Impact of HLA-E gene polymorphism on HLA-E expression in tumor cells and prognosis in patients with stage III colorectal cancer.

Human leukocyte antigen (HLA)-E can contribute to the escape of cancer cells from host immune mechanisms. However, it is unknown whether HLA-E gene polymorphisms might play a role in cancer immune escape. This study aimed to evaluate the correlation between HLA-E gene polymorphisms and HLA-E expression in tumor tissue and determine the effects on clinical outcome of patients with stage III colorectal cancer. Two hundred thirty patients with stage III colorectal cancer were enrolled. HLA-E expression was detected in patient-derived tumor tissues with immunohistochemistry. HLA-E gene alleles in tumor tissues were detected with the polymerase chain reaction-sequence-specific primer method. In colorectal cancer tissue and in the normal tissue adjacent to the tumor, the HLA-E expression rates were 72.2 and 15.1 %, respectively (P < 0.05). Patients with overexpression, low expression, and no expression of HLA-E exhibited disease-free survival of 55.3, 72.9, and 72.1 %, respectively. Patients with HLA-E overexpression exhibited the lowest long-term survival rate. No relationship was observed between the type of HLA-E gene polymorphism and its expression level in tumor tissues; moreover, no polymorphisms appeared to affect the long-term survival of patients with colorectal cancer. The type of HLA-E polymorphism did not have an impact on HLA-E expression in tumors or the prognosis in patients with stage III colorectal cancer. However, the level of HLA-E expression in tumor tissue strongly predicted long-term survival in these patients.

Phase 2 study of capecitabine and irinotecan combination chemotherapy (modified XELIRI regimen) in patients with advanced gastric cancer.

OBJECTIVE: The prognosis of patients with advanced gastric cancer (AGC) remains poor, and no single chemotherapy regimen is recognized as a global standard. A phase 2 trial was conducted to determine the efficacy and tolerability of the modified combination regimen of capecitabine and irinotecan (mXELIRI) in patients with AGC. METHODS: Patients with earlier untreated AGC received intravenous irinotecan (125 mg/m) over 90 minutes on days 1 and 8, and oral capecitabine (850 mg/m) twice daily on days 2 to 15, every 3 weeks. Treatment was continued for at most 8 cycles or until disease progression or intolerable toxicity. RESULTS: Thirty-two patients were enrolled. In total, 141 cycles of mXELIRI were administered. The overall response rate was 43.7%, with 1 complete response and 13 partial responses. At a median follow-up of 16.2 months, median time to progression and overall survival were 5.6 months (95% confidence interval, 4.27-6.93 mo) and 11.0 months (95% confidence interval, 8.71-13.29 mo), respectively. The most common hematological adverse event was neutropenia (n=18, 56.3%); grade 3 neutropenia was observed in 5 patients, with neutropenic fever in only 2 patients. The most common grade 3/4 nonhematological toxicities were anorexia (n=3, 9.4%), nausea (n=3, 9.4%), vomiting (n=2, 6.3%), and diarrhea (n=2, 6.3%). There was no treatment-related death. CONCLUSIONS: mXELIRI is a safe and effective first-line treatment for unresectable and metastatic gastric cancer with a manageable tolerability profile. It can be used as one of the first-line treatment options for patients with AGC.

[Comparison of the clinicopathological characteristics of colorectal cancer between elderly and young patients].

OBJECTIVE: To compare the clinicopathological characteristics between elderly and young patients with colorectal cancer (CRC). METHODS: A total of 727 patients with CRC treated between Jan 2003 and Dec 2005 were divided into elderly group (≥ 60 years old), middle-aged group (36-59 years old), and young group (≤ 35 years old). The clinicopathological characteristics of the 3 groups were analyzed retrospectively. RESULTS: The tumor occurred mainly in the rectum, sigmoid colon and ascending colon of the patients. The major initial symptoms included hemafecia and changes in bowel habits in the elderly and middle-aged cases, as compared to abdominal pain and hemafecia in the young group. The elderly patients had greater ratio of well differentiated neoplasm than the middle-aged and young patients. The ratio of radical operation was markedly higher in the elderly and middle-aged group than in the young group. The elderly patients were more likely to have stage II and III tumors than the middle-aged and young patients, having also significantly higher incidences of such complications as heart and lung diseases upon diagnosis. CONCLUSIONS: Compared with the middle-aged and young patients, elderly patients with CRC are more likely to have well differentiated tumor, multiple complications upon diagnosis, and higher radical operation rate.

