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Liu T, Li S, Ding S, Qiu J, Ren C, Chen J, Wang H, Wang X, Li G, He Z, Dang J. Comparison of post-chemoradiotherapy pneumonitis between Asian and non-Asian patients with locally advanced non-small cell lung cancer: a systematic review and meta-analysis. EClinicalMedicine 2023; 64:102246. [PMID: 37781162 PMCID: PMC10539643 DOI: 10.1016/j.eclinm.2023.102246] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 08/28/2023] [Accepted: 09/13/2023] [Indexed: 10/03/2023] Open
Abstract
Background Pneumonitis is a common complication for patients with locally advanced non-small cell lung cancer undergoing definitive chemoradiotherapy (CRT). It remains unclear whether there is ethnic difference in the incidence of post-CRT pneumonitis. Methods PubMed, Embase, Cochrane Library, and Web of Science were searched for eligible studies from January 1, 2000 to April 30, 2023. The outcomes of interest were incidence rates of pneumonitis. The random-effect model was used for statistical analysis. This meta-analysis was registered with PROSPERO (CRD42023416490). Findings A total of 248 studies involving 28,267 patients were included. Among studies of CRT without immunotherapy, the pooled rates of pneumonitis for Asian patients were significantly higher than that for non-Asian patients (all grade: 66.8%, 95% CI: 59.2%-73.9% vs. 28.1%, 95% CI: 20.4%-36.4%; P < 0.0001; grade ≥2: 25.1%, 95% CI: 22.9%-27.3% vs. 14.9%, 95% CI: 12.0%-18.0%; P < 0.0001; grade ≥3: 6.5%, 95% CI: 5.6%-7.3% vs. 4.6%, 95% CI: 3.4%-5.9%; P = 0.015; grade 5: 0.6%, 95% CI: 0.3%-0.9% vs. 0.1%, 95% CI: 0.0%-0.2%; P < 0.0001). Regarding studies of CRT plus immunotherapy, Asian patients had higher rates of all-grade (74.8%, 95% CI: 63.7%-84.5% vs. 34.3%, 95% CI: 28.7%-40.2%; P < 0.0001) and grade ≥2 (34.0%, 95% CI: 30.7%-37.3% vs. 24.6%, 95% CI: 19.9%-29.3%; P = 0.001) pneumonitis than non-Asian patients, but with no significant differences in the rates of grade ≥3 and grade 5 pneumonitis. Results from subgroup analyses were generally similar to that from the all studies. In addition, the pooled median/mean of lung volume receiving ≥20 Gy and mean lung dose were relatively low in Asian studies compared to that in non-Asian studies. Interpretation Asian patients are likely to have a higher incidence of pneumonitis than non-Asian patients, which appears to be due to the poor tolerance of lung to radiation. Nevertheless, these findings are based on observational studies and with significant heterogeneity, and need to be validated in future large prospective studies focusing on the subject. Funding None.
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Affiliation(s)
- Tingting Liu
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China
- Department of Radiation Oncology, Anshan Cancer Hospital, Anshan, China
| | - Sihan Li
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China
| | - Silu Ding
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China
| | - Jingping Qiu
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China
| | - Chengbo Ren
- Department of Radiation Oncology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei, China
| | - Jun Chen
- Department of Radiation Oncology, Shenyang Tenth People's Hospital, Shenyang, China
| | - He Wang
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China
| | - Xiaoling Wang
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China
| | - Guang Li
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China
| | - Zheng He
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China
| | - Jun Dang
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China
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Consolidation Systemic Therapy in Locally Advanced, Inoperable Nonsmall Cell Lung Cancer-How to Identify Patients Which Can Benefit from It? Curr Oncol 2022; 29:8316-8329. [PMID: 36354716 PMCID: PMC9689287 DOI: 10.3390/curroncol29110656] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Revised: 10/26/2022] [Accepted: 10/29/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Consolidation systemic therapy (ST) given after concurrent radiotherapy (RT) and ST (RT-ST) is frequently practiced in locally advanced inoperable nonsmall cell lung cancer (NSCLC). Little is known, however, about the fate of patients achieving different responses after concurrent phases of the treatment. METHODS we searched the English-language literature to identify full-length articles on phase II and Phase III clinical studies employing consolidation ST after initial concurrent RT-ST. We sought information about response evaluation after the concurrent phase and the outcome of these patient subgroups, the patterns of failure per response achieved after the concurrent phase as well as the outcome of these subgroups after the consolidation phase. RESULTS Eighty-seven articles have been initially identified, of which 20 studies were excluded for various reasons, leaving, therefore, a total of 67 studies for our analysis. Response evaluation after the concurrent phase was performed in 36 (54%) studies but in only 14 (21%) response data were provided, while in 34 (51%) studies patients underwent a consolidation phase regardless of the response. No study provided any outcome (survivals, patterns of failure) as per response achieved after the concurrent phase. CONCLUSIONS Information regarding the outcome of subgroups of patients achieving different responses after the concurrent phase and before the administration of the consolidation phase is still lacking. This may negatively affect the decision-making process as it remains unknown which patients may preferentially benefit from the consolidation of ST.
