Cisplatin Concurrent Chemoradiotherapy Research Articles

Clinical Significance of Arginine Signaling in Patients with Cervical Cancer Receiving Cisplatin Chemoradiation Therapy

Many human malignancies do not produce sustainable amounts of arginine (Arg) because the rate-limiting enzyme, arginosuccinate synthetase 1 (ASS1), in the biosynthesis of Arg has been silenced. We investigated the clinical significance of ASS1 expression on cisplatin chemoradiation therapy for cervical cancer. A total of 118 consecutive patients with FIGO stages IB to IVA cervical cancer who had received platinum-based concurrent chemoradiotherapy were identified and their clinical courses were reviewed. Immunohistochemical studies were performed on their formalin-fixed, paraffin-embedded tissues. The prognostic value of ASS1 was investigated by performing univariate and multivariate analyses on factors affecting patient survival. Median follow-up for all patients was 5.5 years (range: 1 to 23.5 years). Overexpression of ASS1 was an independent prognostic factor. The 5-year disease-free survival for patients with ASS1-positive tumors was 72.3%, compared with 51.6% for patients with ASS1-negative tumors (P = 0.02). Univariate Cox proportional hazards models showed positive ASS1 immunostaining (hazard ratio [HR]: 0.50, 95% CI: 0.28-0.90), FIGO stage (HR: 0.33, 95% CI: 0.18-0.59) and brachytherapy (HR: 0.22, 95% CI: 0.10-0.48) were significant prognostic factors affecting disease-free survival. In multivariate analyses, positive ASS1 remained an independent significant prognostic factor for DFS (HR = 0.45, 95% CI: 0.25-0.83). Overexpression of ASS1 is an independent prognostic factor for cervical cancer patients receiving cisplatin concurrent chemoradiotherapy.

Comparison of Hematotoxicity of Pegylated Recombinant Human Granulocyte Colony-Stimulating Factor (PEG-rhG-CSF) Combined with Dual-Agent Concurrent Chemoradiotherapy and Cisplatin Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer

<h3>Purpose/Objective(s)</h3> Concurrent chemoradiotherapy (CCRT) with cisplatin is the standard treatment for locally advanced cervical cancer (LACC), but there are still some patients who have poor efficacy. Though dual-agent concurrent chemoradiotherapy (dCCRT) can improve the efficacy, the higher hematotoxicity makes it difficult to be popularized in clinical. PEG-rhG-CSF has been recommended by relevant NCCN guidelines for CCRT of malignant tumors in recent years, however there are few reports in LACC. The aim of this study was to evaluate the effect of PEG-rhG-CSF on reducing hematotoxicity in LACC with dCCRT. <h3>Materials/Methods</h3> This study retrospectively analyzed the clinical data of patients with LACC treated with CCRT in the Affiliated Cancer Hospital of Guizhou Medical University. According to patients' clinical protocol, all patients were divided into three groups, single-agent concurrent chemoradiotherapy group(sCCRT), dCCRT group and PEG-rhG-CSF combined with dCCRT group (PEG+dCCRT). Patients in sCCRT received CCRT with cisplatin 40 mg/m² for four to six cycles and patients in dCCRT were treated with paclitaxel 135-175mg/m²+cisplatin 60-80mg/m² or lobaplatin 30mg/m² for two cycles. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) 5ug/kg/d was given to patients in these two groups according to the instructions. Patients in PEG+dCCRT were received dCCRT, and PEG-rhG-CSF 6mg was given in 24 to 72 hours after chemotherapy each cycle. The incidence and duration of grade 3-4 leukocytopenia and neutropenia and febrile neutropenia (FN) (according to CTCAE, V5.0) were the primary endpoints. The second endpoints were completion rate of chemotherapy and radiotherapy, time to complete radiotherapy. <h3>Results</h3> A total of 192 patients were enrolled between July 2019 and December 2021. 51 patients in sCCRT, 68 patients in dCCRT and 73 patients in PEG+dCCRT. The three groups were respectively compared for primary and second endpoints, and the results were shown below. The incidences of grade 3-4 leukocytopenia and neutropenia of the three groups (sCCRT, dCCRT and PEG+dCCRT) were 41.2%, 67.2%, 27.4% and 27.5%, 48.6%, 13.7%, respectively. The incidences of PEG+dCCRT were lowest in the three groups(P<0.05). In the three groups, the duration of grade 3-4 leukocytopenia and FN of PEG+dCCRT were observably reduced(P<0.05). There was no statistical difference of other primary and second endpoints in the three groups. <h3>Conclusion</h3> Prophylactic use of PEG-rhG-CSF during dCCRT makes hematotoxicity manageable, which may make dCCRT have better promotion and improves efficacy of LACC. However, further prospective studies are needed to confirm the results.

