选择性动脉灌注化疗联合靶向药物治疗非小细胞肺癌多发脑转移

背景与目的 本研究旨在回顾性分析选择性动脉灌注化疗联合赖氨酸激酶抑制剂( tyrosine kinase inhibitor,TKI)药物治疗非小细胞肺癌(non-small cell lung cancer,NSCLC)多发脑转移的临床疗效及预后相关因素.方法 自2008年9月-2011年10月共入组31例诊断明确的非小细胞肺癌经CT或MRI证实多发脑转移瘤(＞3个)的患者,行选择性颅内动脉、支气管动脉及相关靶动脉化疗药物灌注化疗2个-6个周期,每周期间隔4周,同步或后续联合厄洛替尼、吉非替尼或埃克替尼治疗.介入治疗2个周期或联合靶向治疗后每4周应用CT和MRI对肿瘤进行疗效评价,直至肿瘤进展或发生不可耐受性化疗药物不良反应.结果 31例患者平均行3个周期介入治疗,随访时间4个-40.9个月,完全缓解5例(16.1％),部分缓解7例(22.6％),疾病稳定11例(35.5％),疾病进展8例(25.8％).客观缓解率( objective response rate,ORR)为38.7％,疾病控制率(disease control rate,DCR)为74.2％.中位无进展生存期(progression free survival,PFS)为13.1个月,中位总生存期(overall survival,OS)为15.1个月.6个月的生存率为79％,1年生存率为61.1％,2年生存率为31.1％.分层分析显示PFS、OS与吸烟状态、病理类型、颅外转移情况、靶向药物应用时间、PS评分具有相关性;与性别、年龄、既往治疗情况、脑转移数目无明显相关.结论 选择性动脉灌注化疗联合靶向药物是治疗非小细胞肺癌多发脑转移安全有效的方法之一,吸烟状态、PS评分、肿瘤病理类型、颅外转移状况、靶向药物应用时间均可影响患者预后.     

Front-line chemotherapy with cisplatin and etoposide for patients with brain metastases from breast carcinoma, nonsmall cell lung carcinoma, or malignant melanoma: a prospective study

BACKGROUND: The conventional treatment of brain metastases not amenable to surgery is most often radiotherapy. Until now, pharmacologic issues related to the blood brain barrier (BBB) prevented a wide evaluation of chemotherapy. The authors previously reported that the combination of cisplatin (P) and etoposide (E) had strikingly high activity in patients with brain metastases from breast carcinoma. The purpose of this study was to assess, in a larger prospective study, the front-line activity of that combination against brain metastases from breast carcinoma (BC), nonsmall cell lung carcinoma (NSCLC), and malignant melanoma (MM) in patients previously untreated with radiotherapy. METHODS: From December 1986 to July 1993, 116 patients received P 100 mg/m2 on Day 1 and E 100 mg/m2 on Days 1, 3, and 5 or on Days 4, 6, and 8 every 3 weeks. An insignificant change in the E schedule using the same dose on a random basis assured the prospective enrollment and the registration of all cases. Six patients were not eligible and three patients were excluded from the analysis because they were lost to follow-up shortly after the date of registration. One-hundred seven patients were considered for analysis. The distribution according to the primary tumor site was BC in 56 patients (52%), NSCLC in 43 (40%), and MM in 8 (8%). The first evaluation of response was performed after two cycles. In cases of no disease progression, chemotherapy was continued to a maximum of six cycles. RESULTS: Among the 56 patients with BC, 7 achieved complete response (CR) (13%), 14 achieved partial response (PR), 12 had no change (NC), 15 had progressive disease (PD), and 8 had insufficient treatment or response was not assessed. The CR plus rate was 38%. Among the 43 patients with NSCLC, 3 achieved CR (7%), 10 achieved PR, 15 had SD, 7 had PD, and 8 had insufficient treatment or response was not assessed. The CR plus PR rate was 30%. None of the eight patients with MM achieved an objective response. The median survival was 31 weeks for patients with BC (range, 0-287), 32 for patients with NSCLC (0-392+), and 17 for patients with MM (2-48). CONCLUSIONS: The combination of P and E is effective for patients with brain metastases from BC and NSCLC. In this study, the response rate was of the same order as that reported for disseminated disease without central nervous system involvement. The survival figures compare favorably with some others reported in the literature for patients given radiotherapy. A randomized study is warranted to compare this chemotherapy followed by radiotherapy with radiotherapy alone for patients with brain metastases from BC or NSCLC not amenable to surgery or radiosurgery.     

