Cisplatin and gemcitabine induction chemotherapy followed by concurrent chemoradiotherapy or surgery for locally advanced non-small cell lung cancer

BACKGROUND: We report a study of induction chemotherapy followed by concurrent chemoradiotherapy for stage IIIA/IIIB non-small cell lung cancer. METHODS: Patients received two cycles of induction chemotherapy with cisplatin 100 mg/m(2) on day 1 and gemcitabine 1000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. If the disease was resectable [corrected] surgery was followed with two further cycles. If unresectable, patients received cisplatin 100 mg/m(2) day 1, 29 with 5-fluorouracil 1000 mg/m(2) per 24 h continuous infusion for 96 h on days 2-5 and days 30-33 of the radiotherapy administration. Radiation therapy consisted of 63 Gy, 35 fractions, 7 weeks. RESULTS: Of 48 patients, 40% had a partial response to induction chemotherapy. Four of eleven patients with stage IIIA tumours had resectable disease. The remaining seven patients plus 37 with stage IIIB disease had chemoradiotherapy. Response at the completion of all therapy was 62% (IIIA 73%, IIIB 59%). For all patients the median survival was 15.3 months: 1 year and 3 years, 58% and 25%, respectively. Those with IIIB disease responding to induction chemotherapy had significantly superior survival to those that did not respond (37 months vs 11 months; P = 0.005). This remained significant from a landmark at 8 weeks after the start of treatment (P = 0.01). CONCLUSION: These results are equivalent to other studies using induction chemotherapy prior to concurrent chemoradiotherapy. Response to induction chemotherapy may have major prognostic significance.     

Concurrent cisplatin and etoposide with radiotherapy in locally advanced non-small cell lung cancer

Twenty consecutive patients with newly diagnosed or locally recurrent non-small cell lung cancer limited to the chest were treated with concurrent radiotherapy and cisplatin plus etoposide. No patient had received prior chemotherapy or radiotherapy. Sixteen of 20 patients (80%) responded to the treatment. Median survival has not been reached but is greater than 13.5 months. Twelve patients have relapsed at a median of 10 months after starting therapy (range, 4-12 months), with only one initial relapse within the radiotherapy port. Hematologic toxicity was mild, with four of 52 wbc count nadirs less than 1000/mm3. Esophageal toxicity was also mild, with all patients maintaining oral intake throughout therapy. We conclude that simultaneous radiotherapy, cisplatin, and etoposide can be safely administered in locoregional non-small cell carcinoma of the lung. A prospective trial of this regimen versus radiotherapy alone is warranted.     

Combination chemotherapy with ifosfamide, mitomycin, and cisplatin in advanced non-small cell lung cancer

Thirty-two evaluable patients with stage III non-small cell lung cancer were treated with the combination of ifosfamide (4 g/m2), with uroprotective mesna, mitomycin (6 mg/m2), and cisplatin (100 mg/m2). The overall response rate was 68.8% (complete response rate, 21.9%; partial response rate, 46.9%). Toxicity was moderate and manageable. Based on the response rate observed, this three-drug combination could be considered for future randomized phase III trials against non-small cell lung cancer.     

Comparing cisplatin plus etoposide with combination of mitomycin, ifosfamide and cisplatin in advanced non-small cell lung cancer patients

