奈达铂联合多西他赛治疗晚期非小细胞肺癌临床疗效及其对于细胞免疫功能的影响

目的：研究奈达铂联合多西他赛治疗晚期非小细胞肺癌临床疗效及其对于细胞免疫功能的影响。方法：研究共对96例晚期非小细胞肺癌患者进行了研究,将入组患者随机分为观察组和对照组,每组48例,观察组接受奈达铂联合多西他赛治疗,对照组接受顺铂联合紫杉醇治疗。对照两组疗效,生存率、无疾病进展时间、T淋巴细胞亚群水平以及并发症的发生情况。结果：观察组的部分缓解（PR）率高于对照组,进展（PD）率低于对照组;对照组治疗后的NK、CD3^＋、以及CD4^＋/CD8^＋水平均低于治疗前,CD8^＋水平高于治疗前,差异均具有统计学意义（P〈0.05）;观察组的NK、CD3^＋、以及CD4^＋/CD8^＋水平均高于对照组,CD8^＋水平低于对照组,差异均具有统计学意义（P〈0.05）;观察组的1年生存率高于对照组,无疾病进展时间长于对照组。结论：奈达铂联合多西他赛治疗晚期非小细胞肺癌可以取得良好的疗效,且生存率高,无疾病进展时间长,而且对于患者细胞免疫功能影响较为轻微。     

多西紫杉醇修饰的人工晶体对眼组织相容性的影响

目的 探讨多西紫杉醇修饰的人工晶体对眼组织相容性的影响,为人工晶体的新型生物材料提供依据。方法 通过空气等离子技术,用多西紫杉醇对疏水性人工晶体表面进行修饰处理。16只日本大耳白兔随机分为对照组和实验组,每组8只。对照组：手术植入疏水性人工晶体;实验组：手术植入表面经多西紫杉醇修饰后疏水性人工晶体。比较人工晶体经多西紫杉醇处理后和处理前其表面亲水性的变化,两组均在手术后24h通过闪耀斑发生情况评估炎症感染程度,光镜下观察人工晶体周围组织炎症反应情况。结果 通过对比多西紫杉醇处理前后的人工晶体亲水性改变,结果显示经过多西紫杉醇处理后晶体的亲水性明显增加,主要表现是接触角差异（78±6°VS 158±9°）,与A组比较,B组的闪耀斑明显低于A组（230±10 VS 260±13）;与A组比较,B组在术后24h植入的人工晶状体周围组织炎症细胞浸润计数结果明显低于A组（11±6 VS 103±22）。结论 多西紫杉醇可通过等离子技术修饰人工晶体表面以增加其亲水性,进而增加了人工晶体和眼组织的组织相容性。     

扶正解毒方联合化疗治疗晚期非小细胞肺癌临床研究

目的观察扶正解毒方联合多西他赛加奈达铂方案治疗晚期非小细胞肺癌临床疗效和毒副反应。方法 76例晚期非小细胞肺癌(NSCLC)随机分为治疗组和对照组,各38例,治疗组采用扶正解毒方联合多西他赛加奈达铂化疗方案,对照组采用多西他赛加奈达铂化疗方案,21d为一周期。结果治疗组有效率为52.63%,对照组为44.74%,两组比较无明显统计学意义(P>0.05);骨髓抑制、胃肠道反应治疗组均明显低于对照组,两组有明显统计学意义(P<0.05);治疗组在生活质量(KPS)评分及细胞免疫功能均显著高于对照组,两组比较有明显统计学意义(P<0.05)。结论扶正解毒方联合多西他赛加奈达铂治疗晚期非小细胞肺癌(NSCLC)疗效确切,明显减轻化疗毒副反应,增强免疫功能,提高患者生存质量,延长生存期。     

顺铂联合多西他赛或吉西他滨治疗晚期非小细胞肺癌的临床对照研究

目的：比较多西他赛联合顺铂与吉西他滨联合顺铂治疗晚期非小细胞肺癌（NSCLC）的近期临床疗效和不良反应。方法：将84例晚期非小细胞肺癌患者随机分为多西他赛和顺铂组（DC组）42例及吉西他滨和顺铂组（GC组）42例。同一方案治疗2个周期评估近期疗效及不良反应。结果：评价入组的84例患者的近期疗效,DC组和GC组有效率分别为45.2%和40.5%,两组之间有效率差异无统计学意义（P〉0.05）。毒副反应主要为骨髓抑制和消化道反应。结论：多西他赛加顺铂与吉西他滨加顺铂方案治疗晚期非小细胞肺癌均具有较好的临床疗效且两者的疗效相似,不良反应可以耐受,可以用于临床一线治疗。     