Gefitinib is active in patients with brain metastases from non-small cell lung cancer and response is related to skin toxicity

Gefitinib is active and well tolerated in patients with advanced non-small cell lung cancer (NSCLC); however, its role in patients with brain metastases has not been clearly defined. We had conducted a prospective study to give gefitinib to NSCLC patients irrespective of their performance status (PS), number of prior treatment regimens and the presence of brain metastases. A total of 76 patients were enrolled. Fifty-seven patients had measurable lesions and the objective response rate was 33.3% (95% confidence interval [95% CI], 20.7-46.0%). For all enrolled patients, the disease control rate was 63.2% (95% CI, 52.1-74.3%) with a median progression-free survival of 5.0 months (95% CI, 3.6-6.5 months) and median overall survival 9.9 months (95% CI, 4.9-14.8 months). Twenty-one patients had simultaneously assessable intracranial lesions (ICLs) and extracranial lesions (ECLs), 17 of them (81.0%) showed comparable tumor response. There was no survival difference between the patients with and without metastatic brain disease. Most drug-related adverse events were mild. Intolerable toxicities happened in five patients, four of them were interstitial pneumonia (5.8%). Severity of skin toxicity was tightly associated with tumor response and patient survival (P = 0.007 and <0.001) and the association was consistent in the analysis using early toxicity profile (P = 0.033 and 0.001). In conclusion, gefitinib is active in patients with brain metastasis from NSCLC and tumor response is related to skin toxicity. It is feasible to conduct randomized trials to identify the role of gefitinib alone or in combination with other modality for treatment of NSCLC patients who have metastatic brain lesion(s).     

Efficacy of platinum-based chemotherapy after cranial radiation in patients with brain metastasis from non-small cell lung cancer

This study was conducted to assess the efficacy of systemic chemotherapy in patients with brain metastasis from non-small cell lung cancer. Sixty-three consecutive patients who were diagnosed as having non-small cell lung cancer (NSCLC) with synchronous brain metastasis (BM) and had not been previously treated were included in this study. After cranial radiation therapy (RT), all patients in 'the chemotherapy arm' (CTX) were treated with platinum-based combination chemotherapy, and best supportive care was selected for patients in 'the no-chemotherapy arm' (no-CTX). Thirty-one of the 63 patients received systemic chemotherapy. The median age of all patients was 55 years. The performance status of all patients was ECOG grade 1-2. Twenty-two patients had a solitary brain metastasis, 37 patients had more than two masses, and 38 patients had extracranial metastatic lesions. In the CTX arm, a paclitaxel-based combination chemotherapy was administered in 38.7%, gemcitabine-based in 25.8%, and vinorelbine-based in 25.8% as the first-line chemotherapy. Seventeen patients were treated with a second-line chemotherapy, and paclitaxel plus gemcitabine was used in 8 patients. For the first-line and second-line chemotherapies, extracranial overall responses were 36 and 35%, the median response durations were 29.1 weeks (range: 9.1-58.1 weeks) and 30.4 weeks (range: 19.4-44.0 weeks), respectively. 'Progression of the extracranial lesion' (58.1%) was more frequent than an 'aggravation of neurologic status' (19.4%) for the pattern of treatment failure in the first-line chemotherapy. The causes of failure were identical in the second-line chemotherapy. The median survival of the CTX arm was longer than that of the no-CTX arm (58.1 vs. 19.0 weeks, p<0.001). Toxicity in the CTX arm was tolerable. The systemic chemotherapy showed an effectiveness to increase the survival of patients with BM from NSCLC, and extracranial progression was the main cause of chemotherapeutic failure, although consideration for non-randomized methods should be made in this study.     