Elevated neutrophil to lymphocyte ratio predicts survival in advanced pancreatic cancer.

BACKGROUND: Elevated neutrophil to lymphocyte ratio (NLR) is linked with worse survival in many malignancies, whereas its association with pancreatic cancer (PC) remains unclear. METHODS: We retrospectively reviewed 95 patients with locally advanced or metastatic PC receiving gemcitabine-based chemotherapy. The prognostic value of NLR was evaluated. RESULTS: Elevated pretreatment NLR (> 5) was observed in 16 out of 89 eligible patients, which was identified as an independent prognostic factor for overall survival (OS). The median OS for patients with elevated and normal NLR were 2.4 months and 7.7 months, respectively (p < 0.001). CONCLUSIONS: Elevated NLR is a predictor of shorter survival in patients with advanced PC.

Carcinoembryonic antigen surge in metastatic colorectal cancer patients responding to irinotecan combination chemotherapy.

BACKGROUND AND OBJECTIVE: Oxaliplatin (OXA)-induced carcinoembryonic antigen (CEA) surge was reported to be associated with a clinical benefit. The aim of this study was to investigate the phenomenon of CEA surge in irinotecan-based chemotherapy. METHODS: We retrospectively reviewed 132 patients with metastatic colorectal cancer treated with irinotecan-based chemotherapy. Incidence of a CEA surge and chemotherapy efficacy were investigated. RESULTS: Eleven of 99 eligible patients (11.1%) had CEA surges. None of the 11 patients showed progressive disease (four had a partial response, seven had stable disease). CONCLUSION: A CEA surge can be induced by irinotecan-based chemotherapy. An early increase in CEA after irinotecan-based chemotherapy does not usually indicate progression of disease and failure of therapy, and should not lead to a change of chemotherapy.

Phase II study of capecitabine plus oxaliplatin (XELOX) as first-line treatment and followed by maintenance of capecitabine in patients with metastatic colorectal cancer.

PURPOSE: The aim of this study is to evaluate the safety and efficacy of the combination of capecitabine and oxaliplatin (XELOX) as first-line treatment in Chinese patients with metastatic colorectal carcinoma (mCRC). Furthermore, we aimed to explore whether a maintenance therapy with oral capecitabine in patients who were non-progression to the XELOX regimen was able to improve the duration of disease control (DDC). PATIENTS AND METHODS: One hundred twenty-four patients with mCRC received a 3-weekly regimen of oxaliplatin plus capecitabine (XELOX) as first-line treatment. Patients without progressive disease after six cycles of XELOX could stop treatment or continue to receive oral capecitabine until disease progression or unacceptable toxicity. RESULTS: A total of 637 cycles (median 6 cycles) of XELOX were given to 124 patients (males 58.1%, median age 52 years). The response rate was 49.1% (complete response in 11 patients and partial response in 50 patients). The median overall survival and progression-free survival were 20.0 and 8.0 months, respectively. Main drug-related grade 3-4 toxicities included neutrapenia (5.6%), nausea/vomiting (4%), thrombocytopenia (2.4%), diarrhea (2.4%) and hand-foot syndrome (2.4%). Among 62 patients achieving objective response or stable disease after at least 6 cycles of XELOX, there were 22 patients received oral capecitabine as maintenance therapy. The median DDC was significantly longer for maintenance therapy group than those of no maintenance group (14 vs. 9 months; P = 0.041). CONCLUSIONS: XELOX is a highly effective first-line treatment for Chinese mCRC patients. The response rate, TTP, and overall survival of patients treated with this regimen are similar to those treated with FU/leucovorin/oxaliplatin. Furthermore, our preliminary data show maintenance therapy with capecitabine for those patients without progressive disease after at least six cycles of XELOX can significantly improve DDC; and further prospective randomized control trial is warranted.

