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Supplementary Figures 1-2 from Lapatinib (Tykerb, GW572016) Reverses Multidrug Resistance in Cancer Cells by Inhibiting the Activity of ATP-Binding Cassette Subfamily B Member 1 and G Member 2

Lapatinib is active at the ATP-binding site of tyrosine kinases that are associated with the human epidermal growth factor receptor (Her-1 or ErbB1) and Her-2. It is conceivable that lapatinib may inhibit the function of ATP-binding cassette (ABC) transporters by binding to their ATP-binding sites. The aim of this study was to investigate the ability of lapatinib to reverse tumor multidrug resistance (MDR) due to overexpression of ABC subfamily B member 1 (ABCB1) and ABC subfamily G member 2 (ABCG2) transporters. Our results showed that lapatinib significantly enhanced the sensitivity to ABCB1 or ABCG2 substrates in cells expressing these transporters, although a small synergetic effect was observed in combining lapatinib and conventional chemotherapeutic agents in parental sensitive MCF-7 or S1 cells. Lapatinib alone, however, did not significantly alter the sensitivity of non-ABCB1 or non-ABCG2 substrates in sensitive and resistant cells. Additionally, lapatinib significantly increased the accumulation of doxorubicin or mitoxantrone in ABCB1- or ABCG2-overexpressing cells and inhibited the transport of methotrexate and E217βG by ABCG2. Furthermore, lapatinib stimulated the ATPase activity of both ABCB1 and ABCG2 and inhibited the photolabeling of ABCB1 or ABCG2 with [125I]iodoarylazidoprazosin in a concentration-dependent manner. However, lapatinib did not affect the expression of these transporters at mRNA or protein levels. Importantly, lapatinib also strongly enhanced the effect of paclitaxel on the inhibition of growth of the ABCB1-overexpressing KBv200 cell xenografts in nude mice. Overall, we conclude that lapatinib reverses ABCB1- and ABCG2-mediated MDR by directly inhibiting their transport function. These findings may be useful for cancer combinational therapy with lapatinib in the clinic. [Cancer Res 2008;68(19):7905–14]

e13015 Background: Eribulin is a non-taxane microtubule inhibitor, which was approved for the third-line treatment of advanced breast cancer (ABC) in China in 2019. However, the efficacy and safety data of eribulin for the ABC in Chinese patients is lacking, whether as first, second, or third-line regimens. This study aimed to evaluate the clinical effectiveness, safety, and treatment pattern of eribulin in first to third-line settings in Chinese ABC patients. Methods: Patients with histologically confirmed advanced breast cancer, who previously received ≤2 lines of treatment for metastatic disease were enrolled. In HR+/HER2- ABC, eribulin monotherapy was used; in HER2+ ABC, eribulin plus anti-HER2 targeted therapy were used; in metastasis triple-negative breast cancer (mTNBC), eribulin plus immunotherapy/chemotherapy were used. Primary outcome was progression-free survival (PFS). Secondary outcomes included disease control rate (DCR) and safety. This study was approved by the SYSMH and SYSUCC Ethics Committee (approval No. 2020-KY-064). Results: Forty-seven patients were enrolled from 2021.1.1 to 2021.10.20, including 41 metastatic and 6 de novo ABC patients. Eribulin was used as first-line therapy in 12 (25.5%) patients, second-line therapy in 24 patients (51.1%), and third-line therapy in 11 (23.1%) patients. More than 90% of the patients did not receive gemcitabine or vinorelbine, and 30.0% of them did not receive anthracycline or taxane previously. DCR was 70.2%, as 24 cases (51.1%) had stable disease and 9 cases (19.1%) had complete or partial remission. In subgroup analysis, median PFSs of 9.6 (95% CI: 6.5-12.7), 7.1 (95%CI: 4.4-9.8), and 5.6 (95%CI: 3.8-7.5) months were observed in patients receiving eribulin as first-, second-, and third-line therapy, respectively. In addition, median PFSs were 7.1 (95% CI: 5.1-9.3), 9.6 (95%CI: 3.6-15.7), 4.6 (95%CI: 4.6-4.6) and 5.8 (95%CI: 4.4-7.3) months for HR+/HER2-, HR+/HER2+, HR-/HER2+, and mTNBC patients, respectively. Other results from the subgroups analysis were shown in table. Common treatment-related toxicity was hematological toxicities including leukopenia (23%), neutropenia (17%), and thrombocytopenia (10%). There was no ≥grade 3 adverse events and no adverse event-related treatment discontinuation. Conclusions: Eribulin monotherapy or combined with targeted therapy was effective and well-tolerated as the first to third lines of treatment in ABC. This promising therapeutic outcome might warrant further studies in early eribulin administration in ABC patients. Clinical trial information: NCT04683445. [Table: see text]

Summary Background Platinum chemotherapy has a role in the treatment of metastatic triple-negative breast cancer but its full potential has probably not yet been reached. We assessed whether a cisplatin plus gemcitabine regimen was non-inferior to or superior to paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer. Methods For this open-label, randomised, phase 3, hybrid-designed trial undertaken at 12 institutions or hospitals in China, we included Chinese patients aged 18–70 years with previously untreated, histologically confirmed metastatic triple-negative breast cancer, and an ECOG performance status of 0–1. These patients were randomly assigned (1:1) to receive either cisplatin plus gemcitabine (cisplatin 75 mg/m 2 on day 1 and gemcitabine 1250 mg/m 2 on days 1 and 8) or paclitaxel plus gemcitabine (paclitaxel 175 mg/m 2 on day 1 and gemcitabine 1250 mg/m 2 on days 1 and 8) given intravenously every 3 weeks for a maximum of eight cycles. Randomisation was done centrally via an interactive web response system using block randomisation with a size of eight, with no stratification factors. Patients and investigator were aware of group assignments. The primary endpoint was progression-free survival and analyses were based on all patients who received at least one dose of assigned treatment. The margin used to establish non-inferiority was 1·2. If non-inferiority of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine was achieved, we would then test for superiority. The trial is registered with ClinicalTrials.gov, number NCT01287624. Findings From Jan 14, 2011, to Nov 14, 2013, 240 patients were assessed for eligibility and randomly assigned to treatment (120 in the cisplatin plus gemcitabine group and 120 in the paclitaxel plus gemcitabine group). 236 patients received at least one dose of assigned chemotherapy and were included in the modified intention-to-treat analysis (118 per group). After a median follow-up of 16·3 months (IQR 14·4–26·8) in the cisplatin plus gemcitabine group and 15·9 months (10·7–25·4) in the paclitaxel plus gemcitabine group, the hazard ratio for progression-free survival was 0·692 (95% CI 0·523–0·915; p non-inferiority superiority =0·009, thus cisplatin plus gemcitabine was both non-inferior to and superior to paclitaxel plus gemcitabine. Median progression-free survival was 7·73 months (95% CI 6·16–9·30) in the cisplatin plus gemcitabine group and 6·47 months (5·76–7·18) in the paclitaxel plus gemcitabine group. Grade 3 or 4 adverse events that differed significantly between the two groups included nausea (eight [7%] vs one [ vs one [ vs ten [8%]), anaemia (39 [33%] vs six [5%]), and thrombocytopenia (38 [32%] vs three [3%]), for the cisplatin plus gemcitabine compared with the paclitaxel plus gemcitabine groups, respectively. In addition, patients in the cisplatin plus gemcitabine group had significantly fewer events of grade 1–4 alopecia (12 [10%] vs 42 [36%]) and peripheral neuropathy (27 [23%] vs 60 [51%]), but more grade 1–4 anorexia (33 [28%] vs 10 [8%]), constipation (29 [25%] vs 11 [9%]), hypomagnesaemia (27 [23%] vs five [4%]), and hypokalaemia (10 [8%] vs two [2%]). Serious drug-related adverse events were seen in three patients in the paclitaxel plus gemcitabine group (interstitial pneumonia, anaphylaxis, and severe neutropenia) and four in the cisplatin plus gemcitabine group (pathological bone fracture, thrombocytopenia with subcutaneous haemorrhage, severe anaemia, and cardiogenic syncope). There were no treatment-related deaths. Interpretation Cisplatin plus gemcitabine could be an alternative or even the preferred first-line chemotherapy strategy for patients with metastatic triple-negative breast cancer. Funding Shanghai Natural Science Foundation.

