[Trastuzumab in combination with chemotherapy versus chemotherapy alone for first-line treatment of HER2-positive advanced gastric or gastroesophageal junction cancer: a Phase III, multi-center, randomized controlled trial, Chinese subreport].

OBJECTIVE: To evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer. METHODS: Fifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival. RESULTS: Eighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively. CONCLUSIONS: Addition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.

[Long-term efficacy and safety of adjuvant trastuzumab for HER2-positive early breast cancer].

OBJECTIVE: To explore the long-term efficacy and safety of adjuvant trastuzumab for HER2-positive early breast cancer. METHODS: The clinicopathological data were collected 31 HER2-positive early breast cancer patients on the 1/2-year adjuvant therapy of trastuzumab at our hospital from October 2001 to October 2003. And the disease-free survival, recurrence-free survival, overall survival and safety were respectively analyzed. SPSS 13.0 software was used for statistical analysis. RESULTS: During a median follow-up period of 9.3 years, 6 cases had recurrence, there were 5 cases of second primary cancer and 4 patients died. In total, the 5 and 10-year recurrence-free survival rates were 83.3% and 80.0%, the 5 and 10-year disease-free survival rates 80.6% and 57.3% and the 5 and 10-year overall survival rates 96.8% and 87.1% respectively. The 10-year recurrence-free survival rate of 13 patients with ER and/or PR positive and 18 ER/PR negative patients were 100.0% and 64.7% (χ² = 5.44, P = 0.019) and 10-year overall survival rate 100% and 77.8% respectively (χ² = 3.163, P = 0.075). Trastuzmab was well-tolerated when used as adjuvant treatment. There was no occurrence of cardiac events. CONCLUSION: Adjuvant trastuzmab has definite efficacies and excellent safety in the treatment of HER2-positive breast cancer patients. And there was no long-term cumulative cardiac toxicity.

R-CHOP regimen can significantly decrease the risk of disease relapse and progression in patients with non-germinal center B-cell subtype diffuse large B-cell lymphoma.

To further explore the role of rituximab when added to the CHOP-like regimen in the treatment of immunohistochemically defined non-germinal center B-cell subtype (non-GCB) diffuse large B-cell lymphoma(DLBCL), 159 newly diagnosed DLBCL patients were studied retrospectively based on the immunohistochemical evaluation of CD10, Bcl-6, MUM-1, and Bcl-2. Altogether, 110 patients underwent the CHOP-like regimen, and rituximab was added for the other 49 patients. Cox regression analysis showed that compared with the CHOP-like regimen, the rituximab-based regimen(R-CHOP regimen) significantly decreased the risk of disease relapse and progression in CD10-negative patients (P=0.001), Bcl-6-negative patients (P=0.01), and MUM-1-positive patients (P=0.003). The risk of disease relapse in patients with non-GCB subtype (P=0.002) also decreased. In contrast, patients with the opposite immunohistochemical marker expression profile and GCB subtype did not benefit from treatment with the R-CHOP regimen. In addition, non-GCB subtype patients had a significantly higher expression rate of Bcl-2 than GCB subtype patients (P=0.042). Although univariate analysis found that both Bcl-2-positive and -negative patients had significantly higher event-free survival rates with the R-CHOP regimen, only Bcl-2 positivity (P=0.004) maintained significance in the Cox regression analysis. We conclude that the addition of rituximab can significantly improve the prognosis of patients with non-GCB subtype DLBCL, which is closely related to the expression of CD10, Bcl-6, MUM-1, and Bcl-2.

Phase I study of chidamide (CS055/HBI-8000), a new histone deacetylase inhibitor, in patients with advanced solid tumors and lymphomas.

