Chemoradiotherapy in Elderly Patients With Non–Small-Cell Lung Cancer: Long-Term Follow-Up of a Randomized Trial (JCOG0301)

Introduction

In the phase III JCOG0301 trial, chemoradiotherapy (CRT) with daily low-dose carboplatin showed significant benefits in elderly patients with locally advanced non–small-cell lung cancer (NSCLC) compared with radiotherapy (RT) alone. However, the long-term patterns and cumulative incidences of toxicity associated with CRT and RT in elderly patients are not well elucidated. We report long-term survival data and late toxicities after a minimum follow-up of 6.4 years.

Randomized double-blind trial of combined modality treatment with or without amifostine in unresectable stage III non-small-cell lung cancer.

PURPOSE: Greater toxicities have been recognized to be a consequence of combined chemotherapy and radiotherapy in the treatment of locally advanced non-small-cell lung cancer (NSCLC). This study was designed to determine if the use of amifostine could reduce treatment-related toxicities associated with the use of paclitaxel plus carboplatin and thoracic radiotherapy. PATIENTS AND METHODS: Sixty patients with unresectable stage III NSCLC were treated with two cycles of paclitaxel 175 mg/m2 and carboplatin (area under the time-concentration curve = 6), followed by thoracic radiotherapy (64 Gy) with concurrent weekly paclitaxel 60 mg/m2. Patients were randomly assigned to receive 740 mg/m2 of amifostine (arm A) or placebo (arm B) before each dose of paclitaxel and carboplatin. Treatment-related toxicities were evaluated at each visit and nerve conduction tests were performed before and after treatment for the objective assessment of neurotoxicity. RESULTS: There was no significant difference between arms A and B in grade 3 to 4 neutropenia. In all 72 neurophysiological parameters measured, there was no significant difference between the two treatment arms, although there was a trend toward fewer patients showing deterioration in arm A for six of the parameters. Grade 2 to 3 esophagitis occurred in 43% of patients in arm A and in 70% of patients in arm B. The difference of -27% (95% confidence limit = -50%, 0.4%) was not statistically significant. Response rates and survival were also not significantly different between the two arms. CONCLUSION: Pretreatment with amifostine showed a trend toward reducing the severity of esophagitis associated with concurrent chemoradiotherapy, but it did not reach statistical significance. There was no significant protective effect on hematologic or neurologic toxicities induced by paclitaxel and carboplatin.     

Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial.

PURPOSE: Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. PATIENTS AND METHODS: Patients with Ho's N2 or N3 stage or N1 stage with nodal size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). RESULTS: Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P =.016). CONCLUSION: Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.     

A randomised phase III study of palliative radiation with concomitant carboplatin for brain metastases from non-small cell carcinoma of the lung

PURPOSE: To determine if the addition of carboplatin chemotherapy to whole brain irradiation improves response and survival in patients with brain metastases from non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-two patients with brain metastases from NSCLC and performance status ECOG 0-2 were randomised to receive either whole brain radiotherapy (WBRT) alone (20Gy in five fractions) or the same radiotherapy plus concomitant carboplatin (70 mg/m(2) intravenously for 5 days). RESULTS: The median survival was 4.4 months in the radiotherapy alone (RT) arm and 3.7 months in the combined treatment (RTC) arm (P = 0.64). The objective response rates of 10% on the RT arm and 29% on the RTC arm were not significantly different (P = 0.24). The trial was closed early because of poor accrual. CONCLUSIONS: Although no firm conclusions can be made regarding the efficacy of the combined treatment, this prospective study highlights the poor objective response rates and relatively poor symptom control despite standard treatment of brain metastases from NSCLC.     

Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer.