A phase III randomized, controlled trial of nedaplatin versus cisplatin concurrent chemoradiotherapy in patients with cervical cancer

BackgroundWe evaluated the non-inferiority of nedaplatin-based and cisplatin-based concurrent chemoradiotherapy in cervical cancer patients.DesignPatients aged 28-82 years with pathologically diagnosed cervical cancer (stage IB-IVA) were randomly chosen for the study. Patients in both the cisplatin and nedaplatin groups received radiotherapy and weekly intravenous nedaplatin 30 mg/m2 or cisplatin 40 mg/m2 concurrently.ResultsOne hundred and sixty patients who received treatment between 10 May 2018 and 31 August 2020 were included. The 3-year overall survival in the nedaplatin group (median 30.5 months) was not significantly different from that in the cisplatin group (28.5 months; hazard ratio 0.131, 95% confidence interval 0.016-1.068; P = 0.058). No significant differences in hematological toxicity were observed between the two groups. Vomiting (40 versus 61), nausea (44 versus 67), and anorexia (52 versus 71) were more common in the cisplatin group whereas effects on liver function, including total bilirubin (7 versus 3), alanine aminotransferase (7 versus 2), and aspartate aminotransferase (6 versus 2), were more common in the nedaplatin group. Four patients in the cisplatin group had grade I creatinine elevation, whereas none in the nedaplatin group had abnormal creatinine levels. Two patients in the nedaplatin group discontinued concurrent chemotherapy because of infusion, and one patient in the cisplatin group discontinued treatment because of infusion-induced dizziness.ConclusionsOur findings suggest that nedaplatin has a milder gastrointestinal reaction but a more significant effect on liver function than cisplatin. In patients with cervical cancer, nedaplatin-based concurrent chemoradiotherapy could serve as an alternative treatment to cisplatin.

Long-term follow-up results of the effects of chronotherapy and conventional chemotherapy combined with intensity modulated radiotherapy on dendritic cells and lymphocyte subsets in nasopharyngeal carcinoma.

e18066 Background: In this study, we compared the effects of chronotherapy with conventional chemotherapy plus intensity modulated radiotherapy (IMRT)on dendritic cells and lymphocyte subsets in locoregionally advanced NPC. Methods: Analysis of 136 patients with treatment locoregionally advanced nasopharyngeal carcinoma enrolled, 68 patients were randomly assigned to the chronotherapy group and 68 patients to the conventional chemotherapy group, and all patients received 2-3 cycles of TPF induction chemotherapy plus 2-3 cycles of cisplatin concurrent chemoradiotherapy with the following schedules: docetaxel (DOC): 60mg / m2, ivgtt, D1 (03:30-04:30); Cisplatin (DDP): 60mg / m2, civ, d1-d5 (10:00-22:00); 5-fluorouracil (5-FU): 600mg / m2 / D 1, civ, d1-d5 (22:00-10:00); Synchronized DDP 100mg / m2, civ, D1 (10:00-22:00). Conventional group: Doc 60 mg / m2, ivgtt, D1; DDP 60mg/m2, ivgtt, d1; 5-FU 600mg/m2 /d 1, civ, d1-d5(120h); Synchronized DDP 100mg / m2, IVGTT, D1. Both groups were treated with IMRT at the same dose。 Lymphocyte and lymphocyte subsets were measured by flow cytometry before induction chemotherapy and 1 year versus 3 years after the end of concurrent chemoradiotherapy in patients, and changes in immune parameters, survival, and long-term toxicities were compared between the two groups. Results: One year after induction chemotherapy and concurrent chemoradiotherapy, the chronotherapy group showed higher plasma dendritic cells (PDC) than the conventional group (P &lt; 0.05). At 1 year after induction chemotherapy and concurrent chemoradiotherapy, CD4 +, activated CD4 +, activated CD8 +, CD3-CD16 +, PDC, and MDC were significantly higher (P &lt; 0.05) in both pre - and post-treatment groups, and at 1 year after induction chemotherapy and concurrent chemoradiotherapy in the conventional group (P &lt; 0.05). At 3 years after induction chemotherapy and concurrent chemoradiotherapy, CD4 +, activated CD4 +, activated CD8 +, CD4 + CD25 +, cd3-cd19 +, and CD3-CD16 + were significantly increased in the chronic group (P &lt; 0.05), and CD4 +, activated CD4 +, activated CD8 +, and CD4 + CD25 + were significantly increased in the conventional group (P &lt; 0.05). In the comparison of toxic effects between the two groups, the incidences of xerostomia and dysphagia in the group at 3 years after treatment were significantly lower than those in the conventional group (P &lt; 0.05). There were no significant differences in PFS, OS, DMFS, LRRFS between the two groups at 3 years (P &gt; 0.05). Conclusions: Chronotherapy with intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma more than conventional chemoradiotherapy reduces damage to dendritic cells and lymphocytes and alleviates toxic effects such as xerostomia and dysphagia at the same survival rate.

