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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). 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. 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). 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.

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.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.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%).The combination of capecitabine and cisplatin is active and well tolerated as a first-line therapy for patients with metastatic NPC.

OBJECTIVE To investigate the efficiency and safety of the oxaliplatin, fluorouracil (5-FU) and leucovorin regimen (FOLFOX) in previously untreated patients with metastatic or recurrent colorectal cancer. METHODS Previously untreated patients with metastatic or recurrent colorectal cancer received 100 mg/m2 of oxaliplatin intravenously (IV) over 2 h on day 1, and IV 400 mg/m2 of leucovorin over 2 h followed by a bolus of 400mg/m2 of 5-FU. Then 2,600~3,000 mg/m2 of 5-FU was administered by continuous infusion over 46 h. RESULTS An evaluated response rate was determined for 97 of 105 treated patients. The overall response rate was 35.1%, 9 patients (9.3%) had a complete response and 25 patients (25.8%) a partial response. Thirty-two patients 33.0%) developed stable disease and 32.0% of the patients progressed. The median time to progression (TTP) was 7.7months and the median overall survival 20.5 months. One and 2-year survival rates were 68% and 32%. Toxic effects based on the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), reaching grade 3/4 were:neutropenia 12.3%, anemia 11.3%, vomiting 4.1% and diarrhea 7.2%. Grade 3 neuropathy was 5.1%. The overall survival rate of patients who had received a radical resection was superior to the patients who had not received a operation, or had received a palliative resection ( P =0.0658). The serum levels of CEA, ALP and LDH had no relationship with survival ( P >0.05). CONCLUSION The FOLFOX regimen containing oxaliplatin, 5-FU plus leucovorin was an efficacious regimen with good tolerability in previously un -treated metastatic or recurrent colorectal cancer patients.

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.

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

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.

Anaplastic T-cell lymphoma in children and adolescents is an aggressive malignant non-Hodgkin's lymphoma (NHL). The optimal treatment regimen needs to be investigated. This study was to evaluate the efficacy of modified B-NHL-BFM-90 protocol on anaplastic T-cell lymphoma in children and adolescents.From October 2002 to January 2008, 18 untreated anaplastic T-cell lymphoma patients aged less than 16 years were enrolled, and treated with modified B-NHL-BFM-90 protocol including cyclophosphamide, vincristine, ifosfamide, etoposide, adriamycin, HD-methotrexate, vindesine, dexamethasone, cytarabine/HD-cytarabine. Intrathecal injection was given every course.Of the 18 patients, 15 (83.3%) achieved complete remission (CR), and three (16.7%) achieved partial remission (PR). The patients were followed up for 4-68 months (median, 31 months). The 3-year event-free survival (EFS) rates were (87.4+/-8.4)% for all patients, 100% for stage II patients, and (85.1+/-9.7)% for stage III/IV patients; 100% for low risk group, (88.9+/-10.5)% for moderate risk group, and (80.0+/-17.9)% for high risk group. Most patients suffered from grade 3-4 myelosuppression and recovered after active support care. One patient with stage IV disease received autologous peripheral blood stem cell transplantation (PBSCT) after CR and was still alive. Two patients had tumor relapsed and died at three and five months after off treatment, respectively.Modified B-NHL-BFM-90 protocol, with tolerable toxicity, is an effective treatment regimen for anaplastic T-cell lymphoma in children and adolescents. It should be used in experienced cancer centers and hematological units.

Burkitt's lymphoma is a kind of highly aggressive B-cell lymphoma. Its clinical characteristics are different between the endemic areas in Africa and the sporadic areas in America and Europe. There is no large-scale report concerning Burkitt's lymphoma in China yet. This study was to summarize the characteristics of Burkitt's lymphoma in China.Clinical data of 69 Burkitt's lymphoma patients, treated from May 1985 to May 2007 in Cancer Center of Sun Yat-sen University, were analyzed.Of the 69 patients, 44 were men and 25 were women, with a median age of 7 (range, 2-72); 5 were at stage I, 9 at stage II, 21 at stage III, and 34 at stage IV, advanced stage (stages III and IV) accounted for 55 (79.7%) patients. Abdomen (63.8%), cervical lymph nodes (68.1%) and faciomaxillary-oropharynx (34.8%) were the most common involved sites. Bone marrow (21.9%) and central nervous system (17.4%) could also be involved. B symptoms were found in 34 patients. Serum lactate dehydrogenase (LDH) level was elevated in 42 of 58 patients, while serum uric acid level was elevated in 13 of 56 patients. Hepatitis B virus (HBV) infection was found in 6 of 57 patients, Epstain-Barr virus (EBV) infection in 7 of 13 patients, human immunodeficiency virus (HIV) infection in 0 of 51 patients. Short-term and high intensive chemotherapy with central nervous system prophylaxis could improve the prognosis.The clinical characteristics of these 69 Burkitt's lymphoma patients are much similar to those from sporadic areas, but the median age is lower, and the most common involved sites are cervical lymph nodes, abdomen and faciomaxillary-oropharynx.

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.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.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.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.