Gefitinib in patients with brain metastases from non-small-cell lung cancer: review of 15 clinical cases

The clinical efficacy of gefitinib, a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), on brain metastases (BMs) from non-small-cell lung cancer (NSCLC) was evaluated. Fifteen patients with recurrent NSCLC with metastasis to the brain were treated with gefitinib. The objective tumor response rate (60%; 9 of 15 patients) for BM was the same as for primary tumors. The median time to response of BM was 26 days. In 8 of 9 patients who exhibited partial response in the thoracic lesion, BM showed dramatic regression, including 1 complete response. One patient with stable primary tumor also exhibited partial response in BM with this monotherapy. Brain metastasis-related neurologic symptoms such as hemiparesis, dysarthria, dysphagia, and vertigo improved or disappeared with the objective response of BM as confirmed by magnetic resonance imaging. Central nervous system toxicities were not observed during the treatment. Four of the 9 BM responders are still under treatment with neither adverse events nor disease progression. Two discontinued the treatment because of severe hepatic toxicity and 3 died because of acquired resistance in pulmonary lesions, even though partial response was observed in the BMs. Finally, median duration of response of BM was 8.7 months and median overall survival was 8.3 months (range, 1.8 to > 15.7 months). Molecular targeted therapy against EGFR could be an option for the treatment of BM from NSCLC refractory to conventional chemotherapy plus radiation therapy because it has demonstrated a distinct therapeutic potential against BM compared with primary lung tumor and extracranial metastases.     

Chemotherapy induces regression of brain metastases in breast carcinoma

This study improves treatment options and ultimately survival by using systemic chemotherapy in brain metastases from breast carcinoma, since most of these patients have disseminated disease and a dismal prognosis when treated by conventional brain irradiation alone. One hundred consecutive patients with symptomatic brain metastases documented by radionuclide and/or computerized tomography scan were treated with systemic chemotherapy. Fifty of 100 patients demonstrated an objective response of brain metastases which was similar for extracranial metastases. There were 10 complete responders (CR), 40 partial responders (PR), 9 stable, and 41 nonresponders. Median duration of remission was 10+ months for CR and 7 months for PR (range, 2-72 months). Primary chemotherapy of brain metastases yielded responses in 27 of 52 patients (52%) treated with Cytoxan (cyclophosphamide) (C), 5-fluorouracil (F) and prednisone (P); 19 of 35 (54%) receiving CFP-methotrexate (M) and vincristine (V); 3 of 7 (43%) treated with MVP, and 1 of 6 (17%) receiving Cytoxan plus Adriamycin (doxorubicin) (CA). Thirteen of 35 patients (37%) who subsequently had relapse of brain metastases were retreated successfully with secondary chemotherapy. The median survival for CR and PR was 39.5 months and 10.5 months, respectively, in contrast with nonresponder patients who had a median survival of 1.5 months. Thirty-one percent of all treated patients survived more than 12 months. These findings suggest that the chemotherapeutic agents used penetrate the blood-brain barrier inducing regression of brain metastases. This approach offers a significant benefit by simultaneously controlling extracranial disease, improving the response and prolonging survival.     

Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain metastases from solid tumors: a Hellenic Cooperative Oncology Group (HeCOG) Phase II study

PURPOSE: To evaluate the efficacy of temozolomide (TMZ) combined with cisplatin (CDDP) in terms of response rate, time to progression (TTP) and overall survival (OS), as well as the tolerability of the regimen in patients with brain metastases from solid tumors. PATIENTS AND METHODS: Patients (n=32) with brain metastases were treated with TMZ 150 mg/m2/day (chemotherapy-pretreated) or 200 mg/m2/day (chemotherapy-naive) for 5 days, combined with CDDP 75 mg/m2 on day 1, every 28 days. Primary tumor sites included breast cancer (n=15), lung cancer (n=12) and other (n=5). Twenty-seven patients had received prior chemotherapy for extracranial disease and 17 had prior radiotherapy to the brain. RESULTS: One patient (3.1%) with non-small cell lung cancer (NSCLC) achieved complete response. Nine patients (28.1%; six with breast cancer, two with melanoma and one with NSCLC) achieved a partial response and five patients (16%) had stable disease. Median OS was 5.5 months and median TTP 2.9 months. One patient died from septicemia/neutropenic fever. Grade III-IV toxicities included anemia (9%), leukopenia (6%), thrombocytopenia (3%), renal toxicity (3%), headache (3%), fatigue (3%), nausea (3%), vomiting (3%), and alopecia (6%). CONCLUSIONS: TMZ combined with CDDP is an active and well-tolerated combination in patients with brain metastases from solid tumors.     

