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1.
Case 1: A man in his sixties underwent extended right lobectomy of the liver for hepatic hilar cholangiocarcinoma (stage III, fCur B)in July2002. CT scans revealed cancerous pleuritis in March 2005, and he was treated with the chemotherapy of GEM alone as first-line, combined chemotherapy of S-1 and GEM as second-line, and CDDP and GEM as third-line treatment. These therapies have been effective for about 20 months. Case 2: A woman in her sixties was diagnosed with advanced gallbladder cancer(stage IVb)in September 2005. She was given combined chemotherapy of S-1+GEM as first-line, and CDDP+GEM as second-line treatment. The main tumor and metastatic lymph nodes were shrunk, allowing us to perform extended hepatectomy. Histopathologic examinations of the resected specimen of the liver involved by the tumor showed the increased infiltration of inflammatorycells and fibrosis. These patients have been managed on an outpatient basis with good QOL and cancer controlled. Although there has been no established standard regimen, the combined chemotherapy based on GEM will be a provisional standard regimen for patients with advanced biliarytract cancers.  相似文献   

2.
We analyzed a treatment outcome and the effect of systemic chemotherapy for patient with unresectable gallbladder carcinoma. Sixteen patients were investigated. Gemcitabine (GEM) was administrated for fifteen patients as the first-line chemotherapy. S-1 was administrated for ten patients as the second-line chemotherapy. The response rate and tumor control rate of the first-line GEM were 14.3% and 78.6%, respectively. The median progression free time of the first-line GEM was 6.0 months. The response rate and tumor control rate of the second-line S-1 were respectively 20.0% and 30.0%. The median progression free time of the second-line S-1 was 1.8 months. The median survival time of all cases was 14.9 months. The outcome of systemic chemotherapy for patients with unresectable gallbladder carcinoma in our hospital was feasible compared with past reports.  相似文献   

3.
BACKGROUND: We retrospectively evaluated the clinical characteristics and outcome of patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) enrolled in first-line chemotherapy trials conducted by our group with respect to receiving or not receiving subsequent treatment. PATIENTS AND METHODS: Data were collected from 634 patients with stage IIIB/IV NSCLC treated with platinum and nonplatinum agent-based first-line regimens. Patient survival was calculated from the day of registration to first-line chemotherapy trials (OS1) as well as from the day of first-line treatment failure or the initiation of second-line chemotherapy (OS2) until death. The decision for administering second-line chemotherapy was, in all cases, at the discretion of the physician. Two hundred twenty-four patients (35.3%) received second-line chemotherapy (second-line group) in the context of second-line clinical trials run by the same group, and 410 (64.7%) received best supportive care (BSC group). There were significant differences between second-line and BSC groups in terms of age, histology, early discontinuation of first-line chemotherapy, and performance status after first-line treatment. RESULTS: Three (1.3%) complete and 25 (11.2%) partial responses to second-line chemotherapy were observed for an overall response rate of 12.5% (95% confidence interval, 8.2%-16.8%). The median OS1 was 13 months and 7 months (P < 0.001) and the OS2, 7 months and 3 months (P < 0.001) for the second-line and BSC groups, respectively. Multivariate analysis revealed that good performance status, disease stage IIIB, response to first-line treatment, and late termination of first-line chemotherapy were significantly associated with increased survival. The administration of second-line chemotherapy was also independently correlated with better outcome. CONCLUSION: The second-line chemotherapy and BSC groups represent different populations of patients with NSCLC. Factors indicative of increased probability of survival could be used to identify the subgroup of patients most likely to benefit from second-line chemotherapy.  相似文献   