Real-world evidence of cisplatin versus carboplatin in patients with locally advanced nasopharyngeal carcinoma receiving concurrent chemoradiotherapy: A multicenter analysis.

Though concurrent chemoradiotherapy (CCRT) with cisplatin remains a standard of care for patients with locally advanced nasopharyngeal carcinoma (LA-NPC), carboplatin has alternatively been used without sufficient supportive evidences. Thus, we evaluated an efficacy and tolerability of carboplatin CCRT compared with cisplatin in LA-NPC patients. Patients with LA-NPC treated with CCRT were identified through the Thai multicenter head and neck cancer database. Patient tolerability and survival were analyzed and compared between regimens. Survivals were calculated by using the Kaplan-Meier method, and compared by the log-rank test. A p-value of<0.05 was considered statistically significant. A total of 135 of 980 patients (13.8%) were treated with carboplatin. Patients treated with carboplatin were significantly associated with older age (p<0.001), smoking (p=0.003), more comorbidity (p=0.014), kidney disease (p=0.016), and lower baseline creatinine clearance (p<0.001). Intensity-modulated radiation therapy was used significantly more in the cisplatin group than carboplatin group (p<0.001). Patients who received carboplatin were associated with delay (p=0.049) and hospitalization (p=0.006), whereas cisplatin CCRT had more dose reduction (p=0.001). Patients treated with cisplatin had CCRT interruption from grade 3-4 mucositis (p=0.019) more than carboplatin, whereas carboplatin had more grade 3-4 thrombocytopenia (p<0.001). The 5-year overall survival (OS) of patients treated with cisplatin and carboplatin was 59% and 49%, respectively (p=0.128). Cisplatin or carboplatin CCRT was not a significant predictor for OS and locoregional recurrence-free survival in multivariate analysis. Carboplatin CCRT provided acceptable efficacy and tolerability profiles in real-world practice. Carboplatin should be considered as an alternative regimen, particularly in cisplatin-ineligible patients with LA-NPC treated with CCRT.

A Phase-III Randomized Controlled Trial of Nedaplatin Versus Cisplatin Concurrent Chemoradiotherapy in Patients with Cervical Cancer

A Phase-III Randomized Controlled Trial of Nedaplatin Versus Cisplatin Concurrent Chemoradiotherapy in Patients with Cervical Cancer

A meta-analysis comparing the efficacy and safety of gemcitabine plus cisplatin induction chemotherapy in patients with locoregionally advanced NPC.

Nasopharyngeal carcinoma (NPC) is a malignant tumor endangering human health. Gemcitabine or cisplatin chemotherapy has been regarded as effective treatment for patients with locoregionally advanced NPC. However, the effect of gemcitabine plus cisplatin concurrent chemoradiotherapy (CCRT) remained controversial among the studies. Therefore, we conducted this meta-analysis to assess the efficacy and safety of induction chemotherapy by gemcitabine and cisplatin (GP regimen) in patients with locoregionally advanced NPC. A systematic literature search was performed using PubMed, Web of Science, and Embase to evaluate the survival benefit and toxicity profiles of patients with locoregionally advanced NPC who were treated with CCRT. A random-effects model or a fixed-effects model was used to pool the data according to the heterogeneity among the included studies. A total of five studies with 1286 patients met the inclusion criteria and were included in this meta-analysis. Pooled estimate showed that GP regimen was associated with significant improvements in OS (HR = 0.57, 95% CI 0.45, 0.73; P < 0.001), DFS (HR = 0.56, 95% CI 0.47, 0.66; P < 0.001), and DRFS (HR = 0.51, 95% CI 0.36, 0.73; P < 0.001), but not in LRFS (HR = 0.54, 95% CI 0.25, 1.19; P = 0.126) and ORR (RR = 1.30, 95% CI 0.54, 3.09; P = 0.556). Moreover, the incidence of adverse events of all grades (RR = 1.15, 95%CI 0.11, 1.38; P = 0.063) or grade 3-4 (RR = 0.96, 95%CI 0.57, 1.29; P = 0.385), was comparable between GP regimen and control treatments. Our meta-analysis indicated that the patients with locoregionally advanced NPC could benefit from the regimen of gemcitabine plus cisplatin induction chemotherapy.