PURPOSE: A phase III study was performed to determine whether concurrent or sequential treatment with radiotherapy (RT) and chemotherapy (CT) improves survival in unresectable stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were assigned to the two treatment arms. In the concurrent arm, chemotherapy consisted of cisplatin (80 mg/m(2) on days 1 and 29), vindesine (3 mg/m(2) on days 1, 8, 29, and 36), and mitomycin (8 mg/m(2) on days 1 and 29). RT began on day 2 at a dose of 28 Gy (2 Gy per fraction and 5 fractions per week for a total of 14 fractions) followed by a rest period of 10 days, and then repeated. In the sequential arm, the same CT was given, but RT was initiated after completing CT and consisted of 56 Gy (2 Gy per fraction and 5 fractions per week for a total of 28 fractions). RESULTS: Three hundred twenty patients were entered onto the study. Pretreatment characteristics were well balanced between the treatment arms. The response rate for the concurrent arm was significantly higher (84. 0%) than that of the sequential arm (66%) (P =.0002). The median survival duration was significantly superior in patients receiving concurrent therapy (16.5 months), as compared with those receiving sequential therapy (13.3 months) (P =.03998). Two-, 3-, 4-, and 5-year survival rates in the concurrent group (34.6%, 22.3%, 16.9%, and 15.8%, respectively) were better than those in the sequential group (27.4%, 14.7%, 10.1%, and 8.9%, respectively). Myelosuppression was significantly greater among patients on the concurrent arm than on the sequential arm (P =.0001). CONCLUSION: In selected patients with unresectable stage III NSCLC, the concurrent approach yields a significantly increased response rate and enhanced median survival duration when compared with the sequential approach.     

Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer: a randomized study

PURPOSE: The superiority of chemoradiotherapy (CRT) over radiation alone in locally advanced non-small cell lung cancer (NSCLC) has been proven, but the relative merits of a concurrent schedule versus their sequential administration are less clear. This study compared the safety and efficacy of concurrent and sequential CRT, with chemotherapy (CT) consisting of a cisplatin and vinorelbine regimen, in patients with locally advanced NSCLC. PATIENTS AND METHODS: One hundred and two previously untreated patients (aged 42-75 years) with locally advanced, stage IIIA (n = 15) or stage IIIB (n = 87) NSCLC were entered into the study. The CT schedule consisted of up to four cycles of cisplatin 80 mg/m(2) on day 1, and vinorelbine 25 mg/m(2) at the first and fourth cycles (12.5 mg/m(2) during the 2nd/3rd cycles) on days 1, 8, 15 of a 28-day cycle. Radiotherapy (RT) was prescribed at a dose of 60 Gy/30 fractions, given as five fractions per week for 6 weeks. In the concurrent arm (arm A), RT was started on day 4 of cycle 2; whilst in the sequential arm (arm B), RT started within 2 weeks after completion of CT. Fifty-two patients were randomized to concurrent treatment and 50 to the sequential schedule. RESULTS: Overall survival was significantly longer in arm A (median survival 16.6 months) versus arm B (median survival 12.9 months) (P = 0.023 by means of log-rank test; hazard ratio HR = 0.61, 95% CI of HR (0.39-0.93)), and time to progression (TTP) was also significantly longer in arm A (median time to progression 11.9 months) versus arm B (median time to progression 8.5 months) (P = 0.024 by means of log-rank test; HR = 0.62, 95% CI of HR (0.38-0.93)). Ninety-eight patients were evaluable for response and 101 for toxicity. The overall response rate was significantly higher in arm A, 80% (with 21% complete response (CR)) compared with 47% (with 17% CR) in arm B (P = 0.001 by means of chi(2)-test). WHO grade 3 or 4 toxicity was more frequent in arm A than in arm B, with a significantly greater incidence of leucopenia (53% versus 19%, P = 0.009 by means of chi(2) test) and nausea/vomiting (39% versus 15%, P = 0.044 by means of chi(2) test). There were no treatment related deaths. CONCLUSION: In this study population, concurrent CRT demonstrated significant benefit in terms of response rate, overall survival and time to progression over sequential CRT. The concurrent CRT schedule was associated with higher toxicity; however, the adverse event profile was acceptable in both arms.     

Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer: Groupe Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe Fran?ais de Pneumo-Cancérologie NPC 95-01 Study.

