Nimotuzumab combined with concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: a retrospective analysis.
ABSTRACT: Nimotuzumab is a blocking monoclonal antibody against epidermal growth factor receptor (EGFR). However, little is known about the safety and preliminary efficacy of nimotuzumab combined with concurrent chemoradiotherapy in locally advanced NPC patients. A total of 42 patients diagnosed between 2011 and 2013 were enrolled. Our results demonstrated 38 patients had a complete response (90.5%), 4 patients had a partial response (9.5%). And no patients had progressive disease at early treatment response evaluation, giving an ORR of 100%. The 2-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.4%, 93.1% and 96.6% respectively. The most common adverse events were mucositis (19 patients), hematology toxicity (14 patients) with 6 and 3 cases of grade 3/4 toxicity respectively. Skin rash was not developed in our 43 patients. Thus, nimotuzumab combined with concurrent chemoradiotherapy showed encouraging outcomes in the treatment of locally advanced nasopharyngeal carcinoma, without accumulation of toxicity and well-tolerated.
Project description:The potential benefits and possible risks associated with combined nimotuzumab and concurrent chemoradiotherapy in patients with advanced nasopharyngeal carcinoma (NPC) have yet to be determined.The databases PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang were systematically searched through February 2017 for studies comparing combined nimotuzumab and chemoradiotherapy versus chemoradiotherapy alone in the treatment of NPC. Primary outcomes were complete and partial responses, and the secondary outcome was adverse reactions. The random-effect model was used to pool relative risks (RRs) and 95% confidence intervals (CIs).Nine randomized control trials and six cohort studies were included in the final analysis (n=1,015 patients). Compared with chemoradiotherapy alone, chemoradiotherapy combined with nimotuzumab was associated with an increased response rate (RR =1.11, 95% CI: 1.01-1.22). Combined treatment further reduced the occurrence rate of erythropenia (RR =0.11, 95% CI: 0.05-0.28) and neutropenia (RR =0.12, 95% CI: 0.05-0.27). The differences in the rates of other complications were not significant.Nimotuzumab combined with concurrent chemoradiotherapy is more effective in patients with advanced NPC than chemoradiotherapy alone. Patients receiving combination therapy did not have a higher rate of adverse reactions. Nimotuzumab can thus be recommended as an adjunct therapy in patients with advanced NPC.
Project description:Nimotuzumab is a humanized anti-epidermal growth factor receptor IgG1 monoclonal antibody. This phase I study assessed the tolerability, safety, efficacy, and pharmacokinetics of nimotuzumab in combination with chemoradiotherapy in Japanese patients with esophageal cancer. Patients with stage II, III, and IV esophageal cancer were enrolled. Patients were planned to receive nimotuzumab (level 1: 200 mg/wk for 25 weeks; or level 2: 400 mg/wk in the chemoradiation period, 400 mg biweekly in an additional chemotherapy period [8 weeks after the chemoradiation period] and a maintenance therapy period [after chemotherapy to 25 weeks]) combined with cisplatin (75 mg/m2 on day 1) and fluorouracil (1000 mg/m2 on days 1-4) in the chemoradiation and additional chemotherapy periods. Radiotherapy was given concurrently at 50.4 Gy. A total of 10 patients were enrolled in level 1. Dose-limiting toxicities were observed in 2 patients (grade 3 infection and renal disorder). Maximum-tolerated dose was estimated to be at least 200 mg/wk and the dose was not escalated to level 2. The most common grade ?3 toxicities were lymphopenia (90%), leukopenia (60%), neutropenia (50%), and febrile neutropenia, decreased appetite, hyponatremia, and radiation esophagitis (30% each). Neither treatment-related death nor grade ?3 skin toxicity was observed in any patient. Complete response rate was 50%. Progression-free survival was 13.9 months. One- and 3-year survival rates were 75% and 37.5%, respectively. Immunogenicity was not reported in any patient. Nimotuzumab in combination with concurrent chemoradiotherapy was tolerable and effective for Japanese patients with esophageal cancer.