紫杉醇与顺铂联合治疗晚期非小细胞肺癌疗效观察(附52例临床报告)

目的：观察及评价紫杉醇联合顺铂化疗非小细胞肺癌的疗效和不良反应。方法：52例初治晚期非小细胞肺癌患者应用紫杉醇135mg/m^2,iv,dl;顺铂30mg/m^2,iv,dl,2,3。每21天一周期,2－3周一疗程。应用抗过敏药物预防紫杉醇的不良反应,还原型谷胱甘肽加小剂量水化预防顺铂引起的肾毒性。结果：完全缓解（CR）4例,部分缓解（PR）15例,稳定（NC）22例,进展（PD）11例,总有效率36．5％;中位生存时间38周,1年生存率43％。结论：紫杉醇与顺铂联合为治疗晚期非小细胞肺癌疗效较佳的方案,抗过敏药物及还原型谷胱甘肽可有效预防该方案的不良反应。     

Prognostic factors to predict survival in non-small-cell lung cancer with brain metastasis

Objective： The purpose of the study was to assess prognostic factors to predict overall survival （OS） and progres- sion-free survival （PFS） in non-small-cell lung cancer （NSCLC） with brain metastasis （BM）. Methods： From November 2011 to March 2013, the clinical data of 31 NSCLC cases with BM treated with multiple modalities including brain radiotherapy alone, systemic chemotherapy, whole brain radiotherapy （WBRT） combined with tyrosine kinase inhibitor （TKIs）. The efficacy and adverse reaction were evaluated after treatment. Results： In terms of intracranial lesions, the objective response rate （ORR） and the disease control rate （DCR） were 22.6% and 90.3%, respectively. As for systemic disease, ORR and DCR were 32.3% and 93.5%, respectively. The median time to progression-free survival （PFS） was 298 days （95% CI： 258.624-337.376 days）, whereas in the epidermal growth factor receptor （EGFR） mutation patients was 331 days. Patients who received EGFR-TKIs combined with brain radiation had better response rate （RR） than those only brain radiation. Univariate analysis showed that the EGFR-mutations could predictive factors for PFS, and not to other clinical pathological features. The most common toxicities were rash and diarrhea, but all were well-tolerated. Conclusion： EGFR-mutations is the independent prognostic factors affecting the survival rates of NSCLC patients with BM. Through the clinical observation, icotinib combined with WBRT may be effective on brain metastases in NSCLC patients, and toxicities are tolerable, which worth further study.     

Outcomes With Pembrolizumab Plus Platinum-Based Chemotherapy for Patients With NSCLC and Stable Brain Metastases: Pooled Analysis of KEYNOTE-021, -189, and -407

IntroductionThis exploratory analysis retrospectively evaluated outcomes in patients with advanced NSCLC to determine whether baseline brain metastases influenced the efficacy of first-line pembrolizumab plus chemotherapy versus chemotherapy alone.MethodsWe pooled data for patients with advanced NSCLC in KEYNOTE-021 cohort G (nonsquamous), KEYNOTE-189 (nonsquamous), and KEYNOTE-407 (squamous). Patients were assigned to platinum-doublet chemotherapy with or without the addition of 35 cycles of pembrolizumab 200 mg every 3 weeks. All studies permitted enrollment of patients with previously treated or untreated (KEYNOTE-189 and KEYNOTE-407 only) stable brain metastases. Patients with previously treated brain metastases were clinically stable for 2 or more weeks (≥4 wk in KEYNOTE-021 cohort G), had no evidence of new or enlarging brain metastases, and had no steroid use at least 3 days before dosing. Patients with known untreated asymptomatic brain metastases required regular imaging of the brain.ResultsA total of 1298 patients were included, 171 with and 1127 without baseline brain metastases. Median (range) durations of follow-up at data cutoff were 10.9 (0.1‒35.1) and 11.0 (0.1‒34.9) months, respectively. Hazard ratios (pembrolizumab + chemotherapy/chemotherapy) were similar for patients with and without brain metastases for overall survival (0.48 [95% confidence interval (CI): 0.32‒0.70] and 0.63 [95% CI: 0.53‒0.75], respectively) and progression-free survival (0.44 [95% CI: 0.31‒0.62] and 0.55 [95% CI: 0.48‒0.63], respectively). In patients with brain metastases, median overall survival was 18.8 months with pembrolizumab plus chemotherapy and 7.6 months with chemotherapy, and median progression-free survival was 6.9 months and 4.1 months, respectively. Objective response rates were higher and duration of response longer with pembrolizumab plus chemotherapy versus chemotherapy regardless of brain metastasis status. Incidences of treatment-related adverse events with pembrolizumab plus chemotherapy versus chemotherapy were 88.2% versus 82.8% among patients with brain metastases and 94.5% versus 90.6% in those without.ConclusionsWith or without brain metastasis, pembrolizumab plus platinum-based histology-specific chemotherapy improved clinical outcomes versus chemotherapy alone across all programmed death ligand 1 subgroups, including patients with programmed death ligand 1 tumor proportion score less than 1% and had a manageable safety profile in patients with advanced NSCLC. This regimen is a standard-of-care treatment option for treatment-naive patients with advanced NSCLC, including patients with stable brain metastases.     

