature, it appears to be similarly effective as regimens using twice-daily fractionation in 3weeks, or once-daily in 6 to 7weeks with higher radiotherapy doses. Further prospective comparisons of hypofractionation with the current recommendations are needed.

P2.02-027 A Randomized Phase II Trial of S-1 plus Cisplatin or Docetaxel plus Cisplatin with Concurrent Thoracic Radiotherapy for Stage III NSCLC: TORG1018

Concurrent chemoradiotherapy (CCRT) is the current standard treatment for inoperable stage III non-small cell lung cancer (NSCLC), and a clearly superior regimen has not yet been identified. This study was conducted to evaluate cisplatin with S-1 (SP) or docetaxel (DP) with concurrent thoracic radiotherapy in patients with inoperable stage III NSCLC. In this open-label, non-comparative phase II trial, patients with inoperable stage IIIA/B NSCLC were randomized (1:1) to SP (S-1 40 mg/m2 twice a day on days 1-14 and 29-42, and cisplatin 60 mg/m2 on days 1 and 29) or DP (docetaxel 50 mg/m2 and cisplatin 60 mg/m2 on days 1 and 29), stratified by institution, gender, histology, and stage. In both arms, concurrent radiotherapy was started on day 1 (total 60 Gy in 30 fractions). After CCRT, patients in each group received two additional cycles of consolidation chemotherapy with the same regimen as that for the CCRT part. The primary endpoint was the 2-year overall survival (OS) rate, and secondary endpoints were OS, progression-free survival (PFS), toxicity profile, dose intensity and objective response rate (ORR). Between May 2011 and August 2014, 110 patients from 19 institutions were enrolled. Finally, 106 patients (56 in each arm) were evaluable for efficacy and safety. The patient characteristics were: male/female, 83/23; median age, 65 (range 42-74) yr; performance status 0/1, 59/47; IIIA/IIIB, 59/47. After a median follow-up of 23.1 months, ORR and median PFS were 71.7% (95% CI: 57.7-83.2) and 11.5 months (95%: 9.00-14.1) in the SP arm, and 67.9% (95% CI: 53.7-80.1) and 17.2 months (95%: 9.62-24.0) in the DP arm, respectively. Grade 3-4 leukopenia (34.0%/62.3%) and neutropenia (28.3%/56.6%) were significantly higher in the DP arm than in the SP arm. Incidences of non-hematological toxicity including febrile neutropenia, anorexia, nausea, diarrhea, radiation pneumonitis and esophagitis tended to be high in the DP arm. No treatment-related death occurred. At this preliminary stage, it appears that although the DP arm may have more toxic effects than the SP arm, it has a favorable PFS. The OS data will be available soon.

P2.02-028 A Phase I/II Study of Carboplatin, Pemetrexed, and Concurrent Radiation Therapy for Patients with Locally Advanced NSCLC. CJLSG0912

A combined concurrent therapy with a platinum-based regimen and radiation is recognized as a standard for patients with unresectable stage III lung cancer. Though combined therapy has improved survival, little improvement was reported after that for decades. Pemetrexed is a new generation drug which is widely recognized as a safe and effective agent for patients with stage IV lung cancer. Moreover pemetrexed is expected to have a synergistic effect with radiation in vitro study. The purpose of this study was to investigate safety and toxicity profile of a regimen of pemetrexed/carboplatin (Pem/CBDCA) plus concurrent thoracic radiotherapy (TRT) followed by consolidation therapy with Pem/CBDCA for Japanese patients with unresectable non-small cell lung cancer (NSCLC). We planned a multi-institutional open clinical phase I/II trial of Pem (500 mg/m2) /CBDCA (AUC=5) plus concurrent TRT for patients with stage IIIA/IIIB NSCLC. Patients were administered two cycles of Pem/CBDCA with three-weeks interval and delivered 60 Gy radiotherapy in 30 fractions concurrently. Additional two cycles of Pem/CBDCA with a three-weeks interval were administered after the safety of concurrent therapy was confirmed. Regarding a phase I study, we confirmed a safety of this therapy every three consecutive patients. In case that three or more DLTs in first six patients occurred, a dose of CBDCA was to be decreased from AUC 5 to 4. We planned to enroll thirty patients in this study in total of phaseIandII. Six patients were included in the phase I study. Median follow-up period was 27.4 month. DLTs were observed in two out of six patients. This fulfilled preplanned criterion to conclude therapeutic dose. The most frequent non-hematologic adverse event was esophagitis (66.7%). Neutropenia was observed rather frequently (83.3%), but no patients developed febrile neutropenia. As to two cases of DLT, one patient experienced grade 2 radiation pneumonitis. The other patient presented prolonged leukocytopenia. Other four patients completed scheduled therapy. Five patients (83.3%) got PR. Two-year survival was 100%. Disease progression was observed in three patients during study period. Because of slow accrual, phase II study was not conducted. Present therapy is feasible for Japanese patients with unresectable stage III NSCLC. Trial registration: UMIN000008426.