Value of adjuvant chemotherapy using paclitaxel plus carboplatin after radical surgery with or without radiotherapy in stage IB-iia cervical adenocarcinoma with risk factors.

e17016 Background: The aim of this study was to evaluate the efficacy and safety of paclitaxel/carboplatin as an adjuvant systemic chemotherapy for stage IB-IIA cervical adenocarcinoma patients after radical hysterectomy and pelvic lymphadenectomy with or without radiotherapy(RT). Methods: The cases of all patients (n = 152) with FIGO IB-IIA cervical adenocarcinoma who were treated by radical hysterectomy and pelvic lymphadenectomy with or without RT at Chinese academy of medical sciences cancer institute and hospital between January 2008 and January 2017 were reviewed. Of these, 35 patients displayed high-risk prognostic factors (high-risk group), 65 displayed intermediate-risk prognostic factors meeting sedlis criteria(intermediate-risk group),and 54 cases presented poorly differentiated status or LVSI, without other risk factors. In the high-risk group,18 patients received adjuvant radiotherapy and concurrent cisplatin chemoradiotherapy(RT-CCRT ) and 17 received adjuvant radiotherapy plus systemic chemotherapy using Paclitaxel Plus Carboplatin (RT-CT ). In the intermediate-risk group, 47 patients were treated with RT-CCRT and 16 were treated with RT-CT ,among the patients with poorly differentiated status or LVSI ,20 were treated with adjuvant chemotherapy using Paclitaxel Plus Carboplatin (CT ) and 34 received no further treatment (NFT). Results: In the high-risk group, adjuvant RT-CT was significantly superior to RT-CCRT with regard to median PFS and 2-year PFS rate(93.07months vs 52,44months, 94.1% vs 72.2%), but the recurrence rate and survival rate showed no significantly difference(11.8% vs 33.3%,100% vs 83.3%) . In the intermediate-risk group, Patients receiving RT-CT showed a better 2-year PFS rate and recurrence rate compared to those with RT-CCRT (100% vs 90.7%, 6.3% vs 12.6%), but the differences were not statistically significant. Among the patients with poorly differentiated status or LVSI, addition of adjuvant systemic chemotherapy resulted in significantly improved 2-year PFS rate compared with the NFT group (95% vs. 75.2%,p = 0.032). Conclusions: Adjuvant systemic chemotherapy using Paclitaxel Plus Carboplatin improved the prognosis of FIGO stage IB-IIA cervical adenocarcinoma patients in the high-risk group and patients who presented 2 or more intermediate-risk factors. Early cervical adenocarcinoma patients with low differentiation or LVSI can also benefit from postoperative adjuvant TC chemotherapy.

Safety and efficacy of docetaxel combined with cisplatin as induction chemotherapy followed by cisplatin concurrent chemoradiotherapy plus gemcitabine as adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: A prospective and multicenter phase II trial.