4.
  目的  探索免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)联合化疗一线治疗晚期胃癌中肝转移状态、中性粒细胞与淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)、体质量指数(body mass index,BMI)等因素与患者预后的关系,以及一线应用ICIs对二线化疗疗效的影响。  方法  收集解放军总医院2018年1月至2022年4月收治的胃癌患者临床资料,通过随访获得生存数据。采用Kaplan-Meier法进行生存分析,Log-rank检验比较胃癌一线程序性细胞死亡受体1(programmed cell death receptor- 1,PD-1)/程序性细胞死亡配体1(programmed cell death-ligand 1,PD-L1)抑制剂联合化疗中不同NLR、BMI和肝转移状态对预后的影响,以及一线应用PD-1/PD-L1抑制剂对二线化疗的影响。应用Cox回归模型确定影响患者生存的预后因素。  结果  共纳入晚期胃癌患者268例,在一线PD-1/PD-L1抑制剂联合化疗组中,总体客观缓解率(objective response rate,ORR)为46.5%,疾病控制率(disease control rate,DCR)为87.7%,中位无进展生存期1(median progression-free survival 1,mPFS1)为6.9(95%CI:6.0~7.8)个月。各亚组中,仅NLR<3组与NLR≥3组的中位PFS1有显著性差异(7.4 vs. 6.7个月,P=0.044)。多因素分析显示,基线NLR<3的患者在PD-1/PD-L1抑制剂联合化疗中能够获得更长的无进展生存期(HR=0.57,95%CI:0.36~0.90;P=0.015),而BMI、肝转移状态与患者预后无明显相关(均P>0.05)。二线治疗中,一线PD-1/PD-L1抑制剂联合化疗进展后仅接受化疗患者的ORR(34.6% vs. 14.6%,P=0.025)和mPFS2(4.4 vs. 2.9个月,HR=0.54,95%CI:0.35~0.82;P=0.004)优于一、二线均仅应用化疗的患者,而DCR及中位总生存期(median overall survival,mOS)比较差异无统计学意义(均P>0.05)。  结论  在一线接受PD-1/PD-L1抑制剂联合化疗的晚期胃癌中,基线NLR<3的患者更易从免疫治疗中获益,而肝转移状态、BMI与患者的预后无明显相关。另外,一线应用含免疫治疗的方案可提高胃癌患者二线化疗的疗效,使其获得更长的无进展生存期。   相似文献   

5.
BACKGROUND: Using data from a large phase III study of previously treated advanced non-small-cell lung cancer (NSCLC) that showed similar efficacy for pemetrexed and docetaxel, this retrospective analysis evaluates the impact of first-line chemotherapy on the outcome of second-line chemotherapy. PATIENTS AND METHODS: In all, 571 patients with advanced NSCLC were randomly assigned to receive pemetrexed 500 mg/m(2) or docetaxel 75 mg/m(2) on day 1 of a 21-day cycle. Comparisons were made based on type of first-line therapy [gemcitabine + platinum (GP), taxane + platinum (TP), or other therapies (OT)], response to initial therapy, time since initial therapy, and clinical characteristics. The two second-line treatment groups were pooled for this analysis due to similar efficacy and were assumed to have no interaction with the first-line therapies. RESULTS: Baseline characteristics were generally balanced. By multivariate analysis, gender, stage at diagnosis, performance status (PS), and best response to first-line therapy significantly influenced overall survival (OS). Additional factors by univariate analysis, histology, and time elapsed from first- to second-line therapy significantly influenced OS. CONCLUSIONS: Future trials in the second-line setting should stratify patients by gender, stage at diagnosis, PS, and best response to first-line therapy.  相似文献   

6.
We previously conducted a phase I/II study of irinotecan (CPT-11) combined with S-1 as first-line chemotherapy for metastatic advanced gastric cancer. In the present study,second-line chemotherapy was given to 32 of 44 patients whose disease became refractory to this first-line treatment. Overall survival time of the patients given second-line chemotherapy was significantly longer than that of patients not given such therapy (444 days vs. 230 days, p = 0.013). The response rate to second-line chemotherapy was 13% (4/32). Survival time of patients who responded to second-line chemotherapy was significantly longer than that of non-responders. Second-line chemotherapy may produce a better clinical response in patients who have progressive disease during first-line chemotherapy. Overall survival time and time to progression after second-line chemotherapy did not significantly differ between patients who received second-line chemotherapy regimens including S-1 and those who received regimens not including S-1.  相似文献   

7.
Gemcitabine hydrochloride (GEM) is a first-line therapeutic agent for advanced pancreatic cancer, but there is no established second-line treatment after GEM failure. We assessed the clinical benefit of systemic combined chemotherapy with 5-fluorouracil and cisplatin (FP therapy) in 19 patients compared with GEM in 32 patients, respectively. Tumor response rates were 10.5% and 15.6% for FP therapy and GEM, respectively. The median survival time in the FP therapy and GEM was 137 days and 241 days, respectively. Although clinical benefit was similar in both types of therapy, median survival time was more favorable for GEM, especially for Stage IVb. Nausea and vomiting were the most commonly observed toxicity in the FP therapy group. Our data indicate that FP therapy is not considered to be a useful second-line agent in patients with GEM pretreated pancreatic cancer.  相似文献   

