纳科思联合顺铂治疗恶性胸腔积液疗效分析

目的分析纳科思联合顺铂胸腔注射治疗恶性胸腔积液的临床疗效。方法23例患者引流尽胸水后胸腔内注入纳科思1500万U+顺铂60mg+生理盐水50ml后闭管,闭管2h后开放引流,并观察治疗效果,效果不佳者1周后重复上述治疗,最多3次用药。结果患者治疗总有效率达86.95%,其副作用发热和胸痛均较轻,患者能耐受,且无严重骨髓抑制,肝、肾功能损害。结论胸腔内应用纳科思联合顺铂治疗恶性胸腔积液具有疗效好、不良反应小、安全性高的特点,值得在临床推广应用。

Prognostic factors in patients with advanced cholangiocarcinoma: Role of surgery, chemotherapy and body mass index

AIM： To study the factors that may affect survival of cholangiocarcinoma in Lebanon. METHODS： A retrospective review of the medical records of 55 patients diagnosed with cholangio- carcinoma at the American University of Beirut between 1990 and 2005 was conducted. Univariate and multivariate analyses were performed to determine the impact of surgery, chemotherapy, body mass index, bilirubin level and other factors on survival. RJ^SULTS： The median survival of all patients was 8.57 mo （0.03-105.2）. Univariate analysis showed that low bilirubin level （〈 10 mg/dL）, radical surgery and chemotherapy administration were significantly associated with better survival （P = 0.012, 0.038 and 0.038, respectively）, in subgroup analysis on patients who had no surgery, chemotherapy administration prolonged median survival significantly （17.0 mo vs 3.5 mo, P = 0.001）. Multivariate analysis identified only low bilirubin level 〈 10 mg/dL and chemotherapy administration as independent predictors associated with better survival （P 〈 0.05）. CONCLUSION： Our data show that palliative and postoperative chemotherapy as well as a bilirubin level 〈 10 mg/dL are independent predictors of a significant increase in survival in patients with cholangiocarcinoma.

SEVEN CASES OF EPITHELIAL OVARIAN CARCINOMA WITH BRAIN METASTASIS

Objective To summarize the clinical characteristics, treatment, and prognosis of brain metastasis in patients with epithelial ovarian carcinoma. Metbods Retrospective analysis was conducted in 7 cases of brain metastases of epithelial ovarian carcinoma from January 1986 to March 2007 in Peking Union Medical College Hospital for summarizing therapy results and prognosisaffecting factors. Results Incidence of brain metastases of epithelial ovarian carcinoma was about 0. 66% （7/1 055 ）. Serous adenocarcinoma was the predominant pathological type in 4 cases and the subsequent was adenocarcinoma in 3 cases. All the patients were diagnosed at late stage, 6 cases with the International Federation of Gynecology and Obstetrics （HGO） stage Ⅲc and 1 with FIGO stage IV. The mean duration from diagnosis of ovarian carcinoma to brain metastasis was 32.7 ± 20. 0 months （range, 23-73 months）. Single metastasis focus occurred in 43% of cases and multiple metastases in 57% of cases. Fifty-seven percent of patients presented extracranial metastasis. Serum CA125 played a role in monitoring reoccur- rence and brain metastases. The average survival time was about 12 months. Better treatment with prolonged survival could be achieved by combination of operation and chemotherapy or combination of radiotherapy with chemotherapy. Concltusions As a rare condition, brain metastasis of epithelial ovarian carcinoma is rising in incidence with improved treatment of ovarian carcinoma and prolonged survival. However, brain metastasis indicates bad prognosis which can be improved by combined therapy.

c-Met targeted therapy of cholangiocarcinoma

Cholangiocarcinoma continues to be a challenging disease to treat. Systemic therapy is used in unresectable disease, disease progression after surgery, and in the palliative setting. Unfortunately, results of multiple phase Ⅱ trials have rarely yielded positive results. As data on the molecular carcinogenesis of cholangiocarcinoma is developing, we are more able to understand the disease process and can use this understanding to create unique targeted therapies. We reviewed the role of c-Met/ hepatocyte growth factor (HGF) in the development of cholangiocarcinoma. Furthermore, we explored the use of the c-Met guided cascade as a target to treat cholangiocarcinoma. We reviewed the current use and options for future development of c-Met agents to treat this disease.