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Käsmann L, Eze C, Taugner J, Roengvoraphoj O, Belka C, Manapov F. Implementation of durvalumab maintenance treatment after concurrent chemoradiotherapy in inoperable stage III non-small cell lung cancer (NSCLC)-a German radiation oncology survey. Transl Lung Cancer Res 2020; 9:288-293. [PMID: 32420068 PMCID: PMC7225149 DOI: 10.21037/tlcr.2020.03.25] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 02/28/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND Durvalumab as maintenance treatment after platinum-based concurrent chemoradiotherapy (cCRT) has become the standard of care in inoperable stage III non-small cell lung cancer (NSCLC). In this nationwide survey, we solicited members of the German Radiation Oncology Society to review the current distribution and clinical settings of durvalumab treatment after cCRT, observed side effects and summarize follow-up management. METHODS We surveyed radiation oncology institutions in Germany via an anonymous online questionnaire sent by e-mail to all members of the German Radiation Oncology Society which agreed their willingness to participate. RESULTS We received a total of 255 responses (response rate: 18%). Of which 203 (80%) were completed and returned and thus eligible for further evaluation. The respondents work in 87 different cities and 44% in a private medical practice, 29% in university and 22% in a general hospital. Durvalumab was implemented in clinical routine by 70% of respondents. Major reasons for failed implementation in clinical practice reported by the respondents were patient's ineligibility (42%), lack of required PD-L1 status (25%), decision of medical oncologists (7%) or absence of updated German guidelines (7%). Thirty-six percent of all respondents report low (≤30%) PD-L1 testing before cCRT based on IHC assay. No respondent had applied durvalumab in less than 14 days after the completion of CRT. Severe side effects requiring hospital admission in more than 10% of all patients were reported by 12% of all respondents. CONCLUSIONS Durvalumab maintenance is already implemented in the radiation oncology community and administered by the absolute majority of respondents. Low testing rates of PD-L1 at initial diagnosis were observed and should be considered a major barrier to universal adoption and integration in the clinical work-flow in countries with durvalumab approval restricted to PD-L1 positive patients. No respondent applies durvalumab in less than 14 days after cCRT.