8.
目的:评估奥沙利铂一线用于治疗晚期结直肠癌后与雷替曲塞联合再引入二线治疗的疗效及安全性。方法:收集2010年5 月至2014年12月广西中医药大学附属瑞康医院收治的48例晚期结直肠癌患者,根据一线应用奥沙利铂的情况分为两组:A 组(一线使用不含奥沙利铂方案)20例;B 组(一线使用含奥沙利铂方案)28例。二线治疗方案:雷替曲塞3 mg/m2,静脉滴注,d1;奥沙利铂100~130 mg/m2,静脉滴注,d1;每21天1 次。结果:48例均可评价疗效,两组有效率分别为30.0%(6/ 20)、32.1%(9/ 28);疾病控制率分别为80.0%(16/ 20)、75.0%(21/ 28);中位无进展生存期分别为6.5 个月、7.0 个月;中位总生存期分别为10个月、13个月;两组有效率、疾病控制率、中位无进展生存期及中位总生存期比较差异均无统计学意义(P = 0.264,0.514,0.713,0.788)。 主要不良反应为骨髓抑制、转氨酶异常和胃肠道反应,以Ⅰ~Ⅱ级为主;两组感觉神经异常Ⅰ~Ⅱ级发生率相近。结论:奥沙利铂再引入联合雷替曲塞二线化疗对曾使用过奥沙利铂一线化疗的患者仍然有效,无耐药性,安全可行,对不能接受伊立替康二线治疗的晚期结直肠癌患者是较好选择。  相似文献   

9.
Purpose We evaluated the tolerability and activity of the combination of weekly paclitaxel (PTX) and gemcitabine (GEM) in second-line treatment of advanced non-small cell lung cancer (NSCLC) after treatment with platinum-based chemotherapy. Patients and methods PTX (100 mg/m2) and GEM (1,000 mg/m2) were administered to patients with previous treated NSCLC on days 1 and 8 every 3 weeks. Results A total of 40 patients (performance status 0/1/2, 7/27/6 pts) were enrolled. The response rate was 32.5% (95% confidence interval: 18.0–47.0%). The median survival time was 41.7 weeks (95% confidence interval: 28.5–54.7 weeks). The median time to disease progression was 19 weeks. Hematological toxicities (grade 3 or 4) observed included neutropenia in 60%, anemia in 15%, and thrombocytopenia in 12.5% of patients. Non-hematological toxicities were mild, with the exception of grade 3 diarrhea, pneumonitis, and rash in one patient each. There were no deaths due to toxicity. Conclusion The combination of weekly PTX and GEM is a feasible, well-tolerated, and active means of second-line treatment of advanced NSCLC.  相似文献   

10.
Objective:To evaluate the efficacy and toxicity of docetaxel and vinorelbine as second-line chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC).Methods:48 histologically or cytologically confirmed NSCLC patients with progressive or recurrent disease after first-line treatment were treated with docetaxel and vinorelbine.The chemotherapy included vinorelbine (25 mg/m2) on days 1,5 and docetaxel (60 mg/m2) on day 1.The treatment was repeated every 3 weeks.Patients receiving at least two cycles were evaluated for efficacy and toxicity.Results:Of 48 patients,1 patient achieved complete response and 16 achieved partial response.Overall response rate for all 48 patients was 35.4% (17/48).Main hematologic toxicities included neutropenia (60.4%) and febrile neutropenia (29.2%) and non-hematologic toxicities were mild.Conclusion:The combination of docetaxel-vinorelbine as second-line chemotherapy is an effective regimen with manageable toxicity for the treatment of advanced NSCLC.Further studies may confirm these results.  相似文献   