Is it relevant that intra-arterial chemotherapy may be effective for advanced pancreatic cancer?

Unresectable pancreatic cancers have an extremely dismal prognosis and chemoresistant nature. The treatment of pancreatic cancer is still problematic. Gemcitabine is a promising new agent that has been studied recently for palliation of advanced pancreatic cancer. However,the response rates have been highly variable,and are often irreproducible. To improve this low response rate,various treatments are needed because no standard treatment exists. Intra-arterial chemotherapy is considered to take advantage of the first pass effect of the drug,generating higher local drug concentrations in tumor cells with lower toxicity. Regional intra-arterial chemotherapy may provide high levels of cytostatic concentrations within the tumor and,simultaneously,a low rate of systemic side effects compared with systemic administration of anti-neoplastic drugs. Intra-arterial chemotherapy has been introduced as an alternative treatment for advanced pancreatic cancer. Further clinical trials of this method should be subjected to a prospective randomized controlled study for advanced pancreatic cancer.

Expression of caveolin-1 and MMP-2 in bladder cancer and its clinical significance

Objective： To explore the expression of caveolin-1 （CAV-1） and matrix metalloproteinase-2 （MMP-2）in bladder cancer and its clinical significance. Methods： The expression of CAV-1 and MMP-2 were detected by the SP immunohistochemical method in 77 cases of bladder cancer. Results： The positive rates of CAV-1, MMP-2 in bladder transitional cell carcinoma （BTCC） and bladder adenocarcinoma were significantly high than those of normal bladder mucosa, the positive rates in the deeper cancer invasion was significantly high than those of superficial bladder cancer （P 〈 0.01）, the positive rates of CAV-1 in grades Ⅰ, Ⅱ and Ⅲ of bladder transitional cell carcinaoma （BTCC） were 15%, 40% and 68%, respectively; the positive rates of MMP-2 in grades Ⅰ, Ⅱ and Ⅲ of bladder transitional cell carcinoma （BTCC） were 20%, 40% and 72%, respectively （P 〈 0.01）. CAV-1 was positive associated with MMP-2 in bladder cancer （r = 0.598, P 〈 0.001）, but not in bladder tissue. Conclusion： CAV-1 and MMP-2 were associated with stage and grade of bladder cancer, which suggested that CAV-1 might improve secretion of MMP-2.

Improved survival for hepatocellular carcinoma with portal vein tumor thrombosis treated by intra-arterial chemotherapy combining etoposide,carboplatin,epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil:A pilo

AIM： To investigate the poor prognosis of HCC with PVTT, we evaluated the efficacy by a new combination chemotherapy for advanced hepatocellular carcinoma （HCC） with portal vein tumor thrombus （PVTT）. METHODS： From 2002 to 2007, a total of 10 consecutive patients with Stage IVA HCC accompanied by PVTT were studied prospectively to examine the efficacy of treatment by intra-arterial infusion of a chemotherapeutic agents consisting of etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil. RESULTS： The mean course of chemotherapy was 14.4 （range, 9-21） too. One patient showed complete response （CR） with disappearance of HCC and PVI-F after treatment, and the two patients showed partial response （PR）, response rate （CR ＋ PR/All cases 30%）. The median survival time after the therapy was 457.2 d. The one-year survival rate was 70%. Adverse reactions were tolerable.CONCLUSION： Although the prognosis of most patients with Stage IVA HCC by PVTT is poor, our combination chemotherapy may induces long-term survival and is an effective treatment and produced anti-tumor activity with tolerable adverse effects in patients for advanced Stage IVA HCC accompanied by PVTT.