吉非替尼(Gefitinib)对非小细胞肺癌的脑部转移具有疗效

目的 比较分析吉非替尼对不同体能表现、既往不同化疗次数、有或无脑部转移病灶的非小细胞肺癌患者的治疗结果。方法 总共有76例患者参加试验。结果 患者的疾病控制率为63．2％(95％CI为52．1％～74．3％)．无疾病恶化牛存期的中位数为5．0个月(95％CI为3．5～6．6个月)，整体生存期的中位数为9．9个月(95％CI为4．9～14．8个月)。其中具有可测量病灶的57例患者的客观反应率为33．3％(95％CI为20．7％～46．0％)。76例患者中有21例患者同时具有可评估的颅内及颅外病灶，其中17例(81．0％)对吉非替尼有相同的颅内及颅外肿瘤反应．而出现脑部转移并不影响患者的生存期。药物引起的副作用大部分是中等反应．仅5例患者发生不可耐受的毒性，其中1例(5．8％)为间质性肺炎。结论 吉非替尼对非小细胞肺癌的脑部转移有疗效．值得进一步没计随机临床试验观察单剂吉非替尼治疗或加上其它形式的治疗在脑部转移的非小细胞肺癌患者中所扮演的角色。     

全身化疗同步或序贯脑放疗治疗非小细胞肺癌脑转移患者的疗效与毒副反应

目的 探讨全身化疗同步脑放疗或序贯脑放疗治疗非小细胞肺癌(NSCLC)脑转移患者的疗效和毒副反应.方法 采用前瞻对照方法,将60例NSCLC脑转移患者分为全身化疗同步脑放疗组(同步组)和全身化疗序贯脑放疗组(序贯组),每组各30例.结果 共59例患者完成治疗,总体客观缓解率(ORR)为22.0%,脑转移灶的ORR为35.6%,中位无进展生存期(PFS)为3个月,中位生存期(MST)为16个月,1年和2年总生存率分别为55.0%和24.4%.同步组和序贯组的总体ORR分别为20.0%和24.1%,脑转移灶的ORR分别为43.3%和27.6%,中位PFS分别为3和4个月,MST分别为16和13个月,差异均无统计学意义(均P>0.05).同步组和序贯组的1年生存率分别为58.5%和52.9%(P=0.365),2年生存率分别为37.2%和18.9%,同步组明显优于序贯组(P=0.011).同步组白细胞减少的发生率低于序贯组,差异有统计学意义(P=0.029);其他毒副反应的发生率差异无统计学意义(P>0.05).结论 全身化疗同步脑放疗治疗NSCLC脑转移可以取得较好疗效,且患者耐受性良好.

Abstract：

Objective To evaluate the efficacy, survival and toxicity in patients with brain metastases from non-small cell lung cancer ( NSCLC), treated with concurrent systemic chemotherapy and whole brain radiation therapy (WBRT) or sequential systemic chemotherapy/WBRT.Methods A total of 60 NSCLC patients with brain metastases were divided into two groups in this prospective clinical study:concurrent systemic chemotherapy and WBRT group (concurrent group ) and sequential systemic chemotherapy/WBRT group (sequential group).Results Of 59 assessable patients, the overall response rate was 22.0%, and the brain response rate was 35.6%;the median progression-free survival time was 3.0 months, and the overall 1- and 2-year survival rates were 55% and 24.4%, respectively, with a median survival time of 16.0 months.The overall response rate was 20.0% in the concurrent group and 24.1% in sequential group (P > 0.05 ).The brain response rates of 43.3% in concurrent group and 27.6% in sequential group were also not significantly different (P > 0.05 ).The median progression-free survival time for the patients in the concurrent group was 3.0 months versus 4.0 months in the sequential group, and the median survival time was 16.0 months versus 13.0 months ( all P >0.05 ).The 1- and 2-year survival rates were 58.5% and 37.2% versus 52.9% and 18.9%, respectively, with a significant difference in the 2-year survival rate between the two groups ( P = 0.011 ).In the sequential group, leukopenia was more frequent during chemotherapy than that in the concurrent group ( P = 0.029).Conclusion Concurrent systemic chemotherapy and WBRT is effective with tolerable adverse events in treating brain metastasis from NSCLC with an encouraging survival, and deserves further large sample and randomized multicenter clinical trials.     

