膀胱癌放疗疗效分析

目的 回顾分析局限于盆腔的肌壁浸润性膀胱癌放疗疗效及影响因素、膀胱功能保存情况及不良反应。 方法 自1999-2016年在我院接受放疗的肌壁浸润性膀胱癌患者 45例(移行细胞癌 41例)。全膀胱 ±盆腔淋巴引流区 ±局部补量放疗,膀胱中位剂量45 Gy,肿瘤局部中位剂量56 Gy,24例接受了同步化疗,14例接受了新辅助化疗,29例放疗前接受过经尿道膀胱肿瘤电切术。 结果 中位随访28个月(4~101月),3年总生存率为51%,同步化放疗、单纯放疗 3年总生存率分别为64%、30%(P=0.001),有无新辅助化疗的 3年总生存率分别为59%和47%(P=0.540),放疗前有无局部电切的 3年总生存率分别为58%和43%(P=0.160),有无复发的 3年生存率分别为20%和79%(P=0.001)。局部复发 9例,远处转移 14例,放疗后≥3个月肠道损伤发生率2级 2例,泌尿道损伤发生率2级 4例、3级 2例。除 7例因膀胱肿瘤未控或放疗损伤严重影响患者膀胱功能外,其余均保持了基本正常膀胱功能。 结论 盆腔局限性肌壁浸润性膀胱癌同步化放疗可取得优于单纯放疗疗效,膀胱癌放疗后大部分患者可以保存正常膀胱功能,不良反应可接受。     

Randomized controlled trial of neoadjuvant chemotherapy with cisplatin and vinorelbine in patients with stage IIIA non-small cell lung cancer in China

Aim:   The aim of this study was to evaluate the efficacy of cisplatin plus vinorelbine as a regimen of neoadjuvant chemotherapy on the improvement of surgical resectability and survival in Chinese patients with stage IIIA non-small cell lung cancer (NSCLC).
Methods:   Fifty-six patients with stage IIIA NSCLC were randomly assigned to undergo either surgery preceded by two cycles of chemotherapy with cisplatin plus vinorelbine (the neoadjuvant chemotherapy arm) or immediate surgery (the primary surgery arm). The patients who had a complete resection received two to four cycles of chemotherapy, and those with incomplete resection received radiotherapy followed by two cycles of chemotherapy after surgery.
Results:   The overall response rate to neoadjuvant chemotherapy was 53.6%, with a complete response of 7.1%. A pathological complete response was seen in two patients (8%). The complete resection rates were 78.6% in the neoadjuvant chemotherapy arm and 60.7% in the primary surgery arm. The median overall survival and median disease-free survival was 30 months and 24 months, respectively, in the neoadjuvant chemotherapy arm as compared to 16 months and 11 months in the primary surgery arm ( P  = 0.04 and P  = 0.048). The 3-year and 5-year survival rate was 49.7% and 31.9%, respectively, for the neoadjuvant chemotherapy arm and 29.2% and 3.6% for the primary surgery arm.
Conclusion:   Neoadjuvant chemotherapy with cisplatin plus vinorelbine regimen is effective and tolerable and can improve the overall survival and disease-free survival time in Chinese patients with stage IIIA NSCLC.     

Phase II trial of concurrent paclitaxel, carboplatin, and external-beam radiation followed by surgical resection in locally advanced non-small-cell lung cancer, protocol 99-444

PURPOSE: We conducted a phase II study to evaluate the utility and outcomes of concurrent weekly low-dose chemotherapy with concurrent radiation in an effort to "downstage" patients with locally advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Eighteen patients with pathologically confirmed stage IIIA (T1-3 N2 or T3 N1) and 3 patients with stage IIB (T3 N0) NSCLC were enrolled. Seventeen of 18 patients with stage IIIA cancer had N2 disease. A chemotherapy/radiation schedule consisted of paclitaxel 50 mg/m(2 )and carboplatin administered at an area under the curve of 2 weekly for 5 weeks along with chest irradiation of 45 Gy. Patients with regressed or stable disease upon restaging were considered surgical candidates. Patients deemed inoperable were given additional radiation therapy. RESULTS: Twenty-one patients were enrolled from April 2000 to March 2004. Data from 21 patients were available for evaluation at the time of analysis. Grade 3/4 constitutional and pulmonary toxicity was 相似文献   

Effect of Neoadjuvant Chemotherapy on Improvement of Surgical Resectibility and Survival of Patients with Stage ⅢA Non Small Cell Lung Cancer