Introduction The aim of the study was to analyze clinicopathologic characteristics and survival and to identify prognostic factors for Chinese patients with HER2-positive metastatic breast cancer. Material and methods A total of 243 patients with HER2-positive metastatic breast cancer, treated during the period 2002 to 2009, were followed up from initial disease diagnosis to death or date of last follow-up (December 2011). Cumulative survival curves were created using Kaplan-Meier analysis with the log-rank test. Prognostic factors were analyzed by univariate and multivariate Cox proportional hazards regression analysis. Results During follow-up, 205 patients died, with a median OS of 27 months (95% CI: 23.5, 30.5 months), and the 1-, 3-, and 5-year survival rates were 84.4%, 38.6%, and 18.1%, respectively. The median OS of HR+ patients was significantly higher than that of HR– patients (p < 0.001). Surgery (hazard ratio = 0.60, p = 0.002), endocrine therapy (hazard ratio = 0.53, p < 0.01), and anti-HER2 therapy (hazard ratio = 0.63, p = 0.003) were favorable independent prognostic factors for patients with HER2-positive metastatic breast cancer. Conclusions These results indicated that surgical intervention, endocrine therapy, and anti-HER2 therapy were good for these HER2 positive patients with metastatic breast cancer, but ECOG performance status < 1 and metastasis to brain were unfavorable independent prognostic factors. HR status was not an independent prognostic factor.

Overexpression of human epidermal growth factor receptor-2 (HER2) in metastatic breast cancer (MBC) is associated with poor prognosis. This single-arm open-label trial (EGF109491; NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), time to response (TTR), duration of response (DoR), central nervous system (CNS) as first site of relapse, and safety. The results showed that there were 23 patients with partial responses and 7 patients with stable disease, resulting in a CBR of 57.7%. The median PFS was 6.34 months (95% confidence interval, 4.93-9.82 months). The median TTR and DoR were 4.07 months (range, 0.03-14.78 months) and 6.93 months (range, 1.45-9.72 months), respectively. Thirteen (25.0%) patients had new lesions as disease progression. Among them, 2 (3.8%) patients had CNS disease reported as the first relapse. The most common toxicities were palmar-plantar erythrodysesthesia (59.6%), diarrhea (48.1%), rash (48.1%), hyperbilirubinemia (34.6%), and fatigue (30.8%). Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample, baseline PIK3CA mutation status was not associated with CBR (P = 0.639) or PFS (P = 0.989). These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC, irrespective of PIK3CA status.

Trastuzumab has been the standard treatment in first-line treatment of HER-2-positive advanced breast cancer (H2ABC). This study explored whether the delayed and repeated use of trastuzumab could influence overall survival (OS). A total of 128 patients with H2ABC who had received at least one line of trastuzumab-based regimens were included. The primary endpoint was OS defined as from the date of first diagnosis of H2ABC to death. The median OS of initiating trastuzumab in first-line group (n = 56), in the second-line group (n = 32), and the third- or more-line group (n = 40) was 40.6 m, 39.5 m, and 38 m, respectively (P = 0.867). For patients who had received over one line of trastuzumab (n = 46), the median OS was 44 m, and for those receiving only one line (n = 67), it was 27.6 m (P = 0.059). The delayed use of trastuzumab has no negative effect on the OS of patients with H2ABC. There is a trend of improved OS over the repeated use of trastuzumab.

The brain is one of the most common metastatic sites of breast cancer. Brain metastases develop in 10%-15% of patients with breast cancer and are associated with poor prognosis. The purpose of this retrospective study was to analyze the clinical characteristics and survival of patients with brain metastases due to breast cancer of different subtypes and to identify the prognostic factors that affect clinical outcome.A total of 89 patients with breast cancer brain metastases diagnosed between October 1997 and July 2008 at Sun Yat-sen University Cancer Center were included in this study. Among the 89 patients, the number of luminal A, luminal B, human epidermal growth factor receptor 2 (HER-2), and triple-negative (TN) subtypes were 30, 20, 16, and 14, respectively; 9 patients had an unknown subtype. The clinical characteristics, pathologic features, and prognostic factors were analyzed both at the initial diagnosis and at the diagnosis of brain metastases. Endocrine therapy for patients with luminal subtypes was further studied.The median age of patients was 46 years (range 28-74 years). The median survival time was 8.0 months (range, 0-80 months), the 1-year survival rate was 32% and the 5-year survival rate was 4%. The time to brain metastasis differed according to clinical stage at the initial diagnosis, and the time for patients with the luminal A subtype was the longest (P0.001). Multivariate analysis demonstrated that performance status score1, multiple brain metastases and without whole brain radiotherapy (WBRT) in combination with chemotherapy were associated with poor prognosis. Compared with the luminal A subtype, features of the HER-2 and TN subtypes included early metastases, rapid progression after first-line treatment (8.0 months vs. 11.0 months), and poor overall survival (25.0 months vs. 63.0 months). The luminal A subtype showed a tendency for good prognosis and slow growth. Tamoxifen could improve the survival of luminal A/B subtypes (median survival 24.0 months vs. 7.0 months, respectively, P = 0.002).The prognosis of brain metastases from breast cancer was poor, especially in patients with HER-2 and TN subtypes. Generally, WBRT in combination with chemotherapy was the standard treatment modality. Patients with the luminal subtypes could benefit from tamoxifen.