6064 Background: Radiation therapy is the only curative treatment modality for nonmetastatic nasopharyngeal cancer (NPC). Concurrent chemoradiation (CCRT) is the standard treatment strategy for NPC in locally advanced stages. However, the results after such treatment are suboptimal. Clearly, novel treatment strategies are needed to further improve patients’ survival rates. This trial aimed to determine the safety and efficacy of a new treatment strategy. Methods: Patients with stage III – IVa-b NPC received TP (docetaxel 75 mg/m2, cisplatin 75 mg/m2 every 3 weeks for 2-3 cycles) followed by cisplatin chemotherapy concurrently with either 3-dimentional conformal radiation therapy or intensity-modulated radiation therapy plus gemcitabine (1000mg/m2 every 2 weeks for 2 cycles) as adjuvant chemotherapy. Objective response rates and acute toxicity were assessed based on RECIST (1.1) and CTCAE v.4.0, respectively. Kaplan-Meier analysis was used to calculate survival rates. This trial is registered with the Chinese Clinical Trials Registry, number ChiCTR-OIC-17011464. Results: From July 2010 to July 2017, 20 eligible patients with nonmetastatic stage III-IVb NPC were enrolled. The objective response rates were 90% (3 complete responses [CRs] and 15 partial responses [PRs]) after two or three cycles of induction chemotherapy (ICT) and 100% (17 CRs and three PRs) after CCRT plus gemcitabine adjuvant chemotherapy, respectively. With a median follow-up time of 41 months, the 3-year overall survival rates were 90% (18/20,95% confidence interval [CI], 76.9%-100%).The 3-year progression-free survival, distant metastasis-free survival, and local progression-free survival rates were 80% (16/20,95% CI, 62.5%-97.5%), 85% (17/20,95% CI, 69.4%-100%),95% (19/20,95% CI, 85,4%-100%), respectively. The most frequent grade 3–4 toxicities were neutropenia (3/20,15%) and nausea (2/20,10%) after ICT and thrombocytopenia (6/20,30%) and leukopenia (6/20,30%) after CCRT plus gemcitabine adjuvant chemotherapy. Conclusions: Neoadjuvant TP followed by concurrent chemoradiation plus gemcitabine as adjuvant chemotherapy was well tolerated and produced promising outcomes in patients with LA-NPC in this hypothesis-generating study. The authors concluded that randomized controlled trials are warranted to definitively confirm this aggressive and potentially efficacious strategy. Clinical trial information: ChiCTR-OIC-17011464.

A comparative study of nab-paclitaxel versus cisplatin concurrent chemoradiotherapy in locally advanced cervical cancer

Background: Approximately, 80%–90% patients presented with locally advanced stage with bulky central disease in our center, thus induction followed by concurrent chemoradiotherapy (CCRT) plays a predominant role in the treatment of cervical cancer. Aim: The purpose of this study was to compare the effects, toxicities, treatment response, and progression-free survival (PFS) of nab-paclitaxel and cisplatin in the management of cervical cancer as CCRT. Materials and Methods: This was a prospective, observational study performed at a tertiary care hospital. A total of 120 patients of squamous cell carcinoma of cervical cancer had received three cycles of induction chemotherapy (CT), paclitaxel 175 mg/m2, and cisplatin 75 mg/m2, three weekly regimen. All patients were divided into two CCRT arm, A and B. In arm A, patients received external beam radiation therapy (EBRT) with weekly cisplatin 40 mg/m2 plus intracavitary brachytherapy (ICBT). In arm B, patients received EBRT with weekly nab-paclitaxel 70 mg/m2 plus ICBT. Results: In this study, International Federation of Gynecology and Obstetrics Stage III B, 53.33% in arm A and 46.66% in arm B. After EBRT, complete response was 48.33% in arm A and 73.33% patients in arm B, and 51.66% in arm A and 26.66% patients in arm B had partial response. Median duration of follow-up was 33 months (range 24–48). The PFS, P = 0.0093 was significant. Conclusion: With this study, we can consider the justification for future approach for locally advanced cervical cancer which incorporates induction CT followed by concurrent nab-paclitaxel with EBRT followed by ICBT.

Impact of Neoadjuvant Chemotherapy on the Administration of Concurrent Chemoradiation for Locally Advanced Nasopharyngeal Carcinoma

ObjectivesThe standard of care for locally advanced nasopharyngeal carcinoma (NPC) is concurrent cisplatin chemoradiotherapy. Neoadjuvant chemotherapy can be administered to downsize tumors before concurrent treatment to optimize radiation volumes. Our hypothesis was that the use of cisplatin in the neoadjuvant phase could limit the amount of cisplatin that patients could tolerate in the concurrent phase of treatment.MethodsThis is a retrospective analysis of Canadian NPC patients who received neoadjuvant chemotherapy with the intention to downsize locally advanced tumors prior to concurrent cisplatin plus radiation. Baseline demographic and treatment data were obtained from institutional databases and chart review; all data were analyzed with SPSS (SPSS Inc. Released 2005. SPSS for Windows, Version 14.0. Chicago: SPSS Inc.) Overall survival (OS), disease-specific survival (DSS), and local/regional relapse-free survival (LRRFS) were analyzed using Kaplan-Meier survival functions. Univariate and multivariate models were used to determine factors associated with the total dose of concurrent chemotherapy.ResultsForty-six patients were identified as receiving neoadjuvant chemotherapy before concurrent chemoradiotherapy. In the univariate and multivariate analyses of patients who received concurrent chemotherapy, receiving over 200 mg/m2 concurrent cisplatin with radiation was associated with a higher neoadjuvant dose of chemotherapy received. The median follow-up time was 2.6 years (range, 0.17 years to 10.6 years). At three years, the OS was 83%, DSS was 86%, and LRRFS was 74%.ConclusionsNPC patients have been treated with neoadjuvant chemotherapy at this center with favorable outcomes. Most patients could tolerate concurrent chemotherapy after radiotherapy. Receiving higher doses of concurrent chemotherapy was associated with also having higher doses of neoadjuvant cisplatin. This suggests that neoadjuvant cisplatin is not a limiting factor in the delivery of full-dose concurrent chemotherapy.