Lymphoblastic lymphoma (LBL) is a highly aggressive lymphoma, for which intensive chemotherapy is necessary. This study was designed to evaluate the efficacy and toxicity of a modified acute lymphoblastic leukemia (ALL)-Berlin-Frankfurt-Münster (BFM)-90-based protocol in Chinese children and adolescents with LBL.From March 1998 to November 2006, 60 untreated patients with LBL (age18 years) from a single institution were enrolled. All patients were treated with the modified ALL-BFM-90 protocol, and prophylactic cranial radiotherapy was omitted.The median age of the patients was 10 years (range, 2.5-18 years). Forty-eight (80%) patients had T-cell LBL, and 59 (98.3%) of the patients were stage III/IV. At the end of induction remission Ia (day 33), 3 patients had died of treatment-related toxicity. In the remaining 57 patients, complete remission (CR) or CR undetermined (CRu) had occurred in 47 (82.45%), who were designated as the moderate-risk group and partial remission (PR) had occurred in 10 patients (17.54%), who were designated the high-risk group. All patients experienced grade 3-4 hematological toxicity. At a median follow-up of 35 months, event-free survival was 78.81%+/-0.05 for all patients; the figure was 88.34%+/-0.05 for the moderate-risk group (90.91%+/-0.08 for stage III, 87.68%+/-0.06 for stage IV, 100% for those with B-cell LBL, 84.78%+/-0.06 for those with T-cell LBL, and 82.94%+/-0.08 for stage IV patients with more than 25% blast cells in bone marrow [BM]). The event-free survival in the high-risk group was 60%+/-0.15.This modified ALL-BFM-90 protocol is an effective regimen and it greatly improved the survival rate of Chinese children and adolescents with LBL compared with the ALL protocols used previously.

Recently, vascular endothelial growth factor-C (VEGF-C) and -D (VEGF-D) have been identified as specific lymphangiogenic factors, and their overexpression are related to lymphatic metastasis. This study was to investigate the expression and clinical significance of VEGF-C and VEGF-D in nasopharyngeal carcinoma (NPC).The expression of VEGF-C, VEGF-D, vascular endothelial growth factor receptor-3 (VEGFR-3), and CD34 in 66 specimens of NPC and 19 specimens of nasopharyngitis tissue were detected by SP immunohistochemistry. Lymphatic microvessel density (LMVD) and microvessel density (MVD) were calculated.The high expression rate of VEGF-C was significantly higher in NPC than in nasopharyngitis tissues (54.5% vs. 26.3%, P0.05). The high expression rate of VEGF-C was significantly higher in the NPC with regional lymph node metastasis than in those without, and higher in the NPC with high T stage than in those with low T stage (P0.05). Both univariate and multivariate logistic regression analyses showed that high expression of VEGF-C was correlated to regional lymph node metastasis (P0.05), but not to age, sex, 5-year survival, LMVD, and MVD (P0.05). The positive rate of VEGF-D was significantly higher in NPC tissues than in adjacent non-cancerous tissues (69.7% vs. 42.1%, P0.05). In NPC tissues, VEGF-D expression had no correlations to age, sex, T stage, regional lymph node metastasis, LMVD, and MVD (P0.05), but was positively related to high expression of VEGF-C. The 5-year survival rate was significantly lower in VEGF-D-positive NPC than in VEGF-D-negative NPC (50.0% vs. 85.0%, P0.05).In NPC, high expression of VEGF-C is closely correlated to regional lymph node metastasis; positive expression of VEGF-D shows no correlation to regional lymph node metastasis, but is positively related to high expression of VEGF-C and closely correlated to 5-year survival rate.

Anemia is a common complication of cancer patients. Recombinant human erythropoietin (rhEPO) can alleviate the symptoms of cancer-related anemia. However, the optimal use of rhEPO is still on investigation. This study was to find out the optimal use of rhEPO in anemic cancer patients undergoing chemotherapy.From May, 2004 to Feb, 2005, 30 patients with cancer-related anemia receiving concurrent chemotherapy were enrolled. This open-labeled, non-randomized, and pilot study evaluated the response rate of induction rhEPO 120,000 U (40,000 U was subcutaneously injected on d1, 3, 5) followed by subcutaneous injection of maintenance dose of 40,000 U once a week for 3 weeks (d8, 15, 22). Hemoglobin (Hb) and hematocrit (Hct) were measured before treatment and fortnightly during the treatment.Mean Hb maintained increasing during treatment. In week 2 (n=29) and week 4 (n=21), there were 27.59% and 61.90% patients, respectively, whose Hb value had increased more than 20 g/L from the baseline (79.56 g/L) and mean Hb were 90.26 g/L and 96.81 g/L respectively (P0.05). And mean Hct at week 2 and week 4 were 27.01% and 30.17% respectively, which were higher than the baseline (24.29%)(P=0.062 and 0.001 respectively). All patients demonstrated fine tolerance.Induction therapy followed by maintenance with rhEPO can improve the level of hemoglobin significantly and quickly in anemic cancer patients.