Objective To assess the effect of neoadjuvant chemotherapy on surgical resectibility and surival in patients with stage III A non small cell lung cancer (NSCLC). Methods 42 patients with stage III A NSCLC were randomized to receive either two cycles chemotherapy followed by surgery (neoadjuvant chemotherapy group) or surgery alone (surgery alone group). All patients received four cycles chemotherapy after surgery. Results The overall response to chemotherapy was 42.9% (38.1% partial response and 4.8% complete response). Toxicity of chemotherapy was minor and consisted mainly of gastroenterological side effects and myelosuppression. Patients treated with neoadjuvant chemotherapy had estimated surgical resection rate of 95.2% (n=20) and a complete resection rate in 52.4% (n=11) compared to 66.7% (n=14) and 28.6% (n=6) respectively, for patients with surgery alone (P<0.05). None of the patients died from the operation. The median survival was 24.6 months in the neoadjuvant chemotherapy group as compared to only 10.8 months in the surgery alone group (P<0.05). The 2-year survival rate was 57.1% in the chemotherapy group as compared to 28.6% in the surgery alone group (P<0.05). Conclusion Neoadjuvant chemotherapy improves the surgical resectibility and increases the median survival and 2-year survival rate of patients with stage III A NSCLC. This study was supported by the Jiangsu Provincial Scientific and Technology Committee (BS200376).     

Phase II Trial of Concurrent Paclitaxel,Carboplatin, and External-Beam Radiation Followed by Surgical Resection in Locally Advanced Non–Small-Cell Lung Cancer,Protocol 99-444

PurposeWe conducted a phase II study to evaluate the utility and outcomes of concurrent weekly lowdose chemotherapy with concurrent radiation in an effort to “downstage” patients with locally advanced non–small-cell lung cancer (NSCLC).Patients and MethodsEighteen patients with pathologically confirmed stage IIIA (T1-3 N2 or T3 N1) and 3 patients with stage IIB (T3 N0) NSCLC were enrolled. Seventeen of 18 patients with stage IIIA cancer had N2 disease. A chemotherapy/radiation schedule consisted of paclitaxel 50 mg/m² and carboplatin administered at an area under the curve of 2 weekly for 5 weeks along with chest irradiation of 45 Gy. Patients with regressed or stable disease upon restaging were considered surgical candidates. Patients deemed inoperable were given additional radiation therapy.ResultsTwenty-one patients were enrolled from April 2000 to March 2004. Data from 21 patients were available for evaluation at the time of analysis. Grade 3/4 constitutional and pulmonary toxicity was ≤ 10%. Grade 3/4 lymphopenia was noted in 9.5% of patients. One treatment-related death from postoperative acute respiratory distress syndrome occurred. Seventeen of 21 patients completed neoadjuvant therapy and 15 patients underwent resection. Four of 15 patients had a complete histopathologic response at the time of resection. Followup data were available on 20 patients. Overall, the median progression-free survival was 14.1 months. The median overall survival was 26.1 months. Six of 20 patients remain relapse free (range, 19.3-70.8 months).ConclusionNeoadjuvant low-dose weekly chemotherapy given concurrently with conventional chest irradiation might improve outcomes in patients with stage IIB and IIIA NSCLC with acceptable toxicity.     

长春瑞滨联合顺铂同步放疗治疗局部晚期非小细胞肺癌

目的观察Ⅲ期非小细胞肺癌患者应用顺铂联合长春瑞滨同步放疗的治疗效果和相关影响因素。方法三维适形放疗联合化疗治疗50例不能手术的ⅢA (N2)~ⅢB期NSCLC患者。顺铂30 mg/m2,第1~3、22~24天;长春瑞滨20 mg/m2,第1、8、22、29天。三维适形放疗在第1天开始,放疗中位剂量64Gy。CTC 3.0版用于评价治疗不良反应。结果50例患者客观缓解率为70%。局部肿瘤无进展中位生存时间和中位生存时间分别为7.5月和16.1月。1、2、3年生存率分别为60%、32.7%和21%。多因素分析结果显示高剂量照射（＞64Gy）组病人的局部区域控制率和生存率好于低剂量照射组（≤64Gy）,总疗程时间是病人生存率的影响因素,疗程时间短的病人生存率好。9名病人出现了3级血液不良反应。20人出现1~2级急性放射性食管炎;26人出现1~2级急性放射性肺炎。结论长春瑞滨联合顺铂和同步放疗治疗局部晚期非小细胞肺癌是可行的。提高放疗剂量或缩短疗程时间可以提高局部晚期非小细胞肺癌病人的生存率。     