PURPOSE: We conducted a phase III study to compare the survival impact of concurrent versus sequential treatment with radiotherapy (RT) and chemotherapy (CT) in unresectable stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomly assigned to one of the two treatment arms. In the sequential arm, patients received induction CT with cisplatin (120 mg/m2) on days 1, 29, and 57, and vinorelbine (30 mg/m2/wk) from day 1 to day 78, followed by thoracic RT at a dose of 66 Gy in 33 fractions (2 Gy per fraction and 5 fractions per week). In the concurrent arm, the same RT was started on day 1 with two concurrent cycles of cisplatin 20 mg/m2/d and etoposide 50 mg/m2/d (days 1 to 5 and days 29 to 33); patients then received consolidation therapy with cisplatin 80 mg/m2 on days 78 and 106 and vinorelbine 30 mg/m2/wk from days 78 to 127. RESULTS: Two hundred five patients were randomly assigned. Pretreatment characteristics were well balanced between the two arms. There were six toxic deaths in the sequential arm and 10 in the concurrent arm. Median survival was 14.5 months in the sequential arm and 16.3 months in the concurrent arm (log-rank test P = .24). Two-, 3-, and 4-year survival rates were better in the concurrent arm (39%, 25%, and 21%, respectively) than in the sequential arm (26%, 19%, and 14%, respectively). Esophageal toxicity was significantly more frequent in the concurrent arm than in the sequential arm (32% v 3%). CONCLUSION: Although not statistically significant, clinically important differences in the median, 2-, 3-, and 4-year survival rates were observed, with a trend in favor of concurrent chemoradiation therapy, suggesting that is the optimal strategy for patients with locally advanced NSCLC.     

Concurrent chemoradiotherapy (CRT) with S-1 and cisplatin (CDDP) in patients (pts) with locally advanced head and neck cancer (HNC)

The standard care for unresectable locally advanced head and neck cancer (HNC) is concurrent chemoradiotherapy (CRT). Although there is no standard regimen of CRT, a platinum-based regimen has shown a better survival benefit than other regimens. The control arm in a randomized trial for unresectable locally advanced HNC is radiotherapy concurrent with CDDP (100 mg/m2, every 3 weeks), which has been considered to be too toxic for clinical practice in Western countries and has required frequent dose modifications. Because the Japanese also have been considered unable to tolerate this regimen, no prospective study of it has been conducted in Japan. Most Japanese patients with locally advanced head and neck cancer have received concurrent chemoradiotherapy with 5-FU and CDDP (70-80 mg/m2). S-1 has shown high activity in HNC with a response rate of 34%. Furthermore, a combination of cisplatin and S-1 therapy for HNC has been reported to have good efficacy. With this rationale in mind, we conducted a phase I study of CRT with S-1 and CDDP for unresectable locally advanced squamous cell carcinoma of the head and neck. The CR rate was very promising, though preliminary, and warrants further investigation. The Japan Clinical Oncology Group (JCOG) is planning a multicenter phase II study of concurrent chemoradiotherapy with S-1 and CDDP for locally advanced unresectable HNC.     

A randomised trial of radiotherapy compared with cisplatin chemo-radiotherapy in patients with unresectable squamous cell cancer of the esophagus.