Project description:This study aimed to compare the efficacy of nimotuzumab (Nimo) versus cetuximab (C225) plus concurrent chemoradiotherapy (CCRT) in locally advanced esophageal squamous cell carcinoma (LA-ESCC). A total of 95 patients with LA-ESCC were retrospectively reviewed, including 65 in Nimo and 30 in C225. The results showed that the ORR in Nimo (61.0%; CR 22.0%, 13/59; PR 39.0% 23/59) was slightly higher than that in C225 (43.5%; CR 8.7%, 2/23; PR 34.8%, 8/23) but without significant difference (p = 0.81). The DCR was 79.7% vs. 73.9% in C225, favoring Nimo plus CCRT (p = 0.04). The median PFS in Nimo was significantly longer than that in C225 (19.6 months vs. 13.0 months, p = 0.02). The median OS of the whole cohort, the Nimo group and the C225 group were 21.3, 24.5, and 20.9 months, respectively. The rates of OS at 1-, 3-year in Nimo were 77.7% and 33.5%, compared to 73.3% and 20.0% in C225 (HR = 1.17, p = 0.23). Grade 3 or worse hematological toxicity and non-hematological toxicity (radiation esophagitis) in Nimo were similar with that in C225 (21.5% vs. 26.7%, p = 0.91; 26.1% vs. 26.7%, p = 0.56). No grade ?3 radiation pneumonitis occurred neither Nimo group nor C225 group. Nimo plus CCRT improved DCR and PFS of patients with LA-ESCC and had a tendency of prolonged survival compared to C225 plus CCRT. Our results suggest that the combination of Nimo and CCRT may be a reasonable option in this population.
Project description:<b>Purpose: </b>We aimed to evaluate the long-term survival outcomes of concurrent chemoradiotherapy (CCRT) combined with nimotuzumab followed by surgery in patients with locally advanced cervical cancer (LACC).<br><br><b>Patients and methods: </b>Patients received whole pelvic intensity-modulated radiation therapy (IMRT) and concomitantly with weekly cisplatin (40 mg/m<sup>2</sup>) or nedaplatin (30 mg/m<sup>2</sup>) and weekly nimotuzumab (200 mg). After assessment of the treatment response, patients then underwent radical surgery.<br><br><b>Results: </b>Between June 2013 and July 2016, 33 patients with FIGO IB2-IIIB cervical cancer were recruited. Clinical complete response and partial response were observed in 8 (24.3%) and 23 patients (69.7%), respectively. Twenty-seven patients (81.8%) were successfully treated with radical hysterectomy and pelvic lymphadenectomy: 9 (33.3%) showed pathological complete response; 10 (37.1%) showed partial response and 8 (29.6%) presented with persistent macroscopic/microscopic residual carcinoma. For the intention-to-treat population, the median follow-up time was 53.7 months. Locoregional recurrence and distant metastases were observed in three and seven patients, respectively. The 5-year overall survival, progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival were 81.5%, 72.7%, 90.9%, and 78.3%, respectively. Both acute and late toxicities were manageable and mainly limited to grade 1 or 2.<br><br><b>Conclusion: </b>Concurrent chemoradiotherapy combined with nimotuzumab followed by surgery for patients with LACC is safe and results in excellent long-term treatment outcomes. Further randomized controlled studies are warranted to confirm the findings.
Project description:Nimotuzumab is a humanized IgG1 monoclonal antibody against the EGFR extracellular domain that has been evaluated in solid tumors as a single agent or in combination with chemotherapy and radiation. Cervical cancer patients who are refractory or progressive to first-line chemotherapy have a dismal prognosis, and no second- or third-line chemotherapy is considered standard. This pilot trial aimed to evaluate the efficacy and safety of nimotuzumab in 17 patients with pre-treated advanced refractory or progressive cervical cancer. Nimotuzumab was administered weekly at 200 mg/m(2) as single agent for 4 weeks (induction phase), then concurrent with 6 21-day cycles of gemcitabine (800 mg/m(2)) or cisplatin (50 mg/m(2)) for 18 weeks (concurrent phase) and then once every 2 weeks (maintenance phase). Nimotuzumab could be continued beyond disease progression. Seventeen patients were accrued and evaluated for safety and efficacy. The median number of nimotuzumab applications was 20 (5-96). The median number of chemotherapy cycles administered was 6 (1-6). No toxicity occurred during induction and maintenance phases (single agent nimotuzumab). In the concurrent phase, grade 3 toxicity events observed were leucopenia, anemia and diarrhea in 11.7%, 5.8% and 11.7% respectively. No complete or partial responses were observed. The stable disease (SD) rate was 35%. The median PFS and OS rates were 163 days (95% CI, 104 to 222), and 299 days (95% IC, 177 to 421) respectively. Nimotuzumab is well tolerated and may have a role in the treatment of advanced cervical cancer.
