Comparison of effectiveness between chemotherapy alone versus chemo-radiotherapy in stage III non-small cell lung cancer

Combined chemotherapy with radiotherapy has been claimed to be superior to radiotherapy alone in stage III non-small cell lung cancer (NSCLC). The present study was designed to give chemo-radiotherapy with 300 cGy only on the day the cytotoxic drugs are administered. The aim was to exploit the cell cycle synergism between the two treatments. Forty-five patients of stage IIIA+B with inoperable NSCLC were randomized in two groups. Group A to be treated with chemotherapy only and group B to be treated with chemotherapy plus radiotherapy. Drugs for group A were: cisplatinum 90 mg/m(2), vindesine 3 mg/m(2) and epirubicin 40 mg/m(2) once every 3 weeks for 8 courses. Group B: cisplatinum 60 mg/m(2), vindesine 3 mg/m(2) and epirubicin 30 mg/m(2) plus 300 cGy radiation, every two weeks for 8 cycles. Then, estimation of response was done. Toxicity was tolerable. In group A the response rate was 52%, in group B 90% (partial and complete). The difference was statistically significant. Additional radiotherapy up to 5,400 cGy was given in patients of group B while patients of group A had palliative radiation on recurrence. Survival rate was significantly longer for patients of group B.     

Second primary cancers in patients with stage III non-small cell lung cancer successfully treated with chemo-radiotherapy

BACKGROUND: Patients successfully treated for non-small cell lung cancer (NSCLC) remain at risk for developing second primary cancer (SPC). The purpose of the current study is to assess the incidence of SPC and the impact of smoking status on the SPC in long-term survivors with stage III NSCLC after chemo-radiotherapy. METHODS: Using the database from the Japan National Hospital Lung Cancer Study Group between 1985 and 1995, information was obtained on 62 patients who were more than 3 years disease-free survivors. Details of clinical information and most smoking history were available from the questionnaire. RESULTS: Nine of the 62 patients developed SPC 3.9-12.2 years (median, 6.2 years) after the initiation of the treatment. The site of SPC was 2 lung, 1 esophagus, 2 stomach, 1 colon, 1 breast, 1 skin and 1 leukemia. Among these nine, three cancers occurred inside the radiation field. The relative risk of any SPC was 2.8 [95% confidence interval (CI) 1.3-5.3]. The risk changed with the passage of time and it increased significantly (5.2 times at or beyond 7 years) after the treatment. In univariate analysis, the patients who were male, had more cumulative smoking and continued smoking, had an increased risk of SPC [relative risk (RR) 2.7, CI 1.1-5.3; RR 3.0, CI 1.2-6.2; RR 5.2, CI 1.6-11.7, respectively]. In multivariate analysis, factors including smoking status and histological type had no effect on the development of a SPC. CONCLUSION: The patients with stage III NSCLC successfully treated with chemo-radiotherapy were at risk for developing SPC and this risk increased with time.     

Sequential chemo-radiotherapy in non-small cell lung cancer

Locally advanced non-small cell lung cancer (NSCLC) stage IIIA/IIIB represents approximately 30% of NSCLC and still has a poor prognosis. In this article we give a short review on several randomized phase III trials that showed a slight but significant survival benefit for sequential chemo-radiotherapy in the treatment of locally advanced NSCLC.     

序贯与同步放、化疗治疗中晚期非小细胞肺癌的疗效观察

目的：比较放、化疗序贯与同步治疗非小细胞肺癌的临床疗效。方法：选择不能手术的中晚期非小细胞肺癌（NSCLC）患者62例,随机分为同步组31例和序贯组31例。化疗方案为异环磷酰胺＋阿霉素＋顺铂,放疔肿瘤剂量为60～65Gy。结果：（1）治疗总有效率：同步组77．42％,序贯组48．39％,两组比较有显著性差异（P〈0．05）;（2）达到上述有效率所用的时间前者平均69天,后者为143天,两组比较有非常显著性差异（P〈0．01）;（3）两组生存率方面无显著性差异（P〉0．05）;（4）两组病人均能耐受冶疗中的不良反应。结论：同步组的近期疗效优于序贯组,且住院周期缩短减轻了患者的经济负担。该方法目前应为非小细胞肺癌治疗的最佳方法。     

