|Year : 2013 | Volume
| Issue : 2 | Page : 109-115
|Concomitant chemoradiotherapy with docetaxel and cisplatin followed by consolidation chemotherapy in locally advanced unresectable non-small cell lung cancer
Celalettin Eroglu1, Okan Orhan1, Dilek Unal1, Gamze G Dogu2, Halit Karaca2, Mustafa Dikilitas2, Ahmet Oztürk3, Metin Ozkan2, Bünyamin Kaplan1
1 Department of Radiation Oncology, Erciyes University, School of Medicine, Kayseri, Turkey
2 Department of Medical Oncology, Erciyes University, School of Medicine, Kayseri, Turkey
3 Department of Biostatistics and Medical Informatics, Erciyes University, School of Medicine, Kayseri, Turkey
|Date of Submission||24-Sep-2012|
|Date of Acceptance||18-Jan-2013|
|Date of Web Publication||30-Mar-2013|
Department of Radiation Oncology, Erciyes University, School of Medicine, M.K. Dedeman Oncology Hospital, 38039 Kayseri
| Abstract|| |
Objectives: To evaluate treatment results and toxicities in patients who received concomitant chemoradiotherapy (CRT) followed by consolidation with docetaxel and cisplatin in locally advanced unresectable non-small cell lung cancer (NSCLC).
Methods: Ninety three patients were included in this retrospective study. The patients received 66 Gy radiotherapy and weekly 20 mg/m 2 docetaxel and 20 mg/m 2 cisplatin chemotherapy concomitantly. One month later than the end of CRT, consolidation chemotherapy with four cycles of docetaxel 75 mg/m 2 and cisplatin 75 mg/m 2 were administered at each 21 days.
Results: Median age of the patients was 57 (range, 30-74). Following concomitant CRT, 14 patients (15%) showed complete and 50 patients (54%) showed partial response (total response rate was 69%). The median follow-up was 13 months (range: 2-51 months). The median overall survival was 18 months (95% confidential interval [CI]: 13.8-22.1 months); local control was 15 months (95% CI: 9.3-20.6 months); progression-free survival was 9 months (95% CI: 6.5-11.4 months). Esophagitis in eight (9%) patients, neutropenia in seven (8%) patients and pneumonitis in eight (9%) patients developed as grade III-IV toxicity due to concomitant CRT.
Conclusion: Concomitant CRT with docetaxel and cisplatin followed by docetaxel and cisplatin consolidation chemotherapy might be considered as a feasible, and well tolerated treatment modality with high response rates despite the fact that it has not a survival advantage in patients with locally advanced unresectable NSCLC.
Keywords: Cisplatin, concomitant chemoradiotherapy, docetaxel, non-small cell lung cancer
|How to cite this article:|
Eroglu C, Orhan O, Unal D, Dogu GG, Karaca H, Dikilitas M, Oztürk A, Ozkan M, Kaplan B. Concomitant chemoradiotherapy with docetaxel and cisplatin followed by consolidation chemotherapy in locally advanced unresectable non-small cell lung cancer. Ann Thorac Med 2013;8:109-15
|How to cite this URL:|
Eroglu C, Orhan O, Unal D, Dogu GG, Karaca H, Dikilitas M, Oztürk A, Ozkan M, Kaplan B. Concomitant chemoradiotherapy with docetaxel and cisplatin followed by consolidation chemotherapy in locally advanced unresectable non-small cell lung cancer. Ann Thorac Med [serial online] 2013 [cited 2020 Oct 20];8:109-15. Available from: https://www.thoracicmedicine.org/text.asp?2013/8/2/109/109824
Eighty-seven percent of lung cancers are non-small cell lung cancer (NSCLC) and one-third of this NSCLC patients are locally, advanced, unresectable stage III (A and B) diseases at the time of diagnosis. , Despite standard treatment was thoracic radiotherapy alone in 1990s, following demonstration of the superiority of chemotherapy and radiotherapy combination over radiotherapy alone in phase II clinical trials, that tendency changed. ,, In latest meta-analysis of six randomized trials ,,,,, that compared concomitant and consecutive chemoradiotherapy (CRT) in locally advanced NSCLC cases, it was shown that concomitant CRT especially provided better loco-regional control and improved survival.  However, the optimal chemotherapy regimen in patients with stage III NSCLC is still controversial. Standard modality in concomitant CRT of local advanced NSCLC is the combination of cisplatin with one of the new generation chemotherapy agents.  Following demonstration of third generation chemotherapeutic agents like vinorelbine, docetaxel and gemcitabine improved survival in combination with cisplatin in cases with advanced/metastatic NSCLC, that combination was started to be administered in locally advanced non-metastatic NSCLC patients. ,,,