COAPC方案联合脑部放射治疗非小细胞肺癌脑转移

背景与目的：放射治疗具有治疗脑转移癌的主要手段。而到目前为止化疗与放疗联合治疗脑转移癌的研究较少,本研究旨在观察COAPC方案化疗与脑部放射同时治疗非小细胞肺癌（non-small cell lung cancer,NSCLC)脑转移患者疗效,不良反应及生存率。方法：45例NSCLC脑转移患者接受COAPC方案化疗,环磷酰胺0．3g/m^2第1天静推,长春新碱1．4mg/m^2第1天静推,阿霉素50mg/m^2第1天静推,顺铂20mg/m^2第1－5天静滴,司莫司汀80mg/m2第1天口服,每3－4周为1疗程,脑部放射治疗于化疗第1疗程的第6天开始,每次2Gy,每天1次,每周5天,脑转移灶1－3个者,全脑放疗40Gy后,缩野放疗至总量60Gy,脑转移灶＞3个者,全脑放疗至总量40Gy.结果：治疗后80％患者神经系统症状改善,对脑转移灶的客观有效率为64．4％,对肺原发灶的有效率为40％,治疗的主要不良反应为骨髓抑制(Ⅲ-Ⅳ度占35％）,中位生存期10个月,1年生存率44．1％,5年生存率6．7％,单纯脑转移患者的中位生存期14个月,高于多发远处转移患者的9个月（P＝0．012）。结论：化疗联合脑部放射治疗NSCLC脑转移患者有效率与生存率较高,且患者耐受性较好。     

Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial.

BACKGROUND: Brain metastases are a common occurrence in patients with non-small-cell lung cancer (NSCLC). Whole-brain radiotherapy (WBRT) is the standard therapy; more aggressive approaches such as surgery or radiosurgery are indicated in a subset of patients only. The role of systemic treatments remains controversial. Gefitinib is an oral, highly tolerable, specific inhibitor of epidermal growth factor receptor-associated tyrosine kinase, which has shown activity in chemotherapy pre-treated NSCLC. The aim of this study was to evaluate the activity and safety of gefitinib in NSCLC patients with brain metastases. PATIENTS AND METHODS: From January 2001 to May 2003, 41 consecutive NSCLC patients with measurable brain metastases were treated with gefitinib, given orally at daily dose of 250 mg. Thirty-seven patients had received previous chemotherapy and 18 patients had been treated previously with WBRT, completed at least 3 months before entering the trial. RESULTS: A partial response (PR) was observed in four patients (10%), with stable disease (SD) in seven cases, for an overall disease control (DC) rate (DC=PR+SD) of 27% (95% confidence interval 13% to 40%). Median duration of PR was 13.5 months. Median progression-free survival (PFS) of the whole population was 3 months. DC rate was higher in patients pre-treated with WBRT (P=0.05) and with adenocarcinoma histological type (P=0.08); adenocarcinoma patients had also a longer PFS (P=0.04). Toxicity was mild and consisted of grade 1/2 skin toxicity and diarrhoea, occurring in 24% and 10% of patients, respectively. CONCLUSIONS: Gefitinib can be active on brain disease in NSCLC patients. Since the results of standard therapy for brain metastases in this clinical setting are particularly disappointing, gefitinib appears to be a possible new treatment option.     