Lapatinib is active at the ATP-binding site of tyrosine kinases that are associated with the human epidermal growth factor receptor (Her-1 or ErbB1) and Her-2. It is conceivable that lapatinib may inhibit the function of ATP-binding cassette (ABC) transporters by binding to their ATP-binding sites. The aim of this study was to investigate the ability of lapatinib to reverse tumor multidrug resistance (MDR) due to overexpression of ABC subfamily B member 1 (ABCB1) and ABC subfamily G member 2 (ABCG2) transporters. Our results showed that lapatinib significantly enhanced the sensitivity to ABCB1 or ABCG2 substrates in cells expressing these transporters, although a small synergetic effect was observed in combining lapatinib and conventional chemotherapeutic agents in parental sensitive MCF-7 or S1 cells. Lapatinib alone, however, did not significantly alter the sensitivity of non-ABCB1 or non-ABCG2 substrates in sensitive and resistant cells. Additionally, lapatinib significantly increased the accumulation of doxorubicin or mitoxantrone in ABCB1- or ABCG2-overexpressing cells and inhibited the transport of methotrexate and E217βG by ABCG2. Furthermore, lapatinib stimulated the ATPase activity of both ABCB1 and ABCG2 and inhibited the photolabeling of ABCB1 or ABCG2 with [125I]iodoarylazidoprazosin in a concentration-dependent manner. However, lapatinib did not affect the expression of these transporters at mRNA or protein levels. Importantly, lapatinib also strongly enhanced the effect of paclitaxel on the inhibition of growth of the ABCB1-overexpressing KBv200 cell xenografts in nude mice. Overall, we conclude that lapatinib reverses ABCB1- and ABCG2-mediated MDR by directly inhibiting their transport function. These findings may be useful for cancer combinational therapy with lapatinib in the clinic. [Cancer Res 2008;68(19):7905–14]

Objective: High dose chemotherapy supported by autologous hematopoietic stem cells transplantation (AHSCT) has developed dramaticly in recent years and become the most effective approach to improve radical treatment for the chemo-sensitive lymphoma. The purposes of this study was to evaluate the efficacy and tolerance of preparative regimen BEAC and hematopoietic reconstitution after high dose chemotherapy in Chinese patients with advanced and recurrent lymphoma. Methods: After confirmed complete or partial remission from conventional chemotherapy, 24 patients with advanced or recurrent lymphoma including 1 recurrent HD and 23 NHL, 16 male and 8 female with median age of 29 (13–50) years, were enrolled into this study and treated by BEAC regimen (CTX 3600–4000 mg/m2, VP-16 1200 mg/m2. BCNU 300 mg/m2 and Ara-C 1500–2000 mg/m2). 3 patients were supported by ABMT and 21 by APBSCT. Mobilization regimen for APBSCT was CTX 3500 mg/m2 + G-CSF 3.5–5 µg/kg + Dexamethasone 10 mg. Autologous hematopoietic stem cells was re-infused 24–48 h after completion of high dose chemotherapy. Results: MNC 1.3 (1.0–1.7)×108/kg and MNC 1.8 (1.0–4.4)×108, CFU-GM 5.1 (1.9–9.6)×105/kg plus CD34 + cells 2.9 (1.9–8.7)×106/kg were re-infused in the ABMT group and APBSCT group respectively. All patients obtained prompt and sustained hematopoietic reconstitution. ANC≥0.5×109/L and Pt≥2.0×109/L were at day 9 (6–17) and day 10 (0–31) respectively. 16 patients were alive with median 21 (2–69) months follow-up till end of May, 2001. 1, 2 and 3 years survival rate were 60.5%, 50.1% and 50.1%, respectively. Non-hematologic toxicity was mild and tolerable. Conclusions: High dose chemotherapy supported by AHSCT in the treatment of previously-untreated poor-prognostic and recurrent lymphoma was a safe and effective modality. Further investigation was warranted.

Objective: A pilot study to test the feasibility and efficacy of hig h dose IFO and standard dose ADR and DTIC with G-CSF support in treatment of advanced soft tissue sarcoma (STS). Methods: 35 patients of no prior chemotherapy with metastatic or locally advanced unresectable STS were treated by this regimen, including 18 rhabdomyosarcomas, 7 malignant fibrous histiocytomas, 2 neurofibrosarcomas, 2 fibrosarcomas, 2 leiomyosarcomas, 2 synoviosarcomas, and 2 malignant hemangiopericytomas. IFO dose was 2 g/m2 on day 1-5 (with mesna uroprotection), ADR 50mg/m 2 on day 1 and DTIC 250 mg/m 2 on day 1-5. G-CSF (2 Ixg/kg/d) was administered on day 6 to 15 or until recovery of leukocytes account. The cycles were repeated every 3 weeks. Result: There were five complete responses (CR including pathologic CR) and eleven partial responses for overall 46% objective response rate. Most responses were observed within two cycles. The median survival was 15 months. Following CR, two patients remain disease free at 45 and 28 months, respectively. 6/120 (5%) cycles were complicated by grade IV neutropenia, 46/120 (38%) cycles had grade III neutropenia. No patients had treatmentrelated deaths. Nonhematologic toxicity consisted predominantly of anorexia and vomiting. No other severe toxicities were seen, especially no severe cardiotoxicity. Conclusion: This regimen is well tolerated and has substantial benefits for patients with advanced soft tissue sarcomas.

Given the use of tamoxifen as standard treatment for hormone receptor&ndash, positive breast cancer, the use of toremifene as an adjuvant endocrine therapy has not been widely examined. The present retrospective study compared the efficacy and safety of toremifene and tamoxifen in the treatment of operable hormone receptor&ndash, positive breast cancer in premenopausal women. Premenopausal patients with hormone receptor&ndash, positive operable breast cancer were eligible. Enrolled patients (n = 1847) received either 60 mg toremifene (n = 396) or 20 mg tamoxifen (n = 1451) daily for a minimum of 5 years after surgery. Disease-free survival (dfs) was the primary endpoint. Overall survival (os) and time to distant recurrence were secondary endpoints. Treatment with toremifene and tamoxifen resulted in no between-group differences in dfs (p = 0.659) or os (p = 0.364). Mean dfs was 10.3 years for both groups. Mean os was 11.2 years for the toremifene group and 11.1 years for tamoxifen group. The 5-year dfs rate was 87.0% in the toremifene group and 85.0% in the tamoxifen group. The 5-year survival rate was 94.3% in the toremifene group and 93.5% in the tamoxifen group. Adverse events rates were similar in the two groups, with the exception of irregular menses, which occurred at a higher rate in the tamoxifen group than in the toremifene group (10.0% vs. 6.3%, p = 0.025). In this retrospective study, the efficacy and safety profiles of toremifene and tamoxifen for the treatment of operable hormone receptor&ndash, positive breast cancer in premenopausal women were similar.