Analysis of Cardiotoxicity from rh-Endostatin Therapy Combined with Chemotherapy

OBJECTIVE To evaluate the cardotoxicity from recombinant human endostatin(rh-endostatin)combined with chemotherapy. METHODS A total of 12 cancer patients treated with rh- endostatin combined with chemotherapy were selected,and their clinical data collected.Their symptoms,including cardiopalmus, chest distress,dyspnea and changes in their electrocardiogram (ECG),myocardium enzymogram and left ventricular ejection fraction(LVEF),were observed during the drug treatment.These indicators were used for early diagnosis of cardiotoxicity. RESULTS Compared with a pre-therapeutic value,there was a significant increase in the CK-MB value at one week after starting the treatment as well as at the end of treatment(P<0.05).There was a significant change in the ECG at the end of treatment, compared to a pre-therapeutic condition(P<0.05),but there was no significant difference when comparing the pre-and post- therapeutic LVEF values. CONCLUSION It was recognized that mild cardiac adverse reactions exist in the regimen of recombinant human endostatin combined with chemotherapy.This therapy caused definite injury to the cardiac muscle,but cardiac functions were not obviously changed.CK-MB and ECG may be used as indicators for early monitoring cardiac toxicity.Vigilance against cardiac adverse reactions should be heightened during a course of rh-endostatin combined with chemotherapy.

Preventing prolonged post-operative ileus in gastric cancer patients undergoing gastrectomy and intra-peritoneal chemotherapy

AIM： To assess the efficacy of metoclopramide （Met） for prevention of prolonged post-operative ileus in advanced gastric cancer patients undergoing D2 gastrectomy and intra-peritoneal chemotherapy （IPC）. METHODS： Thirty-two advanced gastric cancer patients undergoing D2 gastrectomy and IPC were allocated to two groups. Sixteen patients received Met immediately after operation （group A）, and 16 did not （group B）. Another 16 patients who underwent D2 gastrectomy without IPC were enrolled as the control group （group C）. All patients had received epidural pain control. The primary endpoints were time to first post-operative flatus and time until oral feeding with a soft diet without discomfort. Secondary endpoints were early complications during hospitalization. RESULTS： Gender, the type of resection, operating time, blood loss, tumor status and amount of narcotics were comparable in the three groups. However, the group C patients were older than those in groups A and B （67.5±17.7 vs 56.8±13.2, 57.5±11.7 years, P= 0.048）. First bowel flatus occurred after 4.35±0.93 d in group A, 4.94±1.37 d in group B, and 4.71±1.22 d in group C （P〉0.05）. Oral feeding of a sore diet was tolerated 7.21±1.92 d after operation in group A, 10.15±2.17 d in group B, and 7.53±1.35 d in group C （groups A and C vsgroup B, P〈0.05）. There was no significant difference in respect to the first flatus among the three groups. However, the time of tolerating oral intake with soft food in groups A and C patients was significantlyshorter than that in group B patients. Levels of C-reactive protein （CRP） were significantly lower in group C and there was a more prominent and prolonged response in CRP level in patients undergoing IPC. The incidence of post-operative complications was similar in the three groups except for prolonged post-operative ileus. There was no increased risk of anastomotic leakage in patients receiving Met. CONCLUSION： The results suggest that a combination of intravenous Met and epidural pain control may be required to achieve a considerable decrease in time to resumption of oral soft diet in advanced gastric cancer patients who underwent gastrectomy and IPC. Furthermore, the administration of Met did not increase anastomotic leakage. Met has a role in the prevention of prolonged post-operative ileus.

A study of transarterial infusion chemotherapy of gemcitabine plus three dimensional conformal radiotherapy for local advanced pancreatic cancer