PURPOSE: Chidamide (CS055/HBI-8000) is a new benzamide class of histone deacetylase inhibitor with marked anti-tumor activity. This study reports the phase I results. METHODS: Patients with advanced solid tumors or lymphomas received oral doses of 5, 10, 17.5, 25, 32.5, or 50 mg chidamide either twice (BIW) or three times (TIW) per week for 4 consecutive weeks every 6 weeks. Safety, characteristics of pharmacokinetics (PK) and pharmacodynamics (PD), and preliminary efficacy were evaluated. RESULTS: A total of 31 patients were enrolled. No DLTs were identified in the BIW cohorts up to 50 mg. DLTs were grade 3 diarrhea and vomiting in two patients in the TIW cohort at 50 mg, respectively. PK analysis revealed t(1/2) of 16.8-18.3 h, T(max) of 1-2 h in most cases, and a dose-related increase in C(max) and AUC. Significant induction of histone H3 acetylation in peripheral white blood cells was observed after a single dose of chidamide. Four patients with T-cell lymphomas and 1 patient with submandibular adenoid cystic carcinoma achieved a partial response. CONCLUSIONS: Chidamide was generally well tolerated in patients with advanced solid tumors or lymphomas in the tested regimens. Favorable PK and PD profiles, as well as encouraging preliminary anti-tumor activity, were demonstrated.

[Chinese HER2 positive early breast cancer trastuzumab adjuvant therapy: preliminary outcomes].

OBJECTIVE: To evaluate the efficacy and safety of 1-year adjuvant trastuzumab (herceptin) versus 1-year non-trastuzumab observation in Chinese patients with HER2-positive early breast cancer during a median follow-up of 1 year. METHODS: The HERA trial was an international, multicenter, randomized, open-label, phase III trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard adjuvant chemotherapy, radiotherapy or both in patients with HER2-positive node-positive or high-risk node-negative early breast cancer. The primary endpoint was disease-free survival. Secondary end points included recurrence-free survival, distant disease-free survival, overall survival and cardiac safety. The first planned interim analysis comparing the efficacy and safety of treatment with trastuzumab for 1 year versus observation were completed in April 2005. Only the outcomes of recruited Chinese patients were reported. RESULTS: A total of 122 Chinese patients from 8 participating centers were included for planned interim analysis. And they were divided into trastuzumab (n = 68) and observation (n = 54) groups. Three and eight disease-free survival events were observed in the trastuzumab and observation groups respectively. Two-year disease-free survival rates were 92.9% and 81.4% respectively (P = 0.0489); 2-year recurrence-free survival and distant disease-free survivals were 98.1% vs 81.4% (P = 0.0064) and 98.1% vs 83.3% (P = 0.0117) respectively. Trastuzumab was generally well-tolerated with a decent safety profile. Severe cardiotoxicity was not observed. CONCLUSION: One-year treatment with adjuvant trastuzumab improves disease-free survival, recurrence-free survival and distant disease-free survival in Chinese patients with HER2-positive early breast cancer.

Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial.

The efficacy and safety of bevacizumab with modified irinotecan, leucovorin bolus, and 5-fluorouracil intravenous infusion (mIFL) in the first-line treatment of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized clinical trials in Chinese patients. We conducted a phrase III trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan (125 mg/m(2)), leucovorin (20 mg/m(2)) bolus, and 5-fluorouracil intravenous infusion (500 mg/m(2)) weekly for four weeks every six weeks] plus bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co-primary objectives were progression-free survival (PFS) and 6-month PFS rate. In total, 214 patients were enrolled. Our results showed that addition of bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-month PFS rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7 months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group). No wound-healing complications or congestive heart failure occurred. Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC. Clinical benefit and safety profiles were consistent with those observed in pivotal phase III trials with mainly Caucasian patients.

[Analysis of first-line chemoresistance and prediction of chemo-response in non-small cell lung cancer by comparative genomic hybridization].

OBJECTIVE: To explore the association between chromosomal disequilibrium and chemoresistance/chemosensitivity in non-small cell lung cancer (NSCLC) using comparative genomic hybridization (CGH). METHODS: Genomic DNA samples were prepared from the tumor tissues in paraffin-embedded sections derived from 88 patients with advanced NSCLC (18 with chemosensitivity and 16 with chemoresistance). The DNAs were first amplified by a degenerate oligonucleotide prime-polymerase chain reaction protocol and then labeled with fluorescence as probes for CGH analyses. The correlations of the resulting chromosomal imbalances with the chemo-sensitivity and other pathological features of the patients were analyzed. RESULTS: A total of 640 abnormal chromosome regions including 96.12% gains and 3.88% losses were detected in 88 specimens. The results indicated that the most frequently gained chromosome regions were 19p13.1-13.3 (39/88, 44.12%), followed by 9q12-q22 (26/88, 29.41%), 22q12-q13 (26/88, 29.41%), and Xq (29/88, 32.35%). The total number of abnormal regions related with chemo-sensitivity was 188( 182 gains and 6 losses), while the number of the abnormal regions linked to the chemoresistance was 452 (431 gains and 21 losses) (P=0.005). Gains of 14p12-p13 and 19p were significantly correlated with the chemosensitivity of the NSCLC (P=0.006). Gains of 1q12-q22, 10q25-q26, 5p15.1-p15.3, 19q13.2-13.4, 20p11.2-p12, 21q22, and Xp 21-p22.1 were also significantly correlated with the chemoresistance (P]0.005, 0.029, 0.039, 0.029, 0.039, 0.016, and 0.006, respectively). No correlation between the chromosome abnormalities and other clinical features was observed. CONCLUSIONS: The specific gains and losses of chromosome region is correlated with platinum-based first-line chemotherapy in NSCLC patients,as confirmed by CGH detection. This finding is useful for further identifying the chemosensitivity-related functional genes, predicting clinical effectiveness, and achieve individualized treatment in the future.