The clinical significance of bilateral breast cancer is unclear and its influence on prognosis is controversial. We compared the characteristics and prognosis of bilateral breast cancer and unilateral breast cancer.Our study included 4,183 patients with breast cancer who were treated at Sun Yat-sen University Cancer Center between January 1, 2000, and December 31, 2007. Bilateral breast cancer was categorized as synchronous (within 3 months) or metachronous (diagnosed after 3 months of first cancer). SPSS was used for data analysis.106 (2.5%) and 31 (0.7%) patients were diagnosed with metachronous and synchronous bilateral cancer. Women with bilateral cancer had more frequent postmenopause, HER-2 negativity, and advanced disease than in patients with unilateral cancer. Young age at diagnosis, invasive lobular carcinoma, ER/PR negativity, HER-2 positivity, radiation, large tumor size (T5 cm), and stage III disease of the first cancer were risk factors for contralateral cancer. The 5-year disease-free survival and overall survival rates were 76 and 83% for unilateral cancer, while 32 and 72% for bilateral cancer (P = 0.000 for both).Bilateral cancer was associated with shorter disease-free survival and overall survival than unilateral cancer. The prognosis of metachronous bilateral cancer, especially those diagnosed within 2 years after the first cancer was significantly worse than synchronous bilateral cancer.

To investigate general and clinicopathological characteristics of male breast cancer and analyzed the factors affecting the outcomes of the patients based on the data from a single institution.Twenty-five male breast cancer patients treated at Sun Yet-sen University Cancer Center between January 1, 2000 and April 30, 2011 were included into the study. The patients were followed up for 1 to 90 months with a median follow-up of 51 months. The general and clinicopathological characteristics including family history, age, smoking, alcohol drinking, site of tumor, location of tumor, histological type, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), Ki-67, vascular endothelial growth factor (VEGF), P53 expression, neoadjuvant chemotherapy, surgery, adjuvant chemotherapy, adjuvant radiotherapy, adjuvant endocrine therapy, tumor size, lymph node status, distant metastasis and TNM stage were investigated by univariate analysis to evaluate the impact of these factors on patient survival.The 5-year survival rate was 66.5% in these patients. Neoadjuvant chemotherapy, tumor size, lymph node status, distant metastasis and TNM stage were significant predictors for the overall survival. Patients receiving adjuvant endocrine therapy tended to have a better overall survival, though this was not supported statistically (P=0.086). However, patients with neoadjuvant chemotherapy had a poorer overall survival than those without it (P=0.000). Patients in stages I and II had better overall survival than those in stages III and IV (P=0.000).The 5-year survival rate was 66.5% in these male breast cancer patients. Neoadjuvant chemotherapy, tumor size, lymph node status, distant metastasis and TNM stage are significant predictors of the overall patient survival.

To study the biological and clinicopathological characteristics of neuroendocrine tumors of the kidney (KNETs) for improving the diagnosis and treatment of this diseases.The pathological and clinical features of 3 KNET cases treated in Sun Yat-sen University Cancer Center between 1999 and 2010 were summarized, and the the histogenesis, pathological and immunohistochemical characteristics, diagnosis and prognosis of KNETs were analyzed with review of all reported cases worldwide.All the 3 patients had waist masses but without clinical manifestations of carcinoid syndrome, and underwent resection of the tumors. The postoperative pathological diagnosis was carcinoid carcinoma in 2 patients and Wilms tumor with neuroendocrine differentiation in 1 patient. Immunohistochemical examination showed that the tumors were positively stained for cytokeratin and vimentin; positivity for neuron-specific enolase and synaptophysin was found in 2 cases, and chromogranin positivity in 1 case. After the operation, 1 patient received chemotherapy, 1 had biotherapy and radiotherapy, and 1 received no further treatment. During the follow-up from 6 months to 6 years, 1 patient died of tumor metastasis, 1 was lost to follow-up, and 1 showed no recurrence until now.KNETs has specific pathological characteristics. Abdominal masses, acute loin pain and hematuria are the most common symptoms. A definite diagnosis relies on pathology and immunohistochemistry. For early carcinoid carcinoma, surgical resection is curable, but in advanced cases, the prognosis is poor and comprehensive therapy is recommended.

It has been proved that trastuzumab has clinical activity in early and advanced breast cancer with Her2-overexpression. This study was to analyze the safety of trastuzumab after adjuvant chemotherapy in 30 Chinese Her2-positive early breast cancer patients.Trastuzumab was administrated after adjuvant chemotherapy every 21 days. The initial dose was 8 mg/kg, and the subsequent dose was 6 mg/kg, for four to 35 cycles (medium 18 cycles). The side effects of these patients, especially cardiotoxicity, were analyzed.Thirty patients with Her2-positive early breast cancer were entered into the study. The average treatment period was one year (range nine weeks to two years). Two patients had shivering and fever during the first infusion with trastuzumab. Left ventricular ejection fraction (LVEF) level dropped in 18 cases after treatment with trastuzumab, half of which decreased more then 10%û however, no cardiac failure was observed.The post-surgical treatment of trastuzumab in Chinese patients with Her2-positive early breast cancer shows a satisfactory safety profile. However, the potential cardiotoxicity of trastuzumab should be carefully monitored during therapy.

To evaluate the efficacy and toxicity in patients with HER2 overexpressing metastatic breast cancer.Twenty-one patients with HER2 overexpressing metastatic breast cancer entered into the study. Trastuzumab (8 mg/kg day 1, then 6 mg/kg every 21 days or 4 mg/kg, then 2 mg/kg every week) and vinorelbine (25 mg/m(2)) was given on days 1 and 8 every 21 days.Overall 56 cycles were given to the 21 patients enrolled into the study (mean 2, range 1-6). All can be evaluated. The response rate was 33.33% (7/21), one patient achieved complete response (CR), six patients achieved partial response (PR), four patients achieved stable disease (SD), ten patients achieved progressive disease (PD)]. The median time to progression was 3.5 months. One year overall survival was 33%. The major toxicity was myelosuppression and peripheral neuritis. A few patients were observed with fever and lower grade cardiac failure.The combination of trastuzumab and vinorelbine is an effective and well tolerated therapy in patients with pretreated metastatic breast cancer.

HER2 is overexpressed in approximately 20.0% to 30.0% of breast cancer patients. This alteration is associated with poor prognosis, and may affect response to hormonal therapy and chemotherapy. Chemotherapy combined with trastuzumab can significantly improve the treatment efficacy and survival of Her-2/neu overexpressing breast cancer patients. Docetaxel is an effective drug used for metastatic breast cancer recently. This study was to evaluate the efficacy and toxicity of trastuzumab combined with docetaxel in the treatment for metastatic breast cancer patients with overexpressed Her-2/neu.Twenty-two metastatic breast cancer patients with overexpressed HER2/neu were entered into the study. Trastuzumab and docetaxel (75 mg/m(2)) were administrated on day 1 and repeated every 21 days. The initial dose of trastuzumab was 8 mg/kg and subsequent doses were 6 mg/kg.Overall 96 cycles were administrated to the 22 patients (medium three cycles per patient, range 2-6 cycles). All cases were evaluable. The overall response rate was 63.6% (14/22). Two patients achieved complete response (CR), 12 patients achieved partial response (PR), four patients achieved stable disease (SD), and four patients had progressive disease (PD). The median time to progression was 5.4 months. One year overall survival was 59.0%. The major toxicity was myelosuppression. A few patients had fever at first infusion of trastuzumab and minor heart failure.Trastuzumab combined with docetaxel is an effective and well-tolerated therapy for Her-2/neu overexpressing metastatic breast cancer.

