Phase 2 trial of pemetrexed disodium and carboplatin in previously untreated extensive‐stage small cell lung cancer,N0423

BACKGROUND:

In extensive‐stage small cell lung cancer (SCLC), the combination of pemetrexed plus carboplatin has shown activity and appeared to be well‐tolerated. We conducted a trial to confirm the efficacy and to assess the tolerability of this chemotherapy combination.

METHODS:

Patients with untreated extensive‐stage SCLC were enrolled in this phase 2 open‐labeled study. They receive pemetrexed 500 mg/m² and carboplatin (area under the curve of 5) every 21 days for a maximum 6 cycles. The primary endpoint for this trial was the confirmed response rate and the accrual goal was 70 patients.

RESULTS:

Forty‐six eligible patients (29 aged <70 years, 17 aged ≥70 years) were accrued to this study. The efficacy outcomes were similar between the 2 age groups. Overall, the confirmed response rate was 35% (16 of 46; 95% confidence interval [CI], 21%‐50%), where all 16 were partial responses. On the basis of these results, we had strong evidence that the study would not meet the preset efficacy criteria and was, therefore, closed before full accrual. The median duration of response was 4.4 months (95% CI, 2.9‐5.2). Median overall survival for patients aged <70 years and aged ≥70 years was 9.2 months (95% CI, 5.4‐11.6) and 10.8 months (95% CI, 2.2‐14.3), respectively. Grade 3 or higher toxicity rates were similar between the younger and older patients. Grade 3/4 and grade 4 hematological toxicities were observed in 46% and 26% of patients, respectively.

CONCLUSIONS:

Although well‐tolerated, the combination of pemetrexed and carboplatin is not as effective as standard therapy in patients with untreated extensive‐stage SCLC. Cancer 2010. © 2010 American Cancer Society.     

Feasibility study of chemoradiotherapy followed by amrubicin and cisplatin for limited‐disease small cell lung cancer

To evaluate the feasibility of amrubicin plus cisplatin (AP) following chemoradiotherapy for limited‐disease small‐cell lung cancer, chemo‐naïve patients aged 20–70 years with a performance status of 0 or 1 and normal organ functions were treated with etoposide 100 mg/m² on days 1–3, cisplatin 80 mg/m² on day 1 and concurrent thoracic radiotherapy at 45 Gy/30 fractions (EP‐TRT), followed by three cycles of amrubicin 40 mg/m² on days 1–3 and cisplatin 60 mg/m² on day 1 every 3 weeks. The EP‐TRT could be completed in 21 patients (15 male and 6 female patients with a median age of 62 years). Of these, 2, 1 and 18 (86%) patients received one, two and three cycles of AP, respectively. Sixteen (76%) patients required granulocyte‐colony stimulating factor (G‐CSF) support. Grade 3/4 neutropenia occurred in all patients. Grade 3 febrile neutropenia was observed in 9 patients, lasting for 1 day in 5 patients. The incidences of grade 3/4 thrombocytopenia and anemia were 43 and 24%, respectively. Grade 3 infection and anorexia occurred in 2 and 3 patients, respectively. The response rate was 95%. The median (95% confidence interval [CI]) progression‐free survival (PFS) was 41.9 (0–102) months, and the 5‐year PFS rate (CI) was 41.9% (20.4–63.4%). The median overall survival (OS) has not been reached yet, and the 5‐year OS rate (CI) was 57.8% (35.2–80.4%). In conclusion, EP‐TRT followed by AP therapy was well‐tolerated, although a large number of patients required G‐CSF support.     

胸部放疗在广泛期小细胞肺癌治疗中的作用

目的:探讨胸部放疗在广泛期小细胞肺癌治疗中的作用。方法:广泛期小细胞肺癌患者112例。其中化疗+放疗组69例,单纯化疗组43例。胸部放疗剂量:<50Gy 23例,≥50Gy 46例。比较化疗+放疗组和单纯化疗组的治疗效果。结果:全组近期疗效:CR 14.3%(16/112),PR 59.8%(67/112)。生存率:1年49%,2年19%,中位生存期10.3个月。化疗+放疗组69例,疗效评价:CR 19.8%,PR 69%,1年生存率52.9%,2年生存率18.8%,中位生存期11个月。单纯化疗43例,疗效评价:CR 6.8%,PR 47%,1年生存率28.9%,2年生存率7.8%,中位生存期6个月。结论:胸部放疗在广泛期小细胞肺癌治疗中可以较好的缓解症状和体征、改善生存质量和延长生存时间。     