Standard radio-sensitizing agent is cisplatin.  It was shown that docetaxel that was a semi-synthetic taxane had radio-sensitizing effect by pausing cell cycle at G2/M phase, the most sensitive period against radiation.  The combination of docetaxel with cisplatin was shown to be one of the most effective treatment modalities in NSCLC. ,
In this study we presented the results of consolidation chemotherapy following weekly cisplatin and docetaxel combination administered concomitantly with radiotherapy in locally advanced stage III NSCLC patients.
| Methods|| |
This retrospective study was performed at Mehmet Kemal Dedeman Oncology Center, Erciyes University Medical School. The data of 124 consecutive patients who were treated with this protocol for locally advanced NSCLC (stage IIIA and IIIB) between January 2006 and June 2010 were evaluated retrospectively in a single center experience. Of the 124 patients, 93 were enrolled in this present study. Twenty-three patients who could not been reached their information, and 8 early stage NSCLC patients who medically unresectable or rejected the surgery, were excluded from study although they were treated with the same protocol. The study was approved by the local ethic committee of Erciyes University.
The diagnosis of locally advanced unresectable stage III NSCLC was confirmed by a multidisciplinary council before the initiation of the treatment. Staging work-up included chest plain radiographs, computed tomography scan of the chest and abdomen (in some cases abdominal sonography), magnetic resonance imaging of the brain, radionuclide bone scan, bronchofiberscopy, and mediastinoscopy. Patients were staged according to the Tumor Nodes Metastasis (TNM) classification.  Inclusion criteria were; Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; the absence of drainable pleural fluid; normal renal functions (serum creatinine ≤1.5 mg/dL, creatinine clearance ≥60 mL/min); normal hepatic functions (serum total bilirubin ≤1.6 mg/dL, serum transminase levels < 2.5 times higher than upper limit); normal complete blood count level (hemoglobin >10 g/dL, white blood cells ≥4000/μL, platelet ≥100 000/μL); the absence of severe cardiac disease like coronary artery disease or congestive heart failure; the absence of previous radiotherapy/chemotherapy history.
Two-dimensional treatment planning system was used by conventional X-ray simulator and RT was delivered by a linear accelerator device including 6-18 Million Volts photons. Concurrent RT began on day 1 of chemotherapy and a total dose of 66 Gy in 2.0 Gy fractions was given concurrently with weekly docetaxel and cisplatin infusion for 6,5 weeks. The initial planning target volume consisted of the primary tumor, the ipsilateral hilum and mediastinum with a margin of 2 cm. Special blocks were employed in order to prevent the exposure of normal tissues to radiation. This initial field was treated by parallel-opposed anterior and posterior fields to 46 Gy in 23 fractions. Boost dose of radiotherapy was administered after 46 Gy to the primary tumors and the involved nodes were included with a margin of 0.5-1.5 cm from oblique parallel-opposed fields with protecting spinal cord. The target dose to the boost volume was 20 Gy in 10 fractions. No corrections for lung or bone attenuation were made. In this study, patients were excluded if the initial radiation field exceeded half of the ipsilateral lung. The dose was prescribed to isocentre, and portal imaging films were taken in every week of treatment. If grade IV hematologic toxicity occurred during the course of CRT, it was suspended and restarted after recovery to grade III or less. If grade III or greater esophagitis occurred and the physician decided that the RT could not be continued, it was suspended and restarted, after recovery to grade II or less.