P1.07-005 A Retrospective Study of Sequential Chemoradiotherapy for LD-SCLC Patients in Whom Concurrent Therapy is Not Indicated

The standard treatment for limited-disease small-cell lung cancer (LD-SCLC) is a combination of cisplatin-doublet chemotherapy and concurrent thoracic radiotherapy. However, sequential radiotherapy, rather than concurrent radiotherapy, is selected for some cases because of concerns regarding the irradiation field, patient age, comorbidities, or performance status. Nevertheless, the efficacy of sequential chemoradiotherapy in patients in whom concurrent chemoradiotherapy is contraindicated is not well known. We retrospectively analyzed 286 patients with LD-SCLC at the National Cancer Center Hospital and the NTT Medical Center in Japan between 2000 and 2014. We then compared the clinical characteristics and treatment outcomes of patients undergoing sequential radiotherapy with those undergoing concurrent radiotherapy. One hundred and eighty-three patients received concurrent chemoradiotherapy and 30 received sequential chemoradiotherapy. The median age of the patients was 64 years (range, 18-81 years) for the concurrent group and 71.5 years (50-83 years) for the sequential group. The concurrent group contained 43 women (23%), while the sequential group contained 9 women (30%). The major reasons for the selection of sequential radiotherapy were patient age (13 patients), a large irradiation field (8 patients), and comorbidities (5 patients). In the sequential group, 23 (77%) received conventional radiotherapy, whereas 7 (23%) received accelerated hyperfractionated radiotherapy. The median overall survival period was 34.5 months for the concurrent group and 27.6 months for the sequential group (P = 0.39). The 2-, 3-, and 5-year survival rates were 71%, 50%, and 40% for the concurrent group and 56%, 56%, and 35% for the sequential group. Recurrence was seen in 149 patients (81%) in the concurrent group and 19 patients (63%) in the sequential group. We obtained treatment outcomes for patients who could not receive concurrent radiotherapy but could complete sequential radiotherapy that were comparable with the outcomes for those who received concurrent radiotherapy. For patients in whom concurrent chemoradiotherapy is not indicated, sequential chemoradiotherapy should be considered.

P2.02-025 Continuous Intravenous Pumping Endostar Combined with Radiochemotherapy in Unresectable Stage III Non-Small-Cell Lung Cancer

Preclinical models have shown that recombinant human endostatin (Endostar) can transiently normalize the tumor vasculature to make it more efficient for oxygen delivery, which provides a treatment window of enhancing tumor radiosensitivity. This study is to evaluate the safety and efficacy of continuous intravenous pumping (CIP) of Endostar combined with standard concurrent radiochemotherapy for unresectable stage III non-small-cell lung cancer (NSCLC). In this prospective study, patients with unresectable stage IIIA or IIIB NSCLC received CIP of Endostar (7.5mg/m2) over 5 days at weeks 1, 3, 5, and 7. During week 2-8, patients received two 28-day cycles of etoposide 50mg/m2 on day 1-5 and cisplatin 50mg/m2 on day 1, 8, with concurrent thoracic radiation of 60-66 Gy in 30-33 fractions over 6-7 weeks. Acute toxicities were evaluated using CTCAE 3.0. Tumor response was evaluated using RECIST 1.1 criteria. Between Nov. 2012 and May. 2016, 67 patients were eligible for toxicity and efficacy evaluation, including 56 (83.6%) male and 11 (16.4%) female, 44 (65.7%) with squamous cell carcinoma, 20(29.9%) with adenocarcinoma, 1 (1.5%) with large cell carcinoma and 2 (3.0%) with undifferentiated carcinoma, and 28 (41.8%) with stage III A disease and 39 (58.2%) with III B disease, respectively. The median age was 59 (31-69) years. All patients completed the treatment as planned, except that 3 patient missed one cycle chemotherapy. There were 8 (11.9%), 43 (64.2%), 11 (16.4%) and 4 (6.0%) patients achieved complete response, partial response, stable disease and progressive disease, respectively. The objective remission rate (ORR) is 76.1%. There were 23 patients (34.3%) with grade 3+4 neutropenia, 9 (13.4%) with grade 3+4 anemia, and 10 (14.9%) with grade 3+4 thrombocytopenic. Three patients (4.5%) developed grade 3 nausea/vomiting. Grade 3 acute esophagitis, grade 1+2 and grade 3 pneumonitis were observed in 8 (11.9%), 12 (17.9%) and 2 (3.0%) patients, respectively. One patient died of pneumonitis before efficacy evaluation. No grade 2 cardiovascular toxicity was observed. Up to the last follow-up, the med. For patients with unresectable stageIII NSCLC, CIP of Endostar enhanced patient compliance, and combined with concurrent radiochemotherapy is tolerable and the short term outcomes are promising. Long term survival data wait further follow up.