Cisplatin-etoposide (CE) and mitomycin, ifosfamide and cisplatin (MIC) combinations are active conventional regimens in non-small cell lung cancer (NSCLC). In this retrospective study, we compared response rates, survival, duration of response, time-to-progression and toxicity of CE with MIC regimens in treatment of previously untreated patients with stage IIIB and IV NSCLC. We first determined the patients with NSCLC who had stage IIIB or IV and received CE or MIC between January 1997 and December 2002 in our clinic. Out of the eligible patients, 45 received MIC, 167 received CE. In addition 45 MIC patients, we included 46 of the 167 CE patients in the study by selecting one patient of every three patient randomly. In CE protocol, cisplatin 80 mg/m(2) on day 1 and etoposide 100 mg/m(2) on days 1, 2, 3 (every three weeks); in MIC protocol, mitomycin 6 mg/m(2), ifosfamide 3 g/m(2), cisplatin 50 mg/m(2) on day 1 (every three weeks) were performed. For statistical analysis, chi-square, t-test, Kaplan-Meier survival analysis, Cox regression analysis and logistic regression analysis were used by SPSS 11.5 computer program. The overall response rate was 33.3% in the MIC arm and 34.8% in the CE arm. A respective median survival was 28 weeks for the MIC arm and 35 weeks for the CE arm. Median duration of response and time to progression in each groups were 23 and 14 weeks in MIC arm and 32 and 22 weeks respectively. There was no statistical difference for response rates, duration of survival and response, time top progression and toxicity between the two arms. We consider that the combinations of MIC and CE have similar activity and they can be used confidently in advanced NSCLC.     

A prospective, multicentre clinical trial comparing cisplatin plus gemcitabine with cisplatin plus etoposide in patients with locally advanced and metastatic non-small cell lung cancer

OBJECTIVE: Cisplatin-gemcitabine (PG) and cisplatin-etoposide (PE) combinations are active regimens for non-small cell lung cancer (NSCLC). The present study aimed to compare PG with PE in the treatment of patients with stage IIIB and IV NSCLC. METHODOLOGY: We conducted a prospective, multicentre trial. A total of 166 patients were enrolled into the study and received either gemcitabine (1,000 mg/m(2)) on days 1, 8 and 15 plus cisplatin (80 mg/m(2)) on day 2 every 4 weeks, or etoposide (100 mg/m(2)) on days 1, 2 and 3 plus cisplatin (80 mg/m(2)) on day 1 every 3 weeks. RESULTS: The overall response rate was superior in the PG group (54.8%vs 39.0%, P=0.045). There was no significant difference in survival between the two groups, with respective median and 1-year survival of 38 weeks and 33.3% for the PG group, and 34 weeks and 23.2% for the PE group. There was also no statistical difference for time to progression between the two groups. Neutropenia and thrombocytopenia were seen more frequently in the PG group (grade 3 neutropenia, 33.3%vs 15.9%, P=0.012; grade 3 thrombocytopenia, 27.4%vs 3.7%, P<0.001 and grade 4 thrombocytopenia, 10.7%vs 1.2%, P=0.018). CONCLUSION: PG is an active chemotherapy regimen and has a better response rate than PE in advanced NSCLC, although there was no difference in time to progression and overall survival. A higher incidence of haematological toxicity was seen with PG than with PE.     

同步放化疗联合治疗晚期非小细胞肺癌的疗效观察

目的比较紫杉醇加奈达铂方案(TN)与紫杉醇加顺铂方案(TP)联合三维适形放疗治疗晚期非小细胞肺癌(NSCLC)疗效差异。方法收集我院经放化联合治疗的晚期NSCLC患者92例分为:TN方案组(A组,48例)和TP方案组(B组,48例),比较两组治疗晚期NSCLC的疗效、生存率及毒副反应情况。结果 A、B两组的总有效率分别为85.4%和79.2%,无统计学差异(P>0.05),两组1和2年生存率比较无显著性差异(P>0.05),肾功能损害及恶心呕吐发生率TN组明显低于TP组,有统计学差异(P<0.05)。结论 TN方案结合同步放疗治疗晚期NSCLC疗效较TP相当,不良反应较TP方案小,患者耐受性更好。     

Combination chemotherapy for non-small cell lung cancer with doxorubicin and mitomycin or cisplatin and etoposide