[Clinical features of hypersensitivity reactions to oxaliplatin among Chinese colorectal cancer patients].

BACKGROUND AND OBJECTIVE: Oxaliplatin is one of the effective drugs for the treatment of advanced colorectal cancer (CRC). Oxaliplatin-induced allergic reactions in European and American patients have been reported, but in China there are only a few case reports. This study investigated the incidence rate and characteristics of oxaliplatin-induced allergic reactions in Chinese patients with CRC. METHODS: Clinical data of 109 patients with advanced CRC receiving oxaliplatin plus capecitabine (the XELOX regimen) as first-line therapy were collected and analyzed retrospectively. RESULTS: Of 109 patients, 13 (11.9%) patients had hypersensitivity. In 546 cycles, 23 (4.2%) cycles involved hypersensitivity. Grade-I,-II, and -III reactions were seen in 13 cycles, 8 cycles, and 2 cycles, respectively, and no grade-IV reaction was observed. Allergic reactions usually occurred at the median time during the fifth cycle (range, the 1st-8th cycle) of oxaliplatin-containing therapy, and the cumulative oxaliplatin dose was 1200 mg (range, 400-1600 mg). Symptoms associated with anaphylaxis appeared 5-360 min (median, 180 min) after oxaliplatin infusion, and were relieved after withdrawing the oxaliplatin infusion and treating with antiallergic drugs. A total of 8 patients continued to receive oxaliplatin therapy after prophylactic administration of antiallergic drugs, such as steroids, and 4 patients did not report persistent allergic reactions. Compared with men, oxaliplatin-induced allergic reactions were more commonly seen in women patients (P<0.05), while age, body surface area, performance status, tumor location, and pathologic type showed no significant difference. CONCLUSION: Oxaliplatin-induced allergic reactions occurred in Chinese patients with CRC, and the incidence rate, occurrence time, degree of severity, and clinical outcome were consistent with literature published abroad.

[Effect of KRAS mutation on efficacy of Cetuximab combined with chemotherapy in advanced colorectal cancer patients].

OBJECTIVE: To explore the relationship between KRAS gene status and efficacy of Cetuximab (C225) combined with chemotherapy on advanced colorectal cancer in Chinese patients, and to evaluate the safety of C225. METHODS: From May 2006 to March 2009, 81 patients with advanced colorectal cancer received Cetuximab combined with chemotherapy were enrolled in this study. The rate of KRAS mutation and the relationship of KRAS with response rate (RR), progression-free survivor (PFS), overall survival (OS) and adverse reaction of C225 were analyzed retrospectively. RESULTS: All the 81 patients received C225 therapy, and the overall RR was 33.3%. The RR of initiate therapy was 57.1%; of the second line and over the third line therapy was 38.5% and 22.0% respectively. KRAS gene phenotype examination was performed in 44 patients whose tumor samples were available. KRAS mutation was found in 20 cases (45%). Out of 44 patients, 43 were evaluable for response. RR was 5% and 43.48% in KRAS mutation and wild KRAS patients respectively (P =0.002). The median PFS was 7.0 weeks and 18.6 weeks in mutational KRAS patients and wild KRAS patients, reaching statistical significance (P =0.003). The median OS was 15.2 months and 17.3 months in mutational KRAS patients and wild KRAS patients respectively without statistical significance (P =0.463). The common adverse reactions were leucopenia, nausea, vomiting and rash. All the adverse reactions were tolerated. The incidence of skin rash in patients with mutational KRAS and patients without KRAS mutation was 40% and 42% respectively, without statistical significance (P =0.91). CONCLUSION: C225 combined with chemotherapy is well-tolerated in Chinese patients with advanced colorectal cancer, and it can significantly prolong PFS of patients with wild KRAS as compared to patients with KRAS mutation.

[Efficacy of FORFIRI regimen on oxaliplatin-based chemotherapy-failed advanced colorectal cancer].