MA06.11 Phase II Study of Nimotuzumab + Concurrent Chemoradiotherapy (CRT) for Stage III Non-Small Cell Lung Cancer (NSCLC): 5-Year Follow-Up Results

Nimotuzumab, a humanized IgG1 monoclonal anti-EGFR antibody, is approved and widely used in patients (pts) with head and neck cancer or malignant glioma in combination with radiotherapy (RT) in several countries. On in-vitro and in-vivo experiments using NSCLC cell lines, nimotuzumab showed a radio-sensitizing effect. This phase II study evaluated the tolerability and efficacy of nimotuzumab in combination with concurrent CRT in pts with unresectable locally advanced NSCLC. All eligible pts received concurrent thoracic RT (60 Gy, 2 Gy/day, 6 weeks from day 1) and 4 cycles of chemotherapy (cisplatin 80 mg/m2 on day 1, vinorelbine 20 mg/m2 on days 1 and 8) once every 4 weeks as scheduled. Nimotuzumab (200 mg) was administrated once a week from cycle 1 to 4. The primary endpoint was tolerability in combination with concurrent CRT, which was measured by the percentage of pts who completed 60 Gy of RT within 8 weeks, completed 2 cycles of chemotherapy and received more than 75% of nimotuzumab. Of 40 pts enrolled between June 2009 and May 2010, 39 eligible pts received the study treatment. The pts characteristics were as follows: 62 years (median); male/female, 34/5; stage IIIA/B, 21/18; PS0/1, 25/14. Thirty-four pts met the criteria for treatment tolerability, and 38 pts completed 60 Gy of RT within 8 weeks. Infusion reaction, ≥grade 3 skin rash, ≥grade 3 radiation pneumonitis, or ≥grade 4 nonhematological toxicity were not observed. The 3-year and 5-year overall survival rates for the 39 pts were 66.4% and 58.4%, respectively. The median PFS was 16.9 months, and the 5-year PFS rate for pts with squamous cell carcinoma (Sq; n = 16) was 50%, while that for pts with non-squamous cell carcinoma (non-Sq; n = 23) was 13.7%. In terms of the first relapse site, in-field relapse rates were low for both Sq (4/16; 25%) and non-Sq (4/23; 17%). However, the distant relapse rate was significantly higher for non-Sq (15/23; 65%) than that for Sq (4/16; 25%). Cytologic or histologic specimens were examined for the expression of EGFR protein/mutations using the EGFR IHC/FISH methods in 20 pts. EGFR 2+/3+ expression was shown more frequently in sq (8/10) than non-sq (4/10). EGFR mutation was observed in only 2 pts with non-sq. Addition of nimotuzumab to the concurrent CRT in this setting was well tolerated with clinical benefit to the patients. The low in field relapse rates may be attributed to the radio-sensitizing effect of nimotuzumab.

Outcomes and Toxicity of Concurrent Radiotherapy with Carboplatin/Paclitaxel Administrated Every Three Weeks in Inoperable Advanced Non-small Cell Lung Cancer: A Retrospective Study from A Single Center