BACKGROUND AND PURPOSE: Following our phase II experience, a randomised trial was undertaken to evaluate the efficacy of adding chemotherapy to radiotherapy in patients with unresectable squamous cell cancer of the esophagus. PATIENTS AND METHODS: Patients randomised to the RT group received 50 Gy/25 fx/5 weeks of teletherapy followed 1-2 weeks later with 12 Gy/2 fx of high-dose-rate intra-lumenal brachytherapy spaced a week apart. Following the first 3 years of recruitment, due to unexpected late morbidity, brachytherapy was excluded and the protocol modified to 66 Gy/33 fx/6.5 weeks. The CRT group received identical radiotherapy with concurrent weekly cisplatin at 35 mg/m(2) for 6-7 cycles. RESULTS: Between April 1999 and December 2005, 125 patients were randomised to a RT (n=60) or CRT group (n=65). Radiotherapy treatment was completed in 78% (47/60) of the RT group and 89% (58/65) of the CRT group (P=0.10). Six or more cycles of cisplatin could be delivered in 63% (41/65), which resulted in RTOG grade 3 neutropenia of 3%. Late morbidity in the form of ulcers (5% vs. 15% odds ratio 0.29, 95% CI 0.08-1.11, P=0.08) and strictures (13% vs. 28%, odds ratio 0.40, 95% CI 0.16-1.01, P=0.05) was observed in the RT and CRT groups, respectively. At a median follow up of 23 months of all patients alive (range 6-82 months) and with 95/125 events, the median, 1, 2 and 5 year projected survival was 7.1 months, 32.3%, 22.8% and 13.7% vs. 13.4 months, 57.6%, 38.9% and 24.8% for the RT and CRT groups, respectively (hazard ratio 0.65, 95% CI 0.44-0.98, P=0.038). CONCLUSIONS: The addition of concurrent cisplatin to radiotherapy resulted in a modest improvement in survival and was associated with manageable additional acute and late morbidity.     

A phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small-cell lung cancer (a Vanderbilt Cancer Center Affiliate Network Study)

PURPOSE: We conducted a prospective phase II study to determine the response rate, toxicity, and survival rate of concurrent weekly paclitaxel, carboplatin, and hyperfractionated radiation therapy (paclitaxel/carboplatin/HFX RT) followed by 2 cycles of paclitaxel and carboplatin for locally advanced unresectable non-small cell lung cancer (NSCLC). The weekly paclitaxel and carboplatin regimen was designed to optimize the radiosensitizing properties of paclitaxel during the concurrent phase of treatment. METHODS AND MATERIALS: Forty-three patients with unresectable stage IIIA and IIIB NSCLC from the Vanderbilt Cancer Center and Affiliate Network (VCCAN) institutions were entered onto the study from June 1996 until May 1997. Weekly intravenous (IV) paclitaxel (50 mg/m(2)/l-hour) and weekly carboplatin (AUC 2) plus concurrent hyperfractionated chest RT (1.2 Gy/BID/69.6 Gy) were delivered for 6 weeks followed by 2 cycles of paclitaxel (200 mg/m(2)) and carboplatin (AUC 6). RESULTS: Forty-two patients were evaluable for response and toxicities. Three patients achieved a complete response (7.2%) and 30 patients achieved a partial response (71.4%), for an overall response rate of 78.6% [95% C.I. (66.2%-91.0%)]. The 1- and 2-year overall and progression-free survival rates of all 43 patients were 61.6% and 35% respectively, with a median survival time of 14.3 months. The median follow-up time was 14 months. Esophagitis was the principal toxicity. Grade 3 or 4 esophagitis occurred in 11 patients (26%). There was an incidence of 7% grade 3 and 9.5% grade 4 pulmonary toxicities. CONCLUSIONS: Weekly paclitaxel, carboplatin, plus concurrent hyperfractionated RT is a well-tolerated outpatient regimen. The response rate from this regimen is encouraging and appears to be at least equivalent to the more toxic chemoradiation trials. These findings warrant further clinical evaluation of weekly paclitaxel/carboplatin/HFX RT in a phase III study.     