Efficacy and safety of bevacizumab in combination with docetaxel for the first-line treatment of elderly patients with locally recurrent or metastatic breast cancer: results from AVADO

Background

Oncologic treatment in elderly patients is challenging, due to comorbidities, often impaired organ function, limited clinical trial evidence, inadequate guidelines and no consistent ‘elderly’ definition. We report exploratory sub-analyses of safety and efficacy in elderly patients, defined as ?65 years old, in AVastin And DOcetaxel (AVADO) receiving first-line bevacizumab plus docetaxel for metastatic breast cancer (mBC).

Patients and methods

Patients with HER2-negative, locally recurrent or mBC were randomised to 3-weekly docetaxel (100 mg/m²) with placebo, bevacizumab 7.5 mg/kg or bevacizumab 15 mg/kg, for 9 cycles or until disease progression or unacceptable toxicity. Patients had no prior chemotherapy for mBC.

Results

Progression-free survival (PFS) was increased with bevacizumab in the elderly subpopulation (n = 127), the effect being greater with higher dose (hazard ratio = 0.63 [95% confidence interval (CI) 0.383–1.032] versus 0.76 [95% CI: 0.46–1.262], respectively). PFS was numerically similar in the elderly and overall populations, but the former failed to achieve statistical significance. Overall response rates for docetaxel plus placebo, bevacizumab 7.5 mg/kg and 15 mg/kg were 44.7%, 36.6% and 50.0%, respectively. Effects on survival were not statistically significant. Bevacizumab was well tolerated in elderly patients, the most common adverse effects were neutropenia and febrile neutropenia; there was no excess of grade ? 3 cardiovascular events. There was no clear correlation between baseline hypertension and its development during study treatment.

Conclusions

In this exploratory sub-analysis in AVADO, bevacizumab plus docetaxel showed efficacy in elderly patients similar to the overall study population. There were no unexpected safety signals in patients aged 65 years or older.     

Induction chemotherapy with triweekly docetaxel and cisplatin followed by concomitant chemoradiotherapy with or without surgery in stage III non-small-cell lung cancer: a phase II study

Background

The main goal of this study was to evaluate the feasibility and effectivity of triweekly docetaxel/cisplatin followed by weekly docetaxel/cisplatin concomitantly with radiotherapy with or without surgery in locally advanced non–small-cell lung cancer (NSCLC) patients.

Materials and Methods

Thirty five patients with locally advanced NSCLC were enrolled. Combination chemotherapy with triweekly docetaxel/cisplatin (75 mg/m²) was administered as induction regimen. After induction chemotherapy, patients were evaluated for surgery if their disease subsequently downstaged. Six cycles of weekly docetaxel/cisplatin (20 mg/m²) concurrently with radiotherapy up to a 60 Gy were administered after induction chemotherapy with or without surgery. Response, toxicity, time-to-progression and overall survival were evaluated.

Results

Twelve patients with stage IIIA-N2 and 23 patients with stage IIIB-T4N0-2 were evaluated (median age, 54 years). After 94 cycles of induction chemotherapy, partial response was achieved in 20 patients, 9 patients had stable disease and six had progressive disease. After overall treatment, 6 patients achieved complete response, 19 patients had partial response, 8 patients had progressive disease, and 2 patients had stable disease. Two patients experienced grade 3-4 pulmonary toxicity and 1 patient experienced grade 3 esophageal toxicity. Six patients underwent surgery. Median overall survival for all patients was 15 months and time-to-progression was 13 months with a median follow-up of 22 months.

Conclusion

Triweekly docetaxel plus cisplatin followed by weekly docetaxel plus cisplatin concomitantly with radiotherapy is effective and feasible and seems to be an alternative option for patients who have locally advanced NSCLC. Surgery may provide additional benefit for patients whose disease adequately downstaged after induction chemotherapy.     

