Multiple oncogenic mutations related to targeted therapy in nasopharyngeal carcinoma / 癌症

<p><b>INTRODUCTION</b>An increasing number of targeted drugs have been tested for the treatment of nasopharyngeal carcinoma (NPC). However, targeted therapy-related oncogenic mutations have not been fully evaluated. This study aimed to detect targeted therapy-related oncogenic mutations in NPC and to determine which targeted therapy might be potentially effective in treating NPC.</p><p><b>METHODS</b>By using the SNaPshot assay, a rapid detection method, 19 mutation hotspots in 6 targeted therapy-related oncogenes were examined in 70 NPC patients. The associations between oncogenic mutations and clinicopathologic factors were analyzed.</p><p><b>RESULTS</b>Among 70 patients, 12 (17.1%) had mutations in 5 oncogenes: 7 (10.0%) had v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) mutation, 2 (2.8%) had epidermal growth factor receptor (EGFR) mutation, 1 (1.4%) had phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation, 1 (1.4%) had Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and 1 (1.4%) had simultaneous EGFR and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations. No significant differences were observed between oncogenic mutations and clinicopathologic characteristics. Additionally, these oncogenic mutations were not associated with tumor recurrence and metastasis.</p><p><b>CONCLUSIONS</b>Oncogenic mutations are present in NPC patients. The efficacy of targeted drugs on patients with the related oncogenic mutations requires further validation.</p>

Elevated peripheral blood lymphocyte-to-monocyte ratio predicts a favorable prognosis in the patients with metastatic nasopharyngeal carcinoma / 癌症

<p><b>INTRODUCTION</b>Patients with metastatic nasopharyngeal carcinoma (NPC) have variable survival outcomes. We have previously shown that an elevated peripheral blood lymphocyte-to-monocyte ratio (LMR) is associated with an increased metastatic risk in patients with primary NPC. The present study aimed to investigate the prognostic value of pretreatment LMR in a large cohort of metastatic NPC patients.</p><p><b>METHODS</b>Clinical data of 672 patients with metastatic NPC diagnosed between January 2003 and December 2009 were analyzed. The peripheral lymphocyte and monocyte counts were retrieved, and LMR was calculated. Receiver operating characteristic (ROC) curve analysis and univariate and multivariate COX proportional hazards analyses were performed to evaluate the association of LMR with overall survival (OS).</p><p><b>RESULTS</b>Univariate analysis revealed that an elevated absolute lymphocyte count (≥1.390×10(9)/L) and LMR (≥2.475) as well as a decreased monocyte count (<0.665×10(9)/L) were significantly associated with prolonged OS. Multivariate Cox proportional hazard analysis showed that LMR (hazard ratio [HR]=0.50, 95% confidence interval [CI]=0.41-0.60, P<0.001), absolute lymphocyte count (HR=0.77, 95% CI=0.64-0.93, P=0.007), and monocyte count (HR=1.98, 95% CI=1.63-2.41, P<0.001) were independent prognostic factors. By stratification analyses, only LMR remained a significant predictor of prognosis.</p><p><b>CONCLUSION</b>We identified pretreatment LMR as an independent prognostic factor for patients with metastatic NPC. Independent validation of our findings is needed.</p>

Nedaplatin or cisplatin combined with 5-fluorouracil for treatment of stage III-IVa nasopharyngeal carcinoma: a randomized controlled study / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the efficacy and side effects of nedaplatin plus 5-fluorouracil (5-Fu) and cisplatin plus 5-Fu for treatment of stage III-IVa nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>A total of 100 patients with NPC proved by histopathology were divided into nedaplatin plus 5-Fu group (NF group) and cisplatin plus 5-Fu group (PF group), 50 cases in each group. NF group: nedaplatin 30 mg/m(2), d1-d3, 5-Fu 500 mg/m(2) d1-d5, repeated every 3 weeks for 2 cycles. PF group: cisplatin 30 mg/m(2) d1-d3, 5-Fu 500 mg/m(2) d1-d5, repeated every 3 weeks for 2 cycles. χ(2) test was used to compare the efficacy and side-effects of the two groups.</p><p><b>RESULTS</b>All the 100 cases were evaluable and their clinical data in the two groups were comparable. Six patients with complete response were observed, 3 cases in NF group and 3 in PF group. The overall response rates were 86.0% in NF group and 84.0% in PF group, with no significant difference (χ(2) = 0.078, P = 0.779). The rates of leukocytopenia, thrombocytopenia, impairment of hepatic and renal function were similar whereas more patients in the PF group than in the NF group suffered from nausea and vomiting (88.0% vs. 56.0%, P = 0.000).</p><p><b>CONCLUSIONS</b>Nedaplatin plus 5-Fu is an effective treatment regimen for NPC. When compared with PF regimen, the response rate is similar. However, NF regimen shows a significant superiority in reducing nausea and vomiting.</p>