A weekly regimen of cisplatin, paclitaxel and topotecan with granulocyte-colony stimulating factor support for patients with extensive disease small cell lung cancer: a phase II study

The present study was aimed at defining the antitumour activity of the cisplatin-paclitaxel-topotecan (CPT) weekly administration with G-CSF support in chemo-naive SCLC patients with extensive disease (ED-SCLC). Chemonaive ED-SCLC patients received cisplatin 40 mg/m(2), paclitaxel 85 mg/m(2), and topotecan 2.25 mg/m(2)weekly, with G-CSF (5 microg/kg days 3-5) support, for a maximum of 12 weeks. 37 patients were treated, for a total of 348 cycles delivered. 8 complete responses (22%) and 22 partial responses (59%) were recorded, giving an 81% [95% CI = 65-92%] ORR. At a 13-month (range, 4-26) median follow-up, median progression-free and overall survival were 8 months and 12.5 months, with 1-year and 2-year projected survivals of 55% and 21%, respectively. No toxic deaths occurred. Grade 4 neutropenia and thrombocytopenia occurred in 6 and 3 patients, respectively. Only one case of neutropenic sepsis was recorded, while haemorrhagic thrombocytopenia was never observed. Diarrhoea, paraesthesias and fatigue were the main nonhaematologic toxicities being severe in 6, 2 and 10 patients, respectively. The weekly CPT combination with G-CSF support represents a well tolerated therapeutic approach in chemo-naive ED-SCLC patients. The activity rate seems at least similar to that achievable with the standard front-line approaches.     

Concurrent end‐phase boost high‐dose radiation therapy for non‐small‐cell lung cancer with or without cisplatin chemotherapy*

The aim of this study was to audit the results of a high‐dose, combined‐modality prospective protocol for non‐small‐cell lung cancer in terms of survival, disease‐specific survival and toxicity. One hundred and twenty‐one patients with non‐small‐cell lung cancer were treated with a concurrent, end‐phase, boost, high‐dose radiotherapy protocol with 65 Gy in 35 fractions for more than 5 weeks. Sixty‐six patients received radiotherapy alone (group 1), 29 received concurrent chemoradiation (group 2) and 26 received neoadjuvant and concurrent chemotherapy (group 3). Thirty‐four patients had stage I disease, six had stage II and 81 had stage III. Overall median survival was 23 months: 75% at 1 year and 23% at 5 years. Median survivals for patients with stage I and stages II and III disease were 43 and 19 months, respectively. For stages II and III patients by groups 1–3, median survivals were 18, 25 and 18 months, respectively, and 2‐year survivals were 36, 52 and 38%, respectively. Toxicity was acceptable. Overall, 9% had symptomatic pneumonitis and 7% had grades 3 and 4 oesophagitis. For those who had the mediastinum included in the volume, grade ≥3 oesophagitis occurred in 0, 11 and 22% (n = 110, P = 0.001), respectively, for treatment groups 1–3. Overall treatment‐related mortality was 3%, consisting of two septic deaths, one pneumonitis and possibly one late cardiac event, all occurring in patients who had chemotherapy (7% of 55 patients). Treatment‐related mortality declined over the study period. Accelerated radiotherapy was well tolerated, with only moderate increased acute toxicity when combined with concurrent platinum chemotherapy. Toxicity was enhanced by induction chemotherapy. Overall survival outcomes were excellent for this condition. Continued use of this radiotherapy schedule is recommended as the platform for assessment of other chemotherapy schedules.     