Randomised phase II trial of 4 dose levels of single agent docetaxel in performance status (PS) 2 patients with advanced non-small cell lung cancer (NSCLC): DOC PS2 trial. Manchester lung cancer group

Background

The role of chemotherapy for advanced NSCLC patients and ECOG PS2 remains controversial. We evaluated 4 doses of 3-weekly docetaxel to identify a less toxic, clinically effective dose.

Methods

Seventy-three patients with stage III (22%) (unsuitable for radical surgery/radiotherapy) and IV (78%) NSCLC were randomized to receive 4 doses of 3-weekly docetaxel, for 4 cycles: arm (A) 40 mg/m² (n = 17), arm (B) 50 mg/m² (n = 17), arm (C) 60 mg/m² (n = 19), arm (D) 50 mg/m² escalated by 10 mg/m² to a maximum of 70 mg/m² (n = 19). Primary endpoints: maximum tolerated dose, RR, duration of response, symptom improvement, toxicity and QoL. Secondary endpoint: overall survival (OS). Patients and disease characteristics were well balanced. Median age was 67 (range 45-81), there were 32 male and 41 female, histology subtype: squamous/adenocarcinoma/mixed/NOS = 42%/49%/4%/5%.

Results

Seven patients did not receive any treatment because of deterioration in PS or death. 50% of patients in arm D, who received more than one cycle, received dose escalation. There was no statistical difference in the number of cycles administered (arms A, B and D: median 2 cycles and arm C: median 3 cycles) and no difference in RR: arm A = 6%, arm B = 6%, arm C = 10%, and arm D = 0%. There was no statistically significant difference in grade 3/4 neutropenia and thrombocytopenia between the four arms. No difference was observed in hospitalization rate, blood transfusions, antibiotics administration and non-haematological toxicity. QoL: no difference in total scores between baseline and cycles 1-4. There was a significant decrease in pain scores from baseline to post cycles 2 and 3 (p = 0.025 and p = 0.002, respectively). There was no difference in OS (p = 0.992). Median survival and 6-month survival were 61, 86, 88 and 97 days and 29%, 33%, 21% and 26% for arms A, B, C, and D, respectively.

Conclusions

Clinical efficacy of docetaxel was observed at all dose levels. Higher dose levels were not associated with increased toxicities, use of IV antibiotics or hospitalization rates. However, the median survival observed is shorter than historical data and do not support further evaluation of these doses of single agent docetaxel in this population.     

Multicenter phase II study evaluating docetaxel and cisplatin as neoadjuvant induction regimen prior to surgery or radiochemotherapy with docetaxel,followed by adjuvant docetaxel therapy in chemonaive patients with NSCLC stage II,IIIA and IIIB (TAX-AT 1.203 Trial)

Objectives

Neoadjuvant therapy with a platinum based doublet is an option in NSCLC patients with upfront resectable disease. However, the role of neoadjuvant induction in stages IIIA and IIIB and in initially not resectable patients is unclear.

Patients and methods

In this phase II trial, 78 patients with locally advanced NSCLC, of whom 56 were considered not resectable at initial diagnosis, were treated with three neoadjuvant cycles of docetaxel and cisplatin and subjected to radical surgery if resectable. Definitive radiochemotherapy (RCT) using weekly docetaxel was the prespecified alternative if patients were not resectable at restaging. The primary objective was response to neoadjuvant induction.

Results

After induction, 36 (46%) were radically operated and 24 (31%) were treated with RCT. Overall, 32 patients (41%) completed the entire study plan. Partial response to induction therapy was observed in 43 patients (55%); furthermore, 19 of 56 initially not resectable cases (34%) became resectable upon induction. Median progression-free (PFS) and overall survival (OS) were 8.5 and 16.4 months for the whole cohort. Encouragingly, conversion to resectability was predictive for favorable outcome. On the other hand, patients who were not resectable at restaging and received RCT were characterized by a rather unfavorable prognosis (5-year and 10-year OS, whole cohort: 20% and 12%; RCT: 8% and 0%; surgery: 37% and 24%, respectively).

Conclusion

Neoadjuvant induction with the doublet docetaxel/cisplatin and subsequent radical resection resulted in favorable survival. Of note, conversion to resectability was mandatory for the chance of cure in patients considered initially not resectable.