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Affiliation(s)
- Lukas Käsmann
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
- Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany
- German Cancer Consortium (DKTK), partner site Munich, Munich, Germany
| | - Chukwuka Eze
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Julian Taugner
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Olarn Roengvoraphoj
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Claus Belka
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
- Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany
- German Cancer Consortium (DKTK), partner site Munich, Munich, Germany
| | - Farkhad Manapov
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
- Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany
- German Cancer Consortium (DKTK), partner site Munich, Munich, Germany
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Scotti V, Saieva C, Di Cataldo V, Bruni A, Desideri I, Bertocci S, Meattini I, Livi L, Simontacchi G, De Luca Cardillo C, Bendinelli B, Bastiani P, Mangoni M, Agresti B, Biti G. Vinorelbine-Based Chemo-Radiotherapy in Non-Small Cell Lung Cancer. TUMORI JOURNAL 2018; 98:464-70. [DOI: 10.1177/030089161209800411] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Aims and background Concomitant radio-chemotherapy improves survival of patients with locally advanced non-small cell lung cancer, with a better local-regional control. Methods and study design We report our experience with vinorelbine-based chemotherapy in neoadjuvant and radical settings in 43 patients. Regimens consisted of cisplatin plus vinorelbine in 74.4% patients and carboplatin plus vinorelbine in 14.0%; 11.6% underwent mono-chemotherapy with oral vinorelbine. We estimated the crude probability of death or local recurrence by the Kaplan-Meier method. Cox regression models were used to identify the main significant predictors of death or local recurrence. Results A significant effect of the response to treatment was shown on both local disease free-survival (P = 0.004) and overall survival (P <0.0001). Patients with progressive disease after primary treatment had a significantly higher risk of further relapse at both univariate (P = 0.046) and multivariate regression analysis (P = 0.014) than patients with a complete response. They also showed a significantly higher risk of death at both univariate (P = 0.0005) and multivariate regression analysis (P <0.0001) than patients with a complete response. The most common toxicity was hematologic and gastroenteric. We recorded grade III/IV leukopenia in 11%, anemia in 6%, and esophagitis in 14% of the patients. Conclusions Our experience showed that vinorelbine-based chemotherapy is an effective and safe regimen, in association with a platinum compound and thoracic radiotherapy.
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Affiliation(s)
- Vieri Scotti
- Department of Radiation-Oncology, University of Florence, Florence
| | - Calogero Saieva
- Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, ISPO, Florence
| | | | - Alessio Bruni
- Department of Radiation-Oncology, University of Modena, Modena
| | - Isacco Desideri
- Department of Radiation-Oncology, University of Florence, Florence
| | - Silvia Bertocci
- Department of Radiation-Oncology, University of Florence, Florence
| | - Icro Meattini
- Department of Radiation-Oncology, University of Florence, Florence
| | - Lorenzo Livi
- Department of Radiation-Oncology, University of Florence, Florence
| | | | | | - Benedetta Bendinelli
- Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, ISPO, Florence
| | - Paolo Bastiani
- Radiotherapy Unit, Ospedale Santa Maria Annunziata, Florence, Italy
| | - Monica Mangoni
- Department of Radiation-Oncology, University of Florence, Florence
| | | | - Giampaolo Biti
- Department of Radiation-Oncology, University of Florence, Florence
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Lu L, Yang LN, Wang XX, Song CL, Qin H, Wu YJ. Synergistic cytotoxicity of ampelopsin sodium and carboplatin in human non-small cell lung cancer cell line SPC-A1 by G1 cell cycle arrested. Chin J Integr Med 2016; 23:125-131. [DOI: 10.1007/s11655-016-2591-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2012] [Indexed: 12/19/2022]
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Comparison of efficacy and safety of three different chemotherapy regimens delivered with concomitant radiotherapy in inoperable stage III non-small cell lung cancer patients. Tumour Biol 2016; 37:8901-7. [PMID: 26753955 DOI: 10.1007/s13277-015-4776-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2015] [Accepted: 12/29/2015] [Indexed: 12/13/2022] Open
Abstract
Concomitant administration of chemotherapy and radiotherapy is currently recognized as the standard of treatment in locally advanced inoperable non-small cell lung cancer (NSCLC). Our study aimed to compare the efficacy and toxicities of three different chemotherapy regimens delivered concurrently with radiotherapy. We retrospectively reviewed the clinical records of patients who received the PE (cisplatin, 50 mg/m(2), on days 1, 8, 29, and 36 plus etoposide, 50 mg/m(2), on days 1 to 5 and 29 to 33), PD (docetaxel, 20 mg/m(2), on day 1 plus cisplatin, 20 mg/m(2), on day 1, every week), and PC (carboplatin, AUC 2 plus paclitaxel, 45 mg/m(2), on day 1, every week) regimens concurrently with radiotherapy. A total of 227 patients were evaluated in the study. Median follow-up time was 13 months (2-101). There were 27 females (11.9 %) and 200 males (88.1 %) with a median age of 61 (38-82) years. The PD group had higher rates of esophagitis, mucositis, and anemia (p < 0.05). The PC group had higher rates of neuropathy (p = 0.000). The progression-free survival (PFS) time was 10 months for patients in the PC group, 15 months for patients in the PD group, and 21 months for the PE group (p = 0.010). Patients in the PC group had a median overall survival time of 23 months, those in the PD group 27 months, and those in the PE group 36 months (p = 0.098). Combination of cisplatin-etoposide with radiotherapy led to a more favorable outcome compared with the other two regimens. It shows generally manageable toxicity profile and compliance to treatment is noticeable.