The combinations of doxorubicin (40 mg/m2 iv every 3 weeks) and mitomycin (12 mg/m2 iv every 6 weeks) or cisplatin (80 mg/m2 iv every 3 weeks X 3, then every 6 weeks) and etoposide (80 mg/m2 iv on Days 1-3 every 3 weeks X 3, then every 6 weeks) were evaluated in a randomized phase II trial in 77 patients with measurable or evaluable non-small cell lung cancer. No patient had been pretreated with prior chemotherapy. The overall response rate for the doxorubicin and mitomycin regimen was 11% and for the cisplatin and etoposide regimen was 23%. Responses lasted a median of 5.5 months. Median survival was 7.0 months for the doxorubicin and mitomycin regimen and 8.0 months for the cisplatin and etoposide regimen. One treatment-related death was observed after doxorubicin and mitomycin in a patient who had received radiation therapy immediately prior to study entry. Otherwise, the hematologic toxicity of both chemotherapy regimens was moderate, with only six patients (10%) having World Health Organization grade 3 toxicity and no patients having World Health Organization grade 4 toxicity. However, subjective tolerance gastrointestinal upset) of the cisplatin and etoposide combination was poor.     

Neoadjuvant vindesine, etoposide, and cisplatin for locally advanced non-small cell lung cancer. Final report of a phase 2 study

We treated 27 patients with regionally advanced non-small-cell lung cancer (NSCLC) with two cycles of neoadjuvant chemotherapy with etoposide, vindesine, and cisplatin. Twenty-three patients were evaluable for response; 13 had a partial response while ten patients had stable disease or disease progression. Subsequent local therapy consisted of surgery followed by radiotherapy in four patients and of radiotherapy alone in 14 patients. Five patients did not receive local therapy. At completion of local therapy, seven patients were considered free of disease including all four who had undergone surgery. Median time to disease progression for the 13 patients who had a partial response to neoadjuvant chemotherapy was eight months (three to 51+ months). The median survival for all patients registered on study was eight months (three days to 53+ months). Chemotherapy induced toxicities included moderate myelosuppression, nausea and vomiting in all patients, and occasional ototoxicity, neurotoxicity, and wasting syndrome. One patient died of intracerebral hemorrhage due to thrombocytopenia. This trial shows that administration of neoadjuvant chemotherapy to patients with locoregionally advanced NSCLC is feasible and may yield an increased response rate compared to patients with stage IV disease. While no clearly beneficial effect of the use of chemotherapy on patient survival is apparent in this study, further studies utilizing neoadjuvant chemotherapy in patients with NSCLC are warranted and should attempt to identify more active combinations of drugs.     

多西他赛同步放疗局部晚期非小细胞肺癌的临床观察

目的观察多西他赛同步放射治疗局部晚期非小细胞肺癌的近期疗效和急性毒副反应。方法70例Ⅲ期非小细胞肺癌患者随机分为单纯放疗组（单放组）和多谣他赛同步放疗组（放化组）各35例。两组放疗方法相同,2.0Gy／次,1次／天,5次／周,总量DT60-70Gy。放化组放疗同时予多西他赛40mg每周化疗一次,共5-6次。结果单放组和放化组有效率分别为54.3％和80％（P〈0.05）。急性毒副反应主要是I-Ⅱ级放射性食管炎、I-Ⅱ级放射性肺炎和I级骨髓抑制,放化组高于单放组（P〉0.05）。结论多西他赛同步放射治疗局部晚期非小细胞肺癌近期疗效好,毒副反应轻,患者能够耐受。     

Treatment of locally advanced non-small cell lung cancer with combination of chemotherapy and radiation

The treatment of locally advanced non-small cell lung cancer has improved substantially over the past 20 years. Almost three times as many patients are able to achieve long-term survival today compared with the mid-1980s. This improvement has been possible through the cooperation of physicians from different specialties involved in the care of lung cancer patients. More accurate staging, with the use of positron emission tomography, led to more accurate stage classification. Patients with detectable systemic disease can be spared from an aggressive local therapy whereas patients with small volume, stage IIIB, can receive the most appropriate treatment. Clinical trials in the United States and around the world have identified the role of each treatment modality and the appropriate timing of administration. The present standard of care is the concurrent administration of cisplatin-based chemotherapy and radiotherapy. This is a treatment that can be associated with significant morbidity, and patient selection is paramount. Chronological age, by itself, should not be a reason to deny a patient the most appropriate treatment for lung cancer. The presence of comorbidities, on the other hand, is a key factor in deciding the most appropriate treatment. When the concurrent administration of chemo- and radiotherapy is not appropriate, the sequential delivery of these two modalities is superior to each of them given alone. Over the last 6 months, two trials have shown that erlotinib (an epidermal growth factor receptor inhibitor) and bevacizumab (a vascular endothelial growth factor inhibitor) improve survival in non-small cell lung cancer patients. These findings represent a landmark in the care of lung cancer patients. We are entering an era of improved patient identification and more logical therapeutic approaches. The incorporation of these "targeted therapies" in the treatment of patients with locally advanced disease is being actively investigated and will, it is hoped, translate into significant therapeutic benefits for the patients.     