Objective: To evaluate the clinical effect of transarterial infusion chemotherapy of gemcitabine plus three dimen- sional conformal radiotherapy on patients with local advanced pancreatic cancer. Methods: Fifty-one patients with local ad- vanced pancreatic cancer from June 2002 to February 2004 were enrolled, twenty-four patients of combined group were treat- ed with transarterial infusion chemotherapy of gemcitabine plus three dimensional conformal radiotherapy, while twenty-seven patients of control group were treated only with transarterial infusion chemotherapy of gemcitabine. Results: There were significant statistical differences between two groups in clinical benefit response (91.7% versus 74.1%, P < 0.01) and overall remission rate (70.8% versus 33.3%, P < 0.01). The 6-month survival rate, 12-month survival rate and 24-month survival rate of combined group were 83.3%, 62.5% and 37.5% respectively, while that of control group were 55.6%, 33.3% and 11.1% respectively. This showed significant difference between the two groups. Conclusion: Transarterial infusion chemotherapy of gemcitabine plus three dimensional conformal radiotherapy may be better than single transarterial infusion chemotherapy of gemcitabine in improving survival rates and elongating survival time of patients with local advanced pancreatic cancer.

Cytoreduction and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis from pseudomixoma peritonei

AIM： To investigate the most important aspects of hyperthermic intraperitoneal chemotherapy （HIPEC） that has been accepted as the standard treatment for pseudomyxoma peritonei （PMP）, with special regard to morbidity, overall survival （OS） and disease free survival （DFS） over 10 years. METHODS： Fifty-three patients affected by PMP underwent cytoreduction （CCR） and HIPEC with a ＂semi-closed＂ abdomen technique in our institution. The peritonectomy procedure and completeness of CCR were classified according to Sugarbaker criteria. Preoperative evaluation always included thoracic and abdominal CT scan to stage peritoneal disease and exclude distant metastases. Fifty-one patients in our series were treated with a protocol based on administration of cisplatinum 100 mg/m^2 plus mitomycin C 16 mg/m^2, at a temperature of 41.5℃ for 60 min. Anastomoses were always performed at the end of HIPEC. The mean duration of surgery was 12 h including HIPEC. Continuous monitoring of hepatic and renal functions and hydroelectrolytic balance was performed in the postoperative period. RESULTS： Twenty-four patients presented with postoperative complications： surgical morbidity was observed in 16 patients and 6 patients were reoperated. All complications were successfully treated and no postoperative deaths were observed. Risk factors for postoperative morbidity were considered to be gender, age, body surface, duration of surgery,Peritoneal Cancer Index （PCI） and tumor residual value （CC score）. No statistically significant correlation was found during the multivariate analysis： only the CC score was statistically significant. The OS in our experience was 81.8%, with a DFS of 80% at 5 years and of 70% at 10 years. CONCLUSION： In our experience, even if HIPEC combined with cytoreductive surgery involves a high risk of morbidity, postoperative complications can be resolved favorably in most cases with correct patient selection and adequate postoperative care, thus minimizing mortality. The association of CCR and HIPEC can be considered as the standard treatment for PNP. The OS and DFS results confirm the validity of this combined approach for the treatment of this rare neoplasm. The impact of preoperative chemotherapy on OS, in our opinion, is due to a major aggressiveness of tumors in treated patients.

Evaluation of HCPTd_1, d_(14)-double passaged intervening chemotherapy protocol for hepatocellular carcinoma

AIM. To establish a kind of standardization of the clinical chemotherapeutic prototypes for unresectable hepatocellular carcinomas （HCC）. METHODS： 10-Hydroxycamptothecin （HCPT） was applied through transcatheter arterial embolization （TAE） to HCC patients who were categorized into three groups： （1） test group： treatment with HCPT twice （HCPT dl and 14） through TAE and portal venous embolization. （2） Control Ⅰ： treatment with anticancer drugs without HCPT. （3） Control Ⅱ： treatment with HCPT as a major component in anticancer drugs once （HCPT dl）. A set of comparisons between test groups and control Ⅰ and Ⅱ groups were performed before and after the treatment to study the effectiveness of each treatment, in terms of tumor volumes, dynamic variations in serum alpha-fetoprotein （AFP）, gamma-glutamyl transferase hepatoma-specific band （GGT-Ⅱ）, patient survival and adverse events. RESULTS： The general effectiveness rate of the test group reached 62.1% （72/116）, remarkably higher than that of control Ⅰ （32.1%, 40/124） and control Ⅱ （54.7%, 47/56）, （P〈0.01 and P〈0.05, respectively）. Especially, the reduction rate or disappearance of the portal vein tumor emboli was as high as 88.4% （61/69） in the test group, in contrast with 13.9% （10/72） in control Ⅰ and 35.9% （18/51） in control Ⅱ （P〈0.01 and P〈0.01, respectively）. After treatment, AFP decreased or turned to negative levels at 52.3% （34/65） in control Ⅰ, 67.3% （35/52） in control Ⅱ, and 96.8% （60/62） in the test group. Also GGT-Ⅱ declined or became negative at 37.8% （28/74） in control Ⅰ, 69.5% （57/82） in control Ⅱ, and 94.7% （89/94） in test group （P〈0.01 and P〈0.05, respectively）. CONCLUSION： We have designed a good protocol （test group） to treat HCC with excellent advantages of high efficiency, low cost, low toxicity and low adverse events and easy application. It could be recommended as one of the standardizations for HCC treatment in clinical practice.