诱导化疗和紫杉醇每周同期化疗结合三维适形放射治疗不能手术的Ⅲ期非小细胞肺癌的初步结果

背景与目的:局部晚期非小细胞肺癌(non-smallcelllungcancer,NSCLC)单纯放疗局部控制率差,放化疗综合治疗及放疗剂量递增成为提高局控的主要研究方向,但最佳治疗模式尚未确定。本研究观察诱导化疗和三维适形放射治疗(three-dimensionalconformalradiotherapy,3DCRT)联合每周紫杉醇治疗NSCLC的毒性及初步疗效。方法:Ⅲ期NSCLC患者予紫杉醇(175mg/m2,d1)加卡铂(AUC=5～6,d1)诱导化疗2～4疗程,化疗后3～4周内开始3DCRT,剂量在满足V20≤31%,脊髓≤50Gy的条件下给予尽可能的高,联合每周紫杉醇40mg/m2同期化疗。结果:31例患者入组,诱导化疗毒性可耐受。同期放化疗期间,3例因3～4度急性毒性中止治疗,2例因身体虚弱分别中断治疗7天及12天,其余26例按计划完成治疗。白细胞下降发生率为51.6%(16/31,1例为3度,余为1～2度);3度淋巴细胞下降发生率达67.7%(21/31)。主要急性毒性为放射性食管炎和放射性肺炎,3度放射性食管炎3例,3～4度放射性肺炎2例。1～4度后期食管损伤各有1例发生;肺纤维化均不超过2度。肺原发灶总有效率(CR PR)为74.1%(CR1例,PD2例)。中位生存时间18.5个月,1、2、3年生存率分别为74.2%、41.9%、34.6%,中位局部无进展生存时间为14.3个月,1、2、3年局部无进展生存率分别为64.5%、32.3%、20.5%。结论:诱导化疗后3DCRT结合每周紫杉醇治疗局部晚期NSCLC能为大多数患者耐受,初步疗效令人鼓舞。     

A randomised phase III study of accelerated or standard fraction radiotherapy with or without concurrent carboplatin in inoperable non-small cell lung cancer: final report of an Australian multi-centre trial.

PURPOSE: To investigate the effects separately and together of (a) shortening overall treatment time and (b) giving concurrent carboplatin in patients having radical radiotherapy for inoperable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between April 1989 and May 1995, 204 patients with medically inoperable or technically unresectable NSCLC localised to the primary site and regional lymph nodes were randomised to receive one of four treatments using a 2 x 2 factorial design: standard radiotherapy, 60 Gy in 30 fractions in 6 weeks (R6); accelerated radiotherapy, 60 Gy in 30 fractions in 3 weeks (R3); standard radiotherapy as in R6 with carboplatin 70 mg/m2/day for 5 days during weeks 1 and 5 of radiotherapy (R6C); accelerated radiotherapy as in R3 with carboplatin 70 mg/m2/day for 5 days during week 1 of radiotherapy (R3C). RESULTS: The estimated median survival of all randomised patients was 15.7 months and estimated 2-year survival was 31%. The longest survival was seen in patients randomised to R6C (median 20.3 months, 41% surviving at 2 years) but there were no statistically significant differences between treatment arms or treatment factors (carboplatin versus no carboplatin, accelerated versus conventional radiotherapy). Haematological toxicity was significantly greater in patients treated with carboplatin and oesophageal toxicity was significantly greater and more protracted in patients treated with accelerated radiotherapy. CONCLUSIONS: This study failed to show a significant survival advantage for any of the treatment arms or factors. Halving overall treatment time resulted in significantly greater oesophageal toxicity with no suggestion of a survival advantage.     

A phase II trial of preoperative concurrent radiation therapy and weekly paclitaxel/carboplatin for patients with locally advanced non-small-cell lung cancer

This study was designed to evaluate the efficacy and toxicity of a novel preoperative combined-modality regimen in patients with locally advanced non-small-cell lung cancer (NSCLC). Patients with clinical stage IIB, IIIA, or IIIB NSCLC received preoperative combined-modality therapy with concurrent radiation therapy (RT) and weekly paclitaxel/carboplatin for 5 consecutive weeks. After this treatment, patients believed to have resectable disease by standard surgical criteria underwent thoracotomy. Patients whose disease remained unresectable after initial therapy received further RT with concurrent paclitaxel/carboplatin. Of 107 patients entered into this clinical trial, only 20 patients (19%) were considered to have surgically resectable disease at the time of study entry. Ninety-eight patients (92%) completed preoperative combined-modality therapy. Forty-nine patients (46%) underwent thoracotomy and 34 patients had definitive resection. Fourteen patients (13%) had pathologic complete response (pCR). Thirteen of 18 patients (72%) with clinical stage T3 N0 (IIB) tumors had definitive resections, and 33% had pCR. After a median follow-up of 32 months, the 1- and 2-year actuarial survival rates for the entire group are 64% and 42%, respectively. Favorable-prognosis subgroups included patients who had definitive resection and patients with clinical stage T3 N0 tumors (2-year survival rates of 67% for both subgroups). Preoperative therapy with RT and weekly paclitaxel/carboplatin showed activity in this patient population; however, disease in the majority of patients with extensive involvement of mediastinal nodes remained unresectable after this treatment. Results in patients who initially had unresectable disease do not appear different than results achieved with concurrent RT/chemotherapy approaches. Postoperative complications associated with this preoperative combined-modality regimen were more frequent than expected with resection alone.     