Cisplatin concurrent chemoradiotherapy vs adjuvant radiation in stage IB/IIA cervical cancer with intermediate risk factors, treated with radical surgery: a retrospective study.

PurposeTo determine if postoperative cisplatin concurrent chemoradiotherapy (CCRT) improves the outcome in stage IA/IIB cervical cancer patients with intermediate risk factors, when compared with radiation therapy (RT) alone, and identify the potential eligible populations for this treatment.Patients and methodsWe reviewed medical records of 1,240 patients with stage IA/IIB cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy in our hospital between January 2008 and December 2011. Of the 1,240 patients, 436 displayed 1 or more intermediate risk factors. Of these, we screened 306 patients who underwent RT only or CCRT. We analyzed the effects of CCRT on survival and prognosis.ResultsThe 5-year progress-free survival (PFS) in the CCRT group was superior to that in the RT-only group (96.0% vs 89.0%, respectively; P=0.031). The 5-year overall survivals (OSs) were not different between the 2 groups (P=0.141). Compared with RT-only group, CCRT did not improve PFS or OS in patients with 1 risk factor, large tumor size, or deep stromal invasion (P>0.05). Compared with RT-only group, CCRT improved PFS (97.9% vs 82.8%; P=0.017) but did not increase OS (97.9% vs 89.7%; P=0.109) in patients with lymphovascular space invasion plus deep stromal invasion/large tumor size. OS (92.3% vs 70.6%; P=0.048) and PFS (92.3% vs 64.7%; P=0.020) in the CCRT group were superior to those in the RT-only group with 3 risk factors. Compared with RT-only group, CCRT was an independent prognostic factor for favorable PFS (hazard ratio [HR] =0.238; 95% CI =0.0827–0.697, P=0.009) and OS (HR =0.192; 95% CI =0.069–0.533, P=0.002).ConclusionPostoperative CCRT improved survival in stage IA/IIB cervical cancer patients with intermediate risk factors. Patients with 2 or more intermediate risk factors, including lymphovascular space invasion, may benefit from CCRT.

Effects of intensity-modulated radiotherapy and chemoradiotherapy on attention in patients with nasopharyngeal cancer.

This study evaluated the short-term effects of intensity-modulated radiotherapy (IMRT) and cisplatin concurrent chemo-radiotherapy (CCRT) on attention in patients with nasopharyngeal cancer (NPC). Timely detection and early prevention of cognitive decline are important in cancer patients, because long-term cognitive effects may be permanent and irreversible. Thirty-eight NPC patients treated with IMRT (17/38) or CCRT (21/38) and 38 healthy controls were recruited for the study. Neuropsychological tests were administered to each patient before treatment initiation and within a week after treatment completion. Changes in attention performance over time were evaluated using difference values (D-values). Decreased attention was already observable in patients with NPC prior to treatment. Baseline quotient scores for auditory attention, auditory and visual vigilance, and auditory speed were lower in patients treated with CCRT than in healthy controls (P=0.037, P=0.001, P=0.007, P=0.032, respectively). Auditory stamina D-values were higher in patients treated with IMRT alone (P=0.042), while full-scale response control quotient D-values were lower in patients treated with CCRT (P=0.030) than in healthy controls. Gender, depression, education, and sleep quality were each related to decreased attention and response control. Our results showed that IMRT had no negative acute effects on attention in NPC patients, while CCRT decreased response control.