11.
This review summarizes second-line chemotherapy for testicular cancer and urothelial cancer. For testicular cancer, the combination of bleomycin (BLM), etoposide (ETP), and cisplatin (CDDP) (BEP) is commonly used as an induction therapy. The combination of vinblastine (VLB), ifosfamide (IFM) and CDDP (VeIP) or ETP, IFM, and CDDP (VIP) is used for the second-line chemotherapy. When the efficacy of VeIP and VIP is not sufficient, high-dose chemotherapy or chemotherapy with new anticancer agents has been used for the second-line chemotherapy. High-dose chemotherapy showed long-term survival rates of 30-50%, but patients with testicular cancer resistance to CDDP have poor outcomes. Although new anticancer agents, such as paclitaxel (TXL), gemcitabine (GEM) and irinotecan have been introduced, further examinations are needed to evaluate these drugs. The combination of methotrexate, VLB, adriamycin, and CDDP (MVAC) is used as the standard chemotherapy for urothelial cancer. The outcomes of MVAC are favorable, but the duration of response is short and long-term survival cannot be expected. Recently, the efficacy of new anticancer agents including TXL and GEM against urothelial cancers has been demonstrated. Although TXL and GEM combination therapy as the second-line chemotherapy has some effects, more evidence needs to be accumulated to establish it as a second-line treatment.  相似文献   

12.
A 65-year-old man underwent distal gastrectomy for advanced gastric cancer. Histological examination revealed that a lymph node metastasis extended to the para-aortic nodes. After operation, he was treated with TS-1 as first-line chemotherapy. After 10 months of the first-line chemotherapy, the lymph node swelling increased in size, and new lesions were detected. Then, the patient was treated by combination therapy of doxifluridine and weekly paclitaxel. Weekly paclitaxel administration (PTX 80 mg/m(2), 2 consecutive weeks, 1 week break) and oral administration of doxifluridine (600 mg/m(2), 14 consecutive days) were performed as the second-line chemotherapy. After 2 courses, abdominal CT scan showed a remarkable reduction of the para-aortic lymph nodes. The second-line chemotherapy was continued until the 7th course, then stopped without progression of the disease, and the patient maintained good quality of life. PTX/5'-DFUR combination therapy was thought to be an effective chemotherapy for advanced gastric cancer.  相似文献   

13.
Todesco A  Carli M  Iacona I  Frascella E  Ninfo V  Rosolen A 《Cancer》2000,89(12):2661-2666
BACKGROUND: A boy age 14 years who was in complete remission from Stage IIB small cell osteosarcoma, which was misdiagnosed as Ewing sarcoma and consequently was treated, developed inoperable lung metastases when he was off therapy. He received second-line treatment for recurrent Ewing sarcoma, including chemotherapy and radiotherapy, and obtained only a temporary response. A compassionate treatment with all-trans retinoic acid (ATRA) and interferon-alpha (IFNalpha) was then undertaken. METHODS: The patient initially was treated according to the national SE91 protocol for nonmetastatic Ewing sarcoma. After a bilateral pulmonary recurrence, he received second-line chemotherapy and irradiation of the largest metastasis, with a temporary partial response. The patient was then treated with a combination of oral ATRA (90 mg/m(2) for 3 days per week) and subcutaneous IFNalpha (3 x 10(6) U/m(2) 5 days per week) for 4 months. The same therapy also was administered for the control of residual disease after surgery for a total duration of 1 year of ATRA/IFN treatment. During the first 3 weeks of therapy, ATRA pharmacokinetics were studied. RESULTS: After progression of the patient's disease, despite the administration of first-line and second-line chemotherapy, combined treatment with ATRA/IFNalpha yielded a partial remission, which allowed surgical resection of the largest metastasis. The same therapy was effective in preventing tumor recurrence after incomplete removal of the remaining metastases. Treatment was well tolerated, and the patient is in stable complete remission 14 months after the end of therapy. The pharmacokinetics results confirmed the indication of an intermittent schedule for oral ATRA therapy. CONCLUSIONS: ATRA/IFNalpha treatment may be considered as an alternative approach in the treatment of patients with metastatic osteosarcoma who have disease that is resistant to conventional chemotherapy and in the treatment of patients with minimal tumor residue.  相似文献   