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De Tollenaere C, Lievens Y, Vandecasteele K, Vermaelen K, Surmont V. Unresectable stage III non-small-cell lung cancer: Have we made any progress? World J Respirol 2015; 5:140-151. [DOI: 10.5320/wjr.v5.i2.140] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2014] [Revised: 03/27/2015] [Accepted: 06/08/2015] [Indexed: 02/06/2023] Open
Abstract
Lung cancer is responsible for the most cancer deaths worldwide with an incidence that is still rising. One third of patients have unresectable stage IIIA or stage IIIB disease. The standard of care for locally advanced disease in patients with good performance status consists of combined modality therapy in particular concurrent chemoradiotherapy. But despite a lot of efforts done in the past, local control and survival of patients with unresectable stage III non-small-cell lung cancer (NSCLC) remains poor. Improving outcomes for patients with unresectable stage III NSCLC has therefore been an area of ongoing research. Research has focused on improving systemic therapy, improving radiation therapy or adding a maintenance therapy to consolidate the initial therapy. Also implementation of newer targeted therapies and immunotherapy has been investigated as well as the option of prophylactic cranial irradiation. This article reviews the latest literature on improving local control and preventing distant metastases. It seems that we have reached a plateau with conventional chemotherapy. Radiotherapy dose escalation did not improve outcome although increasing radiation dose-intensity with new radiotherapy techniques and the use of newer agents, e.g., immunotherapy might be promising. In the future well-designed clinical trials are necessary to prove those promising results.
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Choy H, Gerber DE, Bradley JD, Iyengar P, Monberg M, Treat J, Govindan R, Koustensis A, Barker S, Obasaju C. Concurrent pemetrexed and radiation therapy in the treatment of patients with inoperable stage III non-small cell lung cancer: a systematic review of completed and ongoing studies. Lung Cancer 2015; 87:232-40. [PMID: 25650301 DOI: 10.1016/j.lungcan.2014.12.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2012] [Revised: 12/09/2014] [Accepted: 12/11/2014] [Indexed: 12/24/2022]
Abstract
Current standard for locally advanced non-small cell lung cancer (NSCLC) is combined concurrent therapy with a platinum-based regimen. Preclinical synergistic activity of pemetrexed with radiation therapy (RT) and favorable toxicity profile has led to clinical trials evaluating pemetrexed in chemoradiation regimens. This literature search of concurrent pemetrexed and RT treatment of patients with stage III NSCLC included MEDLINE database, meeting abstracts, and the clinical trial registry database. Nineteen unique studies were represented across all databases including 11 phase I studies and eight phase II studies. Of the six phase II trials with mature data available, median overall survival ranged from 18.7 to 34 months. Esophagitis and pneumonitis occurred in 0-16% and 0-23% of patients, respectively. Of the ongoing trials, there is one phase III and four phase II trials with pemetrexed in locally advanced NSCLC. Pemetrexed can be administered safely at full systemic doses with either cisplatin or carboplatin concomitantly with radical doses of thoracic radiation therapy. While results from the ongoing phase III PROCLAIM trial are needed to address definitively the efficacy of pemetrexed-cisplatin plus RT in stage III NSCLC, available results from phase II trials suggest that this regimen has promising activity with an acceptable toxicity profile.