A multicenter phase II study of belotecan, a new camptothecin analogue, as a second-line therapy in patients with small cell lung cancer

Belotecan (Camtobell, CKD602) is a new camptothecin derivative antitumor agent that belongs to the topoisomerase inhibitors. The aim of this phase II study was to evaluate the efficacy and safety of single agent belotecan as a second-line therapy in patients with small cell lung cancer (SCLC).Patients who were previously treated for SCLC were entered into the study. Belotecan was given by daily intravenous infusion for five consecutive days, every three weeks.Twenty-five patients were enrolled in this study. On an intention-to-treat basis, belotecan induced an overall response rate of 24%, a median overall survival of 9.9 months, a median time to progression of 2.2 months, and a 1-year survival rate of 38.3%. Grade 3/4 neutropenia developed in 88.0% of patients and grade 3/4 thrombocytopenia in 40.0%. Nonhematologic toxicity of grade 3 or 4 was low.The results suggest that belotecan is relatively active and well tolerated as a second-line agent in patients with SCLC.     

Belotecan, new camptothecin analogue, is active in patients with small-cell lung cancer: results of a multicenter early phase II study.

BACKGROUND: Belotecan (Camtobell, Chong Keun Dang Corp, Seoul, Korea; CKD602) is a new camptothecin analogue. This study aimed to investigate the safety and efficacy of single-agent belotecan for small-cell lung cancer (SCLC). PATIENTS AND METHODS: Twenty-seven patients with chemotherapy-naive or chemosensitive SCLC were treated with belotecan 0.5 mg/m(2)/day on days 1-5 of a 3-week cycle. All 27 patients were assessable for toxicity, and 21 patients assessable for response. RESULTS: Nine patients (42.9%) showed objective tumor responses including one complete response; seven (63.6%) in 11 chemotherapy-naive patients; and two (20.0%) in 10 chemosensitive patients. With a median follow-up of 5 years, median progression-free and survival time for chemotherapy-naive patients were 4.8 months and 11.9 months, respectively, while the corresponding values for chemosensitive patients were 3.3 months and 10.5 months, respectively. The most common toxicity was neutropenia. CONCLUSION: Belotecan was active in SCLC patients as a single agent, warranting further investigations of belotecan in combination with platinum or other active agents.     

多西他赛联合顺铂治疗晚期非小细胞肺癌的临床观察

目的：观察多西他赛联合顺铂方案对晚期非小细胞肺癌的疗效和毒副反应。方法：初治、晚期非小细胞肺癌75例，随机分为观察组和对照组。观察组40例，应用多西他赛联合顺铂化疗；对照组35例，应用异长春花碱联合顺铂化疗。观察两组疗效和毒副反应，2周期后评价疗效。结果：75例患者均可评价疗效，近期有效率分别为50％、42．9％，差异无统计学意义（P〉0．05）。两组Ⅲ、Ⅳ度毒副反应均以骨髓抑制和消化道反应为主，其发生率无显著性差异（P〉0．05）。观察组有2例患者出现严重体液潴留，未出现相关性死亡。结论：多西他赛联合顺铂化疗对晚期非小细胞肺癌有较好的疗效，但可致体液潴留，应用多西他赛时需强调化疗前激素的预处理、化疗后的病情监测和发生体液潴留时的处理。     

Thoracic radiation therapy improves the overall survival of patients with extensive-stage small cell lung cancer with distant metastasis

BACKGROUND:

The authors conducted a retrospective study to evaluate the effects of thoracic radiation therapy (TRT) for patients with extensive‐stage small cell lung cancer (ED‐SCLC).

METHODS:

Between January 2003 and December 2006, the records of 119 patients who were diagnosed with ED‐SCLC (all with distant metastasis [M1]) were included in the study. Sixty patients received chemotherapy (ChT) and TRT (ChT/TRT), and 59 patients received ChT alone. The ChT regimens consisted of either carboplatin and etoposide (CE) or cisplatin and etoposide (PE). The total dose of TRT ranged from 40 to 60 grays (Gy) at 1.8 to 2.0 Gy per fraction.

RESULTS:

For the entire group, the median survival was 13 months, and the 2‐year and 5‐year overall survival (OS) rates were 26.1% and 6.5%, respectively. The median survival and the 2‐year and 5‐year OS rates were 17 months, 35%, and 7.1%, respectively, in the ChT/TRT group and 9.3 months, 17%, and 5.1%, respectively, in the ChT group (P = .014). However, this improvement was achieved at the expense of low toxicity. Multivariate analysis revealed that receiving ≥4 cycles of ChT (P = .032) and TRT (P = .005) were favorable prognostic factors for OS. Of all toxicities, only high‐grade leucopenia (grade >3) was more frequent in the ChT/TRT group.