Strong prognostic value of nodal and bone marrow micro-involvement in patients with pancreatic ductal carcinoma receiving no adjuvant chemotherapy

AIM： To study the prognostic value of adjuvant chemotherapy in patients with pancreatic, ductal adenocarcinoma. METHODS： Lymph nodes from 106 patients with resectable pancreatic ductal adenocarcinoma were systematically sampled. A total of 318 lymph nodes classified histopathologically as tumor-free were examined using sensitive immunohistochemical assays. Forty-three （41%） of the 106 patients were staged as pT1/2, 63 （59%） as pT3/4, 51 （48%） as pNo, and 55 （52%） as pN1. The study population included 59 （56%） patients exhibiting G1/2, and 47 （44%） patients with G3 tumors. Patients received no adjuvant chemoor radiation therapy and were followed up for a median of 12 （range： 3.5 to 139） mo.RESULTS： Immunostaining with Ber-EP4 revealed nodal microinvolvement in lymph nodes classified as ＂tumor free＂ by conventional histopathology in 73 （69%） out of the 106 patients. Twenty-nine （57%） of 51 patients staged histopathologically as pNo had nodal microinvolvement. The five-year survival probability for pN0-patients was 54% for those without nodal microinvolvement and 0% for those with nodal microinvolvement. Cox-regression modeling revealed the independent prognostic effect of nodal microinvolvement on recurrence-free （relative risk 2.92, P = 0.005） and overall （relative risk 2.49, P = 0.009） survival. CONCLUSION： The study reveals strong and independent prognostic significance of nodal microinvolvement in patients with pancreatic ductal adenocarcinoma who have received no adjuvant therapy. The addition of immunohistochemical findings to histopathology reports stratification of patients with may help to improve risk pancreatic cancer.

Multi-disciplinary treatment for cholangiocellular carcinoma

Cholangiocarcinoma(CC)is rare malignant tumors composed of cells that resemble those of the biliary tract.It is notoriously difficult to diagnose,and is associated with a high mortality.Traditionally,CC is divided into intrahepatic and extraheaptic disease according to its location within the biliary tree.Intrahepatic cholangiocellular carcinoma(IH-CCC)or peripheral cholangiocellular carcinoma(CCC)appears within the second bifurcation of hepatic bile duct,and is the second most common primary liver cancer following hepatocellular carcinoma(HCC),IH-CCC or peripheral CCC often presents with advanced clinical features,and the cause for this cancer rise is still unclear.MRI,CT and PET provide useful diagnostic information in those patients.Surgical resection is the only chance for cure,with results depending on selected patients and careful surgical technique.Liver transplantation could offer long-term survival in selected patients when combined with chemotherapy.Chemotherapy,radiation therapy or combination therapies remain as the only treatment for inoperable patients.However,these are uniformly ineffective in patients' survival.