BACKGROUND AND OBJECTIVE: Irinotecan (CPT-11), oxaliplatin, 5-fluorouracil (5-FU) and capecitabine are main active agents for advanced colorectal cancer. FORFIRI regimen is recommended for the patients who were treated with oxaliplatin plus 5-FU or capecitabine previously. This study was to investigate the efficacy and safety of FORFIRI regimen in treating advanced colorectal cancer failing to prior oxaliplatin-based chemotherapy, and analyze the impacts of clinical factors on the responses. METHODS: A total of 90 patients with advanced colorectal adenocarcinoma, who had received prior adjuvant FOLFOX6 regimen and progressed within 12 months after the completion of therapy or had no response to prior FOLFOX6/CapeOX regimen as first-line therapy, were treated with FORFIRI regimen. The efficacy and adverse events were observed. RESULTS: Of the 81 evaluable patients, two achieved complete remission, 20 achieved partial remission and 34 had stable disease. The overall response rate was 27.2% and disease control rate was 69.1%. The median time to progression was 6.8 months (95% CI, 4.9-8.8 months) and median overall survival time was 18.8 months (95% CI, 17.5-20.2 months). The main adverse events time were nausea, vomiting, neutropenia, alopecia, fatigue, impaired liver function, oral mucositis and diarrhea. Grade III adverse events included alopecia in 15 patients (16.7%), vomiting in 10 patients (11.1%), nausea in eight patients (8.9%), neutropenia in five patients (5.6%), impaired liver function in two patients (2.2%) and oral mucositis in two patients (2.2%). CONCLUSION: FOLFIRI regimen is effective and well-tolerated as salvage therapy for advanced colorectal cancer failing to prior FOLFOX6/CapeOX regimen, and thus can be used widely.

[Clinical significance of a transient increase in carcinoembryonic antigen and carbohydrate antigen 19-9 in patients with metastatic colorectal cancer receiving chemotherapy].

BACKGROUND AND OBJECTIVE: An increase in carcinoembryonic antigen (CEA) and/or carbohydrate antigen 19-9 (CA19-9) levels is generally considered as tumor progression in patients with metastatic colorectal cancer (MCRC). However, a transient CEA surge has been observed in patients with MCRC responding to chemotherapy. This study was to investigate the clinical significance of transient CEA/CA19-9 surges in Chinese MCRC patients. METHODS: One hundred and twenty-one MCRC patients with histologically proven adenocarcinoma and baseline ECOG performance status of < or =2 were treated with oxaplatin and (or) irinotecan-based chemotherapy regimens. Serum CEA and CA 19-9 levels were measured before and after chemotherapy. RESULTS: Of the 121 patients, 14 (11.6%) had transient CEA surges with median baseline CEA level of 45 microg/L (9.67-2208 microg/L) and median surge peak level of 80.1 microg/L (13.38-4044 microg/L). The transient CEA surge occurred at a median of 4 weeks (2-6 weeks), and lasted for a medium of 6.5 weeks (4-14 weeks). Of the 14 patients, 11 received oxaplatin-based chemotherapy; three received irinotecan-based chemotherapy. All the 14 patients showed clinical benefit from chemotherapy, among which seven achieved partial response and seven had stable disease. In the meantime, five patients (3.8%) had transient CA19-9 surges. However, no significant correlation was found between an increase in the CA19-9 level and clinical benefits. CONCLUSIONS: Transient CEA surges can be observed in Chinese MCRC patients receiving oxaplatin or irinotecan-based chemotherapy, which does not indicate tumor progression, but good therapeutic efficacy. A transient elevation of CA19-9 is not correlated to short-term clinical benefits.

[Efficacy and prognostic analysis on surgical resection of pulmonary metastasis from colorectal cancer].