During radiotherapy docetaxel 20 mg/m 2 and cisplatin 20 mg/m 2 were administered concomitantly at the 1 st day of the week. One month later after the completion of CRT, response rate of the patients were evaluated and those who were evaluated to show complete response (CR), partial response (PR) or stable disease (SD) received consolidation chemotherapy with docetaxel 75 mg/m 2 and cisplatin 75 mg/m 2 at each 21 days for four cycles.
Treatment and toxicity evaluation
Treatment response evaluation was made according to Response Evaluation Criteria in Solid Tumors 1 month later after the completion of CRT by computerized tomography of the thorax,  based on only the longest diameter of all lesions: CR - the disappearance of all lesions; PR - at least a 30% reduction of the sum of the longest diameters of all lesions, referring to the sum of baseline longest diameters; progressive disease (PD) - at least a 20% increase in the sum of the longest diameters of target lesions, referring to the smallest sum of longest diameters recorded since the treatment started or the appearance of one or more new lesions; SD - neither sufficient lesion shrinkage to qualify for PR nor sufficient lesion growth to qualify for PD, referring to the smallest sum of longest diameters since the treatment started. Toxicity evaluation of the treatment was evaluated according to National Cancer Institute Common Toxicity Criteria version 3.0. 
Body mass index
BMI classification was made according to the cut-off values recommended by the World Health Organization (WHO).  The BMI values were classified as follows: <18.5 kg/m 2 , low; 18.5-24.9 kg/m 2 , normal; 25.0-29.9 kg/m 2 , overweight; 30.0-39.9 kg/m 2 , obese; and >40.0 kg/m 2 , morbidly obese. Patients with a BMI of 25.0 or greater were classified as overweight by WHO criteria.  In the present study, patients were divided into two groups on the basis of their BMI prior to CRT. Patients with a BMI ≥25 kg/m 2 were classified as overweight, and patients with a BMI < 25 kg/m 2 were deemed not to be overweight and were classified as non-overweight.
Overall survival was considered as time from initiation of the treatment to death of any cause or last follow-up. Progression-free survival was considered as time from initiation of the treatment to progression of the disease (local recurrence and/or distant metastasis) or death. Local control was considered as time from initiation of the treatment to pulmonary progression. Distant metastasis time was accepted from beginning of the treatment until the time that distant metastasis was detected. For every patient, a dose density was calculated from the scheduled dose and the dose applied. Median relative dose density was estimated from the dose densities of all patients. Response time was defined in patients who were detected complete and PR as the time, which from 1 st month after CRT until to progression of disease or to death. Median follow-up time was calculated with the reverse Kaplan-Meier method. Kaplan-Meier method was used in survival analysis. Statistical differences between gender (female or male), age (≥65 or < 65), BMI (≥25 or < 25), stage (IIIA or IIIB), and histopathology (Adeno or Others) were calculated with logrank test. Univariate Cox regression analyses were performed to identify risk-factors and P values < 0.05 (P < 0.05) were considered to be significant. SPSS, version 15.0, was used for statistical analysis.
| Results|| |
Patients and treatment characteristics
Median age of the patients were 57 (range, 30-74); nine of them (10%) were females and 84 patients (90%) were males; 27 patients (29%) were in stage IIIA and 66 patients (71%) were in stage IIIB. Histopathologic diagnosis was adenocarcinoma in 16 patients (17%), epidermoid carcinoma in 47 patients (50%) and NSCLC with indefinite subclass in 27 patients (29%) [Table 1].