Combining cetuximab with chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma: A propensity score analysis

ObjectiveTo compare the effectiveness of concurrent cisplatin chemoradiotherapy plus cetuximab with that of concurrent chemoradiotherapy (CCRT) alone in locoregionally advanced nasopharyngeal carcinoma (LRANPC) patients. Materials and methodsA total of 3257 LRANPC patients from a prospectively maintained database were included in this observational study to examine the effectiveness of adding cetuximab to CCRT. We compared overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) using the propensity score method. ResultsIn this cohort, 131 patients received CCRT plus cetuximab. Cetuximab-treated patients were more likely to receive intensity-modulated radiation therapy and were less likely to receive induction chemotherapy or adjuvant chemotherapy. The addition of cetuximab was associated with increased DMFS compared with CCRT alone based on univariable and multivariable analyses (5-year OS, 94.1% vs. 87.3%; P=0.044), but not with increased OS, DFS, or LRRFS. Propensity score matching identified 96 patients in each cohort and confirmed that a DMFS benefit was associated with the addition of cetuximab (HR, 0.38; 95% CI, 0.15–0.99, P=0.044). Subgroup analyses demonstrated a significant DMFS benefit with CCRT plus cetuximab in patients with N2-N3 stage disease compared with N2-N3 patients receiving CCRT alone (87.9% and 66.2%, respectively; P=0.045). ConclusionsIn conclusion, the addition of cetuximab to first-line chemoradiotherapy is associated with an improvement in DMFS in patients with LRANPC. A prospective randomized clinical trial will be necessary to validate this result.

English

AIMS AND OBJECTIVES The objective of this study evaluation of otoprotective effect of antioxidant supplementation with Vitamin E on Sensorineural Hearing Loss (SNHL) in patients treated with cisplatin Concurrent Chemoradiotherapy (CRT) for Head and Neck Squamous Cell Carcinoma (HNSCC). METHODS The study comprised of audiological evaluation of 60 patients prior to and at the completion of treatment using pure tone audiometry. RESULTS At the end of 6 weeks, incidence of SNHL found to be 65.38% seen in patients who have not received Vitamin E supplement as compared to incidence of 10% seen in patients treated with CRT along with Vitamin E seen at higher frequencies and significant otoprotection offered by Vitamin E supplement was observed at 8kHz.

Postsurgical erlotinib and cisplatin concurrent chemoradiotherapy (CRT) promotes favorable outcomes in high-risk locally advanced head and neck squamous-cell cancer (LAHNSCC): A GICOR Working Group trial.

6067 Background: The approach to LAHNSCC including surgery, radiotherapy(RT), and chemotherapy (CT) lacks of significant improvements in long-term survival. In an attempt to explore tolerance and p...

Clinical study of pemetrexed combined with cisplatin concurrent chemoradiotherapy in locally advanced adenocarcinoma of lung

Objective To evaluate short-term effect and acute adverse reactions of pemetrexed combined with cisplatin concurrent chemoradiotherapy in locally advanced adenocarcinoma of lung.Methods 18 patients with locally advanced adenocarcinoma of lung received concurrent chemoradiotherapy(pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 were administrated to patients on the first day of every 3 weeks for 2 cycles),part of the patients were administrated neoadjuvant chemotherapy for 1-2 cycles.Radiotherapy adopted IMRT with a total of 60-70 Gy,1.8-2 Gy/f,5 times per week.Results There were 3 cases of CR,12 cases of PR,2 cases of SD,1 case of PD.The overall response rate (CR + PR) was 83.4％ and the clinical benefiting rate (CR + PR + SD) was 94.5％.The main adverse effects were radioactive esophagitis,bonemarrow suppression and mild gastrointestinal toxicit,tolerated by patients with support treatment.Conclusions Pemetrexed combined with cisplatin concurrent chemoradiotherapy in locally advanced adenocarcinoma of lung has good short-term effect,safety and tolerability.Long-term survival and late complications need further observation. Key words: Pemetrexed; Cisplatin; Chemotherapy; Non-small cell lung cancer; Radiotherapy; Conformal; Intensity-modulated; Concurrent chemoradiotherapy

The Efficacy of Induction Chemotherapy with Docetaxel, Cisplatin and 5-fluorouracil Combined with Cisplatin Concurrent Chemoradiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma: A Matched Pair Analysis

AimsThe role of induction chemotherapy (ICT) for head and neck squamous cell carcinoma (HNSCC) is controversial. The aim of the study was to assess the benefit of ICT with docetaxel, cisplatin and 5-fluorouracil (5-FU) (TPF) when combined with concurrent cisplatin chemoradiotherapy (CRT) for HNSCC. Materials and methodsPatients with HNSCC treated between January 2005 and December 2010 with radical intent with either TPF or cisplatin and 5-FU (PF) ICT and documented intention to proceed with concurrent cisplatin CRT were identified retrospectively. The use and choice of ICT regimen was at the clinician's discretion. In total, 68 patients treated with TPF were identified and were matched for T and N stage and tumour site to 68 patients treated with PF. A survival analysis was carried out using Kaplan–Meier and the Cox proportional hazards model. ResultsThe median follow-up was 29.9 versus 36.3 months for the TPF and PF groups, respectively. Three year locoregional relapse-free survival (RFS), distant RFS, RFS, cancer-specific survival and overall survival rates for the TPF and PF groups were 84.2, 91.6, 82.6, 81.3 and 74.9% versus 73.7, 84.9, 71.9, 72.1 and 62.9%, respectively. On multivariate analysis, treatment with TPF predicted for improved locoregional RFS (P = 0.03) and overall survival (P = 0.05). ConclusionThe addition of docetaxel to a cisplatin doublet ICT regimen before concurrent CRT may improve disease control for locally advanced HNSCC.