OBJECTIVE: To elucidate the efficacy and probable prognostic factors of surgical resection of pulmonary metastasis from colorectal cancer. METHODS: Clinical data and outcomes of 35 colorectal patients with pulmonary metastasis undergone pulmonary metastasectomy were analyzed retrospectively. RESULTS: Median follow-up time was 48.0 months. The median overall survival time was 36.0 months. Five-year survival rate was 33.0%. Nineteen patients died of tumor progression. Sixteen patients were survival including survival with tumor (10 cases) and without tumor (6 cases). One patient was still alive without tumor for 164 months. Univariate analysis revealed that disease free interval (DFI) was a prognostic risk factor, while gender, age, primary tumor site, pulmonary metastasis size and location, surgical procedure, pre-surgical CEA level, re-metastasectomy did not show influence on the survival time after pulmonary metastasectomy. CONCLUSIONS: For some selected patients with indication, pulmonary metastasectomy may be a potential curative method. DFI may be associated with the prognosis after pulmonary metastasectomy.

[Prognostic value of serum CA19-9 in patients with advanced pancreatic cancer receiving gemcitabine based chemotherapy].

BACKGROUND AND OBJECTIVE: Gemcitabine is used as an effective drug for patients with advanced pancreatic cancer. Serum CA19-9 has been proven as the most sensitive and specific serum marker for pancreatic cancer. This study was to investigate the value of serum CA19-9 in evaluating treatment efficacy and predicting prognosis of patients with pancreatic cancer treated by gemcitabine-based chemotherapy. METHODS: Seventy-one patients with histologically confirmed, locally advanced or metastatic pancreatic adenocarcinoma, whose karnofsky's performance status (KPS) score was >or= 70 were treated with gemcitabine alone or with gemcitabine-based chemotherapy. CA19-9 was measured before and after chemotherapy. RESULTS: Ten out of 71 patients had normal baseline CA19-9 levels, and 61 patients had increased baseline CA19-9 levels. The overall survival of patients were similar between the two groups, which were 9.0 months and 7.9 months respectively (P=0.797). The median baseline CA19-9 level for patients who had increased CA19-9 was (682+/-558) U/mL before treatment. Patients whose pretreatment CA19-9 levels were <682 U/mL achieved better survival than those whose pretreatment CA19-9 levels were >or=682 U/mL (9.6 months vs. 5.1 months, p=0.001). In addition, patients with a pretreatment CA19-9 level of <682 U/mL also had a better tumor response (43.5% vs. 15.8%, p=0.051) and clinical benefit response (48.1% vs. 29.2%, P=0.125) than those whose pretreatment CA19-9 level was <682 U/mL, but the differences were not significant. Patients with a fall of >or=25% in the baseline CA19-9 level after chemotherapy achieved a longer median overall survival (10.2 months vs. 5.0 months, p<0.001), better tumor response (47.8% vs. 10.5%, p=0.002) and better clinical benefit response (69.2% vs. 8.0%, P=0.000) than those without a decrease of baseline CA19-9 or with a fall of <25%. Multivariate analysis revealed that the baseline CA19-9 level before chemotherapy, decreased percentage of the CA19-9 level after chemotherapy, and the differentiation degree of tumor cells were independent risk factors for patients whose baseline CA19-9 levels were increased. CONCLUSION: The level of pretreatment base-line CA19-9 and the decreased percentage of baseline CA19-9 level after chemotherapy are of predictive values for survival of patients with advanced pancreatic cancer undergoing gemcitabine-based chemotherapy and with an increased level of baseline CA19-9.

[Impact of adjuvant chemotherapy duration on 3-year disease-free survival of colorectal carcinoma patients after radical resection].

BACKGROUND AND OBJECTIVE: Adjuvant chemotherapy has become a standard postoperative treatment for stage III and high risk stage II colorectal carcinoma patients. However, only a few patients can finish 6-month adjuvant chemotherapy. This study was to find out whether the duration of adjuvant chemotherapy would affect the 3-year disease-free survival. METHODS: Clinical data of 276 colorectal carcinoma patients, receiving at least two cycles of adjuvant chemotherapy including xeloda, 5-fluorouracil/calcium folinate (5-FU/CF) or Tegafur with or without oxaliplatin after radical operation in Sun Yat-sen University Cancer Center from April, 2003 to December, 2007, were analyzed for the impact of adjuvant chemotherapy duration on the 3-year disease-free survival. RESULTS: Of the 276 patients, 216 received chemotherapy including oxaliplatin, 60 received xeloda, 5-FU/CF or tegafur as adjuvant chemotherapy. Of the 216 patients, only 49 finished the 6-month adjuvant chemotherapy. Both univariate and multivariate analyses showed that chemotherapy duration (P=0.032), sex (P=0.001), N stage (P=0.002), and pathologic differentiation (P=0.043) were independent prognosis factors for 3-year disease-free survival. CONCLUSION: Duration of adjuvant chemotherapy is an independent prognosis factor for 3-year disease-free survival of colorectal carcinoma patients.