背景与目的对于局部晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）同步放化疗是推荐的标准治疗。理想的化疗方案并未确立。本研究拟回顾性分析紫杉醇/卡铂（paclitaxel/carboplatin, PC）三周方案同步胸部放疗治疗局部晚期NSCLC的疗效和安全性，并与标准的依托泊苷/顺铂（cisplatin/etoposide, PE）方案进行比较。方法回顾性分析北京协和医院2012年1月-2014年6月收治的局部晚期NSCLC患者共43例，其中15例接受PC三周方案同步胸部放疗，28例接受PE方案同步胸部放疗。比较两组患者的临床特征、疗效和不良反应。结果全组患者：客观缓解率（objective response rate, ORR）为41.9%，疾病控制率（disease control rate, DCR）为90.7%，中位无疾病进展生存时间（progression-free survival, PFS）为10.6个月（95%CI: 7.4-13.8），中位总生存期（overall survival, OS）为19.2个月（95%CI: 15.3-23.1）。PC组和PE组在疗效上无统计学差异（ORR：33.3% vs 46.4%，DCR：86.7% vs 92.9%，P=0.638；PFS：6.6个月vs 12.2个月，P=0.389；OS：16.1个月vs 22.1个月，P=0.555）。不良反应可处理，两组均未发生治疗相关死亡。结论PC三周方案同步胸部放疗治疗局部晚期NSCLC与标准PE方案疗效相似，不良反应可接受，在临床中可采用。

O1-19-2 - Phase I study of carboplatin, S-1 and concurrent thoracic radiotherapy for elderly patients with locally advanced NSCLC

O1-19-2 - Phase I study of carboplatin, S-1 and concurrent thoracic radiotherapy for elderly patients with locally advanced NSCLC

A prospective, multicenter, phase II clinical study of concurrent chemotherapy and thoracic three-dimensional radiotherapy for stage IV non-small cell lung cancer -Impact of clinical factors on survival (PPRA-RTOG003)

Objective To investigate the impact of clinical factors on survival in patients receiving concurrent chemotherapy and three-dimensional radiotherapy (3DRT) for stage IV non-small cell lung cancer (NSCLC). Methods A total of 203 patients were enrolled in a prospective clincial study from 2008 to 2012, and among these patients, 178 patients were eligible for analysis of clinical factors. All patients were treated with platinum-based doublets chemotherapy, with a median number of chemotherapy cycles of 4(2-6 cycles) and a median dose of 3DRT of 60.3 Gy (36.0-76.5 Gy). The Kaplan-Meier method was used to calculate overall survival (OS) rates, the log-rank test was used to compare survival rates between groups, and the Cox regression model were used for multivariate analysis. Results The 1-, 2-, and 3-year overall survival rates were 56%, 16%, and 10%, respectively, and the median survival time was 13 months (95% CI=11.500-14.500). The univariate analysis showed that platelet count ≤221×109/L, neutrophil count ≤5.2×109/L, white blood cell count<7×109/L, and improvement in Karnofsky Performance Scale (KPS) after treatment significantly prolonged OS (P=0.000, 0.022, 0.003, and 0.029), and metastasis to a single organ and hemoglobin≥120 g/L tended to prolong OS (P=0.058 and 0.075). The multivariate analysis showed that white blood cell count<7×109/L, platelet count ≤221×109/L, and improvement in KPS after treatment were beneficial to OS (all P<0.05). Conclusions White blood cell count and platelet count before treatment and KPS after treatment are prognostic factors for patients with stage IV NSCLC receiving concurrent chemotherapy and 3DRT. Clinical Trial Registry ClinicalTrials.gov, registration number: ChiCTRTNC10001026. Key words: Carcinoma, non-small cell lung/three-dimensional radiotherapy; Carcinoma, non-small cell lung/concurrent chemoradiotherapy; Clinical factors; Prognosis

Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is a high-grade neuroendocrine tumor characterized by rapid growth, early metastatic spread, and initial responsiveness to therapy. Although the incidence of SCLC is declining, it remains one of the common causes of cancer-related mortality. Initial evaluation of patients with SCLC should focus on determining the extent of disease and the ability of the patient to tolerate specific therapy. Positron emission tomography (PET) can improve the accuracy of staging and treatment planning in many patients. Limited-stage (LS) SCLC is a potentially curable disease with long-term survival of 20 to 25% when treated with platinum-based chemotherapy plus concurrent thoracic radiation. Hyperfractionated (twice daily) thoracic radiation and prophylactic cranial irradiation (PCI) may improve survival in selected patients with LS-SCLC. For patients with extensive-stage (ES) SCLC, combination chemotherapy prolongs survival and improves quality of life, but long-term survival is rare. The use of PCI and sequential thoracic radiation has been reported to improve survival in selected patients with ES-SCLC. Many chemotherapeutic drugs have activity in SCLC, but little progress has been made in the systemic treatment of SCLC in almost three decades. Although many potential molecular targets have been identified in the preclinical studies of SCLC, molecularly targeted therapy has yet to demonstrate consistent clinical activity. Nevertheless, future advances in SCLC will depend on the development of rational therapeutic strategies which target the molecular mechanisms that drive cellular proliferation, survival, and immunological avoidance.