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Affiliation(s)
- Hak Choy
- University of Texas Southwestern Medical Center, Dallas, TX, USA.
| | - David E Gerber
- University of Texas Southwestern Medical Center, Dallas, TX, USA
| | | | - Puneeth Iyengar
- University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Matthew Monberg
- Eli Lilly and Company or one of its subsidiaries, Indianapolis, IN, USA
| | - Joseph Treat
- Eli Lilly and Company or one of its subsidiaries, Indianapolis, IN, USA
| | | | - Andrew Koustensis
- Eli Lilly and Company or one of its subsidiaries, Indianapolis, IN, USA
| | - Scott Barker
- Eli Lilly and Company or one of its subsidiaries, Indianapolis, IN, USA
| | - Coleman Obasaju
- Eli Lilly and Company or one of its subsidiaries, Indianapolis, IN, USA
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Bi N, Wang L. Superiority of concomitant chemoradiation over sequential chemoradiation in inoperable, locally advanced non-small cell lung cancer: challenges in the selection of appropriate chemotherapy. Semin Radiat Oncol 2014; 25:122-32. [PMID: 25771417 DOI: 10.1016/j.semradonc.2014.11.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Treatment of inoperable, locally advanced non-small cell lung cancer (LA-NSCLC) is challenging and requires a multidisciplinary approach considering both local therapy and systemic therapy. Based on the results from several phase III studies and 2 meta-analyses, the use of concomitant chemoradiation therapy (ChRT) could significantly improve overall survival and is considered the standard of care in LA-NSCLC with good performance status. Currently, no evidence has shown a significant survival benefit of third-generation regimens applied in combination with ChRT compared with second-generation regimens. For regimens concomitant with radiation therapy, full-dose chemotherapy (such as cisplatin and etoposide or cisplatin and vinblastine) might be preferred. Additional full-dose consolidation paclitaxel-carboplatin is recommended when patients receive weekly paclitaxel-carboplatin ChRT. Effective novel chemotherapy agents or targeted therapies are required to further improve the outcome of patients with LA-NSCLC. In addition, personalized medicine concomitant with radiation therapy is a promising approach. However, little evidence exists concerning the effectiveness of this novel approach.
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Affiliation(s)
- Nan Bi
- Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Luhua Wang
- Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
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Phase 2 study of pemetrexed plus carboplatin, or pemetrexed plus cisplatin with concurrent radiation therapy followed by pemetrexed consolidation in patients with favorable-prognosis inoperable stage IIIA/B non-small-cell lung cancer. J Thorac Oncol 2014; 8:1308-16. [PMID: 23981966 DOI: 10.1097/jto.0b013e3182a02546] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION There is no consensus chemotherapy regimen with concurrent radiotherapy (RT) for inoperable stage IIIA/B non-small-cell lung cancer. This trial evaluated pemetrexed with carboplatin (PCb) or cisplatin (PC) with concurrent RT followed by consolidation pemetrexed. METHODS In this open-label, noncomparative phase II trial, patients with inoperable stage IIIA/B non-small-cell lung cancer (initially all histologies, later restricted to nonsquamous) were randomized (1:1) to PCb or PC with concurrent RT (64-68 Gy over days 1-45). Consolidation pemetrexed monotherapy was administered every 21 days for three cycles. Primary endpoint was 2-year overall survival (OS) rate. RESULTS From June 2007 to November 2009, 98 patients were enrolled (PCb: 46; PC: 52). The 2-year OS rate was PCb: 45.4% (95% confidence interval [CI], 29.5-60.0%); PC: 58.4% (95% CI, 42.6-71.3%), and in nonsquamous patients was PCb: 48.0% (95% CI, 29.0-64.8%); PC: 55.8% (95% CI, 38.0-70.3%). Median time to disease progression was PCb: 8.8 months (95% CI, 6.0-12.6 months); PC: 13.1 months (95% CI, 8.3-not evaluable [NE]). Median OS (months) was PCb: 18.7 (95% CI, 12.9-NE); PC: 27.0 (95% CI, 23.2-NE). The objective response rates (ORRs) were PCb: 52.2%; PC: 46.2%. Grade 4 treatment-related toxicities (% PCb/% PC) were: anemia, 0/1.9; neutropenia, 6.5/3.8; thrombocytopenia, 4.3/1.9; and esophagitis, 0/1.9. Most patients completed scheduled chemotherapy and RT during induction and consolidation phases. No drug-related deaths were reported during chemoradiotherapy. CONCLUSIONS Because of study design, efficacy comparisons cannot be made. However, both combinations with concurrent RT were active and well tolerated.