Docetaxel as salvage chemotherapy in patients with advanced non-small cell lung cancer after failure of cytotoxic agents and gefitinib treatment

Objective： We conducted a prospective phase II trial of single-agent salvage chemotherapy with docetaxel in patients with advanced non-small cell lung cancer （NSCLC） after failure of chemotherapy and gefitinib to assess the efficacy and toxicity of docetaxel in this setting. Methods： Patients with histologically confirmed NSCLC who were failure of chemotherapy and gefitinib were given docetaxel 75 mg/m^2 intravenously for 30 rain every 3 weeks until the toxicity was unacceptable or disease progressed. The response evaluation criteria in solid tumors （RECIST） guidelines were used for the evaluation of an- titumor activity. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria version 2.0. Results： In total, 31 patients were enrolled in this phase II trial between February 2004 and December 2006, and 84 cycles （average 2.7 cycles） were given. We observed 4 partial responses （PRs） and 10 stable disease （SD） states in 31 eligible patients. The objective response rate was 12.9%, and the disease control rate was 45.2%. The median survival time （MST） was 10 months （95% CI, 5.05-15.08 months）. The 1-year survival rate was 40.6%. The most common toxicities were neutropenia, anemia, and peripheral neuropathy that occurred as follows： 45% of the patients experienced grade 3 or 4 neutropenia, 29% experienced grade 3 anemia, and 25.8% had grade 3 peripheral neuropathy. No patient terminated docetaxel chemotherapy due to toxicity. Conclusion： Docetaxel is beneficial as salvage chemotherapy in patients with advanced NSCLC after failure of cytotoxic agents and gefitinib.

Portal thrombosis and steatosis after preoperative chemotherapy with FOLFIRI-bevacizumab for colorectal liver metastases

In order to discuss the role of preoperative chemo- therapy for colorectal liver metastases, which is used frequently before hepatic resection, even in patients with resectable disease at presentation, we herein report the development of two complications, partial portal vein thrombosis and hepatic steatosis with Iobular inflammation, during the course of preoperative chemotherapy with FOLFIRI plus bevacizumab for colorectal liver metastases, which recognition led to timely discontinuation of chemotherapy as well as a change in the surgical strategy to resect the tumors and the damaged liver through advanced techniques. We conclude that duration of treatment and drug doses and combinations may impact the development of chemotherapy-induced liver injury. Surgeons and medical oncologists must work together to devise safe, rational, and oncologically appropriate treatments for patients with multiple colorectal liver metastases, and to improve the understanding of the pathogenesis of chemotherapyinduced liver injury.

REPEATED RECURRENCE OF OSTEOSARCOMA TREATED BY RESECTIONS AND CHEMOTHERAPY

This paper presents 5 patients with repeated recurrence of osteosarcoma (RROS). The primary focus of 3 patients were in the distal portion of femur, and 2 patients were in the proximal Portion of tibia. Three patients, whose chest X ray film were negative, were treated by amputation and chemotherapy. Two patients had isolated metastatic focus l. 5 cm in diameter in lung, were treated by amputation after 1 week of chemotherapy and then treated by lobectomy after 2 weeks of chemotherapy. After operation, the chemotherapy was carried out for 3 courses of treatment. The roentgenogram of chest and affected limb were taken once every two months. There were metastatic focuses found in the lung of 1 patient and in the distal portion of femur of 2 patients. One patient was operated on for 4 times. UP to now, 3 patients have been living for 5 yeara and 2 patients for 6 years after operation.

Limited influences of chemotherapy on healthy and metastatic liver parenchyma

AIM: To examine the expression of E-cadherin, β-catenin,γ-catenin, VEGF, and p53 in 39 patients with hepatic metastasis from colorectal cancer immunohistochemically.METHODS: The patients were divided into two groups:those (n = 16) who had no chemotherapy for at least 6 mo before the liver resections and those (n = 23)who were treated with chemotherapy before liver resections. A score from 0 to 3 was given for the number of positive cells and from 0 to 3 for the intensity of staining in these cells, in both healthy and metastatic liver parenchyma.RESULTS: No significant differences in the expression of E-cadherin, β- and γ-catenin, VEGF and p53, could be observed between patients who received and did not receive chemotherapy, in both normal and metastatic liver parenchyma.CONCLUSION: Despite the assumption that chemotherapy had an effect on liver metastasis, no influences were noticed immunohistochemically.