Stereotactic radiotherapy following chemo-radiotherapy for lymph node metastasis of stage III non-small-cell lung cancer

It has been expected that stereotactic radiotherapy (SRT) is one of the useful treatments for non-resectable early lung cancer. In the case radiotherapy was thought to be difficult due to the wideness of irradiation area, it is probable to undergo chemo-radiotherapy safely using SRT for a primary lesion. We report two cases of Stage III non-small-cell lung cancer, which underwent SRT for primary tumors following chemo-radiotherapy for the lymph node metastasis. In both two cases, a reduction of V?? (the normal pulmonary volume to receive radiation exposure: more than 20 Gy) was a possibility, and symptomatic radiation pneumonitis was not observed.     

Radiotherapy versus radiotherapy enhanced by cisplatin in stage III non-small cell lung cancer.

Between January 1987 and June 1991, 173 patients with inoperable non-small cell lung cancer, Stage III, were entered into a randomized trial comparing radiotherapy only (RT) (45 Gy/15 fractions/3 weeks) (arm A) versus RT and a daily low dose of cDDP (6 mg/m2) (arm B). An overall response rate of 58.9% was observed in arm A and 50.6% in arm B, respectively. No differences in the pattern of relapse were noted between the two treatment groups. Median time to progression was 10.6 months for arm A and 14.2 months for arm B. Median survivals were 10.3 months and 9.97 months, respectively. Toxicity was acceptable and no treatment-related death occurred in either treatment schedule. In this study no significant advantage of the combined treatment over radiation therapy only was found. The encouraging results achieved in some trials together with the intractability of the disease suggest that further efforts should be made to optimize clinical trial protocols, perhaps by reviewing the radiobiological and pharmacological basis of the combined treatment.     

Combined modality therapy for stage III non-small cell lung cancer

Lung cancer remains the leading cause of cancer death in the U.S. among both men and women. Approximately 45% of patients present with stage III disease. A proportion of these patients is amenable to surgical resection; however, the majority are "unresectable." For patients with unresectable stage IIIA/B disease, thoracic radiation therapy (TRT) was considered the standard of care until the late 1980s despite a very poor 5-year survival rate. Several clinical trials demonstrated that the combination of chemotherapy and TRT was superior to TRT alone. Based on these data, combined modality therapy became the standard of care for patients with good performance status. Recent trials have shown that concurrent chemoradiotherapy offers a significant survival advantage over sequential chemoradiotherapy. Despite a substantial number of clinical trials, important questions on the optimal treatment paradigm remain. The most effective chemotherapy combination, the use of induction or consolidation chemotherapy in addition to the concurrent portion of therapy, and the optimal dose of chemotherapy with concurrent TRT have yet to be determined. The optimal total dose, fractionation, acceleration, treatment volume, and tumor targeting remain questions related to the TRT portion of therapy. Although significant progress has been made, the majority of patients experience locoregional or distant progression of their disease and die within 5 years of diagnosis. Thus, continued development and participation in clinical trials is crucial to further improvements in the treatment of patients with stage III disease.     

Non-platinum induction chemotherapy for stage III non-small cell lung cancer

We conducted combination chemotherapy with gemcitabine (GEM) and paclitaxel (TXL) for stage III non-small cell lung cancer. The chemotherapy schedule consisted of GEM 800 mg/m2 and TXL 70 mg/m2 once a week for 6 consecutive weeks. The patients were 7 males and 3 females with a median age of 66 years. There were 5 adenocarcinomas and 5 squamous cell carcinomas, 7 stage IIIA and 3 IIIB. Eight patients completed 6 cycles of planned administration. Of 9 patients who were evaluable for response, 6 patients achieved PR (66.7%), 2 patients had SD, and 1 patient had PD. The cancers were resectable in 7 out of 9 patients, and were resected completely in 5 patients. Grade 3 anemia and leucopenia were observed in 1 patient and 2 patients, respectively, but they were mild. In our experience, a non-platinum weekly regimen with GEM and TXL is well tolerated and effective, which suggests the possibility of induction chemotherapy and outpatient treatment.     