Radiotherapy was applied as 66 Gy to 74 (80%) patients. Median numbers of concomitant chemotherapy cycles and relative dose density were 6 and 0.91 (range: 0,52-1,16) respectively. Consolidation chemotherapy was administered for a median of four cycles (range: 1-4). Second line chemotherapy was started in cases that showed progression in any stage of the treatment. Treatment characteristics was shown in [Table 2].
When response to concomitant CRT was evaluated, 14 patients (15%) showed CR, 50 patients (54%) showed partial response, 12 patients (13%) showed SD and 17 patients (18%) showed progression. Median duration of the response was 6, 5 months (range: 1-48 months) in cases who showed response.
The median follow-up was 13 months (range: 2-51 months). At the cut-off date, 66 (71%) deaths have occurred in the patients. The median overall survival was 18 months (95% confidential interval [CI]: 13,8-22,1 months); local control was 15 months (95% CI: 9,3-20,6 months); progression free survival (PFS) was 9 months (95% CI: 6,5-11,4 months). Overall survival for one and 2 years, local control and PFS were 67% and 36%; 57% and 32%; 42% and 18%, respectively. Median survival times according to risk-factors in the overall survival were shown in [Table 3].
|Table 3: Median survival times according to risk factors in the overall survival of Kaplan Meier analysis|
Click here to view
Grade III-IV toxicities due to concomitant CRT was esophagitis in 8 (9%), neutropenia in 7 (8%) and pneumonitis in 8 (9%) patients [Table 4]. The treatment was suspended in six patients who developed esophagitis and in five patients who developed neutropenia. Generally, consolidation chemotherapy was well-tolerated, and there were no treatment-related deaths. The most common adverse events were neutropenia (33%) and nausea (28%) in all grades. Similarly, the most common grade III and IV toxicities were also neutropenia (8%) and nausea (3%). All the side effects were improved after dose delays with no further dose modifications.
The median distant metastases time was 6 months (range: 1-22 months). The median survival time without distant metastases was 17 months (95% CI: 14.26-19.73 months). The locations of distant metastases were as follow: Brain in 15 cases (16%), liver in eight patients (9%), bone in eight patients (9%), adrenal glands in four patients and skin in one patient (1%). Of these patients in whom distant metastases developed, five patients (14%) had adenocarcinoma, six patients (17%) had epidermoid carcinoma, and two patients (6%) had unclassified carcinoma.
Univariate and multivariate analyses
Overall survival was statistically higher in patients whose BMI is ≥25 kg/m 2 (P = 0.049) [Figure 1]. PFS was also higher in patients both whose BMI is ≥25 kg/m 2 (P = 0.033) [Figure 2]. On the other hand, there was no any difference in survival rates according to gender, age, stage, and histopathology (P > 0.05). In univariate analyses, BMI ≥25 kg/m 2 (hazard ratio, 0.605; 95% CI: 0.373-0.981; P = 0.042) found a statistically significant variable for progression-free survival. Additionally, BMI ≥25 kg/m 2 has a trend statistically significant difference for the overall survival (P = 0.068). Univariate analyses, according to risk-factors for overall survival of the patients are only presented in [Table 5]. In multivariate analyses, no significant difference was observed in the overall survival, local control, and progression-free survival rates according to age, gender, BMI, stage, distant metastasis, and histophatology (P > 0.05).
|Figure 1: Overall survival rates of Body mass index (BMI) ≥25 kg/m2 (n=40) and BMI <25 kg/m2 (n=53) patients with locally advanced NSCLC. Overall survival was significantly better in the BMI ≥25 kg/m2 group than in the BMI <25 kg/m2 group (P=0,049).|
Click here to view
|Figure 2: Progression‑free survival rates of body mass index ≥25 kg/m2 (n = 40) and BMI < 25 kg/m2 (n = 50) patients with locally advanced non‑small cell lung cancer. Progression‑free survival was significantly better in the BMI ≥25 kg/m2 group than in the BMI < 25 kg/m2 group (P = 0.033)|
Click here to view
| Discussion|| |
The gold standard of treatment for unresectable stage III NSCLC is CRT. However, since local recurrences and distant metastases are frequent, overall survival rates are low. Concomitant chemotherapy and radiotherapy administration not only increase the control of locoregional disease, but prevent the development of micrometastases. Since distant metastases are the major reason of treatment failure, addition of induction and/or consolidation chemotherapy regimens to concomitant CRT might improve survival rates. Gandara et al. showed the contribution of consolidation chemotherapy to survival rate in phase II Southwest Oncology Group 9504 trial and other studies. , In our study, we evaluated the safety and effectiveness of consolidation treatment with docetaxel and cisplatin following weekly administration of these agents concomitantly with radiotherapy.