Acute esophageal toxicity in non-small cell lung cancer patients after high dose conformal radiotherapy.

BACKGROUND AND PURPOSE: To correlate acute esophageal toxicity with dosimetric and clinical parameters for non-small cell lung cancer (NSCLC) patients treated with radiotherapy (RT) alone or with chemo-radiotherapy (CRT). PATIENTS AND METHODS: We analyzed the data of 156 patients with medically inoperable or locally advanced NSCLC. Seventy-four patients were irradiated with high dose RT only, 45 patients with sequential CRT (Gemicitabine/Cisplatin) and 37 patients with concurrent CRT (Cisplatin daily 6 mg/m(2)). The radiation dose delivered ranged from 49.5 to 94.5 Gy (2.25-2.75 Gy per fraction) with an overall treatment time of 5-6 weeks. For all patients the maximal acute esophageal toxicity (RTOG/EORTC criteria) was scored and related to dose-volume parameters, as well as to clinical and treatment-related parameters. All parameters were tested univariable and multivariable in a binary logistic regression model. The toxicity data of a homogeneous subgroup was fitted to the Lyman-Kutcher-Burman model. RESULTS: Grade 2 acute esophageal toxicity or higher occurred in 27% (n=42) of the patient population of which nine patients developed grade 3 toxicity and one patient grade 4. All 10 patients with grade>or=3 esophageal toxicity received concurrent CRT. At multivariable analysis, the most significant clinical parameter to predict acute esophageal toxicity was the concurrent use of CRT. The most significant dosimetric parameter was the esophagus volume that received at least 35 Gy. The data of the patients who did not receive concurrent CRT were well described by the Lyman-Kutcher-Burman normal tissue complication probability model. The optimal fit of the data of non-concurrent treated patients to this model was obtained using the following values for the parameters: TD(50)=47 Gy (41-60 Gy), n=0.69 (0.18-6.3) and m=0.36 (0.25-0.55) where the numbers between brackets denote the 95% confidence interval. Acute esophageal toxicity was not significantly increased for patients treated with sequential CRT. CONCLUSION: Both concurrent CRT and the volume that receives at least 35 Gy were predictors of acute esophageal toxicity.     

同步放化疗和单纯放疗治疗ⅡB～ⅢB期宫颈癌的疗效比较

背景与目的:同步放化疗已成为局部晚期宫颈癌的标准治疗模式,但对于放疗联合何种方案的化疗效果最佳,目前尚无一致意见.本研究中我们比较同步放化疗与单纯放疗,以及同步放化疗不同化疗方案的疗效及毒副反应.方法:2003年1月至2004年12月江西省妇幼保健院收治的符合人组标准的ⅡB～ⅢB期宫颈癌患者285例,按住院序号随机分为单纯放疗组142例,同步放化疗组143例.同步放化疗组又按化疗方案不同分为:BP(博来霉素 顺铂)方案同步放化疗51例,TP(紫杉醇 卡铂)方案同步放化疗47例,FP(氟尿嘧啶 顺铂)方案同步放化疗45例.比较单纯放疗组与同步放化疗组患者的3年生存率和不良反应,同时对同步放化疗三种不同化疗方案组的3年生存率及不良反应进行比较.结果:全组中位随访时间为42个月,单纯放疗组与同步放化疗组的3年生存率分别为65%和75%,两组比较差异有统计学意义(P=0.042).单纯放疗组Ⅲ～Ⅳ度急性毒副反应低于同步放化疗组(P<0.001),迟发性毒副反应两组差异无统计学意义(P=0.613).同步放化疗组BP方案、TP方案、FP方案的3年生存率分别为74%、80%和71%,三组间比较差异无统计学意义(P=0.792).三组Ⅲ～Ⅳ度急性及迟发性毒副反应发生率相似.结论:与单纯放疗相比,同步放化疗可明显提高ⅡB～ⅢB期宫颈癌患者的疗效.在同步放化疗三种不同的化疗方案中,紫杉醇联合卡铂方案组患者3年生存率略高于其他两种化疗方案,毒副反应可耐受,值得进一步研究.     