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Dang J, Li G, Zang S, Zhang S, Yao L. Risk and predictors for early radiation pneumonitis in patients with stage III non-small cell lung cancer treated with concurrent or sequential chemoradiotherapy. Radiat Oncol 2014; 9:172. [PMID: 25074618 PMCID: PMC4120001 DOI: 10.1186/1748-717x-9-172] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Accepted: 07/23/2014] [Indexed: 12/25/2022] Open
Abstract
Background The rate of radiation pneumonitis (RP) for patients receiving chemoradiotherapy has been various across studies. Whether it is related to different chemotherapy schedules used in combination with radiation therapy were evaluated in this study. New factors associated with RP were also investigated. Methods and materials A total of 369 consecutive patients with Stage III non small cell lung cancer treated with chemoradiotherapy were followed after radiotherapy (RT). Among them 262 patients received concurrent chemoradiotherapy followed by consolidation chemotherapy and 107 patients received only sequential chemotherapy after RT. RP was graded according to Common Terminology Criteria for Adverse Events version 4.0. Results The rate of grade ≥ 2 were 39.7%, 31% and 33.6% in the concurrent DP (docetaxel/cisplatin), concurrent NP (vinorelbine/cisplatin) and sequential group, and grade ≥ 3 RP were 18.4%, 9.5%, and 11.2% respectively. The rate of grade ≥ 3 RP was significantly higher in concurrent DP group than that in concurrent NP group (p = 0.04). RP occurred earlier in concurrent DP group than that in the other two groups. There were no significant differences in response rate among the three groups. In the multivariate analysis, age (OR = 1.99, p = 0.038 and OR = 8.90, p < 0.001), chemotherapy schedule (OR = 1.45, p = 0.041 and OR = 1.98, p = 0.013), mean lung dose(OR = 1.42, p < 0.001 and OR = 1.64, p < 0.001), and planning target volume(OR = 1.004, p = 0.001 and OR = 1.005, p = 0.021) were predictors for both grade ≥ 2 and grade ≥ 3 RP. Response to treatment was a new predictor for grade ≥ 3 RP only (OR = 4.39, p = 0.034). Conclusions Response to treatment was found to be a new predictor for grade ≥ 3 RP. Compared to concurrent NP schedule, concurrent DP schedule achieved similar response to treatment but resulted in a higher risk of grade ≥ 3 RP.
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Affiliation(s)
| | - Guang Li
- Department of Radiation Oncology, The First Hospital of China Medical University, No,155 Nanjing Road, Heping District, Shenyang 110001, China.
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Tomasini P, Greillier L, Khobta N, Barlesi F. The place of pemetrexed in the management of non-small-cell lung cancer patients. Expert Rev Anticancer Ther 2014; 13:257-66. [PMID: 23477511 DOI: 10.1586/era.12.171] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer death worldwide. Chemotherapy is included in the management of the majority of NSCLC patients either in addition to a local treatment (surgery/radiotherapy) or alone. In this setting, pemetrexed has become one of the most important partners of current chemotherapy regimens for nonsquamous NSCLC patients. Indeed, pemetrexed demonstrated a comparable efficacy to other previously available drugs in NSCLC, with however a better safety profile and an easier schedule of administration. In addition, pemetrexed demonstrated a greater efficacy in nonsquamous NSCLC that lead to an exploration of the underlying potential biological background. It is now suggested that the tumor thymidylate synthase level may act as a predictor of pemetrexed efficacy, therefore potentially providing clinicians in the future with a predictor of efficacy, which it is usually lacking with standard chemotherapies.