Project description:Currently, adjunctive therapy for gastric cancer is not standardized worldwide and the most effective combination of different modalities has not been clearly determined. The aim of the present study was to retrospectively analyze the efficacy and toxicity of the combination of perioperative epirubicin, capecitabine and oxaliplatin (EOX) chemotherapy and postoperative concurrent chemoradiotherapy in the treatment of locally advanced gastric cancer. A total of 41 patients with locally advanced gastric cancer who had undergone perioperative EOX chemotherapy and surgical resection followed by chemoradiotherapy, were assessed. The perioperative EOX regimen consisted of 50 mg/m2 epirubicin and 130 mg/m2 oxaliplatin on day 1, with 625 mg/m2 capecitabine administered twice daily on days 1-21. The perioperative regimen was repeated 2-3 times every 3 weeks. After complete resection following the perioperative EOX regimen, concurrent chemoradiotherapy with capecitabine (4,500 cGy in daily fractions of 180 cGy administered 5 days per week for 5 weeks, with 625 mg/m2 capecitabine twice daily during radiotherapy) and 2 cycles of the EOX regimen 4 weeks after radiotherapy, were performed. In total, 30/41 patients (73.2%) completed all the planned treatments, including perioperative chemotherapy, surgical resection and chemoradiotherapy. The effective rate of preoperative chemotherapy (partial and complete response) was 56.1%; 30/41 patients received R0 resection, and the overall 3-year survival rate was 57.7%. Grade 3/4 gastrointestinal toxicity (nausea/vomiting) occurred in 22% of the patients, while 18 patients (43.9%) developed grade 3/4 hematological toxicity (granulocytopenia). The results of the present study indicated that the combination of perioperative EOX chemotherapy and postoperative concurrent chemoradiotherapy is feasible and effective for locally advanced gastric cancer.
Project description:Background: Anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR mAbs), such as cetuximab and nimotuzumab have been used in the treatment of nasopharyngeal carcinoma (NPC), yet their efficacy and safety are undetermined. Materials and Methods: We performed two meta-analyses based on systematic searches of PubMed, EMBASE, the Cochrane Library and SinoMed: comparison 1 (standard therapy plus mAbs vs. standard therapy) and comparison 2 (radiotherapy plus concurrent mAbs vs. concurrent chemoradiotherapy) to explore the treatment value of anti-EGFR mAbs in NPC. Primary outcomes were overall survival (OS) and disease-free survival (DFS); secondary outcomes, locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and grade 3 and above acute adverse events. Results: Four randomized controlled trials and thirteen observational studies were eligible. Comparison 1 (twelve studies): adding mAbs to standard therapy (radiotherapy or chemoradiotherapy) significantly improved OS (HR, 0.51; 95% CI, 0.39-0.66) and DFS (HR, 0.68; 95% CI, 0.54-0.86), but increased the frequency of skin rashes and mucositis. Comparison 2 (six studies): OS (HR, 1.17; 95% CI, 0.81-1.70) and DFS (HR, 1.16; 95% CI, 0.86-1.57) were not significantly different when mAbs replaced conventional cytotoxic chemotherapy concurrently with radiotherapy, with fewer hematological, gastrointestinal and renal toxicities and more skin rashes in the mAb group. Conclusion: We recommend anti-EGFR mAbs enhance-but should not replace-current treatment paradigms for locoregionally advanced NPC. Further evidence from phase III clinical trials is required.