In various studies that were performed in patients with stage III NSCLC, it was shown that median survival time was 17 months and 2 years survival rate was about 40% when vindesine, mitomycin, vinblastine, paclitaxel, gemcitabine was used in combination with cisplatin and concomitant radiotherapy. ,,,,,,,,, The list of studies in which docetaxel, a novel agent that was known to have radiosensitizing effect, was used in combination with cisplatin and concomitant radiotherapy (± consolidation chemotherapy) was presented in [Table 6]. In phase I/II studies employing docetaxel and cisplatin concomitantly with radiotherapy, median survival rate was reported as 10.5-27 months and dose limiting toxicity was determined as esophagitis with various doses and administrations. ,,,,,,
|Table 6: Studies of synchronous chemoradiotherapy with docetaxel+cisplatin (±Consolidation chemotherapy)|
Click here to view
Recently, Segawa et al. performed a phase III study with cisplatin, vindesin and mitomycin as reference arm in concomitant CRT and found that median survival was longer in cisplatin and docetaxel arm although the difference was not statistically significant (26.8 months vs. 23.7 months, P > 0.05). They suggested that combination as an alternative. Docetaxel and cisplatin were administered at a dose-level of 40 mg/m 2 /week for 6 weeks and response rate was reported as 79%, median PFS was reported as 13.4 months, 2-year survival rate was reported as 60% and dose limiting toxicities were reported as esophagitis and radiation pneumonia. 
When we compared our sample size with previous studies, we saw that we had a larger sample size except the study of Segawa et al. [Table 6]. Since, we used lower doses than Kiura et al. we obtained lower toxicity levels. Hence, lower response an survival rates might be related with lower doses as well.  We also used similar doses and administrations with Kaya et al. However, they had higher response and survival rates, which may related with success of surgery.  The only difference with the study of Nakamura et al. was higher dose of cisplatin; we found higher response rate, However, our survival rate was lower.  The differences of our study from the study of Huber et al. were determination the dose of concomitant cisplatin as 25 mg/m 2 and recommending the dose of cisplatin and docetaxel as 60 mg/m 2 during consolidation period; they found higher survival rates and lower response rates.  Segawa et al.  was used cisplatin and docetaxel at a dose level of 40 mg/m 2 and did not administer consolidation treatment; their survival rates were similar to the results of Huber et al.  However, particularly CR rates were lower than from other studies. ,,,,,
The investigators of Southwest Oncology Group evaluated 2531 cases and reported that performance status, gender, age, and cisplatin based chemotherapy were independent prognostic factors for advanced stage NSCLC.  On the other hand, North Central Cancer Treatment Group performed a study on 1053 patients and reported high leukocyte count (WBC), low-hemoglobin level, ECOG performance >0, BMI < 18.5 kg/m 2 and being at stage IV were prognostic factors.  Ademuyiwa et al. found that high-hemoglobin levels and forced expiratory volume (1) over 2 L were related with increased survival rates.  In a study on patients with NSCLC, which aimed to identify predictors of survival, low BMI (<18.5 lb/in 2 ), advanced stage (IIIB or IV), higher neutrophil count (>8 × 10 3 /mcl) and platelet count (300-826 × 10 12 /L) were found to be independent prognostic factors for shorter survival.  In another study on patients with advanced NSCLC (45 years old or younger), male gender, low BMI (<25 kg/m 2 ), stage IV disease, and anemia were found to be associated with shorter survival.  We did not find any relationship between survival rate and gender, age, stage, distant metastases, and histopathologic classification, but low BMI (<25 kg/m 2 ) is found to have significantly shorter survival time although it was not a prognostic factor.