[Assessment of the protective effect of calcium-magnesium infusion and glutathione on oxaliplatin-induced neurotoxicity].

OBJECTIVE: To assess the efficacy of calcium-magnesium (Ca/Mg) infusion and glutathione (GSH) for preventing the neurotoxicity induced by oxaliplatin. METHODS: This is a randomized, double blind, placebo controlled clinical trail. The patients receiving FOLFOX4 chemotherapy for their solid tumor were randomized to receive Ca/Mg, GSH or normal saline with chemotherapy simultaneously. The incidence and severity of oxaliplatin-induced neurotoxicity were observed. The ECOG performance status was recorded and compared among the 3 groups. RESULTS: Ninety-three patients admitted in our department from Mar 2006 to Dec 2007 were entered into this study, including 29 patients in the Ca/Mg group, 33 in the GSH group and 31 in the chemotherapy alone group. The incidences of acute neurotoxicity were 82.8%, 90.9% and 93.5%, respectively. At the third cycle, the incidences of grade 1-2 chronic neurotoxicity were 37.9%, 48.5% and 42.0%, respectively. No grade 3 neuropathy was observed. After 6 cycles, the incidence of grade 1-2 neuropathy was increased to 68.2%, 88.9% and 85.2%, respectively. A lower percentage was observed in Ca/Mg arm without a statistically significant difference, and grade 3 neuropathy occurred in 5 patients. After 9 cycles, the incidence of grade 1-2 neuropathy was increased to 81.3%, 90.0% and 92.9%, respectively. Grade 3 neuropathy occurred in another 2 patients. No statistically significant difference was observed among the 3 arms. Changes of patient's ECOG score after chemotherapy were similar. CONCLUSION: This study didn't provide evidence that Ca/Mg infusion and GSH can prevent the oxaliplatin-induced neurotoxicity.

[Clinical characteristics and treatment of desmoplastic small round cell tumor].

OBJECTIVE: To investigate the clinical characteristics and treatment of desmoplastic small round cell tumor. METHODS: Five patients with DSRCT were diagnosed and treated in our Hospital from January 1999 to May 2009. Forty-eight cases with complete clinical data were collected and reviewed from 23 published reports. Therefore totally 53 patients with DSRCT were analysed. The survival rate was calculated by Kaplan-Meier method and compared by log-rank test. RESULTS: The median age of all cases was 23 (1.5 - 66) years old at the time of diagnosis. 75.5% of patients were male. The most common presenting complaint was intra-abdominal mass or pain (77.4%). In 46 patients (86.8%), the primary tumor was located in the abdomen or pelvis. Fifteen (28.3%) had positive lymph nodes or distant parenchymal metastases. The median follow-up was 1.8 years (range, 0.1 - 10.0 years). The overall 1-, 3- and 5-year survivals were 45.8%, 20.8% and 5.7%, respectively. Forty-seven patients underwent surgery. Complete tumor resection was significantly correlated with long survival. The 1- and 3-year survival rates were 70.5% and 53.7% in patients treated with complete tumor resection compared to 37.2% and 4.8% in the incomplete tumor resection cohort (P = 0.0020). Thirty-four patients received chemotherapy and the 1- and 3-year survival rates were 60.1% and 35.2%, respectively, however, only 29.7% and 12.7% in patients without chemotherapy (P = 0.0396). Twelve patients had radiotherapy and the 1- and 3-year survival rates were 75.0% and 38.9%, respectively, compared with 36.9% and 14.8% in those without radiotherapy (P = 0.0314). CONCLUSION: Complete tumor resection results in improved survival in patients with DSRCT. Chemotherapy and radiotherapy correlate with improved patient outcome. Multimodal therapy may improve the survival in patients with DSRCT.

