Weekly docetaxel with concurrent radiotherapy in locally advanced non-small cell lung cancer: a phase I/II study with 5 years' follow-up.

This Phase I/II study investigated weekly docetaxel (Taxotere) with concurrent radiotherapy in 42 patients with untreated stage III non-small cell lung cancer (NSCLC). All patients were treated with chest irradiation: 2Gy administered 5 days/week for 5 weeks, to a total of 50Gy. Docetaxel (1-h infusion) was administered on days 1, 8, 22, and 29< or =2 h before radiation fractions 1, 6, 16, and 21 (i.e. every week excluding the third week of treatment). In the Phase I study (n=12), docetaxel was started at 20 mg/m2 per week (n=3) and escalated in 10 mg/m2 increments (30 mg/m2, n=3; 40 mg/m2, n=6). Dose-limiting toxicity (grade 3-4 esophagitis) occurred with docetaxel 40 mg/m2. The Phase II study (n=30), therefore, evaluated docetaxel 30 mg/m2 (considered recommended dose). All patients except one experienced asymptomatic grade 3-4 lymphopenia; four patients (9.5%) had grade 3-4 esophagitis. The overall response rate was 45.5%, with eight (24.2%) complete responses. The median time to progression at the recommended dose of 30 mg/m2 (n=33) was 12.0 months and the median survival time was 13.6 months. The 1-year survival rate was 60.6%. Five patients (one from Phase I and four from Phase II) were alive after >5 years. In conclusion, weekly docetaxel 30 mg/m2 plus radiotherapy is active and well tolerated in stage III NSCLC.

Hypofractionated palliative radiotherapy (17 Gy per two fractions) in advanced non-small-cell lung carcinoma is comparable to standard fractionation for symptom control and survival: a national phase III trial.

PURPOSE: To investigate whether the effect of hypofractionated thoracic radiotherapy (TRT) is comparable to more standard fractionated radiotherapy (RT) in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 421 patients with locally advanced stage III or stage IV NSCLC tumors were included. Inclusion criteria were inoperable, disease too advanced for curative radiotherapy, and chest symptoms or central tumor threatening the airways. Patients were randomly assigned to three arms: A, 17 Gy per two fractions (n = 146); B, 42 Gy per 15 fractions (n = 145); and C, 50 Gy per 25 fractions (n = 130). Four hundred seven patients were eligible for the study; 395 patients (97%) participated in the health-related quality-of-life (HRQOL) study. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and EORTC QLQ-lung cancer-specific module (LC13) were used to investigate airway symptom relief and changes in HRQOL. Assessments were performed before TRT and until week 54. Clinicians' assessments of symptom improvement were at 2, 6, and 14 weeks after completion of TRT. The patients were observed for a minimum of 3 years. Results Baseline prognostic data were equally distributed in the treatment groups. Patient compliance with respect to the HRQOL investigation was minimum 74%. HRQOL and symptom relief were equivalent in the treatment arms. No significant difference in survival among arms A, B, and C was found, with median survival 8.2, 7.0, and 6.8 months, respectively. CONCLUSION: Our data indicate that protracted palliative TRT renders no improvement in symptom relief, HRQOL, or survival when compared with short-term hypofractionated treatment in advanced NSCLC.

The value of prognostic factors in small cell lung cancer: results from a randomised multicenter study with minimum 5 year follow-up.

We have evaluated the prognostic value of 22 pretreatment attributes in 436 small cell lung cancer (SCLC) patients included in a prospective multicenter study with a minimum 5-year follow-up. Pretreatment clinical and laboratory parameters were registered. Possible prognostic factors were evaluated by univariate analysis (log rank test) and by the Cox multivariate regression model. In the univariate analysis of all patients, only age, nodal metastasis, and skin metastasis were not associated with survival. The multivariate Cox model identified gender, extent of disease, performance status (PS), weight loss, platelet count, LDH, and NSE as independent prognostic factors. In subset multivariate analyses according to extent of disease, we found haemoglobin level, PS, NSE, and total WBC as significant prognostic indicators for survival in limited-stage disease (LD-SCLC), while PS, weight loss, LDH, number of metastases, liver metastases, and brain metastases were identified as independent prognostic factors in extensive-stage disease (ED-SCLC). There was a significant correlation between serum LDH and NSE levels. In conclusion, gender, extent of disease, PS, weight loss, haemoglobin, WBC count, platelet count, LDH, and NSE were all found to be independent prognostic factors for SCLC survival. However, the prognostic value of these factors depends highly on whether all or subsets of SCLC patients are studied.

Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up.

PURPOSE: To investigate whether chemotherapy with etoposide and cisplatin (EP) is superior to cyclophosphamide, epirubicin, and vincristine (CEV) in small-cell lung cancer (SCLC). PATIENTS AND METHODS: A total of 436 eligible patients were randomized to chemotherapy with EP (n = 218) or CEV (n = 218). Patients were stratified according to extent of disease (limited disease [LD], n = 214; extensive disease [ED], n = 222). The EP group received five courses of etoposide 100 mg/m(2) intravenously (IV) and cisplatin 75 mg/m(2) IV on day 1, followed by oral etoposide 200 mg/m(2) daily on days 2 to 4. The CEV group received five courses of epirubicin 50 mg/m(2), cyclophosphamide 1,000 mg/m(2), and vincristine 2 mg, all IV on day 1. In addition, LD patients received thoracic radiotherapy concurrent with chemotherapy cycle 3, and those achieving complete remission during the treatment period received prophylactic cranial irradiation. RESULTS: The treatment groups were well balanced with regard to age, sex, and prognostic factors such as weight loss, and performance status. The 2- and 5-year survival rates in the EP arm (14% and 5%, P =.0004) were significantly higher compared with those in the CEV arm (6% and 2%). Among LD patients, median survival time was 14.5 months versus 9.7 months in the EP and CEV arms, respectively (P =.001). The 2- and 5-year survival rates of 25% and 10% in the EP arm compared with 8% and 3% in the CEV arm (P =.0001). For ED patients, there was no significant survival difference between the treatment arms. Quality-of-life assessments revealed no major differences between the randomized groups. CONCLUSION: EP is superior to CEV in LD-SCLC patients. In ED-SCLC patients, the benefits of EP and CEV chemotherapy seem equivalent, with similar survival time and quality of life.