We think that, consolidation chemotherapy with 4 cycles docetaxel plus cisplatin after concurrent CRT with the same agents could not show survival advantage according to usage of fewer chemotherapy cycles or not. That's why we decided not to routinely give consolidation chemotherapy to all patients. Although lack of using modern radiotherapy techniques is a limitation of this study, planning with modern radiotherapy methods, concomitant use of cisplatin and docetaxel at higher doses and surgery following CRT, could have improved our results.
| Conclusion|| |
As a, concomitant CRT with docetaxel and cisplatin followed by docetaxel and cisplatin consolidation chemotherapy might be considered as a feasible, and well tolerated treatment modality with high response rates despite the fact that it has not a survival advantage in patients with locally advanced unresectable NSCLC.
| References|| |
|1.||Yang P, Allen MS, Aubry MC, Wampfler JA, Marks RS, Edell ES, et al. Clinical features of 5,628 primary lung cancer patients: Experience at Mayo Clinic from 1997-2003. Chest 2005;128:452-62. |
|2.||Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: Analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 2006;24:4539-44. |
|3.||Le Chevalier T, Arriagada R, Quoix E, Ruffie P, Martin M, Tarayre M, et al. Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: First analysis of a randomized trial in 353 patients. J Natl Cancer Inst 1991;83:417-23. |
|4.||Dillman RO, Herndon J, Seagren SL, Eaton WL Jr, Green MR. Improved survival in stage III non-small-cell lung cancer: Seven-year follow-up of cancer and leukemia group B (CALGB) 8433 trial. J Natl Cancer Inst 1996;88:1210-5. |
|5.||Pfister DG, Johnson DH, Azzoli CG, Sause W, Smith TJ, Baker S Jr, et al. American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: Update 2003. J Clin Oncol 2004;22:330-53. |
|6.||Clamon G, Herndon J, Eaton W, Rosenman J, Maurer LH, Cooper MR, et al. A feasibility study of extended chemotherapy for locally advanced non-small cell lung cancer: A phase II trial of cancer and leukemia group B. Cancer Invest 1994;12:273-82. |
|7.||Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol 1999;17:2692-9. |
|8.||Curran WJ, Scott CB, Langer CJ, Komaki R, Lee JS, Hauser S, et al. Longterm benefit is observed in a phase III comparison of sequential versus concurrent chemo-radiation for patients with unresected stage III NSCLC: RTOG 9410. Proc Am Soc Clin Oncol 2003;22:621. (abstr 2499). |
|9.||Ulutin HC, Güden M, Oysul K, Sürenkök S, Pak Y. Splitcourse radiotherapy with or without concurrent or sequential chemotherapy in non-small cell lung cancer. Radiat Med 2000;18:93-6. |
|10.||Fournel P, Robinet G, Thomas P, Souquet PJ, Léna H, Vergnenégre A, et al. Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer: Groupe Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe Français de Pneumo-Cancérologie NPC 95-01 Study. J Clin Oncol 2005;23:5910-7. |
|11.||Belderbos J, Uitterhoeve L, van Zandwijk N, Belderbos H, Rodrigus P, van de Vaart P, et al. Randomised trial of sequential versus concurrent chemo-radiotherapy in patients with inoperable non-small cell lung cancer (EORTC 08972-22973). Eur J Cancer 2007;43:114-21. |
|12.||Aupérin A, Le Péchoux C, Rolland E, Curran WJ, Furuse K, Fournel P, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol 2010;28:2181-90. |