The clinical observation of combined chemotherapy of irinotecan and cisplatin in the treatment of relapsed advanced small cell lung cancer

Objective： To evaluate the efficacy and safety of the irinotecan and cisplatin combination in relapsed advanced small cell lung cancer （SCLC）. Methods： Eligible patients with SCLC who had progressed or relapsed after therapy were treated with cisplatin and irinotecan. The regimen consisted of irinotecan 60 mg/m^2 on days 1, 8, 15 and cisplatin 60 mg/m^2 on day 1; the plan was given every 28 days. Results： In 23 evaluable patients, responses included 5 complete remissions and 7 partial remissions （overall response rate, 43.4%）, 6 patients had stable disease and 7 had progressive disease. Median time to progression and median survival were 4.6 and 8.3 months. The main toxicities were the hematologic toxicity, nausea and vomiting. Grade Ⅲ, IV leukopenia were seen in 15 patients （65.2%）, thrombocytopenia was seen in 8 patients （34.8%）; Nausea and vomiting were seen in 19 patients （82.6%）; Grade Ⅲ, IV nausea and vomiting were seen in 4 patients （65.2%） and diarrhea was seen in 20 patients （87.0%）. There were no treatment-related deaths. Conclusion： The combination of irinotecan and cisplatin is highly active and tolerable in patients with relapsed SCLC when it is administered as second-line treatment.

Studies on the relationship of objective response by chemotherapy and senescence induced in vitro for non-small cells lung cancer

Objective： To investigate the relationship between the objective response to combination chemotherapy of taxanes plus cisplatin in non-small cell lung cancer （NSCLC） and docetaxel plus cisplatin （DC regime） induced senescence of tumor cells in vitro. And its relation to mutant P53 protein （m-P53） was also to be evaluated. Methods： Sixty-seven specimen obtained from NSCLC patients from January 1, 2003 to June 30, 2006. The patients consisted of 48 males and 19 females, ranging in age from 54 to 82 years （mean, 67.5 years）, 41 cases were diagnosed as pathological stage Ⅲb, 26 cases were diagnosed as stage Ⅳ. Thirty-nine tumors were confirmed to be adenocarcinomas, 28 were confirmed to be squamous cell carcinomas. All patients accepted 2-6 cycles combination chemotherapy of Taxanes （docetaxel 40 mg/m^2, d1; d8, or paclitaxel 175 mg/m^2, d1） plus cisplatin （CDDP, 25 mg/m^2, d2-4）. Patients were divided into chemoresponsive （CR ＋ PR） and chemoresistant （SD ＋ PD） groups according to objective response status which was evaluated by RECIST system. Tumor cells from specimens of bronchoscopic, surgical biopsy and pleural effusion cell collection had been cultured and treated with DC in vitro. The m-P53 of culture supernatant was measured by ABC-ELISA kit before DC treatment. The telomerase activity was determined by the telomeric repeat amplification protocol （TRAP） based PCR-ELISA kit and apoptosis was determined by TdT-mediated d-UTP-X nick-end labeling （TUNEL） assay. Data represent as both actual detected and positive value. The senescence of tumor cells defined as that, apoptosis rate increased more than 50% to control, and telomerase activity decreased less than 50% to control. Results： There was no significant difference between clinical treatment response and sex, pathological type, specimen origin, or m-P53 status in cultured cell supernatant. Telomerase activity and apoptosis rate was positive in 61.1% （41/67） and 25.4%（17/67） of all samples respectively. A significant difference of senescence of tumor cells treated by DC, was existed between chemoresponsive and chemoresistant patients groups （P 〈 0.05）. Multinomial logistic regression analyses shew that telomerase activity decreased less than 50% in vitro may be an indicator of clinical response for taxanes plus cisplatin chemotherapy. Odds ratio was 4.226, P 〈 0.05. Conclusion： For NSCLC, DC induce lung cancer tumor cells senesce in vitro may be a promising predicator for clinical response, but the relationship between objective response by chemotherapy and detectable m-P53 or DC induced apoptosis is still obscure.