Efficacy in high burden locally advanced cervical cancer with concurrent gemcitabine and cisplatin chemoradiotherapy plus adjuvant gemcitabine and cisplatin: Prognostic and predictive factors and the impact of disease stage on outcomes from a prospective randomized phase III trial

ObjectiveWe recently published results of a phase III trial demonstrating superior outcomes in patients with locally advanced cervical cancer (LACC) when concurrent cisplatin chemoradiotherapy is supplemented with concurrent gemcitabine and adjuvant gemcitabine/cisplatin. We present prognostic and predictive factors identified in that study, along with analyses of the effect of disease stage and post-study therapy. Patients and methodsIn that trial, 515 patients with stage IIB–IVA LACC were administered concurrent cisplatin chemoradiotherapy with or without gemcitabine and adjuvant gemcitabine/cisplatin. Cox models were used to identify prognostic and predictive factors. Survival was estimated using the Kaplan–Meier method. ResultsAdvanced (stage III–IVA) disease, squamous histology, low hemoglobin, the presence of ≥1 enlarged para-aortic lymph nodes, and large tumor size, were associated with poorer prognosis, regardless of treatment assigned. Tumor size and histology were predictive of treatment efficacy. Chemoradiotherapy supplemented with gemcitabine produced relatively greater benefit in patients with stage III/IVA disease. Post-study therapy did not appear to affect the overall survival outcome. ConclusionPrognostic factors identified in this study are consistent with other reports. The finding of relatively greater benefit in advanced-stage patients makes for an important factor in consideration of treatment for these patients and the design of future studies.

The PARADIGM trial: A phase III study comparing sequential therapy (ST) to concurrent chemoradiotherapy (CRT) in locally advanced head and neck cancer (LANHC).

5501 Background: PARADIGM is a multicenter phase III study comparing TPF (docetaxel, cisplatin, and 5-fluorouracil)-based ST (Arm A) to upfront cisplatin CRT (Arm B) in patients (pts) with LAHNC. Pt accrual was terminated in 12/2008 due to slow enrollment with 145 of 300 planned analyzable patients accrued. Safety data was previously presented at the 2010 ASCO annual meeting showing no unusual pattern of toxicities in either arm. Here we present the survival results. Methods: Pts were randomized to receive arm A-ST (as induction chemotherapy (ICT) with TPF x 3) followed by CRT with either weekly carboplatin and once daily radiotherapy, or weekly docetaxel and accelerated boost radiotherapy based on adequate response to ICT; or arm B - accelerated boost CRT with bolus cisplatin x 2. The primary endpoint was survival. With original accrual target of 300 analyzable patients, this study was powered at 80% to detect an improvement in 3-year survival from 55% (arm B) to 70% (arm A). Results: A total of 145 previously untreated pts were enrolled (Arm A: 70; Arm B: 75), of whom 127 were male and 127 were Caucasian. Median age was 55; patients had PS of 0 (97) or 1 (48). Sites of disease were oropharynx: 80, larynx: 24, hypopharynx: 15, and oral cavity: 26. Disease stages were II (1 pt), III (20 pts) and IV (124 pts). After a median follow-up of 49 months, 41 pts have died (20 in arm A and 21 in arm B). Three-year survival was 73% (arm A) and 78% (arm B) (HR1.09; 95% CI 0.59 to 2.03 p=0.77). Three-year progression-free survival was 67% (arm A) and 73% (arm B) (HR 1.2; 95% CI 0.65 to 2.22; p=0.55). Patterns of failure will be presented at the meeting. Conclusions: Althoughthese results suggest no survival differences between CRT and ST for patients with LAHNC, the study was terminated before the planned accrual could be reached. HPV status for the oropharynx cases which represented the majority of patients was not available for stratification; and excellent survival was seen in both arms.