Long term complications and prognostic factors in locally advanced nasopharyngeal carcinoma treated with docetaxel,cisplatin, 5-fluorouracil induction chemotherapy followed by concurrent chemoradiotherapy: A retrospective cohort study

This study was conducted to evaluate the long term complications and their risk factors including of survival outcomes in patients with locally advanced nasopharyngeal cancer (NPC) treated with docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy (CCRT).Among the patients who were diagnosed as NPC, we consecutively evaluated the late complications in 104 patients who completed 3 cycles of TPF induction chemotherapy followed by CCRT and received regular follow-up by otolaryngologist and oncologist. The prognostic factors for overall survival, relapse free survival and each complication were analyzed based on clinical characteristics.Over a median follow-up of 54 months (range, 7.9–152.9 months), 5-year overall survival rate was 87% for stage II, 89% for stage III, 87% for stage IV patients. The significant prognostic factor for survival is complete response rate after CCRT in multivariate analysis. The most frequent toxicity was ear complication (29.8%) including of hearing loss requiring hearing aid (6.7%) and bone necrosis (3.8%). Decreased renal function over grade 2 was occurred in only 4 patients (3.8%) regardless of the cumulative dose of cisplatin. The long term complications did not affect the survival outcome. Patients who received radiation therapy more than 5400 cGy had better survival outcome than those who did not. However, ear complication was significantly related to radiation dose (≥ 6,600 cGy) and type of radiation therapy (conventional). Age over 65 years was a significant risk factor for both ear and renal toxicity. In conclusion, close follow-up to monitor long-term complications should be performed in patients treated with TPF induction chemotherapy followed by CCRT treatment, especially in elderly patients. Reestablishing the optimal chemotherapeutic agent during CCRT and adjustment of radiation dose after induction chemotherapy could be helpful to reduce the toxicity associated with the subsequent treatment strategy for locally advance NPC patients.     

应重视局部晚期非小细胞肺癌的综合治疗与患者的生存率

根据国际抗癌联盟1997肺癌分期和美国癌症研究联合会2002年的分期标准，Ⅲ期肺癌包括Ⅲ小ⅢЗ期，ⅢA期非小细胞肺癌（NSCLC）包括4种情况：T3N1M0、T1N2M0、T2N2M0和T3N2M0，ⅢЗ期包括7种情况：T4N0M0、T4N1M0、T4N2M0、T1N3M0、T2N3M0、T3N3M0、T4N3M0，局部晚期非小细胞肺癌（locally advanced non-small cell lung cancer，LANSCLC）是指除含有N2、N3、T4之一的Ⅲ期患者，占就诊肺癌患者的1／3以上，以往多以手术或放疗为主，国内外大宗病例研究结果显示，ⅢA期手术的5年生存率为23％-26．3％，ⅢB期手术的5年生存率为6％-7％，单纯常规放疗60Gy的5年生存率约为4％-6％，三维适形放疗为19％。近几年的多中心随机研究和荟萃分析结果表明，放化综合治疗的疗效优于化疗、放疗和手术的单一治疗，值得提倡。     