Twice-daily reirradiation for recurrent and second primary head-and-neck cancer with gemcitabine, paclitaxel, and 5-fluorouracil chemotherapy

PURPOSE: We previously demonstrated the efficacy of concurrent gemcitabine, paclitaxel, and 5-fluorouracil in conjunction with twice-daily (1.5-Gy) radiotherapy delivered on alternating weeks (TFGX(2)) in locally advanced head-and-neck cancer. Here, we report the clinical outcome and late toxicity of TFGX(2) in a subset of patients previously irradiated to the head and neck. METHODS AND MATERIALS: Twenty-nine previously irradiated patients, presenting with recurrent or second primary head-and-neck cancer, underwent TFGX(2). Twelve patients underwent attempted surgical resection before chemoradiotherapy, 10 of whom were left with no measurable disease. Patients with measurable disease received a median radiation dose of 72 Gy; those with no measurable disease received a median dose of 61 Gy. The cumulative dose ranged from 74.4 to 156.4 Gy (mean, 125.7 Gy; median, 131.0 Gy). RESULTS: The median follow-up was 19.1 months (50.9 months for living patients). The 5-year overall survival rate was 34.5%, and the locoregional control rate was 54.5%. In patients with measurable disease at treatment, the 5-year overall survival and locoregional control rate was 26.3% and 45.1%, respectively, compared with 50.0% (p = 0.14) and 70% (p = 0.31), respectively, for those with no measurable disease. Measurable disease and radiation dose were highly statistically significant for overall survival and locoregional control on multivariate analysis. Of 14 patients assessable for late toxicity, 3 developed Grade 4-5, 8 Grade 2-3, and 3 Grade 0-1 toxicity. CONCLUSION: Aggressive reirradiation with chemotherapy in locally advanced head-and-neck cancer provides a chance for long-term cure at the expense of toxicity. Attempted surgical resection before chemoradiotherapy improved disease control and survival.     

Escalated hyperfractionated accelerated radiation therapy for locally advanced non-small cell lung cancer: a clinical phase II trial.

BACKGROUND AND PURPOSE: To evaluate the feasibility, toxicity and the efficacy for locally advanced non-small cell lung cancer (NSCLC) treated with escalated hyperfractionated accelerated radiation therapy (EHART) combined with chemotherapy. PATIENTS AND METHODS: The EHART consisted of irradiation delivered twice per day with >6-h interval and five treatment days per week. In the first and second weeks, 1.2 Gy/fraction b.i.d, was given, and then 1. /fraction b.i.d in the third week; 1.4 Gy/fraction b.i.d in the fourth week; and 1. /fraction b.i.d in the fifth week, respectively. The total tumor dose delivered was 66 Gy/50 fractions/5 weeks. All patients received neoadjuvant and adjuvant chemotherapy. The chemotherapeutic regimen used was either MVP (mitomycin C, vindesine, cis-platinum), or EP (etoposide and cis-platinum). RESULTS: From February 1997 to February 1999, 73 eligible patients were registered. All were in stage IIIb with median age of 60 years (33-70). Of the 73 patients, 12 cases were withdrawn from the study due to Grade (Gr) III acute complications, distant metastases, or intercurrent diseases. Sixty-one patients completed the combined treatment as planned. A median of 4 cycles of chemotherapy (1-7) was administered and 66 Gy/50 fractions/36 days was delivered finally. The most common acute complication was radiation esophagitis, which occurred in 56 cases (77%), with Gr III in 11 cases (15%). Twenty-nine patients (40%) had acute pulmonary toxicity; with Gr III in 6 cases (8%). The median survival time was 13 months for the entire group. The 1-year and 2-year survival rates were 51 and 10%, respectively. Of the 61 patients who finished EHART, 34 were found to have locoregional progression. Thirty-two patients failed inside radiation fields, and 2 patients, outside radiation fields. The 1-year and 2-year locoregional progression-free rates were 71 and 34%, respectively. The 1-year and 2-year distant metastasis rates were 57 and 84%, respectively. CONCLUSIONS: EHART combined with chemotherapy could be tolerated by most of the stage IIIb NSCLC patients with acceptable complications. Locoregional control was improved, but the long survival was not prolonged significantly predominantly due to distant metastases.     