CONCLUSIONS:

The addition of TRT to ChT improved the OS of patients with ED‐SCLC. Furthermore, receiving ≥4 cycles of ChT and TRT were independent, favorable prognostic factors for OS. Cancer 2011;. © 2011 American Cancer Society.     

Phase II study of nab‐paclitaxel + carboplatin for patients with non‐small‐cell lung cancer and interstitial lung disease

The prognosis of non‐small‐cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) is poor, and 5%‐20% of those receiving chemotherapy experience ILD exacerbation. To evaluate the safety and efficacy of nab‐paclitaxel plus carboplatin for NSCLC patients with ILD, we undertook a multicenter phase II study. Chemotherapy‐naïve patients with advanced NSCLC and mild or moderate ILD received nab‐paclitaxel (100 mg/m², days 1, 8, and 15) plus carboplatin (area under the curve = 6, day 1) every 3 weeks for 4 cycles (maximum, 6 cycles). Interstitial lung diseases were diagnosed based on criteria for fibrosing interstitial pneumonia. The primary endpoint was the prevalence of exacerbation‐free ILD 28 days after completion of protocol treatment. Secondary endpoints were response rate, progression‐free survival, overall survival, prevalence of exacerbation‐free ILD, and toxicity. Ninety‐four patients were enrolled, and 92 patients received any protocol treatment. Median age was 70 years, and 58% had nonsquamous histology. In the primary analysis, the prevalence of exacerbation‐free ILD 28 days after protocol treatment was 95.7% (88/92; 90% confidence interval, 90.3‐98.5), which met the primary endpoint. Response rate was 51% (95% confidence interval, 40%‐62%). At the time of data cut‐off, median progression‐free survival was 6.2 months, and median overall survival was 15.4 months. The most common grade 3/4 adverse events were neutropenia (75%), leukopenia (53%), anemia (48%), and thrombocytopenia (20%). Two treatment‐related deaths (1 each of pulmonary infection and ILD exacerbation) were observed. This study showed that a combination of nab‐paclitaxel with carboplatin was tolerable in NSCLC patients with mild or moderate ILD in terms of safety. This study is registered at the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN 000012989).     

A phase 2 study of irinotecan, cisplatin, and simvastatin for untreated extensive-disease small cell lung cancer

BACKGROUND:

The objective of this study was to investigate the efficacy of simvastatin in combination with irinotecan and cisplatin in chemotherapy‐naive patients with extensive‐disease small‐cell lung cancer (ED‐SCLC).

METHODS:

In this phase 2 study, 61 patients received treatment with irinotecan (65 mg/m²) and cisplatin (30 mg/m²) on Days 1 and 8 every 3 weeks until either death or disease progression occurred. Patients also received oral simvastatin (40 mg daily) during the course of chemotherapy. The primary endpoint was 1‐year survival. Secondary endpoints included the response rate (RR), progression‐free survival (PFS), and toxicity.

RESULTS:

The 1‐year survival rate was 39.3%. The median overall survival (OS) was 11 months, and the median PFS was 6.1 months. Overall, the RR was 75%. The most common grade 3/4 toxicity was neutropenia (67%). Efficacy of the treatment was associated significantly with smoking status. Compared with never‐smokers, ever‐smokers had a better RR (40% vs 78%; P = .01), a longer PFS (2.5 months vs 6.4 months; P = .018), and had a trend toward an improved OS (9.0 months vs 11.2 months; P = .095). The effect of smoking on survival was apparent when ever‐smokers were subdivided according to pack‐years (PY) of smoking. Ever‐smokers who had smoked >65 PY had a significantly longer OS compared with ever‐smokers who had smoked ≤65 PY or never‐smokers (20.6 months vs 10.6 months vs 9.0 months, respectively; log‐rank P = 0.032). In multivariate analysis, PY >65 was predictive of longer survival (hazard ratio, 0.280; 95% confidence interval, 0.113‐0.694).

CONCLUSIONS:

The current results indicated that simvastatin in combination with irinotecan and cisplatin did not improve the survival of patients with ED‐SCLC. Although the subgroup analysis by smoking status was exploratory, the addition of simvastatin to irinotecan and cisplatin may improve the outcome of heavy smokers with ED‐SCLC. Cancer 2011. © 2010 American Cancer Society.     