Outcomes of home anti-cancer chemotherapy--estimation of hepatic arterial infusion chemotherapy for patients with multiple liver metastases

A total of 18 patients (13: colon cancer, 5: gastric cancer) with multiple liver metastases (H3) underwent hepatic arterial infusion chemotherapy (HAI) using an implanted arterial port with portable syringe pumps in our outpatient clinic. Clinical perspective: overall response rate was 22.2% (CR: 1 case, PR: 3 cases (1 case: hepatectomy after HAI), NC: 12 cases, PD: 2 cases), however, 7 of 12 cases of NC were long NC (more than 6 months). No major complications with HAI were experienced. Patient Perspective: After HAI in our outpatient clinic, the 50% survival was 341 days, 50% hospital free days were 319 days and home stay rate was 92.9%. Societal Perspective: cost and hospital stay days were significantly reduced. Home anti-cancer chemotherapy using HAI for gastrointestinal cancer patients with multiple liver metastases was safe and efficient from the viewpoint of medical outcomes.     

吉西他滨加奥沙利铂治疗老年晚期非小细胞肺癌的临床观察

目的:观察吉西他滨加奥沙利铂治疗老年非小细胞肺癌的近期疗效和毒性反应。方法:吉西他滨1000mg/m2,静脉滴注,第1、8天;奥沙利铂130mg/m2,静脉滴注,第1天,21天为一个周期。结果:全组35例共化疗92个周期。CR 2.9%(1/35)、PR 40%(14/35)、NC 25.7%(9/35)、PD 31.4%(11/35),有效率CR PR42.9%(15/35),临床受益率CR PR NC 68.6%(24/35)。中位缓解期6.5个月。主要毒副反应为骨髓抑制,Ⅲ级~Ⅳ级白细胞减少14.3%(5/35),Ⅲ级~Ⅳ级血小板减少11.4%(4/35)。神经毒性发生率71.4%,均为轻度。结论:吉西他滨加奥沙利铂对老年晚期非小细胞肺癌有效率较高,临床受益率大,毒性反应可耐受。     

紫杉醇、卡铂方案与异环磷酰胺、鬼臼乙叉甙、卡铂方案治疗晚期非小细胞肺癌的比较

背景及目的:以铂类为基础的联合化疗已证实对晚期非小细胞肺癌(non-smallcelllungcancer,NSCLC)患者有益。含卡铂的联合化疗方案与含顺铂者相比,前者虽然有效率稍低,但生存期较长、毒性较低。对于姑息治疗而言,较低的毒性及较长的生存期比有效率更有意义,因此我们选择了以卡铂为基础的联合化疗方案犤紫杉醇、卡铂(PC)与异环磷酰胺、鬼臼乙叉甙、卡铂(IEC)犦治疗晚期NSCLC,并比较这两种方案的疗效和毒性。方法:68例晚期NSCLC患者分别接受PC与IEC化疗,PC方案35例,IEC方案33例。两组病人特征具有可比性(P>0.05)。结果:PC组PR14例,NC19例,PD2例,有效率为40.0%(14/35,95%可信区间犤CI犦:23.8%-56.2%),中位生存期9.1个月(95%CI:7.2-11.0个月),1年生存率为25.7%(95%CI:11.2%-40.2%);IEC组PR7例,NC24例,PD2例,有效率为21.2%(7/33,95%CI:7.3%-35.1%),中位生存期7.8个月(95%CI:6.2-9.4个月),1年生存率为20.0%(95%CI:6.0%-34.0%)。PC组的有效率、中位生存期及1年生存率均优于IEC组,但均无统计学差异(有效率:P=0.094,χ2检验;生存期P=0.684,Log-rank检验)。PC组血液学毒性较IEC组低,其中两组白细胞减少(P<0.0005,秩和检验)及血红蛋白减少(P=0.006,秩和检验)差异有统计学意义;血尿及药物热IEC组较高,过敏反应则PC组较     

Front-line paclitaxel/cisplatin-based chemotherapy in brain metastases from non-small-cell lung cancer