Phase II study of gemcitabine-cisplatin-paclitaxel triplet as induction chemotherapy in inoperable, locally-advanced non-small cell lung cancer

PURPOSE: Our objective was to determine the activity in terms of response rate, surgical resectability, and the tolerability of the new three-drug combination gemcitabine-cisplatin-paclitaxel (GCP) in unresectable stage IIIA(N2) and IIIB non-small cell lung cancer (NSCLC). PATIENT AND METHODS: Forty-two chemo-naive patients with stage IIIA(N2)-IIIB NSCLC, median age of 59 years, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and the ability to tolerate pneumectomy, received gemcitabine (Gem) 1000 mg/m(2) IV days 1 and 8, cisplatin (CDDP) 50 mg/m(2) IV days 1 and 8, paclitaxel 125 mg/m(2) 1h infusion IV days 1 and 8, every 21 days for 3 cycles. After induction chemotherapy, patients were evaluated for surgery or definitive radiotherapy. RESULTS: Grade 3-4 neutropenia was the main hematologic toxicity, occurring in 28% of patients. Grade 3-4 thrombocytopenia was observed in only 11% of cases. No neutropenic fever or bleeding episodes were recorded. Severe non-hematologic toxicity was uncommon. Thirty (71%, 95% CI: 57.2-84.7%) of the 42 eligible patients had objective responses (1 complete and 29 partial responses). After induction chemotherapy, 21 patients (50%) went to surgery. Complete resection was obtained in 16 patients (38%). Viable tumor was present in 18 of 21 resection specimens. In three cases only necrotic tumor cells were identified, for a pathological complete response of 7%. With a median follow-up of 13.9 months, median time to progression was 17.4 months, median survival 21.7 months and estimated 1-year survival 92%. CONCLUSIONS: GCP combination is active and well tolerated in locally-advanced, non-resectable NSCLC. The activity profile, in terms of response and surgical resection rate, is comparable to that obtained with standard doublets.     

Induction chemotherapy plus three-dimensional conformal radiation therapy in the definitive treatment of locally advanced non-small-cell lung cancer

PURPOSE: To evaluate our institution's experience using chemotherapy in conjunction with three-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS: From 1991 to 1998, 152 patients with Stage III non-small-cell lung cancer (NSCLC) were treated with 3D-CRT at Memorial Sloan-Kettering Cancer Center. A total of 137 patients (90%) were surgically staged with either thoracotomy or mediastinoscopy. The remainder were staged radiographically. Seventy patients were treated with radiation therapy alone, and 82 patients received induction chemotherapy before radiation. The majority of chemotherapy-treated patients received a platinum-containing regimen. Radiation was delivered with a 3D conformal technique using CT-based treatment planning. The median dose in the radiation alone group was 70.2 Gy, while in the combined modality group, it was 64.8 Gy. RESULTS: The median follow-up time was 30.5 months among survivors. Stage IIIB disease was present in 36 patients (51%) in the radiation-alone group and 57 patients (70%) in the combined-modality group. Thirty-nine patients had poor prognostic factors (KPS < 70 or weight loss > 5%), and they were equally distributed between the two groups. The median survival times for the radiation-alone and the combined-modality groups were 11.7 months and 18.1 months, respectively (p = 0.001). The 2-year rates of local control in the radiation-alone and combined-modality groups were 35.4% and 43.1%, respectively (p = 0.1). Grade 3 or worse nonhematologic toxicity occurred in 20% of the patients receiving radiation alone and in 16% of those receiving chemotherapy and radiation. Overall, there were only 4 cases of Grade 3 or worse esophagitis. CONCLUSION: Despite more Stage IIIB patients in the combined-modality group, the addition of chemotherapy to 3D-CRT produced a survival advantage over 3D-CRT alone in Stage III NSCLC without a concomitant increase in toxicity. Chemotherapy thus appears to be beneficial, even in patients who are receiving higher doses of radiation therapy than are typically given with conventional techniques. Because locoregional failure remains a major challenge in patients with advanced disease, 3D-CRT in conjunction with chemotherapy may allow safe treatment to the dose levels required to further enhance local control.     