Cutoff value of carcinoembryonic antigen and carbohydrate antigen 19-9 elevation levels for monitoring recurrence in patients with resectable gastric adenocarcinoma.

BACKGROUND: The aim of this longitudinal study was to try and improve the specificity of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in monitoring tumor recurrence in patients with resectable gastric adenocarcinoma by setting suitable elevation levels. METHODS: One hundred eighty-one patients with resectable gastric adenocarcinoma were considered. Serum samples were obtained preoperatively and every 3 months postoperatively. RESULTS: Preoperative CEA and CA19-9 positivity rates were 19.9% and 18.2%. The specificity and sensitivity of CEA elevation to monitor recurrence were 92.9% and 23.4% versus 76.5% and 78.9% in CEA-negative versus CEA-positive patients, respectively. For CA19-9 the specificity and sensitivity were 95.0% and 18.8% versus 60.0% and 83.3% in CA19-9-negative versus CA19-9-positive patients, respectively. When we set the elevation level of CEA at 5 ng/mL, the specificity of CEA elevation to monitor recurrence increased to 94.1% for CEA-positive patients. The specificity increased to 93.3% for CA19-9-positive patients when the CA19-9 elevation level was set at 100 U/mL. CONCLUSIONS: For CEA- or CA19-9-positive patients with resectable gastric adenocarcinoma we can increase the specificity of CEA and CA19-9 by setting the elevation level of CEA at 5 ng/mL and CA19-9 at 100 U/mL.

A pilot study of oxaliplatin, fluorouracil and folinic acid (FOLFOX-6) as first-line chemotherapy in advanced or recurrent gastric cancer.

BACKGROUND: To evaluate the efficacy and toxicity of an oxaliplatin, fluorouracil (5-FU), and folinic acid (FOLFOX-6) combination therapy in patients with advanced or recurrent gastric cancer. METHODS: Patients with previously untreated advanced or recurrent gastric cancer received oxaliplatin 100 mg/m(2) and leucovorin 400 mg/m(2) (2-hour intravenous infusion) followed by a 5-FU bolus of 400 mg/m(2) (10-min infusion) and then 5-FU 2,600-3,000 mg/m(2) (46-hour continuous infusion). The chemotherapy was repeated every 14 days. RESULTS: Fifty-one patients were enrolled in this study. Of these, 46 were assessable for efficacy, and all patients were assessable for toxicity. Three of 51 patients achieved a complete response, and 18 had partial responses, giving an overall response rate of 41.2%. Stable disease was observed in 11 (21.6%) patients and progressive disease in 14 (27.5%). The median time to progression was 5.4 months, and the median overall survival was 12.1 months. NCI-CTC grade 3/4 hematological toxicities were neutropenia and anemia in 9.8 and 7.8% of the patients, respectively. Grade 3 peripheral neuropathy was recorded in 3 (5.9%) patients. Other NCI-CTC grade 3 or 4 toxicities included diarrhea in 3 patients (5.9%) and vomiting in 5 (9.8%). There were no treatment-related deaths. CONCLUSIONS: This oxaliplatin/5-FU/folinic acid regimen shows good efficacy and an acceptable toxicity profile in advanced or recurrent gastric cancer patients; further clinical trials are warranted.

[Correlation of tumor vessel function to synergistic antitumor effect of Avastin combined cyclophosphamide].