T-cell non-Hodgkin lymphoma was heterogeneous and relatively high incident in our country. It's response and prognosis were poor. This study was to analyze clinical feature and survival of T-NHL.Records of 103 cases with T-NHL, treated from Dec 1998 to Dec 2004 in Cancer Center of Sun Yat-sen University, were retrospectively analyzed. All the patients were classified according to WHO 2001 Classification Criteria.Median age of the whole group was 35 (ranged 2-78) years-old. Of the 103 cases, 68 were male, 35 were female; 25 (24.3%) received chemoradiotherapy, 70 (68.0%) received chemotherapy alone, 3 received radiotherapy and 5 received stem cell transplantation after complete remission. Median survival was 24.1 (ranged 0.8-84) months. 5-year survival rate was 24.3%. Kaplan-Meier analysis discovered that age60 years, advanced stage (stage II, IV), extranodal involvement, bulky disease, B symptom, performance status (PS)or = 2, LDH elevated, hypoalbumin, median-high IPI (IPIor = 2) were bad to prognosis, but Cox regression found that ageor = 60 years, performance status (PS)or = 2S, hypoalbumin were the independent bad factors to prognosis.This study proved that age, albumin, PS were the independent factors to prognosis.

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.

Chemotherapy is one of major treatments of metastatic breast cancer. Anthracyclines and taxanes are usually considered as the most active agents in breast cancer and are often used as adjuvant or first-line therapy. Gemcitabine and vinorelbine are active agents in breast cancer. This study was to evaluate the efficacy of gemcitabine combined vinorelbine on the patients with metastatic breast cancer, who had previously received treatment of anthracyclines and/or taxanes.Thirty-four patients with metastatic breast cancer, who had been previously treated with anthracyclines alone or with taxanes, were enrolled. The patients received 30-minute intravenous injection of gemcitabine (1 000 mg/m(2)) and intravenous bolus injection of vinorelbine(25 mg/m(2)) on Days 1 and 8; the regimen was repeated every 21 days.A total of 109 cycles were given to the 34 patients (median, 3 cycles; range, 1-6 cycles). The treatment responses were evaluable in all patients. Of the 34 patients, 9 achieved partial remission (PR), 19 had stable disease (SD), 6 had progressive disease (PD)û the response rate was 26.47%. The median time to progression was 5.4 months. The median overall survival was 17.8 months. The 1-year overall survival rate was 68% [95% confidence interval (CI): 50%-86%], the 2-year overall survival rate was 46% (95% CI: 26%-66%). The major adverse events were grade I-II myelosuppression, peripheral neurologic toxicities, nausea and vomiting. Some patients had rash and hepatic dysfunction.The combination of gemcitabine and vinorelbine is an effective and well tolerated regimen for the patients with metastatic breast cancer.

This study was designed to evaluate the efficacy and toxicity of modified BFM-90 regimen originated from Germany authors in the treatment of Chinese childhood and adolescent lymphoblastic lymphoma.Thirty-six untreated lymphoblastic lymphoma patients aged from 3 to 18 years were included, with 1 patient in stage II , 9 in stage III and 26 in stage IV. Of these 36 patients, 28 (77.7%) were diagnosed as T cell phenotype, 26 (72. 2%) were found to have mediastinal mass, 21 (58. 3%) had bone marrow involvement. All patients received chemotherapy of modified BFM-90 regimen consisting of induction remission, central nerve system prophylaxis, re-induction remission and maintenance therapy. Total treatment duration was two years. The difference from standard BFM-90 is that we omitted cranial radiotherapy but gave regular high dose methotrexate (MTX) iv infusion and intrathecal MTX therapy during maintenance therapy period. Kaplan-Meier method was used to evaluate survival rate.Of 36 patients, 32 (88%) achieved complete remission (CR) , 1 (2. 7%) partial remission (PR) with an overall response rate of 90.7%. One patient had disease progression ( DP). Two patients received autologous stem cell transplantation at CR1, and two patients received radiotherapy to mediastinum. Totally, 5 patients relapsed, while 2 of them were still alive after salvage chemotherapy. The other 3 died of tumor progression. Two patients died during induction remission, 1 of fungal septicemia, the other of cerebral hemorrhage; one PR and one DP patient died of disease, therefore, totally 7 patients died at last. Median follow-up time was 28 months. Overall three-year survival rate was 78. 3%. The major toxicity was myelosuppression.Modified BFM-90 protocol can improve the efficacy and survival of Chinese childhood and adolescent lymphoblastic lymphoma with tolerable toxicity. However, this modified protocol should only be used in experienced cancer center or hematological unit.

The prognosis of breast cancer patients with liver metastasis is poor. How to improve treatment efficacy and prolong survival of these patients is a challenge in clinic. This study was to explore the efficacy of chemotherapy and transcatheter arterial chemoembolization (TACE) on breast cancer patients with liver metastasis, and analyze prognostic factors.Clinical data of 98 breast cancer patients with liver metastasis, treated from 1996 to 2005 in Cancer Center of Sun Yat-sen University, were analyzed retrospectively. The prognostic factors correlated to clinical features and treatment approaches were determined using Cox multivariate model.The total response rate was 45.9% for all patients, 48.6% for the 74 patients received systemic chemotherapy, 23.1% for the 13 patients received TACE, and 54.6% for the 11 patients received chemotherapy plus TACE. At a median follow-up of 17 months (3-56 months), the 1-, 2-, 3-, and 4-year survival rates were 36%, 19%, 13%, and 3%, respectively; the median survival was 17 months (3-56 months), and the progression-free survival was 6 months (0-50 months).The combination of systemic chemotherapy and TACE may prolong the survival of breast cancer patients with liver metastasis.

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.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.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.Yiyoutasai and Aisu have similar efficacy on and toxicity to advanced breast cancer patients.

To evaluate the efficacy and toxicity of the B-NHL-BFM-90 protocol in the treatment of Chinese childhood and adolescent B-cell non-Hodgkin's lymphomas (B-NHL).Forty-two untreated childhood and adolescent B-NHL were enrolled in the present study. Of them 18 cases were Burkitt's lymphoma, 16 diffuse large B cell lymphoma and 8 anaplastic lymphoma. There were 10 cases in stage II and 32 in stage III/IV. The patients were grouped by risk factors into low, medium and high risk groups. All patients were treated with the B-NHL-BFM 90 (Berlin-Frankfurt- Münster) protocol. The low risk group received A, B courses for 4 cycles, the medium risk group AA, BB courses for 6 cycles, and the high risk group AA, BB, CC courses for 6 cycles.Complete remission (CR) was obtained in 37 patients (88%), and partial remission (PR) in 5 (12%). Of the 5 PR patients, I received autologous hematopoietic stem cell transplantation, 3 received radiotherapy for residual disease and 1 just under watching. Major toxicity was myelosuppression and mucositis, especially in AA, BB and CC cycles, but was tolerant and manageable. Median follow-up was 20 (4 - 89) months. Kaplan-Meier method was used to analyse survival data. Two year event free survival (EFS) for all patients was 86. 24%, being 100% for stage II and 80.95% for stage III/IV.Short term and intensive chemotherapy can improves the efficacy and survival rate of childhood and adolescent B-NHL, especially for advanced stage patients.