Ⅳ期非小细胞肺癌化疗同期胸部三维放疗的前瞻性临床研究(一)——疗效与不良反应

目的 研究Ⅳ期非小细胞肺癌(NSCLC)化疗同期胸内病灶三维放疗的疗效和安全性.方法 2003-2010年共入组201例,可疗效分析182例,安全性分析201例.化疗以铂类为基础二药联合方案,中位周期数为4个.胸内病灶中位计划靶体积剂量为63 Gy.分析患者的生存情况,胃肠道、血液学不良反应,放射性肺炎和食管炎.用Kaplan-Meier法进行生存分析,Cox回归模型进行多因素分析.结果 201例的随访率为97.5％,随访满＜1、1～2、≥3年者分别为201、170、134例.全组182例中4～5个周期化疗同期三维放疗和同期三维放疗≥63 Gy的1、2、3年生存率以及中位生存期(MST)分别为54％和66％、20％和23％、13％和19％以及14.3个月和16.1个月;相似放化疗强度下单器官和多器官转移的MST分别为13.0个月和8.5个月(x2=10.10,P=0.001);同期放疗≥63 Gy 和＜63 Gy的MST在全组、4～5个周期化疗的分别为14.9个月和8.4个月(x2=20.48,P=0.000)、16.1个月和8.8个月(x2 =11.75,P=0.001),单器官、多器官的分别为16.0个月和9.0个月(x2=10.51,P=0.001)、11.0个月和7.0个月(x2=7.90,P=0.005).多因素分析显示4～5个周期化疗同期放疗≥63 Gy(β=0.243,P=0.019)、治疗后卡氏评分变化(β=1.268,P=0.000)对生存有影响.201例患者的2+3级胃肠反应发生率为45.0％;3+4级白细胞、血小板、血红蛋白不良反应发生率分别为35.0％、18.0％、15.0％;2+3级放射性肺炎和食管炎发生率分别为9.5％和13.4％.结论 Ⅳ期NSCLC化疗同期原发灶高剂量三维放疗可能使生存期延长,不良反应可接受.     

Is trimodality approach better then bimodality in stage IIIA, N2 positive non-small cell lung cancer?

BACKGROUND: Neoadjuvant treatment followed by surgery is currently being investigated for locally advanced non-small cell lung cancer (NSCLC). This study reports efficacy, toxicity and feasibility of neoadjuvant chemotherapy with concurrent radiotherapy (CCRT) in stage IIIA, N2 positive NSCLC. METHODS: From March 2001 to February 2004, 52 patients with histologically confirmed stage IIIA, N2 positive NSCLC were registered. Patients received preoperative CCRT that consisted of weekly paclitaxel plus platinum chemotherapy and concurrent radiotherapy followed by surgery. RESULTS: Overall response rate was 76.9% (95% CI, 64-88%). The major grade 3-4 toxicities were radiation esophagitis (15.4%) and neutropenia (11.5%), and treatment-related mortality rate was 1.9%. Forty-two of 52 patients (80.8%) subsequently underwent surgical resection and 35 of 52 patients (67.3%) underwent complete resection. Among them, pathological complete response was obtained in 4.8%. Pathological downstaging rate to N0-1 and stage 0-II at surgery were 69.0% and 66.7%, respectively. The perioperative major morbidity rate was 23.8% and perioperative mortality was 2.4%. At a median follow-up of 33.9 months (range: 16.4-49.9), the median progression-free survival and overall survival were 16.5 months (95% CI, 6.2-26.8) and 25.6 months (95% CI, 14.6-36.6), respectively. Multivariate analyses identified that patients achieved mediastinal nodal clearance (downstage to pathological N0 or N1) after CCRT (p=0.02) and age at diagnosis<60 years (p=0.01) showed significantly improved survival. CONCLUSION: Neoadjuvant CCRT showed a high overall response rate with tolerable toxicity profile. Downstaging after CCRT may increase the rate of complete tumor resection and result in survival benefit in stage IIIA, N2 positive NSCLC patients.     

Phase III study comparing chemotherapy and radiotherapy with preoperative chemotherapy and surgical resection in patients with non-small-cell lung cancer with spread to mediastinal lymph nodes (N2); final report of RTOG 89-01. Radiation Therapy Oncology Group