14.
Pulmonary pleomorphic carcinoma is a rare tumor of the lung, which is believed to spread at an early stage and to have an aggressive clinical course. The efficacy of chemotherapy for advanced pulmonary pleomorphic carcinoma has not been defined. The objective of this study was to evaluate the efficacy of palliative chemotherapy for pulmonary pleomorphic carcinoma. Thirteen consecutive patients who received palliative chemotherapy for advanced pulmonary pleomorphic carcinoma were investigated. All 13 patients were treated using chemotherapy regimens known to be active for the treatment of advanced non-small cell lung cancer (NSCLC). Eleven patients (85%) had progressive disease and two (15%) had stable disease after first-line chemotherapy. No patient achieved an objective response (objective response rate, 0%; 95% confidence interval, 0-23%). Of the 13, eight were given second-line chemotherapy, and all had progressive disease after second-line chemotherapy (objective response rate, 0%; 95% CI, 0-32%). Median overall survival from the initiation of first-line palliative chemotherapy was only 5 months (range, 2-12) with a median follow-up of 16 months. Advanced pulmonary pleomorphic carcinoma showed poor response to chemotherapy regimens that provide active treatment for NSCLC. Novel treatment approaches are required for pulmonary pleomorphic carcinoma.  相似文献   

15.
Both oxaliplatin (OXA) and gemcitabine (GEM) have shown single agent activity in patients with recurrent ovarian cancer. Response rates to second-line therapies remain low and there is a need to develop more effective regimens. In view of the synergistic effect of using GEM followed by OXA, we studied these agents in elderly patients with recurrent ovarian cancer refractory or resistant to first-line chemotherapy using platinum with or without paclitaxel. The aim of the study was to evaluate the efficacy and toxicity of combination GEM 1000 mg/m(2) Day 1 i.v. and OXA 100 mg/m(2) in 2h infusion Day 2; treatment was repeated every 2 weeks for 6 courses or until progression of disease or intolerable toxicity. The study was monoinstitutional and started in November 2002. 21 patients, median age 68.6 years (range 65-82) have been treated. Median Performance Status was 0-1, all had at least 1 prior platinum based chemotherapy and 11 had received also a taxane. Patients received a median of 6 cycles of treatment (range 4-11). There were 2 patient (9%) with complete response, 3 patients (14%) achieved a partial response. Low profile toxicity (grade 1-2, WHO criteria) was observed: nausea/vomiting 52%, thrombocytopenia 13%, neuropathy 28%. The GEMOX combination is well tolerated and even in this small group of patients, encouraging responses were documented.  相似文献   

16.
Abstract

Both oxaliplatin (OXA) and gemcitabine (GEM) have shown single agent activity in patients with recurrent ovarian cancer. Response rates to second-line therapies remain low and there is a need to develop more effective regimens. In view of the synergistic effect of using GEM followed by OXA, we studied these agents in elderly patients with recurrent ovarian cancer refractory or resistant to first-line chemotherapy using platinum with or without paclitaxel. The aim of the study was to evaluate the efficacy and toxicity of combination GEM 1000 mg/m2 Day 1 i.v. and OXA 100 mg/m2 in 2h infusion Day 2; treatment was repeated every 2 weeks for 6 courses or until progression of disease or intolerable toxicity. The study was monoinstitutional and started in November 2002. 21 patients, median age 68.6 years (range 65-82) have been treated. Median Performance Status was 0-1, all had at least 1 prior platinum based chemotherapy and 11 had received also a taxane. Patients received a median of 6 cycles of treatment (range 4-11). There were 2 patient (9%) with complete response, 3 patients (14%) achieved a partial response. Low profile toxicity (grade 1-2, WHO criteria) was observed: nausea/vomiting 52%, thrombocytopenia 13%, neuropathy 28%. The GEMOX combination is well tolerated and even in this small group of patients, encouraging responses were documented.  相似文献   

17.

Background

The objective of this study was to evaluate the efficacy of a gemcitabine and docetaxel (GD) combination as a second-line treatment for patients with metastatic urothelial carcinoma (UC) after failure of first-line treatment with platinum-based chemotherapy.

Methods

From June 2006 to January 2012, 38 patients with metastatic UC previously treated with platinum-based chemotherapy received GD therapy. This consisted of gemcitabine 800 mg/m2 and docetaxel 40 mg/m2 on days 1 and 8 of each 21-day cycle as second-line chemotherapy. All the patients were evaluated for toxicity and assessed every cycle by imaging. We analyzed the efficacy of GD as second-line chemotherapy in the follow-up study.