Project description:In this study, we tried to explore if xeroderma pigmentosum complementation group-A (XPA) expression is likely a prognostic prediction factor for locally advanced nasopharyngeal carcinoma (NPC) patients treated with platinum-based chemoradiotherapy, which was considered to bring chemotherapy-related severe toxicity compared with radiotherapy alone. Firstly, MTT assay revealed that downregulating XPA expression in NPC HONE1 and CNE1 cells decreased IC50 of cisplatin and sensitized cells to cisplatin. XPA expression was detected by immunohistochemistry in cancer tissues from locally advanced NPC patients treated with platinum-based chemoradiotherapy. The relationships between XPA expression and clinicopathologic features, overall survival and progression-free survival of patients were evaluated. The results showed that XPA expression was not associated with clinicopathologic parameters, but was likely an independent prognostic factor for patient survival. High XPA level predicts a poor prognosis, and the prediction values were higher in subgroups of younger, higher EBV antibody titer, or treated with concurrent chemoradiotherapy. Combining XPA levels and T/N classifications, we successfully classified these patients into low, medium and high risk groups for platinum-based chemoradiotherapy. These findings suggest that XPA levels may be a potential predictor of prognosis in locally advanced NPC patients treated with platinum-based chemoradiotherapy, and helpful for selecting patients likely to need and benefit from this treatment in future.
Project description:Locally advanced head and neck squamous cell carcinomas (HNSCC) are commonly treated with chemoradiotherapy (CRT) or induction chemotherapy followed by radiotherapy/CRT or surgery. The purpose of our study was to identify expression signatures and molecular markers able to anticipate tumor response to therapy and clinical outcome. We performed a study with 63 pre-treatment tumor biopsies from locally advanced HNSCC treated with either of the two standard treatments. Cluster analysis identified three tumor subtypes associated with significant differences in local recurrence-free survival (LRFS) and overall survival (OS). Tumor subtype 1, associated with low LRFS and OS, showed features of epithelial-mesenchymal transition and undifferentiation. It also overexpressed genes related to cell adhesion, NF-κB and integrin signalling pathways. Tumor subtype 3, associated with a high LRFS and OS, showed a high degree of differentiation and overexpressed genes located in chromosome regions 19q13 and 1q21. Tumor subtype 2, with a LRFS that was similar to subtype 3 and an OS similar to subtype 1, overexpressed genes involved in branching morphogenesis. ROC analysis identified genes associated with local recurrence and survival. Using qRT-PCR we confirmed the association of RAB25, DUOX1 and THBS1 expression with LRFS and OS. Patients whose tumors displayed high RAB25 or DUOX1 mRNA levels had longer LRFS and OS than patients with low mRNA levels. In contrast, patients bearing tumors with high THBS1 levels had a shorter OS than patients with low THBS1 levels. RAB25, DUOX1 and THBS1 could be good molecular markers to identify patients who would benefit from genotoxic treatment. Sixty three pretreatment HNSCC biopsies and five normal mucosas were assayed using the Affymetrix HG-U133A2.0 array.
Project description:The primary objective of this study was to assess the 1-year survival of patients with locally advanced, unresectable pancreatic cancer treated with the combination of bevacizumab, capecitabine, and radiation. Secondary end points were toxicity, progression-free survival (PFS), and response rate (RR).Patients with locally advanced pancreatic cancer without duodenal invasion were treated with 50.4 Gy per 28 fractions to the gross tumor with concurrent capecitabine 825 mg/m(2) orally twice daily on days of radiation and bevacizumab 5 mg/kg on days 1, 15, and 29 followed by maintenance gemcitabine 1 g/m(2) weekly for 3 weeks and bevacizumab 5 mg/kg every 2 weeks, both in 4-week cycles until progression. Treatment plans were reviewed for quality assurance (QA).Between January 2005 and February 2006, 82 eligible patients were treated. The median and 1-year survival rates were 11.9 months (95% CI, 9.9 to 14.0 months) and 47% (95% CI, 36% to 57%). Median PFS was 8.6 months (95% CI, 6.9 to 10.5), and RR was 26%. Overall, 35.4% of patients had grade 3 or greater treatment-related gastrointestinal toxicity (22.0% during chemoradiotherapy, 13.4% during maintenance chemotherapy). Unacceptable radiotherapy protocol deviations (ie, inappropriately generous volume contoured) correlated with grade 3 or greater gastrointestinal toxicity during chemoradiotherapy (45% v 18%; adjusted odds ratio, 3.7; 95% CI, 0.98 to 14.1; P = .05).The addition of bevacizumab to chemoradiotherapy followed by bevacizumab and gemcitabine resulted in a similar median survival to previous Radiation Therapy Oncology Group studies in patients with locally advanced pancreatic cancer. Prospective QA may help limit toxicity in future trials.