PURPOSE: To compare the outcome of treatment of mediastinoscopy-verified N2 non-small-cell lung cancer treated with induction chemotherapy followed by either surgery or radiotherapy (RT), with both options followed by consolidation chemotherapy. METHODS AND MATERIALS: A randomized Phase III trial for Stage IIIA (T1-T3N2M0) non-small cell lung cancer was conducted by the Radiation Therapy Oncology Group (RTOG) and Eastern Cooperative Oncology Group between April 1990 and April 1994. After documentation of N2 disease by mediastinoscopy or anterior mediastinotomy, patients received induction chemotherapy with cisplatin, vinblastine, and mitomycin-C. Mitomycin-C was later dropped from the induction regimen. Patients were then randomized to surgery or RT (64 Gy in 7 weeks) followed by cisplatin and vinblastine. RESULTS: RTOG 89-01 accrued 75 patients, of whom 73 were eligible and analyzable. Twelve patients received induction chemotherapy but were not randomized to RT or surgery thereafter. Forty-five patients were randomized to postinduction RT or surgery. Of the analyzable patients, 90% had a Karnofsky performance score of 90-100, 18% had weight loss >5%, 37% had squamous cell histologic features, and 54% had bulky N2 disease. The distribution of bulky N2 disease was uniform among the treatment arms. The incidence of Grade 4 toxicity was 56% in patients receiving mitomycin-C and 29% in those who did not. Only 1 patient in each group had acute nonhematologic toxicity greater than Grade 3 (nausea and vomiting). No acute Grade 4 radiation toxicity developed. The incidences of long-term toxicity were equivalent across the arms. Three treatment-related deaths occurred: 2 patients in the surgical arms (one late pulmonary toxicity and one pulmonary embolus), and 1 patient in the radiation arm (radiation pneumonitis). Induction chemotherapy was completed in 78% of the patients. Complete resection was performed in 73% of 26 patients undergoing thoracotomy. Consolidation chemotherapy was completed in 75% of the patients. No statistically significant difference was found among the treatment arms. The overall progression-free survival rate was 53% at 1 year and 17% at 3 years. The median progression-free survival was 14 months. No difference in the 1-year survival rate (70% vs. 66%) or median survival time (19.4 vs. 17.4 months) between the surgery and RT arms. The median survival in the patients receiving induction chemotherapy only was 8.9 months. Mitomycin-C had no impact on survival (p = 0.75). No statistically significant difference was noted in the time to local failure between the surgical and RT arms. CONCLUSION: The patient accrual to this trial made its results inconclusive, but several observations are notable. In this trial, histologic confirmation of N2 disease in the surgical and nonsurgical arms eliminated the usual biases from clinical staging. In this setting, local control and survival were essentially equal between the surgical and RT arms. The 3- and 5-year survival rates of nonsurgical therapy were comparable to published surgical trials of N2 disease.     

Second-line,low-dose,weekly paclitaxel in patients with stage IIIB/IV nonsmall cell lung carcinoma who fail first-line chemotherapy with carboplatin plus paclitaxel

BACKGROUND: Second-line chemotherapy with docetaxel improves survival and quality of life (QoL) in patients with nonsmall cell lung carcinoma (NSCLC) who fail first-line platinum-based regimens. The authors sought to determine the activity of second-line, low-dose, weekly paclitaxel in patients with NSCLC who failed first-line chemotherapy with carboplatin plus paclitaxel. METHODS: Patients with Stage IIIB/IV NSCLC who had received first-line carboplatin/paclitaxel were treated with low-dose (80 mg/m(2)), weekly paclitaxel at the time of disease progression. Response rates, QoL, and survival were outcome end points. RESULTS: Sixty-two patients were included in this analysis. The median age was 62 years (range, 32-76 years), 55% of patients were male, 89% of patients had Stage IV NSCLC, and the Karnofsky performance status was 90-100% in 31% of patients, 70-80% in 55% of patients, and 60% in 14% of patients. Twenty-six percent of patients experienced disease progression as their best response to first-line carboplatin plus paclitaxel, whereas 52% of patients had stable disease, and 23% of patients had achieved a response. The median time from first-line carboplatin plus paclitaxel to second-line, low-dose, weekly paclitaxel was 9.5 weeks (range, 1-78 weeks). The toxicity profile was extremely favorable, with no Grade 4 toxicity and < 10% Grade 3 hematologic or nonhematologic toxicity in all patients with the exception of neuropathy. Ten percent of patients experienced both Grade 2 and Grade 3 neuropathy. The overall objective response rate was 8%. The median survival was 5.2 months (95% confidence interval [95%CI], 3.6-6.2 months), and the 1-year and 2-year survival rates were 20% (95%CI, 10-30%) and 9% (95%CI, 1-16%), respectively. CONCLUSIONS: Second-line, low-dose, weekly paclitaxel had activity in selected patients with Stage IIIB/IV NSCLC who failed first-line chemotherapy with carboplatin plus paclitaxel. The toxicity profile of this approach is extremely favorable, and outcome expectations are similar to the outcome expectations with other single agents in this setting.     