|13.||National Comprehensive Cancer Network: Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer, Version 2. 2012. Available from: http://www.nccn.org [Last accessed on 22 Aug 2012]. |
|14.||Kubota K, Watanabe K, Kunitoh H, Noda K, Ichinose Y, Katakami N, et al. Phase III randomized trial of docetaxel plus cisplatin versus vindesine plus cisplatin in patients with stage IV non-small-cell lung cancer: The Japanese Taxotere Lung Cancer Study Group. J Clin Oncol 2004;22:254-61. |
|15.||Rudd RM, Gower NH, Spiro SG, Eisen TG, Harper PG, Littler JA, et al. Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: A phase III randomized study of the London Lung Cancer Group. J Clin Oncol 2005;23:142-53. |
|16.||Kiura K, Ueoka H, Segawa Y, Tabata M, Kamei H, Takigawa N, et al. Phase I/II study of docetaxel and cisplatin with concurrent thoracic radiation therapy for locally advanced non-small-cell lung cancer. Br J Cancer 2003;89:795-802. |
|17.||Vokes EE, Herndon JE 2 nd , Crawford J, Leopold KA, Perry MC, Miller AA, et al. Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: Cancer and leukemia group B study 9431. J Clin Oncol 2002;20:4191-8. |
|18.||Kaplan B, Altýnbas M, Eroglu C, Karahacioglu E, Er O, Ozkan M, et al. Preliminary results of a phase II study of weekly paclitaxel (PTX) and carboplatin (CBDCA) administered concurrently with thoracic radiation therapy (TRT) followed by consolidation chemotherapy with PTX/CBDCA for stage III unresectable non-small-cell lung cancer (NSCLC). Am J Clin Oncol 2004;27:603-10. |
|19.||Milas L, Milas MM, Mason KA. Combination of taxanes with radiation: Preclinical studies. Semin Radiat Oncol 1999;9:12-26. |
|20.||Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, et al. The IASLC Lung Cancer Staging Project: Proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2007;2:706-14. |
|21.||Therasse P, Eisenhauer EA, Verweij J. RECIST revisited: A review of validation studies on tumour assessment. Eur J Cancer 2006;42:1031-9. |
|22.||National Cancer Instýtute-Common Toxicity Criteria (NCI-CTC). NCI-CTC version 3.0, January 30; 2006. |
|23.||World Health Organization. Report of a WHO Expert Consultation. WHO Technical Report Series number 854. Physical Status: The Use and Interpretation of Anthropometry. Geneva: World Health Organization; 1995. |
|24.||World Health Organization. Obesity: Preventing and Managing the Global Epidemic: Report of a WHO Consultation on Obesity. Geneva, Switzerland: World Health Organization; 1998. |
|25.||Gandara DR, Chansky K, Albain KS, Gaspar LE, Lara PN Jr, Kelly K, et al. Long-term survival with concurrent chemoradiation therapy followed by consolidation docetaxel in stage IIIB non-small-cell lung cancer: A phase II Southwest Oncology Group Study (S9504). Clin Lung Cancer 2006;8:116-21. |
|26.||Huber RM, Borgmeier A, Flentje M, Willner J, Schmidt M, Manegold C, et al. Concurrent chemoradiation therapy with docetaxel/cisplatin followed by docetaxel consolidation therapy in inoperable stage IIIA/B non-small-cell lung cancer: Results of a phase I study. Clin Lung Cancer 2010;11:45-50. |
|27.||Mudad R, Ramsey M, Kovitz K, Curiel TJ, Hartz R, Nedzi LL, et al. Concomitant weekly docetaxel, cisplatin and radiation therapy in locally advanced non-small cell lung cancer: A dose finding study. Lung Cancer 2003;39:173-7. |