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Affiliation(s)
- Pascale Tomasini
- Aix-Marseille Université - Assistance Publique Hôpitaux de Marseille, Multidisciplinary Oncology & Therapeutic Innovations Department, Chemin des Bourrely, 13915 Marseille Cedex 20, France
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Fakhrejahani F, Hashemi Sadraei N, Mekhail T. The Role of Consolidation Treatment in Locally Advanced Unresectable NSCLC. Curr Oncol Rep 2013; 15:424-32. [DOI: 10.1007/s11912-013-0330-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Genova C, Rijavec E, Truini A, Coco S, Sini C, Barletta G, Dal Bello MG, Alama A, Savarino G, Pronzato P, Boccardo F, Grossi F. Pemetrexed for the treatment of non-small cell lung cancer. Expert Opin Pharmacother 2013; 14:1545-58. [PMID: 23683110 DOI: 10.1517/14656566.2013.802774] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
INTRODUCTION Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide. Although advanced NSCLC is still incurable, various anti-neoplastic agents have become available for the treatment of this disease. Pemetrexed , a multi-target folate antagonist, has improved the survival of non-squamous NSCLC patients. Currently, pemetrexed is approved for first-line treatment in combination with a platinum derivate, for second-line treatment as a single agent and, more recently, as maintenance treatment after first-line chemotherapy. AREAS COVERED The authors analyzed the state of the art of pemetrexed through a review of the literature. Clinical trials and meta-analyses involving pemetrexed in NSCLC were evaluated. Pemetrexed improved survival of non-squamous NSCLC in first-line, maintenance, and second-line treatments; this benefit is limited to non-squamous histology. Because pemetrexed has become part of the standard of care, current clinical trials are designed to compare it to other investigational combinations. Limited data on resectable disease are available, and additional clinical trials are being conducted. EXPERT OPINION Pemetrexed has shown effectiveness and a favorable toxicity profile. Histology-driven indications and the relationship of pemetrexed with thymidylate synthase expression suggest that a more precise definition of predictive biomarkers could be further investigated.
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Affiliation(s)
- Carlo Genova
- IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Lung Cancer Unit, Genova, Italy.
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Phase I study of pemetrexed and cisplatin with concurrent high-dose thoracic radiation after induction chemotherapy in patients with unresectable locally advanced non-small cell lung cancer. Lung Cancer 2013; 80:68-74. [DOI: 10.1016/j.lungcan.2012.12.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2012] [Revised: 11/28/2012] [Accepted: 12/03/2012] [Indexed: 11/21/2022]
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16
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Salama JK, Vokes EE. New radiotherapy and chemoradiotherapy approaches for non-small-cell lung cancer. J Clin Oncol 2013; 31:1029-38. [PMID: 23401449 DOI: 10.1200/jco.2012.44.5064] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Recent advances in systemic cytotoxic and molecularly targeted therapies coupled with technologic strides in radiotherapy have the potential to improve outcomes for patients with non-small-cell lung cancer (NSCLC). Investigations are ongoing to identify optimal cytotoxin-based chemoradiotherapy platforms. The influence of specific histologic and molecular mutation status on the combination of targeted therapies and radiotherapy is also being actively studied. Although there are no convincing randomized phase III data to date supporting a survival advantage for combining molecularly targeted agents with radiation or chemoradiotherapy in the setting of locally advanced NSCLC, phase II and III studies targeted to elderly patients and those with poor performance status are elucidating preferred chemoradiotherapy strategies. Radiotherapy dose escalation did not improve chemoradiotherapy outcomes, although increasing radiation dose-intensity with modern techniques is being actively studied. As modern radiotherapy techniques have been shown to improve outcomes of some patients with limited metastatic disease, investigations are ongoing regarding how to optimally integrate them with standard chemotherapy platforms.