早期非小细胞肺癌立体定向放疗研究进展

靶区确定、治疗实施和影像引导技术的不断发展进步,使立体定向放疗技术广泛应用于体部肿瘤治疗成为可能.本文从立体定向放疗开始成为早期非小细胞肺癌的一种治疗手段,早期非小细胞肺癌立体定向放疗技术建立的关键,早期非小细胞肺癌立体定向放疗治疗结果及常见的毒副反应等几个方面综述立体定向放疗应用于早期非小细胞肺癌治疗的研究进展.     

Hyperfractionated radiotherapy for clinical stage II non-small cell lung cancer.

BACKGROUND AND PURPOSE: Patients with stage II non-small cell lung cancer who are not suitable for or refuse surgery are treated with radiotherapy, but the results reported so far are not satisfactory. To improve the prognosis of such patients, we have used hyperfractionated radiotherapy. In this paper, we retrospectively analyzed results of the treatment. MATERIALS AND METHODS: Between 1988 and 1993, 67 patients were treated with hyperfractionated radiotherapy with 1.2 Gy twice daily to a total dose of 69.6 Gy. All patients were technically operable, but 43 had medical problems and 24 refused surgery. The median age and Karnofsky performance status score was 60 and 90 years, respectively. No patient received chemotherapy or immunotherapy. The median follow-up period was 61 months. RESULTS: The median survival time and the 5-year survival rate were 27 months and 25% (standard error, SE, 6%), respectively. The 5-year local control rate was 44% (SE,7%). Univariate analysis of prognostic factors revealed that a higher Karnofsky performance status score, weight loss of < or =5% before treatment, and T1 stage were associated with better prognosis, and peripheral location was of borderline significance (P = 0.053). There were two bronchopulmonary and two esophageal acute grade 3 toxicities, and one bronchopulmonary and two esophageal late grade 3 toxicities. No grade 4 or 5 toxicity was observed. CONCLUSION: These results are encouraging and further studies on the use of hyperfractionation seem to be warranted for stage II non-small cell lung cancer.     

Carbon ion radiotherapy for stage I non-small cell lung cancer.

BACKGROUND AND PURPOSE: Heavy ion radiotherapy is a promising modality because of its excellent dose localization and high biological effect on tumors. Using carbon beams, a dose escalation study was conducted for the treatment of stage I non-small cell lung cancer (NSCLC) to determine the optimal dose. MATERIALS AND METHODS: The first stage phase I/II trial using 18 fractions over 6 weeks for 47 patients and the second one using nine fractions over 3 weeks for 34 patients were conducted by the dose escalation method from 59.4 to 95.4 Gray equivalents (GyE) in incremental steps of 10% and from 68.4 to 79.2 GyE in 5% increments, respectively. The local control and survival rates were obtained using the Kaplan-Meier method. RESULTS: Radiation pneumonitis at grade III occurred in three of 81 patients, but they fully recovered. This was not a dose-limiting factor. The local control rates in the first and second trials were 64% and 84%, respectively. The total recurrence rate in both trials was 23.2%. The infield local recurrence in the first trial was significantly dependent on carbon dose. The doses greater than 86.4 GyE at 18 fractions and 72 GyE at nine fractions achieved a local control of 90% and 95%, respectively. The 5 year overall and cause-specific survivals in 81 patients were 42% and 60%, respectively. CONCLUSIONS: With our dose escalation study, the optimum safety and efficacy dose of carbon beams was determined. Carbon beam therapy attained almost the same results as surgery for stage I NSCLC although this was a I/II study.     

Preoperative treatment strategies in stage III non-small cell lung cancer

Recent experience has emphasized the need to include systemic chemotherapy in combined-modality management of locally advanced non-small cell lung cancer stage III. If definitive surgery is planned in these situations, preoperative application of drugs-induction chemotherapy-has many advantages in comparison to postoperative delivery. Patients' compliance to treatment, achievable dose intensities of drugs, possible locoregional downstaging, and frequent postoperative problems following complex resections are some of the arguments favouring preoperative chemotherapy. Despite numerous phase-II investigations, little evidence from randomized phase-III trials has been generated. Early inclusion of radiotherapy prior to definitive resection may help to improve preoperative downstaging. Besides available mature phase-II data, phase-III results from ongoing randomized trials are lacking to define the overall value of such a complex approach. Important issues in the future will aim at individualizing these intensive programs according to findings in clinical prognostic factor analyses and to prospectively validate a prognostic risk stratification. Data from translational and molecular research may further help to develop such evidence-based guidelines.