Combination chemotherapy with carboplatin and weekly Paclitaxel in patients with advanced non-small cell lung cancer

BACKGROUND: The objective of this study was to evaluate the efficacy and toxicity of carboplatin plus weekly paclitaxel as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Forty-nine patients were analyzed retrospectively. Every 4 weeks patients received 70 mg/m(2)paclitaxel on days 1, 8, and 15, and AUC 5-6 carboplatin on day 1. RESULTS: A median of four cycles (range, 1-7) was administered. Twenty-four patients had a partial response, and the overall response rate was 48.9%. The median survival time was 12.8 months and the 1-year survival was 50.7%. Overall toxicities were mild. The most common toxicity was neutropenia, grade 3/4 in 32% of the patients. Grade 3/4 hematologic toxicities included anemia (16%) and thrombocytopenia (8%). Grade 3/4 non-hematologic toxicities included febrile neutropenia (2%), pneumonia (10%) and interstitial pneumonia (2%). Grade 2 peripheral neuropathy was seen in one patient (2%). CONCLUSIONS: These results demonstrate that this regimen is an active and tolerable treatment for patients with advanced NSCLC. It is suggested that this weekly regimen should be considered as one of the standard therapies for future chemotherapy in advanced NSCLC.     

Final toxicity results of a radiation-dose escalation study in patients with non-small-cell lung cancer (NSCLC): predictors for radiation pneumonitis and fibrosis

PURPOSE: We aimed to report the final toxicity results on a radiation-dose escalation trial designed to test a hypothesis that very high doses of radiation could be safely administered to patients with non-small-cell lung cancer (NSCLC) by quantifying the dose-volume toxicity relationship of the lung. METHODS AND MATERIALS: A total of 109 patients with unresectable or medically inoperable NSCLC were enrolled and treated with radiation-dose escalation (on the basis of predicted normal-lung toxicity) either alone or with neoadjuvant chemotherapy by use of 3D conformal techniques. Eighty-four patients (77%) received more than 69 Gy, the trial was stopped after the dose reached 103 Gy. Estimated median follow-up was 110 months. RESULTS: There were 17 (14.6%) Grade 2 to 3 pneumonitis and 15 (13.8%) Grade 2 to 3 fibrosis and no Grade 4 to 5 lung toxicity. Multivariate analyses showed them to be (1) not associated with the dose prescribed to the tumor, and (2) significantly (p<0.001) associated with lung-dosimetric parameters such as the mean lung dose (MLD), volume of lung that received at least 20 Gy (V20), and the normal-tissue complication probability (NTCP) of the lung. If cutoffs are 30% for V20, 20 Gy for MLD, and 10% for NTCP, these factors have positive predictive values of 50% to 71% and negative predictive value of 85% to 89%. CONCLUSIONS: With long-term follow-up for toxicity, we have demonstrated that much higher doses of radiation than are traditionally administered can be safely delivered to a majority of patients with NSCLC. Quantitative lung dose-volume toxicity-based dose escalation can form the basis for individualized high-dose radiation treatment to maximize the therapeutic ratio in these patients.     

长春瑞滨联合顺铂治疗既往使用紫杉类的晚期非小细胞肺癌临床分析

目的　评价长春瑞滨联合顺铂治疗既往使用紫杉类的晚期非小细胞肺癌的疗效和毒性。方法　 3 0例既往紫杉类药物治疗过的ⅢB或Ⅳ期非小细胞肺癌患者 ,体能状况评分 (ECOG) 0～ 1分。 15例用NP方案 (长春瑞滨 +顺铂 )治疗 ,15例用MVP方案 (丝裂霉素 +长春地辛 +顺铂 )治疗。结果　NP组和MVP组有效率分别为 13 .3 %和 0 (P >0 .0 5)。NP组患者疾病进展时间较MVP组长(分别为 6个月和 3个月 ,P <0 .0 5) ,NP组中位生存时间较MVP组长 (分别为 9个月和 6个月 ,P <0 .0 5) ,NP组 1年生存率 (40 .0 % )明显高于对照组 (0 ,P <0 .0 5)。两组Ⅲ、Ⅳ度不良反应差异无显著性 (P >0 .0 5) ,患者可以耐受。结论　NP方案对既往使用紫杉类的、体能状况较好的晚期非小细胞肺癌患者有一定疗效 ,可使患者疾病进展推迟 ,中位生存期延长 ,1年生存率提高 ,且毒性可耐受     

Phase II study of gemcitabine and vinorelbine combination chemotherapy in patients with non-small-cell lung cancer not responding to previous chemotherapy