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Abstract
Lung cancer is the most commonly diagnosed cancer in the world. “Driver” and “passenger” mutations identified in lung cancer indicate that genetics play a major role in the development of the disease, progression, metastasis and response to therapy. Survival rates for lung cancer treatment have remained stagnant at ~15% over the past 40 years in patients with disseminated disease despite advances in surgical techniques, radiotherapy and chemotherapy. Resistance to therapy; either intrinsic or acquired has been a major hindrance to treatment leading to great interest in studies seeking to understand and overcome resistance. Genetic information gained from molecular analyses has been critical in identifying druggable targets and tumor profiles that may be predictors of therapeutic response and mediators of resistance. Mutated or overexpressed epidermal growth factor receptor (EGFR) and translocations in the echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) genes (EML4-ALK) are examples of genetic aberrations resulting in targeted therapies for both localized and metastatic disease. Positive clinical responses have been noted in patients harboring these genetic mutations when treated with targeted therapies compared to patients lacking these mutations. Resistance is nonetheless a major factor contributing to the failure of targeted agents and standard cytotoxic agents. In this review, we examine molecular mechanisms that are potential drivers of resistance in non-small cell lung carcinoma, the most frequently diagnosed form of lung cancer. The mechanisms addressed include resistance to molecular targeted therapies as well as conventional chemotherapeutics through the activity of multidrug resistance proteins.
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Affiliation(s)
- Janet Wangari-Talbot
- Fox Chase Cancer Center, Developmental Therapeutics Program, 333 Cottman Ave, Philadelphia, PA, USA
| | - Elizabeth Hopper-Borge
- Fox Chase Cancer Center, Developmental Therapeutics Program, 333 Cottman Ave, Philadelphia, PA, USA
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Niho S, Kubota K, Nihei K, Sekine I, Sumi M, Sekiguchi R, Funai J, Enatsu S, Ohe Y, Tamura T. Dose-Escalation Study of Thoracic Radiotherapy in Combination With Pemetrexed Plus Cisplatin Followed by Pemetrexed Consolidation Therapy in Japanese Patients With Locally Advanced Nonsquamous Non–Small-Cell Lung Cancer. Clin Lung Cancer 2013; 14:62-9. [DOI: 10.1016/j.cllc.2012.03.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2012] [Revised: 03/07/2012] [Accepted: 03/12/2012] [Indexed: 12/28/2022]
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Stinchcombe TE, Bogart JA. Novel approaches of chemoradiotherapy in unresectable stage IIIA and stage IIIB non-small cell lung cancer. Oncologist 2012; 17:682-93. [PMID: 22531360 DOI: 10.1634/theoncologist.2012-0020] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Approximately one third of patients with non-small cell lung cancer have unresectable stage IIIA or stage IIIB disease, and appropriate patients are candidates for chemoradiotherapy with curative intent. The optimal treatment paradigm is currently undefined. Concurrent chemoradiotherapy, compared with sequential chemotherapy and thoracic radiation therapy (TRT), results in superior overall survival outcomes as a result of better locoregional control. Recent trials have revealed efficacy for newer chemotherapy combinations similar to that of older chemotherapy combinations with concurrent TRT and a lower rate of some toxicities. Ongoing phase III trials will determine the roles of cisplatin and pemetrexed concurrent with TRT in patients with nonsquamous histology, cetuximab, and the L-BLP25 vaccine. It is unlikely that bevacizumab will have a role in stage III disease because of its toxicity. Erlotinib, gefitinib, and crizotinib have not been evaluated in stage III patients selected based on molecular characteristics. The preliminary results of a phase III trial that compared conventionally fractionated standard-dose TRT (60 Gy) with high-dose TRT (74 Gy) revealed an inferior survival outcome among patients assigned to the high-dose arm. Hyperfractionation was investigated previously with promising results, but adoption has been limited because of logistical considerations. More recent trials have investigated hypofractionated TRT in chemoradiotherapy. Advances in tumor targeting and radiation treatment planning have made this approach more feasible and reduced the risk for normal tissue toxicity. Adaptive radiotherapy uses changes in tumor volume to adjust the TRT treatment plan during therapy, and trials using this strategy are ongoing. Ongoing trials with proton therapy will provide initial efficacy and safety data.
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Affiliation(s)
- Thomas E Stinchcombe
- Division of Hematology and Oncology, Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill, North Carolina 27599-7305, USA.
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