OBJECTIVE: Paclitaxel-cisplatin is considered to be a standard therapy for metastatic non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the activity and toxicity of this combination with vinorelbine or gemcitabine as front-line therapy in brain metastases from NSCLC. METHODS: Twenty-six chemotherapy-naive patients with an ECOG performance status of 0-2 were treated with paclitaxel (135 mg/m(2)) on day 1, cisplatin (120 mg/m(2)) on day 1, and either vinorelbine (30 mg/m(2)) on days 1 and 15 or gemcitabine (800 mg/m(2)) on days 1 and 8. Whole-brain irradiation was offered early in case of progression and later as consolidation treatment. RESULTS: All patients were evaluated for toxicity and 25 for response. An intracranial response rate was observed in 38% of the patients (95% CI: 22-59%). WHO grade 3-4 neutropenia and thrombocytopenia occurred in 31 and 4% of the patients, respectively. There was one treatment-related death. Non-hematological toxicities were mild. After a median follow-up of 46 months, the median overall survival for all patients was 21.4 weeks and the median time to progression was 12.8 weeks. CONCLUSIONS: Paclitaxel and cisplatin combined with vinorelbine or gemcitabine as front-line therapy in brain metastases seem to achieve responses similar to those for extracranial disease, suggesting a meaningful role in this setting.     

厄洛替尼治疗非小细胞肺癌脑转移的回顾性分析

背景与目的:非小细胞肺癌(non-small-cell lung cancer,NSCLC)脑转移预后差,缺乏有效的治疗方法。厄洛替尼是小分子EGFR酪氨酸激酶抑制剂,广泛应用于晚期NSCLC患者,可延长患者的中位无进展生存及总生存期,经选择患者获益更为明显。目前厄洛替尼也逐渐用于NSCLC脑转移的治疗。本文通过分析厄洛替尼治疗NSCLC脑转移的疗效及安全性,探讨NSCLC脑转移的靶向治疗。方法:回顾性分析中山大学肿瘤防治中心2006年至2011年间收治的53例NSCLC脑转移患者的临床资料。所有患者均口服厄洛替尼150mg/d直至疾病进展、死亡或不良反应不可耐受,每2～3月评估疗效。结果:53例患者均可评价疗效。厄洛替尼对脑转移灶客观缓解率和疾病控制率分别为35.8%和81.1%,其中完全缓解(complete response,CR)3例,部分缓解(partialresponse,PR)16例,稳定(stable disease,SD)24例。全身病灶的客观缓解率和疾病控制率分别为35.8%和64.2%,其中CR 1例,PR 18例,SD 15例。脑转移灶的中位进展时间为7.3个月,全组中位无进展生存时间及中位总生存时间分别为5.6个月和15.9个月。1年、2年生存率分别为37.7%和11.3%。多因素分析显示,年龄、PS评分及EGFR状态为影响生存的因素。最常见的不良反应为皮疹和腹泻,发生率分别为75.5%和37.7%。结论:厄洛替尼对NSCLC脑转移有一定疗效,且毒性可以耐受。     

Mitomycin plus vinorelbine salvage chemotherapy in non-small cell lung cancer: a prospective study

SUMMARY: We aimed to evaluate, in a phase II study, the efficacy of the mitomycin-vinorelbine combination in non-small cell lung cancer (NSCLC) patients, relapsing after taxane-based regimens, a situation in which no standard chemotherapy is currently available. Patients with NSCLC progressing or relapsing after taxane therapy, with a Karnofsky performance status 50-100, and without clinical or biological contra-indications, were given mitomycin (8 mg/m(2) day 1) plus vinorelbine (25mg/m(2) days 1 and 8) every 3 weeks. Responses were assessed every three cycles. Sixty-five eligible patients were registered between December 2000 and December 2005. Taxanes and cisplatin were previously administered in 100% and 88% of the patients, respectively. All but four received at least two previous chemotherapy regimens. Two hundred and twenty-two cycles of chemotherapy were administered. The main grade 3-4 toxicity was leucopenia, in 47% of the patients. Among 60 assessable patients, response rate was 10% (95% confidence interval [CI]: 4-21). Median progression-free survival (PFS) was 9.7 weeks (95% CI: 8.4-11.1) and median survival (MST) was 28.4 weeks (95% CI: 23.0-34.8). Patients always progressing on all chemotherapy regimens administered before mitomycin-vinorelbine (primary failures) had shorter median PFS (8.1 weeks) than those having at least once partial response (PR) or no change (NC) (secondary failures) (10.4 weeks) (p=0.02). Respective MST were 23.7 weeks and 29.3 weeks (p=0.16). In conclusion, mitomycin-vinorelbine combination is a moderately active regimen in heavily pre-treated patients with NSCLC relapsing or progressing after taxanes and platinum-based chemotherapy. Its toxicity is limited.