Hormone and Herceptin therapy for metastatic breast cancer is commonly based on expression of estrogen receptor (ER) and progestin receptor (PR), and over-expression of HER-2 in primary breast cancer, but studies comparing receptor statuses in primary and metastatic focuses of the same patient are limited. This study was designed to investigate discordance of ER, PR,and HER-2 statuses between primary and metastatic focuses of breast cancer.Immunohistochemistry assay was used to detect expression of ER, PR, and HER-2 receptor in primary and metastatic focuses of 65 cases of breast cancer.Positive rate of ER in primary focuses was 56.9% (37/65), significantly higher than that in metastatic focuses (33.8%, 22/65)(P0.01); while positive rates of PR and HER-2 receptor have no significant difference between primary and metastatic focuses. Total discordance rates of ER, PR, and HER-2 were 35.4%, 29.2%, and 16.9%, respectively.Difference in expression level of ER between primary and metastatic focuses of breast cancer was significant, while differences of expression of PR, and HER-2 wasn't significant, but we still should think highly of the expression differences of ER,PR,and HER-2 in our clinical practices.

Capxol is a Cremophor-free,protein stabilized, nanoparticle formulation of paclitaxel. This phase I study was designed to evaluate the tolerability/safety, toxicity profile, and maximum tolerated dose (MTD) of Capxol administered intravenously in Chinese patients with advanced solid tumor, and to provide the recommending dose for the phase II trial.Capxol was administered intravenously over 30 minutes, no premedication was required. Doses of Capxol ranged from 135 to 350 mg/m(2). The treatment was repeated at 3 weeks interval.22 patients were treated with Capxol and totally 94 treatments cycles were completed. No acute hypersensitivity reactions were observed during the infusion period. The treatment was tolerated well. Most of AEs (95%) were grade 1/2;/= grade 3 AEs were only 5%. The most common toxicities were mild leucopenia and peripheral sensory neuropathy. The dose-limiting toxicities,which occurred at dose level of 350 mg/m(2),were grade 4 neutropenia (1 out of 3 patients) and grade 3 diplopia (1 out of 3 patients). The MTD was thus determined at 300 mg/m(2). Among 21 patients who were evaluable for efficacy, 1 CR, 7 PR, 9 SD, 4 PD were observed, overall response rate (CR+PR) was 38%.This phase I trial has demonstrated that Capxol has several advantages on clinical application, which include non-premedication required, shorter infusion time,higher paclitaxel MTD and safer toxicity. The results support for that a phase II clinical trial to further evaluate the antitumor activity of this drug in Chinese patients is worthy. The recommended dose for phase II clinical trial is 260 mg/m(2), I.V. over 30 minutes,and treatment repeats at every 3 weeks.

Patients with B-cell non-Hodgkin's lymphoma (B-NHL) usually have a poor immune response. CD8(+)CD28(-) T cells (Ts) and CD3(+)CD56(+) NKT cells (NKT) are new types of immune suppressor cells. This study was to analyze proportions and changes of them in peripheral blood of patients with B-NHL, explore their effects on immunosuppression of B-NHL, and the influnce factors, to provide reference for intervening in immune function of B-NHL patients.Peripheral blood samples were got from 79 naive patients with B-NHL before treatment, and 25 healthy people, samples of 18 patients who got complete remission (CR) after 4-6 cycles of chemotherapy were collected either before chemotherapy or after CR. Proportions of Ts and NKT were analyzed by flow cytometry (FCM).Compared with control group, proportions of Ts, and NKT in peripheral blood of B-NHL patients before chemotherapy were (18.19+/-5.03)%, and (6.08+/-3.29)%, significantly higher than those of healthy people [(11.20+/-3.49)%, P0.01; (3.52+/-1.56)%, P0.01]. There were no significant differences of proportions of Ts among patients with B-NHL of different clinical stages (P0.05), and different malignant grade (P0.05), and between before treatment and after CR (P=0.55). No significant difference of proportions of NKT was found among patients with B-NHL of different clinical stages (P0.05), and different malignant grade (P0.05), and between before treatment and after CR (P=0.39).Populations of Ts and NKT commonly increased in peripheral blood of patients with B-NHL, they may play roles in immunosuppression of B-NHL.

B cell non-Hodgkin's lymphoma (B-NHL) in childhood and adolescence is aggressive. Routine CHOP regimen can improve the survival rate of patients with early-stage disease, but its effect on patients with advanced disease was poor. Therefore, it is worthwhile to further investigate how to treat patients with B-NHL at different stages. This study was designed to retrospectively analyze and compare CHOP, CHOP+HD-MTX, and BFM-90 regimens in the survival rate of children and adolescents with B-NHL,and explore the optimal therapeutic strategy and protocols.Thirty cases of 3- to 17-year-old untreated patients with B-NHL were enrolled in CHOP group, with 13 in Stage I/II, and 17 in stage III/IV (St Jude staging), all patients received standard CHOP for 2 to 8 cycles, the regimen was repeated every 3 weeks. Eighteen cases of 3- to 14-year-old untreated patients with B-NHL were enrolled in CHOP+HD-MTX group, with 6 in Stage I/II, and 12 in stage III/IV (St Jude staging), all patients received CHOP+HD-MTX and intrathecal injection for 2 to 8 cycles, the regimen was repeated every 4 weeks. Twenty-five cases of 1.5- to 15-year-old untreated patients with B-NHL were enrolled in BFM-90 group, with 7 in Stage I/II,and 18 in stage III/IV (St Jude staging). The patients with stage I/II disease received A schema alteration with B schema of BFM-90 regimen for 4 to 6 cycles, while the patients with stage III/IV disease received AA schema alteration with BB schema of BFM-90 regimen for 6 cycles, the interval of cycles was 18-21 days. The survival rates were evaluated by Kaplan-Meier method.In CHOP group,complete response (CR) rate was 70% (21/30), and partial response (PR) rate was 13% (4/30). In CHOP+HD-MTX group, CR rate was 83%, PR rate was 16%. In BFM-90 group, CR rate was 96% (24/25), and PR rate was 4% (1/25). The hematologic toxicity incidence was higher in BFM-90 group than in the other 2 groups. In CHOP group, the overall 2-year survival rate was 52.79% (72.73% for Stage I/II, and 37.82% for stage III/IV). In CHOP+HD-MTX group, the overall 2-year survival rate was 55.56 % (83.33 % for Stage I/II, and 41.67 % for stage III/IV). There was no significant difference between CHOP group and CHOP+HD-MTX group in survival rate (P=0.78). In BFM-90 group,2-year event-free survival rate (EFS) was 84.01 % (100% for Stage I/II, and 77.04 % for stage III/IV). The differences in survival rate between BFM-90 group and CHOP group, CHOP+HD-MTX group were both significant (P=0.013, and P=0.034).BFM-90 regimen can greatly improve the survival rate of children and adolescents with B-NHL, especially of patients with advanced NHL. CHOP, and CHOP+HD-MTX regimens work better for the early stage patients, but produce low survival rate for patients with advanced NHL. A high intensive chemotherapy like BFM-90 regimen is necessary for children and adolescents with advanced B-NHL.