BACKGROUND & OBJECTIVE: Dysfunction of tumor vessels renders high interstitial pressure, hypoxia and acidosis, causing the barrier of cytotoxic efficacy of chemotherapeutic agents. This study was to observe the dynamic alteration of vessel function in neuroblastoma (NB) after treatment of Avastin, and explore the correlation of tumor vessel function to synergistic antitumor effect of Avastin plus cyclophosphamide (CPM). METHODS: Human NB cells were incubated and transplanted into nude mice to form NB xenografts. Avastin at a dose of 5 mg/kg was administered to the mice through the tail veins. The mice were killed on the 6th hour, 3rd day, 6th day and 9th day after Avastin treatment, separately. Tumor vessel function was tested with fluorescein Hoechst33342 staining. NB-bearing mice were treated with Avastin plus CPM. The synergistic antitumor effects were compared when CPM was administered simultaneously with Avastin (combined regimen I) or at the time the tumor vessel function was mostly improved after Avastin administration (combined regimen II). RESULTS: The tumor vessel function was mostly improved on the 6th day after Avastin treatment. Tumor inhibition rates were 36.4% in Avastin monotherapy group, 38.2% in CPM monotherapy group, 55.9% in combined regimen I group, and 66.8% in combined regimen II group at 3 weeks after treatment. The synergistic antitumor effect was better when CPM was administered on the 6th day after Avastin treatment as compared with it used simultaneously with Avastin (P<0.05). CONCLUSION: The synergistic antitumor effect can be augmented when CPM is administered at the time the tumor vessel function is mostly improved after Avastin treatment.

The effectiveness of lamivudine in preventing hepatitis B viral reactivation in rituximab-containing regimen for lymphoma.

In rituximab-containing regimen for lymphoma, the role of lamivudine therapy has not been well established. Therefore, in this nonrandomized phase II clinical study, hepatitis B virus (HBV) carriers with B-cell lymphoma who received rituximab-containing regimen were treated with oral administration of lamivudine. The incidence and severity of hepatitis along with other adverse clinical outcomes were analyzed. Between January 2003 and March 2006, 29 consecutive patients were enrolled. Four of the 29 patients (13.8%) developed hepatitis during chemotherapy, none of which was attributed to HBV reactivation. According to WHO acute toxicity assessment criteria, the severity of hepatitis was grade I in two patients (6.9%) and grade II in two patients (6.9%). In these four patients, only one (3.5%) had interval delay in chemotherapy. No patient had total abnormal bilirubin. No patient had died as the result of hepatitis during the treatment. Interestingly, one of the 29 patients developed HBV activation 5.1 months after the withdrawal of lamivudine. This patient recovered after reinstallation of lamivudine therapy and is still alive. Consequently, our study confirmed previous reports that prophylactic lamivudine therapy can prevent HBV reactivation in HBV carriers who were receiving rituximab-containing regimen for lymphoma.

Phase II study of capecitabine and cisplatin combination as first-line chemotherapy in Chinese patients with metastatic nasopharyngeal carcinoma.

PURPOSE: Cisplatin combined with 5-fluorouracil (5-Fu) is widely used in the management of advanced nasopharyngeal carcinoma (NPC). However, catheters and pumps are necessary for the continuous infusion of 5-Fu, which add to the cost, immobility and inconvenience of treatment. Capecitabine, an oral fluoropyrimidine, is a potentially more active and more convenient substitute to 5-Fu. A phase II study was conducted to evaluate the efficacy and safety of a capecitabine and cisplatin combination in metastatic NPC. PATIENTS AND METHODS: In the multicenter, open-label, single-arm phase II study, patients with metastatic NPC who previously received no palliative chemotherapy were enrolled. Patients received oral capecitabine (1,000 mg/m(2) twice daily from day 1 to 14) and intravenous cisplatin (80 mg/m(2), day 1) every 3 weeks. RESULTS: A total of 48 patients were enrolled and included in the intention-to-treat analysis of efficacy and adverse events. There were 3 patients (6.3%) with complete response and 27 patients (56.3%) with partial response, giving an overall response rate of 62.5% (95% CI, 49.1-76.4%). The median duration of response in the 30 responding patients was 7.5 months (range 1.4-22.4 months). With a median follow-up period of 13.3 months (range 2.3-50 months), the median time to progression and median overall survival for all patients were 7.7 months (95% CI, 6.3-9.2 months) and 13.3 months (95% CI, 9.4-17.2 months), respectively. Toxicities were moderate and manageable. Grade 3/4 toxicities included neutropenia (14.6%), anemia (4.2%) and thrombocytopenia (2.1%), nausea (8.3%), vomiting (10.4%), diarrhea (8.3%), stomatitis (6.3%) and hand-foot syndrome (HFS) (4.2%). CONCLUSIONS: The combination of capecitabine and cisplatin is active and well tolerated as a first-line therapy for patients with metastatic NPC.