Colorectal cancer is one of the most common malignant tumors in China. Synchronous liver metastases occur in 10%-25% colorectal cancer patients. This study was to elucidate the prognostic factors and treatment choices for colorectal cancer patients with synchronous liver metastases.Records of 220 colorectal cancer patients with synchronous liver metastases initially treated at Cancer Center of Sun Yat-sen University from Dec. 1995 to Dec. 2002 were reviewed. Prognostic factors were analyzed by Kaplan-Meier method and Cox regression model with SPSS12.0 software.The 5-year overall survival rate was 5.52%, the median survival time of the patients was 12.93 months. Univariate analysis of clinical characteristics revealed that the number, size and distribution of liver metastases, extrahepatic disease, serum CEA level at diagnosis, N status, and histology were prognostic factors. Univariate analysis of clinical treatment factors showed that treatment modality, primary site resection, and chemotherapy regimen were prognostic factors. Multivariate analysis showed that the number and size of liver metastases, extrahepatic disease, serum CEA value at diagnosis, treatment modality, primary tumor resection, and chemotherapy regimen were independent prognostic factors of colorectal cancer patients with synchronous liver metastases.Liver metastases larger than 5 cm in diameter, bilobar liver metastases, extrahepatic invasion or metastases, and CEA level more than 200 microg/L at diagnosis are adverse prognostic factors. Primary tumor resection and liver resection should be considered for all suitable patients with colorectal metastases to the liver alone. Liver-target intervention and/or systemic chemotherapy might be a good choice for inoperable patients. If possible, systemic chemotherapy containing oxaliplatin is preferred.

To investigate the expression of survivin and caspase-3, and its correlation with prognosis in diffuse large B-cell lymphoma (DLBCL).From 1997 to 2000, 94 DLBCL patients were studied on the expression of survivin and caspase-3 detected by immunohistochemical stain. The relationship between the expression of surviving and caspase-3 and prognosis were analyzed by SPSS 10.0.The positive expression rate of survivin and caspase-3 was 68.1% and 76.6%, respectively. The expression of survivin and caspase-3 were significantly correlated with the "international prognostic index" (IPI) (P0.05). Patients with positive expression of survivin and caspase-3 were found to have higer replase risk, and patients with positive survivin expression had poorer overall 5-year survival than those with negative expression (31.3% vs 64.0%, P0.05). Positive survivin expression was found to be an independent poor prognostic index for DLBCL by Cox regression model.Survivin and caspase-3 are useful in therapeutic and prognostic assessment. Poor prognostic patients can be screened out in the early treatment period using expression of survivin and caspase-3 combined with IPI, which may help to improve the outcome of diffuse large B-cell lymphoma.

Gastrointestinal tract is the most common extranodal involvement site of lymphoma. The purpose of this study was to investigate the clinical and pathological features of primary intestinal non-Hodgkin's lymphoma (NHL) and to discuss the relationship between clinical data and the prognostic factors.From January 1980 to January 2000, 53 cases with primary intestinal NHL were included. All these patients were treated in Department of Abdominal Surgery or Department of Medical Oncology, Cancer Center, Sun Yat-sen University. The relationship between clinical data and prognosis were analyzed by SPSS 10.0.The 5-year and 10-year survival rates of primary intestinal NHL patients were 49.59% and 41.33%, respectively. Log-rank univariate analysis showed that histological immunophenotype,B symptom,serum lactate dehydrogenase(LDH) level,clinical staging (Musschoff and Rohitiner), performance status, complete resection, single or multiple lesions were closely associated with survival (P0.05); while age,gender,tumor size,and therapy modality were not associated with overall survival. Cox model multivariate analysis indicated that only histological immunophenotype was closely associated with overall survival.The histological immunophenotype was an independent prognostic risk factor for primary intestinal NHL. Primary intestinal T cell lymphoma was characterized by short clinical course, poor response and prognosis; more effective therapy strategy should be further explored.

Phase II clinical trails showed that paclitaxel is effective in treatment of advanced gastric cancer (AGC). The combination of paclitaxel and 5-fluorouracil (5-FU) in the treatment of advanced gastric cancer is effective and safe. This study was designed to evaluate the efficacy and the toxicity of paclitaxel combined with semimonthly 5-FU/Leucovorin for the AGC patients.Twenty-five measurable patients with AGC proved pathologically were enrolled into this study. The chemotherapy regimen was comprised of paclitaxel,75 mg/m(2) i.v. in a 3-hour infusion followed by 2-hour infusion of leucovorin 200 mg/m(2), then 10-minute intravenous bolus of 5-FU 375 mg/m(2), then 48-hour infusion of 5-FU 2.8 g/m(2) using an ambulatory pump. The regimen was given per 14 days. One cycle consisted of twice chemotherapy regimens. All enrolled patients received at least two cycles of treatment.After two cycles of chemotherapy, the complete remission and the partial remission were 8% and 60%, respectively. The median duration of response was 4 months. No treatment-related death occurred. Phlebitis,feeling disorder, and alopecia were main side effects.Semimonthly 5-FU/LV combined with paclitaxel has high release rate but comparatively mild toxicity for AGC patients.