长春瑞宾联合顺铂治疗晚期非小细胞肺癌的临床观察

目的观察长春瑞宾联合顺铂治疗晚期非小细胞肺癌（NSCLC）的疗效及毒副作用。方法45例晚期NSCLC接受长春瑞宾和顺铂方案化疗,其中,男性31例,女性14例;腺癌27例,Ⅲ期25例,Ⅳ期20例;初治25例,复治20例。结果21例获得部分缓解（PR）,17例稳定（sD）,7例进展（PD）,总体有效率为47％。主要毒性反应为骨髓抑制,总体白细胞减少症发生率89％,Ⅲ～IV度为20％;局部静脉炎发生率51％。结论长春瑞宾联合顺铂治疗晚期NSCLC是可行的,有效,毒副反应较低。     

安罗替尼联合化疗三线治疗晚期非小细胞肺癌的临床分析

目的 探讨安罗替尼联合化疗三线治疗晚期非小细胞肺癌(NSCLC)的临床效果.方法 回顾性分析我院2018年6月至2019年9月收治的接受安罗替尼联合化疗三线治疗的晚期NSCLC患者11例,采用门诊或电话随访至2020年4月30日,观察患者疗效及不良反应,并进行生存分析.结果 11例患者客观缓解率(ORR)为9.09％(...     

新辅助化疗在局部晚期非小细胞肺癌外科手术的应用价值

目的探讨新辅助化疗在局部晚期非小细胞肺癌(NSCLC)手术中的临床效果。方法 110例Ⅲ期NSCLC患者随机分为观察组和对照组各55例,观察组患者在接受2个周期的全身化疗后手术,对照组确诊后直接手术。比较两组患者的手术情况和术后生存率。结果观察组的手术切除率为89.1%,显著高于对照组的74.5%(P<0.05);观察组的术中出血量和手术时间显著低于对照组(P<0.05);观察组术后1年、2年、3年生存率分别为85.5%、67.3%、56.4%,对照组分别为69.1%、54.5%、47.3%,两组间比较有统计学差异(P<0.05)。结论术前新辅助化疗可以提高NSCLC的手术切除率,增加患者的术后生存率。     

健择联合顺铂治疗晚期非小细胞肺癌的临床观察

目的观察健择(GEM)加顺铂(DDP)联合治疗晚期非小细胞肺癌,临床疗效及毒副反应。方法健择1000mg/m3静滴30min第1、8天,顺铂40mg静滴,第1、2、3天。每21~28天为1周期,2周期后评价疗效及毒副反应。结果临床疗效50例患者均接受2个周期化疗。其中CR0例,PR24例,NC19例,PD7例,总有效率为48%,其中Ⅲb期有效率为53.8%(15/28),Ⅳ期有效率为40.9%(9/22)。结论健择加顺铂联合治疗晚期非小细胞肺癌疗效确切,副作用较少,是一种值得推荐的化疗方案。     

Definitive chemoradiotherapy with capecitabine and cisplatin for elder patients with locally advanced squamous cell esophageal cancer

Purpose

The aim of this retrospective study is to evaluate the feasibility and efficacy of concurrent chemoradiotherapy (CCRT) or sequential chemoradiotherapy (SCRT) with capecitabine and cisplatin for elderly patients with locally advanced esophageal squamous cell carcinoma (ESCC).

Methods

A total of 75 patients elder than 65 years with histologically proven stage II–III ESCC were enrolled, in whom 40 patients were treated with CCRT consisted of two cycles of intravenous cisplatin and oral capecitabine during and after radiotherapy and 35 patients were treated with SCRT as two cycles of capecitabine plus cisplatin before and after radiotherapy. Response rate, overall survival, progression-free survival and toxicity were compared.

Results

The overall response rate (CR + PR) in the CCRT group (91.6 %) was significantly higher than that in the SCRT group (67.7 %), P = 0.023. The median PFS and median OS were significantly higher in CCRT group (19.7 and 33.6 months) than those in SCRT group (11.6 and 15.7 months), P < 0.05. The acute toxic effect was more severe in the CCRT group than in the SCRT group, but the grade 3–4 acute toxicities were similar in two groups.

Conclusions

It suggested that both CCRT and SCRT with capecitabine and cisplatin are tolerable and effective for elderly patients with locally advanced ESCC. Concurrent CRT might be superior to SCRT.