[Prognostic analysis of patients with liver metastases from colorectal cancer treated with different modes of therapy].

OBJECTIVE: To investigate the potential prognostic factors for patients with liver metastases from colorectal cancer treated with different modes of therapy. METHODS: The clinicopathological data of 300 patients with liver metastases from colorectal cancers were retrospectively reviewed and analyzed. RESULTS: The median survival of patients with recurrence (MSR) treated with complete and palliative resection of liver metastases and unresectable patients was 48, 19 and 18 months, respectively (P = 0.000). In patients with unresectable liver metastases, systemic chemotherapy plus regional therapy demonstrated a median survival time of 23 months, significantly longer than the 6 months in untreated patients (P = 0.000). Patients who showed response to the first-line therapy demonstrated an improved survival versus the patients who had no response, with a median survival time of 24 vs. 16 months (P = 0.000). Univariate analysis revealed that resection modes of primary diseases and liver metastases, treatment modality for liver metastases, and response to first-line therapy were prognostic factors. Multivariate analysis showed that resection modes of liver metastases, multimodality treatment after liver metastases, and the response to first-line therapy were all independent prognostic factors for patients with liver metastases from colorectal cancer. CONCLUSION: Resection of liver metastases, multimodality treatment after liver metastases, and response to first-line chemotherapy are all independent prognostic factors for patients with liver metastasis from colorectal cancer.

[Relationship between the level of RRM1 expression and the sensitivity to gemcitabine in the esophageal squamous cell carcinoma cell lines].

OBJECTIVE: Ribonucleotide reductase subunit M1 (RRM1) is the intracellular target of gemcitabine (GEM). The aim of this study is to explore the relationship between the level of RRM1 expression and the sensitivity to GEM in the esophageal squamous cell carcinoma cell lines. METHODS: Four esophageal squamous cell carcinoma cell lines (Kyse-150, Kyse-450, 9706 and Eca-109) were cultured in vitro. In the same period, RRM1 expression level was measured by RT-PCR and Western blot, and cell sensitivity to GEM was determined by CCK-8 assay. The relation between cell sensitivity and RRM1 expression was further analyzed. Kyse-450 cells were continuously cultured in the medium containing 50 nM GEM. RRM1 expression was measured at different time points to monitor the dynamic changes in the surviving cells. Inhibition of RRM1 expression by RNAi method was applied and the effect on GEM-sensitivity was further examined. RESULTS: The IC(50) of Eca-109, Kyse-150, Kyse-450 and 9706 cells were (0.92 +/- 0.17), (0.48 +/- 0.11), (0.29 +/- 0.06) and (0.02 +/- 0.01) mmol/L, respectively. The expressions of RRM1 protein and mRNA of Eca-109 cell line were the highest detected by Western blot and RT-PCR, followed by Kyse-150 and Kyse-450, and the lowest one was 9706 cell line. When Kyse-450 cells were continuously treated with 50 nmol/L GEM, the level of RRM1 protein was increasing in the surviving cells. RRM1 siRNA could effectively knock down the expression of RRM1 and significantly increase the cell sensitivity to GEM (P = 0.035). CONCLUSION: The level of RRM1 expression correlates with the cell sensitivity to gemcitabine. The cells with a lower level of RRM1 expression are more sensitive to gemcitabine.

[Comparison of the efficiency of CHOP-based regimen with or without high dose consolidation treatment combined with hematopoietic stem cell transplantation in 63 lymphoblastic lymphoma patients].