EGFR-TKIs联合放疗在局部晚期非小细胞肺癌治疗中的地位和作用

不可手术切除的局部晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）从组织分型看,标准治疗模式为同期化放疗,但从分子分型看,表皮生长因子受体（epidermal growth factor receptor,EGFR）外显子19、21突变阳性的NSCLC患者一线应用EGFR酪氨酸激酶抑制剂（EGFR-TKIs）,将在生存上最大程度地获益。放疗具有手术不可比拟的空间和化疗无法取得的局部优势,放疗可激活EGFR信号通路,通过诱导细胞增殖和增强DNA修复而导致放疗抵抗,EGFR-TKIs具有放疗增敏作用。临床研究结果提示EGFR-TKIs联合胸部放疗治疗局部晚期或转移NSCLC患者,总体上毒性反应可以耐受,但生存获益程度不一,可能与病例选择不同有关。对于EGFR基因突变的不可切除的NSCLC患者,EGFR-TKIs同步个体化放疗目前缺乏大样本多中心的临床研究结果,也许是今后一线治疗的一种选择。     

诱导化疗配合同期放化疗治疗Ⅲ期非小细胞肺癌

目的：评价诱导化疗结合同期放化疗治疗Ⅲ期不能手术的非小细胞肺癌(NSCLC)疗效。方法：143例不能手术或不愿手术的Ⅲ期NSCLC随机分为2个组：72例为诱导化疗联合放疗组(CHT／RT)，连续2个疗程，然后同期放化疗，单纯放疗组(RT)71例。两个组均采用6MVX线放射治疗，照射野包括肺部原发灶和纵隔淋巴引流区，剂量为65～70Gy。结果：CHT／RT组1、2、3年生存率分别为62．5％、30．6％、23．6％。RT组1、2、3年生存率分别为45．1％、15．4％、9．9％。2个组比较有显著性差异(P=0．012)。照射野内肿瘤进展，CHT／RT与RT组1、2、3年生存率分别为19．4％、31．9％、48．6％和35．8％、57．7％、84．5％，2个组有显著性差异(P=0．016)。CHT／RT组Ⅲ、Ⅳ级骨髓抑制要远高于RT组(P=0．012)。结论：CHT／RT组治疗Ⅲ期的NSCLC3年生存率明显高于RT组。     

Uracil/tegafur plus cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer: a multi-institutional phase II trial.

PURPOSE: To evaluate the efficacy and toxicity of a novel combination treatment using concurrent radiotherapy with cisplatin plus UFT, which is comprised of uracil and tegafur, in locally advanced non-small cell lung cancer (NSCLC) patients. EXPERIMENTAL DESIGN: In this Phase II trial, patients with unresectable stage III NSCLC were treated with the oral administration of UFT (400 mg/m(2)/d tegafur) on days 1-14 and days 29-42 whereas 80 mg/m(2) cisplatin was administered i.v. on days 8 and 36. Radiotherapy, with a total dose of 60 Gy, was delivered in 30 fractions from day 1. RESULTS: Seventy patients were enrolled and eligible, as follows: 57 males/13 females; mean age 61 ranging from 36 to 74; performance status 0/1:45/25; stage IIIA/IIIB, 14/56. A complete response was observed in two patients and a partial response in 54 patients, and the overall response rate was 81% (95% confidence interval; 70-89%). The median survival, the 1- and 2-year survival rates were 16.5 months, 67% and 33%, respectively. Grade 3/4 leukopenia occurred in 14%/1% of the patients. Grades 3 non-hematological toxicities were only reported in three patients with nausea, two with esophagitis and one with pneumonitis whereas no grade 4 non-hematological toxicity was observed. CONCLUSIONS: UFT plus cisplatin with concurrent radiotherapy is considered to be a feasible and effective treatment for locally advanced NSCLC patients. Additional study of this concurrent chemoradiotherapy is warranted.     