1193P - Comparison of combined chemoradiotherapy regimens; Paclitaxel plus carboplatin and cisplatin plus etoposide for locally advanced non-small-cell lung cancer: A randomized phase III trial

The optimal chemotherapy regimen to use with radiotherapy in stage III non–small-cell lung cancer (NSCLC) is unknown. This phase III comparative randomized trial was conducted to determine the optimal chemotherapy regimen with standard daily concurrent thoracic radiation therapy (CTRT), in patients with locally advanced unresected stage III NSCLC. We recruited 108 patients aged 18–72 years with stage III, histologically confirmed NSCLC, an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, an estimated life expectancy of greater than 3 months, and adequate organ function from January 2011 to December 2014. Patients were randomised (1:1) to paclitaxel plus carboplatin and cisplatin plus etoposide arms. Patients with unresected stages IIIA and IIIB NSCLC received carboplatin (AUC = 2) and paclitaxel (45 mg/m2) given weekly with CTRT (63 Gy) followed by two cycles of consolidation therapy (carboplatin AUC = 6, paclitaxel 200 mg/m2) (arm CP) and cisplatin (50 mg/m2 on days 1, 8, 29, and 36) plus etoposide (50 mg/m2 daily on days 1 to 5, and 29 to 33) with CTRT followed by consolidation cisplatin plus etoposide (arm EP) were included. Ninety nine eligible patients were evaluated. With median follow-up time of 39.4 months, median overall survival was 17.1 and 16.6 months for arms CP and EP, respectively (P = 0.279). But patients in arm EP, compared with patients in arm CP, had more grade 4 neutropenia (18.1% vs 11.1%, p < 0.001), grade 3-4 mucositis/esophagitis (22.2% vs 12.1%, p < 0.001) and acute kidney disease (27.2% vs 14.1%, p < 0.001). In patients with stage III NSCLC treated with cisplatin plus etoposide and carboplatin plus paclitaxel had similar overall survival, but cisplatin plus etoposide arm was associated with increased toxicity.

Increased Biological Effective Dose of Radiation Correlates with Prolonged Survival of Patients with Limited-Stage Small Cell Lung Cancer: A Systematic Review.

ObjectiveThoracic radiotherapy (TRT) is a critical component of the treatment of limited-stage small cell lung cancer (LS-SCLC). However, the optimal radiation dose/fractionation remains elusive. This study reviewed current evidence and explored the dose-response relationship in patients with LS-SCLC who were treated with radiochemotherapy.Materials and MethodsA quantitative analysis was performed through a systematic search of PubMed, Web of Science, and the Cochrane Library. The correlations between the biological effective dose (BED) and median overall survival (mOS), median progression-free survival (mPFS), 1-, 3-, and 5-year overall survival (OS) as well as local relapse (LR) were evaluated.ResultsIn all, 2389 patients in 19 trials were included in this study. Among these 19 trials, seven were conducted in Europe, eight were conducted in Asia and four were conducted in the United States. The 19 trials that were included consisted of 29 arms with 24 concurrent and 5 sequential TRT arms. For all included studies, the results showed that a higher BED prolonged the mOS (R2 = 0.198, p<0.001) and the mPFS (R2 = 0.045, p<0.001). The results also showed that increased BED improved the 1-, 3-, and 5-year OS. A 10-Gy increment added a 6.3%, a 5.1% and a 3.7% benefit for the 1-, 3-, and 5-year OS, respectively. Additionally, BED was negatively correlated with LR (R2 = 0.09, p<0.001). A subgroup analysis of concurrent TRT showed that a high BED prolonged the mOS (p<0.001) and the mPFS (p<0.001), improved the 1-, 3-, and 5-year OS (p<0.001) and decreased the rate of LR (p<0.001).ConclusionThis study showed that an increased BED was associated with improved OS, PFS and decreased LR in patients with LS-SCLC who were treated with combined chemoradiotherapy, which indicates that the strategy of radiation dose escalation over a limited time frame is worth exploring in a prospective clinical trial.

Carboplatin (CBDCA), S-1 and concurrent thoracic radiotherapy (TRT) for elderly patients with locally advanced non-small cell lung cancer (NSCLC): A phase I study.

e20050Background: S-1 is an oral anticancer agent containing a mixture of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate, which has been shown to have a radiosensitizing effect in ...