OBJECTIVE: To retrospectively analyze and compare the treatment efficiency of CHOP-based regimens with or without high-dose consolidation treatment combined with hematopoietic stem cell transplantation (HDT-HSCT) in the patients with lymphoblastic lymphoma (LBL). METHODS: From 1989 to 2004, totally 63 patients with LBL were initially treated with a standard CHOP-based regimen. Forty-two of the 63 patients achieved complete response (CR), 26 of those subsequently received consolidation HDT-HSCT, while the other 16 had 6-8 cycles of standard CHOP-based treatment only. RESULTS: Of the 63 patients, 57 had a T-LBL and 6 B-LBL, with a median age of 20 years, 19 (30.2%) had a stage I-II diseases and 44 (69.8%) stage III-IV diseases, 61.9% presented with a mediastinal mass. Bone marrow involvement presented in 28.6% of the patients. Fourteen percent had central nervous system involvement. The median follow-up period was 24 months, and the estimated 5-year overall survival and disease-free survival of this series was 31.2% and 29.3%, respectively. Of the 42 patients who achieved CR, the 5-year OS rate of the patients who received HDT-HSCT as a consolidation therapy was 59.8% versus 14.6% of the patients treated by CHOP-based regimens alone (P=0.004). Bone marrow involvement, age > or =20 years, short response duration and primary refractory disease were factors significantly associated with poor outcome. Among the 18 patients with bone marrow involvement, 3 received allogeneic HSCT and were all still alive at the follow up time of 22, 32 and 37 months, respectively, while another 4 received auto-HSCT and all died of the disease within 14 months. CONCLUSION: Short term treatment with a CHOP-based regimen is not sufficient for the patients with lymphoblastic lymphoma. High-dose consolidation treatment and hematopoietic stem cell transplantation may improve overall survival and disease free survival. Bone marrow involvement, age >20 years, and short response duration and primary refractory disease are all the factors significantly associated with poor outcome. For the patients with bone marrow involvement, allohematopoietic stem cell transplantation is superior to auto-hematopoietic stem cell transplantation.

[Analysis of prognostic factors in 300 colorectal cancer patients with liver metastases].

OBJECTIVE: To analyse the clinical characteristics and potential prognostic factors of colorectal cancer patients with liver metastases. METHODS: The clinical and pathological data of 300 colorectal cancer patients with liver metastases were retrospectively reviewed and analyzed. RESULTS: The median survival time of these patients was 19.0 months. The 1-, 2- and 5-year survival rates after liver metastases were 79.0%, 29.0% and 3.0%, respectively. Univariate analysis revealed that performance status (KPS), histological grading, primary tumor, N status, lymphatic and vascular invasion, stage at diagnosis, the number, size and distribution of liver metastases and other accompanied metastases were prognostic factors. Multivariate analysis showed that KPS, lymphatic and vascular invasion, the number and size of liver metastases were independent prognostic factors of colorectal cancer with liver metastases. CONCLUSION: Performance status, lymphatic and vascular invasion, the number and size of liver metastases are independent prognostic factors of colorectal cancer with liver metastases.

[Combined-modality therapy for 150 cases of early-stage Hodgkin's lymphoma].

OBJECTIVE: To compare the efficacy of chemotherapy alone, radiotherapy alone and combined-modality therapy in the treatment for early-stage Hodgkin's lymphoma (HL). METHODS: From 1999 to 2002, totally 150 patients with stage I or II HL were treated in our hospital. They were stratified into several groups based on initial treatment strategy: chemotherapy alone (CT group, n = 22), radiotherapy alone (RT group, n = 18), combined-modality therapy (CMT group, n = 109) and surgical resection (SR group, n = 1). Chemotherapy regimens were mainly ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) and MOPP (mechlorethamine, vincristine, procarbazine and prednisone). Radiotherapy modes included involved field radiotherapy (IFRT), extended field radiotherapy (EFRT) and sub-total nodal irradiation (STNI). RESULTS: The pathological types included nodular sclerosis (NS, n = 84), mixed-cellularity (MC, n = 39), lymphocyte-predominant (LP, n = 23), lymphocyte-depleted (LD, n = 3) and nodular lymphocyte predominant Hodgkin's disease (NLPHD, n = 1). Of those, 72 were evaluble in terms of prognostic factors. No poor prognostic factor was found in 36.1% or 29.2% of the patients according to EORTC or GHSG criteria, respectively. There were 33 patients with complete response (CR), 109 with partial response (PR), 5 with stable disease (SD) and 3 with progressive disease (PD) after initial therapy. The median follow-up period was 71.5 months. The overall 7-yr survival rate was 89.3%, and treatment failure rate at 6 years was 18.8%. The response rate of CMT group was superior to that of CT group, and the patients with nodular sclerosis or mixed-cellularity type had significantly lower risk of treatment failure (P = 0.009 and 0.019, respectively). The multivariate analysis revealed that the treatment strategies affected the prognosis significantly. The risk of failure of chemotherapy alone was 2.52 times higher than that of combined-modality therapy (P = 0.004). No predictive factor affecting OS was identified by either univariate or multivariate analysis. The patients in CMT group suffered more adverse effects than those in either CT or RT groups, which mainly consisted of leucopenia, alopecia and gastrointestinal symptoms. CONCLUSION: Combined-modality therapy is more effective than chemotherapy alone or radiotherapy alone in the treatment for early stage Hodgkin's lymphoma. Though its acute adverse effects are more severe than that of chemotherapy or radiotherapy alone, it may reduce the risk of treatment failure.