It is well known that the patients with B-Non-Hodgkin's Lymphoma (B-NHL) usually have a poor immune response. CD4(+)CD25(+)-Tregs is a new type of suppressor cell. It plays an important role in the tumor immune suppression. But its distribution and the mechanism of immune suppression in B-NHL are still unknown. The present study was designed to evaluate the proportion of Tregs in peripheral blood of the patients with B-NHL with or without chemotherapy to investigate the mechanism of immune suppression in B-NHL and the effect of chemotherapy on immune system and provide evidence for effective intervention in immune function.The peripheral blood was collected from 39 patients with B-NHL before chemotherapy, 32 patients with B-NHL who achieved partial remission (PR) or complete remission (CR) after 4-6 cycles of chemotherapy, and 25 healthy people. The population of CD4(+), CD8(+), CD4(+)CD25(+), and CD4(+)CD25(+)CTLA4(+) T cells was evaluated by flow cytometry.The total number of lymphocyte, the proportion of CD4(+)T cells, and the ratio of CD4/CD8 in the group of B-NHL before chemotherapy was significant less than those of the healthy group (1.3+/-0.39 x 10(9) versus 2.1+/-0.41 x 10(9); 27.5%+/-4.1% versus 32.9%+/-5.8%; 0.9+/-0.21 versus 1.31+/-0.4), but the percentages of CD4(+)CD25(+)-Tregs and CD4(+)CD25(+)CTLA4(+)-T cells were significantly higher than those of the healthy donors (14.7%+/-3.1% versus 8.4%+/-2.5%; 7.4%+/-1.6% versus 5.1%+/-1.4%). In the group of chemotherapy, although the CD4/CD8 ratio (1.19+/-0.3) was almost near to that of the healthy group, the total number of lymphocytes (0.8+/-0.53 x10(9)) was less than those of the other two groups, and the proportions of CD4(+)CD25(+)-Tregs (20.3%+/-4.1%) and CD4(+)CD25(+)CTLA4(+)-T cells (11.5%+/-2.2%) were higher than those of the other two groups.The population of CD4(+)CD25(+)-Tregs in peripheral blood of the patients with B-NHL with or without chemotherapy was significantly higher than those in healthy donors, which may be one of the important reasons of immunosuppression in B-NHL.

To evaluate the efficacy and safety of capecitabine as first-line therapy in patients with advanced and recurrent colorectal cancer.From December 2000 to November 2001, sixty patients with advanced and recurrent colorectal cancer received first-line capecitabine treatment given at a dose of 1250 mg/m(2) twice daily, on days 1 - 14 every 21 days. At least 2 cycles were administered.The overall response rate was 23.3% with 14 PR, 24 SD (40.0%) and 15 PD. The median survival time was 14.7 months. The survival rate was 63.9% at 12-months and 33.4% at 24-months. Grade III-IV adverse effects were diarrhea in 4 patients (6.6%), anemia in 2 (3.3%) and hand-foot syndrome (HFS) in 1 (1.7%); Grade I-II adverse effects were hyperpigmentation in 20 (33.3%), HFS in 18 (30.0%) and diarrhea in 10 (16.7%).Capecitabine is an efficacious and better-tolerated alternative treatment for the patients with advanced and recurrent colorectal cancer.

Neuroblastoma is one of common solid tumors in children. The major treatment modality for neuroblastoma (NB) is chemotherapy combined with operation or irradiation. But the survival rate is still low for advanced patients. Further study is needed for improving cure rate of neuroblastoma. This study was designed to evaluate the efficacy of children with neuroblastoma treated in Cancer Center, Sun Yat-sen University, and to explore reasonable therapy strategy.The clinical data of 30 children with NB aged from 7 months to 13 years were analyzed retrospectively. These patients were treated with chemotherapy plus operation or radiation. The stages were as follow: II, n=2; III, n=12; IV, n=15; IVS, n=1. Chemotherapy regimen was CAV (cyclophosphamide 750 mg/m(2) d1, vincristine 1.5 mg/m(2), d1, Adriamycin 50 mg/m(2) d1) alternated with EP (teniposide or etoposide 60 mg/m(2) d1-d5, cisplatin 20 mg/m(2) d1-d5). The resection would be done after 4 to 6 cycles of chemotherapy if possible. The chemotherapy or radiation would be done after resection. If operation was not available, the patients continued to receive the chemotherapy. The patients with stage IVS only received cyclophosphamide plus vincristine.Among 30 patients, 2 cases achieved complete remission (CR 6.7%) by chemotherapy alone; 21 cases achieved partial remission (PR 70%); 6 cases showed no change (NC 20%); 1 cases showed progressive diseases (3.3%). Overall response rate (CR+PR) were 76.7% by chemotherapy alone. Of 21 PR patients, 9 cases could be resected;4 cases achieved CR after operation; 1 case achieved CR after radiation. The 2-year overall survival rate was 47.8% for all patients; 100% for Stage II/IVS, 34% for stage III, 22% for stage IV, respectively. Grade III/IV hematological toxicity occurred in 41.2% of the CAV regimen and 26.6% of the EP regimen.Chemotherapy plus operation or radiation is the major treatment for neuroblastoma. CAV/EP alternative chemotherapy is the active regimen for NB. The toxicity is tolerable. Advance stage NB needs further study for improving the prognosis.

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.

In most instances, advanced non-small cell lung cancer (NSCLC) is treated with primary chemotherapy. Many chemotherapy regimens can palliate cancer-related symptoms and modestly improve survival and quality of life. This clinical trial was designed to compare the efficacy and toxicity of two regimens: PG regimen [cisplatin and gemcitabine] versus PN regimen [cisplatin and vinorelbine].A total of 64 patients were enrolled in this study, 31 patients received PG regimen and 33 patients received PN regimen. Patients in both groups were well-matched with baseline disease characteristics (P0.05).In PG group, the response rate was 32.3% [10/31, 95% confidence interval (CI):16.3%-48.7%][1 complete response (CR), 9 partial response (PR), 17 no change (NC), 4 progressive disease (PD)]; whereas in group PN, the response rate was 29.03% (9/31,95% CI:13.1%-44.9%) (0CR, 9PR, 17NC, 5PD). The difference of response rates between two groups was not statistically significant (P=0.526, Chi-square test). The median survival were 12 months for group PG (95%CI:10-14 months) and 11 months for group PN (95% CI:10-12 months). The difference of median survival between two groups was not statistically significant(P=0.5799, log-rang test). The major toxicity was myelosuppression. Leucopenia was more pronounced in group PN (P=0.009), Thrombocytopenia was more pronounced in group PG(P=0.01).PG and PN are two effective regimens for the patients with advanced NSCLC; the major toxicity was myelosuppression. Leucopenia was pronounced in group PN. Thrombocytopenia was pronounced in group PG. Neurotoxicity was observed in group PN.