C-KIT overexpression and mutation in nasopharyngeal carcinoma cell lines and reactivity of Imatinib on these cell lines / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>We previously reported that C-KIT overexpression and mutation exist in biopsy samples of nasopharyngeal carcinoma (NPC). Yet whether Imatinib had an inhibitory effect on the proliferation of NPC in vitro was still unknown. So, this study examined whether sensitivities to Imatinib of other cell lines are different and whether C-KIT expression and mutations exist, to analyze the correlations between them.</p><p><b>METHODS</b>The expression of C-KIT in NPC cell lines, including CNE-1, CNE-2, Hone-1, C-666, SUNE-1, 5-8F, and nasopharyngeal epithelial (NPE) cell line NP-69, were detected by Western blot. Direct sequencing of polymerase chain reaction (PCR) products was performed to analyze the sequences of C-KIT from the above-mentioned cell lines. Inhibitory effects on proliferation by Imatinib on these cell lines were determined by CCK-8 assay. Pearson product moment correlation and t test were used to analyze the correlation betweeen C-KIT overexpression, C-KIT gene mutation, and the inhibitory effect of Imatinib.</p><p><b>RESULTS</b>Compared with NPE cell line NP-69, NPC cell lines CNE-1, CNE-2, Hone-1, C-666, SUNE-1, and 5-8F had significantly higher levels of C-KIT expression. Heterozygous IVS17+78T>C were found in CNE-1, CNE-2, Hone-1, and NP-69 cell lines, homozygous IVS17+78T>C was found in C-666, and no mutation was found in SUNE-1 or 5-8F. Imatinib had a dose-dependent inhibitory effect on proliferation for CNE-1, CNE-2, Hone-1, C-666, SUNE-1, and 5-8F. No significant correlation between the inhibitory effects of Imatinib, C-KIT overexpression, or C-KIT mutation was found.</p><p><b>CONCLUSION</b>C-KIT overexpression and intron mutation were found in NPC cell lines and Imatinib had a dose-dependent inhibitory effect on proliferation for NPC cell lines, yet no significant correlation between C-KIT overexpression, C-KIT mutation, or the inhibitory effect of Imatinib was found.</p>

Phase I study of TPF neoadjuvant chemotherapy followed by radical radiotherapy in advanced nasopharyngeal carcinoma / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>PF regimen is the standard chemotherapy for advanced head and neck cancers including nasopharyngeal cancer. Recently PF has been found to enhance the tumor control by addition of Taxotere. The purpose of this study was to evaluate the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of TPF neoadjuvant regimen (taxotere, cisplatin (DDP) and 5-fluorouracil (5-FU)) followed by radical radiotherapy in advanced nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>Between December 2006 and May 2008, 41 patients with newly diagnosed UICC stage III or IV advanced nasopharyngeal cancer were enrolled. There were 29 male and 12 female patients, with a median age of 47 years (range, 29-60 years), and ECOG performance status < or = 2. The initial dose was taxotere 40 mg/m(2) d1, DDP 40 mg/m(2) d1, and 5-FU 400 mg/m(2) d1-5. The treatment was repeated every 3 weeks for two cycles. Each dose of taxotere and DDP was increased by 5 mg/m(2) and 5-FU by 50 mg/m(2), respectively. The dose was escalated after six patients completed two cycles at the initial dose and DLT was assessed. Radiotherapy was started from the 5th week, with 68-72 Gy/34-36 fractions delivered to the nasopharynx and 60-66 Gy/30-33 fractions to the node-positive area.</p><p><b>RESULTS</b>Forty patients (79 cycles) were evaluated for toxicity and efficacy of the therapy. No DLT occurred at the dose levels 1-4. At dose level 5, three of six patients experienced DLT including grade III/IV neutropenia lasting more than 1 week. Two of them also had grade III mucositis, leading to the interruption of radiotherapy for more than 1 week. Three more new patients were retreated with the same dose (at dose level 6) under the G-CSF support, and no DLT occurred. Dose escalation continued to level 7, and DLT was found in all of the four patients, including three grade IV neutropenia, one of them had fever and pneumonitis; three grade III diarrhea; and one grade III mucositis lasting 10 days. Dose escalation was stopped and three more new patients were treated again at dose level 5 and no DLT was found. Other severe toxicities included grade III anemia (1 patients), grade III vomiting (4 patients), and grade III weight loss (9 patients). No severe hepatic and renal toxicities were found.</p><p><b>CONCLUSION</b>TPF neoadjuvant chemotherapy is a safe and effective regimen in the treatment of advanced NPC, with recommended doses of taxotere 60 mg/m(2) d1, DDP 60 mg/m(2) d1, and 5-FU 600 mg/m(2) d1-5.</p>