[Multicenter phase II clinical trial of uroacitides injection in the treatment for advanced malignant tumors].

OBJECTIVE: To investigate the efficacy, safety and the life quality improvement of uroacitides injection in the treatment for patients with advanced malignant tumors. METHODS: A total of 160 patients with advanced stage cancers were enrolled into this multicenter, open and non-randomized phase II clinical trial, including cancers of the lung (33 cases), liver (45 cases), breast (17 cases), esophagus (11 cases), stomach (18 cases), colon (19 cases), pancreas (3 cases) and kidney (4 cases), and glioma (10 cases). Uroacitides was administrated in a dose of 300 ml daily via the superior vena cava catheter for consecutive 4-8 weeks. RESULTS: Of the 160 patients, 21 dropped out and one patient died during the trial. Efficacy could be evaluated in 138 patients and safety in 160. The total objective response rate (ORR, CR + PR)) and tumor control rate (CR + PR + MR + SD) of the 138 evaluable patients were 5.8% and 65.2%, respectively. Clinical benefit response (CBR) rate was 57.2%. Major adverse effects were grade I - II and reversible nausea/vomiting (21.9%) and pain (6.3%). CONCLUSION: Uroacitides injection is effective in the control for various kinds of advanced cancers with mild, reversible and tolerable adverse effects, and can also improve the patient's quality of life. It is worth being studied further.

[Phase III clinical study of zoledronic acid in the treatment of pain induced by bone metastasis from solid tumor or multiple myeloma].

OBJECTIVE: To evaluate the efficacy and safety of zoledronic acid in the treatment of bone pain in patients with bone metastasis from solid tumor or multiple myeloma. METHODS: A randomized, double-blind, double-simulated and multi-center phase III clinical trail with pamidronate as control was conducted. Patients with moderate to severe bone pain (VAS > 50 mm) induced by solid tumor or multiple myeloma were randomized to receive intravenous zoledronic acid 4 mg or pamidronate 90 mg. Then the change of VAS and urinary NTX/Cr and CTX/Cr were observed in two groups. RESULTS: From July 2005 to September 2006, 228 patients with bone pain induced by bone metastasis from 15 cancer centers were randomize into two groups: 116 patients in zoledronic acid group and 112 patients in pamidronate group. The VAS value was decreased gradually after treatment in these two groups. Significant improvement in bone pain after treatment were observed both in zoledronic acid group and the control group when compared with baseline VAS on D8 (-11.77% vs. -10.87%), D15 (-24.60% vs. -21.06%) and D28 (-32.37% vs. -31.26%) (P< or =0.0001), but no significant difference existed between two groups (P =0.6587). Compared with baseline, urine NTX/Cr and CTX/Cr level were decreased rapidly after treatment in both groups, the nadir was on D8, the median decreased on D28, which was -36.9% vs. -32.1% for NTX/Cr (P = 0.7922) and -63.2% vs. -47.9% for CTX/Cr (P =0.834). The frequently observed adverse events were pyrexia (19.0% vs. 31.3%), vomiting (6.0% vs. 8.9%), nausea (4.3% vs. 4.5%), fatigue (3.4% vs. 2.7%) and constipation (2.6% vs. 1.8%) in the two groups. Compared with baseline, the serum creatinine level was not significantly increased throughout the study. CONCLUSION: Intravenous injection of 4 mg zoledronic acid can significantly reduce bone pain and bone resorption marker in urine in the Chinese patients with bone metastasis from solid tumor or multiple myeloma, which is tolerable and also comparable to pamidronate in the efficacy and safety.