Continuously infused carboplatin used as radiosensitizer in locally unresectable non-small-cell lung cancer: a multicenter phase III study.

PURPOSE: To determine the radiosensitizing effect of prolonged exposure of carboplatin in patients with locally unresectable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with histologically proven NSCLC, performance score <2, weight loss <10%, and normal organ functions were randomized between carboplatin 840 mg/m2 administered continuously during 6 weeks of radiotherapy or thoracic radiotherapy alone (both 60 Gy). Toxicity was evaluated with National Cancer Institute Common Toxicity Criteria (NCI CTC) and the Radiation Therapy Oncology Group (RTOG) criteria. Quality of life was measured with European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30/LC13 questionnaires. RESULTS: One-hundred and sixty patients were included. Pathologically confirmed persistent tumor was present in 53% of patients in the combination arm versus 58% in the radiotherapy alone arm (P=0.5). Median survival in the combination arm was 11.8 [95% confidence interval (CI) 9.3-14.2] months and in the radiotherapy alone arm 11.7 (95% CI 8.1-15.5) months; progression-free survival was not different between arms [6.8 and 7.5 months, respectively (P=0.28)]. Acute toxicity was mild, late toxicity was radiation-induced cardiomyopathy (three patients) and pulmonary fibrosis (five patients). Quality of life was not different between arms, but in all measured patients cough and dyspnea improved, pain became less, and slight paresthesia developed 3 months after treatment. CONCLUSION: Addition of continuously administered carboplatin as radiosensitizer for locally unresectable NSCLC does not improve local tumor control or overall survival.     

Integrating concurrent navelbine and cisplatin to hyperfractionated radiotherapy in locally advanced non-small cell lung cancer patients treated with induction and consolidation chemotherapy: feasibility and activity results

OBJECTIVES: The purpose of this study was to determine the effectiveness and toxicity of a new combination schedule based on concurrent navelbine, cisplatin and hyperfractionated radiotherapy in patients with locally advanced NSCLC treated with platinum and gemcitabine induction and consolidation chemotherapy. MATERIALS AND METHODS: The 37 patients with pathological confirmed advanced NSCLC (non-surgical stages IIIA and IIIB) were included in the study. All of them were assessable for survival and 32 for response. The treatment schedule consisted of cisplatin (100 mg/m2) or carboplatin (400 mg/m2) on day 1 with gemcitabine (1000 mg/m2) on days 1, 8 and 15. Treatment was given every 28 days for two courses, followed by concurrent administration of accelerated modified hyperfractionated radiotherapy, with concomitant boost, with a total dose of 61.64 Gy administered for 5 weeks, with cisplatin and navelbine, for two courses, finally followed by two courses of the same initial chemotherapy. RESULTS: Four patients achieved complete response (12.5%) and 14 (44%) partial response, for an overall objective response rate of 56.5%. After a minimum follow-up duration of 35.5 months, median progression free survival was 12.2 months. The median survival was 15.4 months with actuarial 1-, 2- and 3-year survival of 67, 21 and 15%, respectively. The main toxicity was hematological. There was esophagitis (grades III and IV) in 30% of the patients and there were two treatment-related deaths. CONCLUSION: Combined treatment with concurrent radiotherapy and chemotherapy in non-surgical NSCLC is an acceptable treatment modality. However, the toxicity was not negligible.