[Analysis of twelve cases of angiofollicular lymph node hyperplasia with literature review].

BACKGROUND & OBJECTIVE: Angiofollicular lymph node hyperplasia (AFH) is a rare lymphoproliferative disorder disease. This study was to investigate the clinical characteristics, treatment and prognosis of AFH. METHODS: Clinical data of 12 AFH patients, admitted in Guangdong Provincial People's Hospital from Oct. 1989 to Dec. 2006, were analyzed. All cases were diagnosed by lymph node biopsy. RESULTS: Of the 12 cases of AFH, 9 were unicentric disease characterized by localized lymph node enlargement, and 3 were multicentric disease characterized by multiple lymph node enlargement accompanied by systemic symptoms. The 9 patients with unicentric disease received tumor resection and were followed up for a median of 30 months; 8 responded well to surgical resection and 1 was lost. Of the 3 patients with multicentric disease, 2 were treated with chemotherapy and achieved partial remission, 1 received no antitumor therapy and died of multi-organ failure in 21 months. CONCLUSION: Unicentric AFH can be cured by surgery alone and have a good prognosis after operation; multicentric AFH needs aggressive and systemic chemotherapy.

[Efficacy of modified B-NHL-BFM-90 protocol on Burkitt's lymphoma in Chinese children and adolescents].

BACKGROUND & OBJECTIVE: Burkitt's lymphoma is an aggressive non-Hodgkin's lymphoma (NHL) and often involves bone marrow and central nerve system. The efficacy of CHOP regimen on Burkitt's lymphoma is poor. The optimal chemotherapy regimen needs to be investigated. This study was to evaluate the efficacy of modified B-NHL-BFM-90 protocol on Burkitt's lymphoma in children and adolescents, and observe the survival status. METHODS: From Oct. 1999 to Nov. 2006, 31 untreated Burkitt's lymphoma patients aged less than 20 were enrolled. The median age of these patients was 5 (range, 1.5-20 years old). Of the 31 patients, 20 (64.5%) were male, 11 (35.5%) were female. According to St Jude staging system, 1 (3.2%) was at stage I, 6 (19.4%) at stage II, 8 (25.8%) at stage III, 16 (51.6%) at stage IV; 24 (77.4%) were at stage III/IV. According to clinical stage, lactate dehydrogenase (LDH) level and treatment response, these patients were divided into low, moderate and high risk groups. They received modified B-NHL-BFM-90 protocol: cytotoxic drugs such as cyclophosphamide, vincristine, ifosfamide, etoposide, adriamycin, HD-methotrexate, vindesin, dexamethasone, cytarabinec/HD-cytarabine and intrathecal injection. RESULTS: One patient died of tumor lysis syndrome during prophase. The efficacy was evaluable in 30 patients. Of the 30 patients, 25 (83.3%) achieved complete remission (CR), 3 (10.0%) achieved partial remission (PR), 2 (6.7%) had progressive disease (PD)û 1 had tumor relapse. Grade 3-4 myelosuppression occurred in most patients and were recovered by active support care and did not affect next course of chemotherapy. At a median follow-up of 33 months (range, 3-98 months), the 3-year event-free survival (EFS) rate was 86.0% for all patients, with 100% for stage I/II patients and 82.1% for stage III/IV patients, 100% for low risk group, 92.0% for moderate risk group, and 70.0% for high risk group. CONCLUSIONS: Modified B-NHL-BFM-90 protocol can improve the responses and survival of Burkitt's lymphoma in Chinese children and adolescents, with tolerable toxicity. It should be used in the experienced cancer center and hematological unit.