|28.||Segawa Y, Ueoka H, Kiura K, Moritaka T, Kamei H, Takigawa N, et al. A phase I/II study of docetaxel (TXT) and cisplatin (CDDP) with concurrent thoracic radiotherapy (TRT) for Locally advanced non-smallcell Lung cancer (LA-NSCLC). Proc Am Soc Clan Oncol 2000;19:508a. Abstract 1988. |
|29.||Yamamoto N, Nishimura Y, Nakagawa K, Matsui K, Fukuoka M. Phase I/II study of weekly docetaxel dose escalation in combination with fixed weekly cisplatin and concurrent thoracic radiotherapy in locally advanced non-small cell lung cancer. Cancer Chemother Pharmacol 2006;58:285-91. |
|30.||Wu HG, Bang YJ, Choi EK, Ahn YC, Kim YW, Lim TH, et al. Phase I study of weekly docetaxel and cisplatin concurrent with thoracic radiotherapy in Stage III non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2002;52:75-80. |
|31.||Nakamura M, Koizumi T, Hayasaka M, Yasuo M, Tsushima K, Kubo K, et al. Cisplatin and weekly docetaxel with concurrent thoracic radiotherapy for locally advanced stage III non-small-cell lung cancer. Cancer Chemother Pharmacol 2009;63:1091-6. |
|32.||Kaya AO, Buyukberber S, Benekli M, Coskun U, Sevinc A, Akmansu M, et al. Concomitant chemoradiotherapy with cisplatin and docetaxel followed by surgery and consolidation chemotherapy in patients with unresectable locally advanced non-small cell lung cancer. Med Oncol 2010;27:152-7. |
|33.||Segawa Y, Kiura K, Takigawa N, Kamei H, Harita S, Hiraki S, et al. Phase III trial comparing docetaxel and cisplatin combination chemotherapy with mitomycin, vindesine, and cisplatin combination chemotherapy with concurrent thoracic radiotherapy in locally advanced non-small-cell lung cancer: OLCSG 0007. J Clin Oncol 2010;28:3299-306. |
|34.||Albain KS, Crowley JJ, LeBlanc M, Livingston RB. Survival determinants in extensive-stage non-small-cell lung cancer: The Southwest Oncology Group experience. J Clin Oncol 1991;9:1618-26. |
|35.||Mandrekar SJ, Schild SE, Hillman SL, Allen KL, Marks RS, Mailliard JA, et al. A prognostic model for advanced stage nonsmall cell lung cancer. Pooled analysis of North Central Cancer Treatment Group trials. Cancer 2006;107:781-92. |
|36.||Ademuyiwa FO, Johnson CS, White AS, Breen TE, Harvey J, Neubauer M, et al. Prognostic factors in stage III non-small-cell lung cancer. Clin Lung Cancer 2007;8:478-82. |
|37.||Luo J, Chen YJ, Narsavage GL, Ducatman A. Predictors of survival in patients with non-small cell lung cancer. Oncol Nurs Forum 2012;39:609-16. |
|38.||Hsu CL, Chen KY, Shih JY, Ho CC, Yang CH, Yu CJ, et al. Advanced non-small cell lung cancer in patients aged 45 years or younger: Outcomes and prognostic factors. BMC Cancer 2012;12:241. |
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
|This article has been cited by|
||Definitive Bimodality Concurrent Chemoradiotherapy in Patients with Inoperable N2-positive Stage IIIA Non-small Cell Lung Cancer
| ||Jae Myoung Noh,Yong Chan Ahn,Hyebin Lee,Hongryull Pyo,BoKyong Kim,Dongryul Oh,Hyojung Park,Eonju Lee,Keunchil Park,Jin Seok Ahn,Myung-Ju Ahn,Jong-Mu Sun |
| ||Cancer Research and Treatment. 2015; 47(4): 645 |
|[Pubmed] | [DOI]|
||Risk and predictors for early radiation pneumonitis in patients with stage III non-small cell lung cancer treated with concurrent or sequential chemoradiotherapy
| ||Jun Dang,Guang Li,Shuang Zang,Shuo Zhang,Lei Yao |
| ||Radiation Oncology. 2014; 9(1): 172 |
|[Pubmed] | [DOI]|