Both gemcitabine and vinorelbine are new anticancer drugs that have shown activity in the treatment of chemona?ve non-small-cell lung cancer (NSCLC). Their role in the second-line treatment of NSCLC is less clear. We conducted a phase II study of gemcitabine and vinorelbine combination chemotherapy in patients with NSCLC who had not responded to previous platinum-based chemotherapy, to assess the response and toxicity of this regimen. Seventeen patients were enrolled from September 1998 to February 2001. Treatment consisted of vinorelbine 20 mg/m2 and gemcitabine 800 mg/m2 intravenous infusion on days 1, 8, and 15 every 4 weeks. Sixty-five cycles of treatment were given, with a median of four cycles. All patients were evaluable for the toxicity profile, and 16 patients were evaluable for the response rate. The major toxicity was myelosuppression. Grade III or IV neutropenia occurred in 9 patients (52.9%) during treatment. Febrile neutropenia occurred in only 1 patient (5.9%). Grade III anemia and thrombocytopenia occurred in two and three patients, respectively. Other toxicities were few and mild in severity. After 2 cycles of treatment, 5 of 16 patients (31.3%) had a partial response (95% CI 8.6-64%). The median time to disease progression was 4.6 months and the median survival was 8.3 months. The 1-year survival rate was 34.3%. In conclusion, gemcitabine and vinorelbine salvage chemotherapy produces a relatively high response rate, low toxicity profile, and good survival in Chinese patients with NSCLC who have not responded to previous platinum-based chemotherapy. Further study is needed to confirm its activity.     

培美曲塞联合顺铂治疗晚期复治性非小细胞肺癌临床观察

目的：观察培美曲塞联合顺铂方案治疗晚期复治的非小细胞肺癌的疗效和毒副反应。方法：31例既往化疗或靶向治疗失败的晚期非小细胞肺癌患者接受培美曲塞联合顺铂方案化疗,其中培美曲塞500mg/m2加入0.9%氯化钠注射液100ml静脉点滴超过10min;顺铂25mg/m2,静滴1小时,第1-3天,每21d重复,2周期评价疗效。结果：31例患者中,部分缓解（PR）8例,稳定（SD）16例,进展（PD）7例,总有效率为25.81%,临床获益率为77.42%。中位无进展生存期3.1个月,中位生存期8.9个月,1年生存率29.03%（9/31）。主要毒副反应为骨髓抑制,白细胞降低率70.97%,均为1-2度;血小板降低率16.13%,均为1度。结论：培美曲塞联合顺铂方案是一线治疗失败的晚期非小细胞肺癌的理想方案之一。     

Pneumonectomy after chemoradiation: the Dana-Farber Cancer Institute/Brigham and Women's Hospital experience

BACKGROUND: The current study was conducted to examine the outcomes of pneumonectomy after induction chemoradiotherapy in patients with locally advanced nonsmall cell lung cancer (NSCLC). METHODS: All patients undergoing pneumonectomy after induction therapy at the Brigham and Women's Hospital were retrospectively evaluated for 30-day and 100-day mortality and treatment-related complications with Institutional Review Board approval. Multivariate and univariate analyses for clinical factors correlating with toxicity and/or survival were calculated. RESULTS: Between 1995 and 2005, 73 patients underwent pneumonectomy for NSCLC after induction therapy. All patients received radiation (median dose of 54 gray [Gy]) and 69 patients (95%) received concurrent chemotherapy. The median age was 62 years and 43 patients (59%) were male; Thirty-seven patients (51%) had American Joint Committee on Cancer stage IIIA NSCLC, 27 (37%) had stage IIIB, 6 had stage IIB, and 4 had stage IV NSCLC because of a resected solitary brain metastasis. A majority (44; 60%) of patients received the combination of carboplatin and paclitaxel, whereas 15 (21%) received the combination of cisplatin and etoposide. Forty-five patients (62%) underwent left pneumonectomy. With a median follow-up of 28 months, the 1-year and 2-year overall survival rates were 70% and 49%, respectively. The 30-day and 100-day mortality rates were 6% and 10%, respectively. Only 4 of 73 patients (6%) died of acute respiratory distress syndrome. The rate of nonfatal treatment-related morbidity was 11%. On univariate analysis, right-sided pneumonectomy was associated with a higher risk of treatment-related mortality (P = .099). CONCLUSIONS: With an acceptable mortality rate, a single-institutional series demonstrated that trimodality therapy including pneumonectomy can be safely accomplished in patients with advanced NSCLC.