[Clinical features and treatment outcomes of peripheral T-cell lymphoma, unspecified: a report of 78 cases].

OBJECTIVE: To summarize the clinical features and treatment outcomes of peripheral T-cell lymphoma, unspecified (PTCL-US). METHODS: The medical records of 78 patients with PTCL-US classified according to the revised European and American lymphoma (REAL) or WHO criteria, 58 males and 20 females, aged 39 (9 - 75), 46 of them (59%) being at the stages III/VI and 40 cases (51.2%) with extranodal involvement), treated from Jan 1994 to Dec 2004 in the Cancer Hospital/Institute, Chinese Academy of Medical Sciences, were retrospectively analyzed. The patients were followed up for 58 months. RESULTS: Thirty patients (38%) were with high level lactate dehydrogenase (LDH). 34 cases (43. 7%) were treated with chemoradiotherapy, and 43 (55%) with chemotherapy alone. After the first line treatment the complete recovery (CR) rate and partial recovery (PR) rate were 55.1% (43/78) and 25.6% (20/78) respectively. 15 cases (19.2%) showed progressive disease (PD) or stable disease (SD). Achieving CR or PR after first-line treatment, 13 cases received autologous peripheral blood stem cell transplantation (APBSCT). The 5-year overall survival rate (OS) and 5-year progressive-free survival rate (PFS) were 41.4% and 33.8% respectively. The 5-year OS of the CR, PR, and PD/SD groups were 65.1%, 21.9%, and 0% respectively. The 5-year OS for the patients treated with first-line APBSCT was 61.5%, not significantly different from that of the patients treated with conventional dose therapy alone (52.3%, P = 0.894). Univariate analysis showed that the factors associated with a worse OS included stage III/IV (P = 0.001), high LDH (P = 0.0001), behavior state score >or= 2 (P = 0.001), and bone marrow involvement (P = 0.011). Multivariate analysis showed that LDH level was an independent factor predictive of survival (P = 0.001). International prognostic index and prognostic index for peripheral T-cell lymphoma both predicted the overall survival. CONCLUSION: A rare lymphoma with aggressive presentation, PTCL-US responds poorly to conventional treatment. The prognosis of the cases with high risk is bad. APBSCT is safe and feasible when CR or PR is achieved after first line treatment.

[Randomized controlled trial of two kinds of home-produced docetaxel in China for advanced breast cancer].

BACKGROUND & OBJECTIVE: Two kinds of home-produced docetaxel in China, injection Yiyoutasai and injection Aisu, have the same structure. Data from preclinical study had shown that injection Yiyoutasai has the same pharmacokinetics and toxicity as injection Aisu. This study was to evaluate the efficacy and toxicity of injection Yiyoutasai in treating advanced breast cancer. METHODS: Eligible breast cancer patients were enrolled and randomly assigned to study group and control group, and received injection of 75 mg/m(2) Yiyoutasai or Aisu, respectively. The injections were repeated every 3 weeks. All patients received at least 2 cycles. The efficacy of Yiyoutasai and Aisu were evaluated after treatment. RESULTS: A total of 67 patients were enrolled: 33 in study group, and 34 in control group. Of the 31 evaluable cases in study group, 1 achieved complete remission (CR), 9 achieved partial remission (PR), 11 had stable disease (SD), and 10 had progressive disease (PD); the total response rate was 22.22%. There were 1 CR, 5 PR, 19 SD, and 9 PD in control group; the total response rate was 15.15%. There was no significant difference between the 2 groups (P=0.662). The median follow-up was 16.5 months (8-28 months). In study group, the median progression-free survival time was 6.2 months (2-12 months), the 1-year survival rate was 68.51%, and the 2-year survival rate was 40.12%; in control group, the median progression-free survival time was 7.1 months (2.3-11 months), the 1-year survival rate was 65.23%, and the 2-year survival rate was 39.71%. There was no significant difference between the 2 groups (P=0.102, 0.098, 0.089, respectively). Common adverse events were myelosuppression, transient transaminase elevation, and alopecia. One patient in study group suffered from severe allergic reaction after infusion, 1 in control group suffered from whole body edema. CONCLUSION: Yiyoutasai and Aisu have similar efficacy on and toxicity to advanced breast cancer patients.