Outcomes in patients with stage III non-small cell lung cancer (NSCLC) treated with cisplatin and irinotecan with concurrent thoracic radiotherapy (CRT): A multi-disciplinary thoracic oncology experience at East Carolina University.

e20019Background: Platinum-based doublet chemotherapy with concurrent radiation is the standard of care for unresectable locally advanced NSCLC. The National Cancer Database reports a median overal...

Dose-Escalation Study of Thoracic Radiotherapy in Combination With Pemetrexed Plus Cisplatin in Japanese Patients With Locally Advanced Nonsquamous Non–Small Cell Lung Cancer

We performed a post hoc analysis of progression-free survival (PFS), overall survival (OS), and recurrent sites in patients with locally advanced nonsquamous non-small cell lung cancer who were enrolled in a phase I trial of combination chemotherapy consisting of pemetrexed plus cisplatin with concurrent thoracic radiotherapy. Patients received pemetrexed (500 mg/m²) plus cisplatin (75 mg/m²) on day 1 every 3 weeks for 3 cycles plus concurrent thoracic radiotherapy consisting of 60 Gy (n=6) or 66 Gy (n=12); 4 to 6 weeks thereafter, patients received consolidation treatment with pemetrexed (500 mg/m) every 3 weeks for up to 3 cycles. We reviewed the medial records to collect data on progression, recurrent sites, late toxicity, and survival. No late radiation morbidity was observed. Thirteen patients (72%) exhibited disease progression: 8 patients had distant metastases, 8 patients had local recurrence (within the radiation field [n=6], outside the radiation field [n=2], and both [n=1]), and 3 patients had local recurrence plus distant metastases. The median PFS was 10.5 months (95% confidence interval [CI], 8.8-12.3), and the 3-year PFS rate was 28% (95% CI, 7.0-48.6). Ten of the 18 patients died of lung cancer. The median follow-up time for the censored cases was 42.8 months (range, 38.1 to 52.9 mo). The median OS was 27.3 months (95% CI, 13.1-41.6), and the 3-year OS rate was 50% (95% CI, 26.9-73.1). The median PFS and OS in our study were comparable to those of historical chemoradiotherapy controls.

Feasibility study of chemoradiotherapy followed by amrubicin and cisplatin for limited‐disease small cell lung cancer

To evaluate the feasibility of amrubicin plus cisplatin (AP) following chemoradiotherapy for limited‐disease small‐cell lung cancer, chemo‐naïve patients aged 20–70 years with a performance status of 0 or 1 and normal organ functions were treated with etoposide 100 mg/m2 on days 1–3, cisplatin 80 mg/m2 on day 1 and concurrent thoracic radiotherapy at 45 Gy/30 fractions (EP‐TRT), followed by three cycles of amrubicin 40 mg/m2 on days 1–3 and cisplatin 60 mg/m2 on day 1 every 3 weeks. The EP‐TRT could be completed in 21 patients (15 male and 6 female patients with a median age of 62 years). Of these, 2, 1 and 18 (86%) patients received one, two and three cycles of AP, respectively. Sixteen (76%) patients required granulocyte‐colony stimulating factor (G‐CSF) support. Grade 3/4 neutropenia occurred in all patients. Grade 3 febrile neutropenia was observed in 9 patients, lasting for 1 day in 5 patients. The incidences of grade 3/4 thrombocytopenia and anemia were 43 and 24%, respectively. Grade 3 infection and anorexia occurred in 2 and 3 patients, respectively. The response rate was 95%. The median (95% confidence interval [CI]) progression‐free survival (PFS) was 41.9 (0–102) months, and the 5‐year PFS rate (CI) was 41.9% (20.4–63.4%). The median overall survival (OS) has not been reached yet, and the 5‐year OS rate (CI) was 57.8% (35.2–80.4%). In conclusion, EP‐TRT followed by AP therapy was well‐tolerated, although a large number of patients required G‐CSF support.

Which Chemotherapy with Radiation for Locally-Advanced Non–Small-Cell Lung Cancer?

For local-regional advanced non–small-cell lung cancer (NSCLC), curative intent chemoradiation yields 5-year overall survival rates of approximately 20% to 25%. Adjusting the systemic therapies in combination with radiation has been one strategy to improve clinical outcomes. To compare the efficacy and safety of two such approaches, investigators conducted a randomized phase III trial (PROCLAIM), in which 555 patients with stage IIIA/B nonsquamous NSCLC received concurrent thoracic radiation (60–66 Gy) with either …