In the management of relapsed or refractory non-Hodgkin's lymphoma(NHL), there is still no standard salvage chemotherapy regimen so far. Potentiation of effectiveness and reduction of toxicity for some anti-cancer agents through continuous intravenous infusion were shown in some pre-clinical and clinical studies. The purpose of this study was to evaluate the efficacy and toxicity of EPOCH regimen.A prospective phase II study of EPOCH regimen (doxorubicin/epirubicin,vincristine,etoposide over 96 hours infusion with bolus cyclophosphamade and oral prednisone) was administered to 26 patients with relapsed or refractory/resistant aggressive NHL. There were 20 patients (84.7%) among them treated by over 2 kinds of chemotherapy regimen with median regimen types of 2 (range,1-6 types) and median chemotherapy cycles of 8 (range,3-16 cycles) given for all patients. Fifteen patients (65.7%) were chemo-resistant recurrence.All the 26 patients were assessable. The response rate for the whole group was 50.0% with complete remission (CR) rate of 19.2%. Among the 7 patients with T-cell lymphoma and the 19 patients with B-cell lymphoma, the response rates were 28.6% and 57.9%,respectively. Major toxicity was myelosuppression with 34.8% and 8.7%incidence of grade III-IV neutropenia and thrombocytopenia respectively in all 46 cycles of EPOCH. Other toxicities were mild.EPOCH was effective for the patients with relapsed or refractory/resistant aggressive non-Hodgkin's lymphoma. Continuous infusion schedules of several chemotherapeutic agents may partially reverse chemo-resistance and reduce toxicity. EPOCH can be used as standard salvage regimen. Further clinical study is warranted.

Hodgkin's disease (HD) is a chemo- and radio-sensitive hematologic malignancy. At present, improvement of cure rate, reduction of long-term toxicity, and maintenance of good quality of life are the major issues in the treatment of HD. The results of long term follow-up from Cancer Center, Sun Yat-sen University were analyzed retrospectively in terms of efficacy and late side effects in this article.The results of 295 patients with histology-proven HD from 1970 to 2000, especially from 1980 to 2000 were analyzed. Meanwhile, multivariant analysis (COX model) was employed to determine the prognostic factor.A total of 295 HD patients were treated by chemotherapy-predominant comprehensive modality. The 5, 10, and 20 years overall survival for 295 HD patients were 63.5%, 55.8%, and 47.1%, respectively, with median survival time of 172.3 months (28-351.9 months) at the median follow-up time of 42.9 months (17-351.9 months). The 5, 10, and 20 years overall survival and disease-free survival were 79.6%, 74.5%, and 66.8% as well as 74.5%, 69.4%, and 69.4% respectively for the patients treated with regular chemotherapy and radiotherapy from 1980 to 2000. The incidence rate of late toxicities was low. Multivariate analysis demonstrated that age over 45-year-old, B symptoms and stage III/IV were the main prognostic factors (P = 0.000, P = 0.035, and P = 0.047) in this clinical study. The prognosis of the patients with stage I/II and nodular sclerosis was better in comparison to stages III/IV and other histologic subtypes.Chemotherapy-predominant combined with involved fields irradiation play an important role in HD treatment with promising long term survival and lower late toxicities. Further investigation for this simplified and convenient comprehensive modality is warranted.

The treatment of the patients with relapsed and refractory non-Hodgkin's lymphoma(NHL) remains difficult. It was reported that DHAP regimen(cisplatin + Ara-C + dexamthsone) was an effective salvage therapy, but there was no report about it in China. The current study was designed to observe the efficacy and toxicity of DHAP regimen for the patients with relapsed and refractory NHL.Seventeen patients with relapsed and 10 with refractory intermediate or high grade NHL was involved in this study. These patients were treated with cytarabine 1 g/m2 intravenous(i.v.) every 12 hours on day 1 to 2, cisplatin 20 mg/m2 i.v. on day 1 to 4, dexamethone 40 mg i.v. on day 1 to 4. Four patients with CR after DHAP were followed by autologous peripheral blood stem cell transplantation(APBPCT).Overt responses to DHAP were seen in 12 patients (44.4%) including 8 complete responses(CR) (29.6%) and 4 partial responses (PR) (14.8%). The effective release time lasted a median of 4.8 months. Median survival time was 8.3 months. 1-year and 2-year survival rate were 30.8% and 19.3%, respectively. Myelosuppression was the major toxicity; 15 patients(57.7%) had grade III-IV neutropenia and 21 patients (80.8%) had grade III-IV thromcytopenia, but there was no treatment-related death.The authors conclude that DHAP regimen is an effective salvage therapy for the patients with relapsed and refractory NHL, but the remission duration time is short and long-term prognosis remains poor. High dose chemotherapy supported by APBPCT is necessary for improvement in long-term survival.

Tao Qin,* Zhongyu Yuan,* Roujun Peng, Bing Bai, Yanxia Shi, Xiaoyu Teng, Donggeng Liu, Shusen Wang Department of Medical Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China *These authors contributed equally to this work Purpose: The efficacy of trastuzumab in Chinese breast cancer (BC) patients has rarely been reported. This study was designed to compare the clinical outcomes of HER2-positive BC patients receiving or not receiving trastuzumab treatment and HER2-negative BC patients. Patients and methods: This study involved three groups of patients. The first group was 115 human epidermal growth factor receptor 2 (HER2)-positive BC patients treated with trastuzumab who were enrolled at Sun Yat-sen University Cancer Center between January 2002 and July 2010; the second group was a matched control group of 115 HER2-positive patients who did not receive trastuzumab treatment; the third group was a matched group of 115 HER2-negative patients who received conventional therapy in the adjuvant setting. The primary endpoint was 3-year and 5-year disease-free survival (3-DFS and 5-DFS, respectively). The Kaplan–Meier method, log-rank test, and multivariate Cox proportional hazard regression model were used for survival analysis. The differences in survival rates among the three groups were also analyzed according to two different periods: 2002–2006 and 2007–2010. Results: The median duration of follow-up was 36 months (range, 12–111 months). The 3-DFS rates in the HER2-negative group, the HER2-positive group who received trastuzumab treatment, and the HER2-positive group who did not receive trastuzumab treatment were 82.6%, 89.6%, and 67.0%, respectively. The 3-DFS rate for the total study population was statistically significant (P < 0.001). Further analysis indicated a statistically significant difference in 3-DFS between either of the first two groups and the third group (P < 0.01), but the difference between the first two groups was not statistically significant (P = 0.157). Among the three groups, the 3-DFS rates during 2002–2006 did not have a significant difference compared with that during 2007–2010. Conclusion: This study has further confirmed the efficacy of trastuzumab for HER2-positive operable BC in Chinese patients. It has also demonstrated that the 3-DFS and 5-DFS rates between HER2-positive patients receiving trastuzumab treatment and HER2-negative patients are comparable. Keywords: breast cancer, HER2, trastuzumab, adjuvant treatment, survival analysis