66例广泛期小细胞肺癌患者预后分析

目的:分析广泛期小细胞肺癌的独立预后因素。方法:回顾性分析安阳市肿瘤医院2005年7月至2009年7月治疗的66例广泛期小细胞肺癌的临床资料,所有患者均经组织病理或细胞学确诊。生存分析采用Kaplan-Meier法计算生存率,Log-rank检验进行单因素分析,并对有意义的单因素通过COX风险模型筛选影响预后因素。结果:广泛期患者1、2、3年生存率分别为40.9%、13.6%、6.1%,中位生存时间为10个月。单因素分析显示体重减轻情况、一线化疗疗效、总化疗周期数、治疗方式、低钠血症与患者预后相关,具有统计学差异。多因素分析显示一线化疗疗效、总化疗周期数、低钠血症对患者的总生存时间具有显著影响。结论:一线化疗疗效、总化疗周期数和低钠血症是影响广泛期小细胞肺癌的独立预后因素。     

培美曲塞联合顺铂与吉西他滨联合顺铂治疗晚期非小细胞肺癌的临床研究

目的:评估培美曲塞联合顺铂与吉西他滨联合顺铂治疗晚期非小细胞肺癌（NSCLC）的近期疗效及毒副反应。方法:收集有明确病理诊断的晚期NSCLC患者78例,随机分为2组。PP组:选择培美曲塞联合顺铂;GP组:选择吉西他滨联合顺铂化疗。每组各39例,21天为1个周期,2个周期后评价疗效。结果:PP组和GP组总缓解率分别为41.0%和43.6%,无显著性差异（P＞0.05）。PP组血液学毒性的发生率明显低于GP组（P＜0.05）,其他毒副反应比较无统计学差异（P＞0.05）。结论:PP和GP方案均为治疗晚期NSCLC的有效方案,疗效、疾病控制率及中位生存期均相近,但PP方案血液学毒性和脱发较GP方案明显轻,PP方案组患者耐受性更好。     

去甲长春花碱联合顺铂治疗Ⅲb—Ⅳ期非小细胞肺癌疗效观察

目的：研究去甲长春花碱（NVB）,顺铂（DDP）联合治疗Ⅲb-Ⅳ非小细胞肺癌疗效,并与MVP方案作随机对照。方法：NBV＋DDP治疗16例,MVP组治疗20例,结果：NVB＋DDP组有效率50．05,MVP组有效率40．05。两组主要毒性反应为骨髓抑制和消化道反应。Ⅱ-Ⅳ度静脉炎发生率NVB＋DDP组（37．5％）高于MVP组（0．0％）（P＜0．01）。Ⅱ-Ⅳ度周围神经毒性发生率MVP组（10．0％）高于NVB＋DDP组（0．0％）（P＞0．05）。结论：NVB、DDP联合治疗非小细胞肺癌,有效率高、毒性可耐受,是临床治疗非小细胞肺癌切实可的方案。     

诺维本联合顺铂治疗晚期非小细胞肺癌疗效观察

目的观察诺维本联合顺铂治疗晚期非小细胞肺癌的疗效与毒性反应。方法110例符合条件的患者接受下述联合方案化疗2~6周期,诺维本25mg/m2iv d1、8,顺铂75mg/m2iv d1或25 mg/m2iv d1~3,至少2周期进行评价。结果本组患者总有效率为48.18%;IIIA期与IV期比较疗效有显著性差异(P=0.041),而IIIB期与IV期比较、III期及IV期与复发转移者比较疗效均无显著性差别(P>0.05);鳞癌及腺癌与腺鳞癌比较疗效有显著性差异(P=0.020),而鳞癌与腺癌比较疗效无显著性差异(P>0.05);初治者疗效明显优于复治者(P=0.033)。毒性反应以骨髓抑制为主,III~IV度白细胞减少发生率61.82%,其中粒细胞减少性发热30.91%,末梢神经毒性发生率32.31%。其它不良反应耐受性良好。结论诺维本联合顺铂是治疗晚期非小细胞肺癌有效、耐受性良好和比较经济的方案,值得推广应用。