Results

The median number of GD treatment cycles was 4 (range 2–9); the objective response rate was 47.4 %; and the median progression-free survival and median overall survival were 4.1 and 10.8 months, respectively. Univariate and multivariate analyses on the GD treated group showed that the existence of lung metastases was the only prognostic factor for tumor response. Grade 3 treatment-related toxicity included neutropenia (31.6 %) and thrombocytopenia (15.8 %), and only one patient with grade 4 toxicity had thrombocytopenia (2.6 %).

Conclusions

The GD regimen as second-line chemotherapy was especially effective for lung metastatic UC and yielded favorable results in patients whose first-line platinum-based chemotherapy had failed. Given the safety and benefit profile seen in this study, a large prospective study is warranted to consider the potential utility of GD chemotherapy as a second-line for UC.  相似文献   

18.
Stahl M  Müller C  Köster W  Wilke H 《Onkologie》2005,28(10):499-502
BACKGROUND: The role of second-line chemotherapy in gastric cancer is not yet established. We analyzed patients receiving second-line treatment after chemotherapy with cisplatin, infusional 5-fluorouracil, folinic acid (PLF). PATIENTS AND METHODS: 27 patients took part in this retrospective analysis. The second-line chemotherapy consisted of different regimens depending on the recommendations of the attending physician based on response to and toxicity of first-line treatment. RESULTS: In 3 of 27 patients, partial response was achieved (11%, 95%-confidence interval 0-23%). The progression-free survival and overall survival was 3.1 (2.1-4.3) and 5.1 (3.8-6.6) months, respectively. Progression-free intervals (PFI) of more than 7 months after first-line therapy were a predictor for patients who may benefit from the treatment (median survival from the start of second-line therapy: 10.6 (6.6-13.1) months). CONCLUSION: Second-line chemotherapy after cisplatin / 5-FU rarely induced tumor response, and progression-free survival as well as overall survival remained short. Based on our data, we hypothesize that the PFI after first-line treatment may be a selection criterion for patients suitable for second-line chemotherapy.  相似文献   

19.
Efficacy of third-line chemotherapy treatment for small cell lung cancer (SCLC) is unknown. We present our experience with third-line chemotherapy for recurrent SCLC. Between January 1996 and July 2004 all consecutive patients treated for SCLC were retrospectively studied. We recorded patient characteristics, treatment details for each subsequent regimen, response to chemotherapy and survival. From 191 patients treated with chemotherapy 35 patients (18%) received third-line chemotherapy. At the start of third-line therapy, median age was 58 years (range 36-77), male/female 54%/46%, and ECOG performance score was 0/1/2/3 in 15%/64%/12%/9% of patients. Median time from diagnosis till start of third-line treatment was 15 months (range 5-34). Tumor response to first-line, second-line, and third-line therapy was 91%, 51%, and 26%, respectively. Median survival time estimated from the start of third-line treatment was 5 months (range 1-15). No toxic deaths were observed. Comparison of characteristics of patients who were treated with third-line chemotherapy with patients treated with maximally two lines of chemotherapy revealed that those who received third-line therapy were younger (p<0.001), had a better performance score (p<0.001), and had a better response to first-line treatment (p=0.004). In conclusion, third-line chemotherapy is still active in one in four SCLC patients.  相似文献   

20.
A 73-year-old woman with carcinoma of the pancreatic head underwent Whipple?s operation and intraoperative radiation therapy(20 Gy). After surgery, adjuvant chemotherapy with gemcitabine hydrochloride(GEM 1,000 mg every two weeks)was conducted. After 15 courses, the tumor marker CA19-9 gradually increased to 3,770 U/mL, and a supraclavicular lymph node metastasis(Virchow?s node)was detected. We selected the combination of GEM and nedaplatin(1,000 mg and 50 mg every two weeks, respectively)as salvage chemotherapy. After six courses of this nedaplatin/GEM combination, her CA19-9 level was markedly reduced to 657 U/mL and the lymph node metastasis disappeared. There were no adverse reactions. Combined nedaplatin/GEM therapy was continued for nine months(18 courses)until lung metastases occurred. This combination can be effective in some patients with GEM-refractory pancreatic cancer.  相似文献   

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