Jan Vilsvik

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.

Palliative chemotherapy beyond three courses conveys no survival or consistent quality-of-life benefits in advanced non-small-cell lung cancer.

This randomised multicentre trial was conducted to establish the optimal duration of palliative chemotherapy in advanced non-small-cell lung cancer (NSCLC). We compared a policy of three vs six courses of new-generation platinum-based combination chemotherapy with regard to effects on quality of life (QoL) and survival. Patients with stage IIIB or IV NSCLC and WHO performance status (PS) 0–2 were randomised to receive three (C3) or six (C6) courses of carboplatin (area under the curve (AUC) 4, Chateluts formula, equivalent to Calverts AUC 5) on day 1 and vinorelbine 25 mg m−2 on days 1 and 8 of a 3-week cycle. Key end points were QoL at 18 weeks, measured with EORTC Quality of Life Questionnaire (QLQ)-C30 and QLQ-LC13, and overall survival. Secondary end points were progression-free survival and need of palliative radiotherapy. Two hundred and ninety-seven patients were randomised (C3 150, C6 147). Their median age was 65 years, 30% had PS 2 and 76% stage IV disease. Seventy-eight and 54% of C3 and C6 patients, respectively, completed all scheduled chemotherapy courses. Compliance with QoL questionnaires was 88%. There were no significant group differences in global QoL, pain or fatigue up to 26 weeks. The dyspnoea palliation rate was lower in the C3 arm at 18 and 26 weeks (P<0.05), but this finding was inconsistent across different methods of analysis. Median survival in the C3 group was 28 vs 32 weeks in the C6 group (P=0.75, HR 1.04, 95% CI 0.82–1.31). One- and 2-year survival rates were 25 and 9% vs 25 and 5% in the C3 and C6 arm, respectively. Median progression-free survival was 16 and 21 weeks in the C3 and C6 groups, respectively (P=0.21, HR 0.86, 95% CI 0.68–1.08). In conclusion, palliative chemotherapy with carboplatin and vinorelbine beyond three courses conveys no survival or consistent QoL benefits in advanced NSCLC.

Irinotecan Plus Carboplatin Versus Oral Etoposide Plus Carboplatin in Extensive Small-Cell Lung Cancer: A Randomized Phase III Trial

PURPOSE A Japanese randomized trial showed superior survival for patients with extensive-disease (ED) small-cell lung cancer (SCLC) receiving irinotecan plus cisplatin compared with etoposide plus cisplatin. The present trial evaluated the efficacy of irinotecan plus carboplatin (IC) compared with oral etoposide plus carboplatin (EC). PATIENTS AND METHODS Patients with ED SCLC were randomly assigned to receive either IC, which consisted of carboplatin (area under the curve = 4; Chatelut formula) and irinotecan (175 mg/m2) intravenously both on day 1, or EC, which consisted of carboplatin as in IC and etoposide (120 mg/m(2)/d) orally on days 1 through 5. Courses were repeated every 3 weeks with four cycles planned. Doses were reduced by one third in patients with a WHO performance status (PS) of 3 to 4 and/or age older than 70 years. Primary end point was overall survival (OS). Secondary end points were quality of life (QOL) and complete response (CR) rate. RESULTS Of 220 randomly assigned patients, 209 were eligible for analysis (IC, n = 105; EC, n = 104). Thirty-five percent were older than 70 years, and 47% had a PS of 2 to 4. The groups were well balanced with respect to prognostic factors. OS was inferior in the EC group (hazard ratio = 1.41; 95% CI, 1.06 to 1.87; P = .02). Median survival time was 8.5 months for IC compared with 7.1 months for EC. One-year survival rate was 34% for IC and 24% for EC. CR was seen in 18 IC patients compared with seven EC patients (P = .02). There were no statistically significant differences in hematologic grade 3 or 4 toxicity. Grade 3 or 4 diarrhea was more common in the IC group. QOL differences were small, with a trend toward prolonged palliation with the IC regimen. CONCLUSION IC prolongs survival in ED SCLC with slightly better scores for QOL.

Multicenter Phase II Trial of Paclitaxel, Cisplatin, and Etoposide With Concurrent Radiation for Limited-Stage Small-Cell Lung Cancer

PURPOSE To investigate the feasibility, efficacy, and safety of adding paclitaxel to cisplatin/etoposide chemotherapy and concurrent thoracic radiotherapy (TRT) in treatment of limited-stage small-cell lung cancer (LD-SCLC). PATIENTS AND METHODS Patients received five courses of chemotherapy (paclitaxel 175 mg/m2 1-hour intravenous [IV] infusion day 1; cisplatin 50 mg/m(2) IV day 1; etoposide 100 mg/m2 IV day 1; oral etoposide 100 mg bid days 2 to 5) at 3-week intervals. TRT (42 Gy administered in 15 fractions) was administered concurrent with chemotherapy cycle 3. All patients were evaluated before starting TRT and 4 weeks after termination of chemotherapy. Patients achieving complete remission (CR) were administered prophylactic cranial irradiation. RESULTS Thirty-nine patients were included, and the median age was 63 years. The median follow-up was 36 months (range, 19 to 57 months). The overall response rate was 92% (CR, 81%; partial response, 11%), and the median survival was 21 months. The 1- and 2-year disease-specific survival rates were 69% and 37%, respectively. Of 29 CR patients, 83% have relapsed. Brain metastasis was as frequent as local recurrences (42%). Hematologic toxicity included grade 3 to 4 leukopenia in 74% of patients and grade 3 thrombocytopenia in 10%. One treatment-related death occurred as a result of severe neutropenia and septicemia. Hematotoxicity caused dose reductions in 31% of courses. One patient had an anaphylactic reaction during the first paclitaxel infusion. Paclitaxel-related neuropathy and myalgia were reversible. Grade 3 esophagitis was seen in five patients during and shortly after TRT. CONCLUSION This novel multimodal regimen is effective and well tolerated in patients with LD-SCLC. It compares favorably with previously published phase II studies.

Efficacy and duration of salmeterol powder inhalation in protecting against exercise-induced bronchoconstriction

BACKGROUND The protective effect of a new long acting beta 2-agonist, salmeterol, against exercise-induced bronchoconstriction has been documented when given as inhaled aerosol. OBJECTIVE The aim of the present study was to examine the duration of the protective effect of a single dose of salmeterol, 50 micrograms, inhaled as dry powder, against exercise-induced bronchoconstriction. METHODS Sixteen patients with reproducible exercise-induced bronchoconstriction were challenged on a treadmill on two prestudy visits and six study days. The patients were challenged 4, 8, and 12 hours postdosing. The study was designed as a double blind placebo-controlled randomized crossover trial. RESULTS Statistically significant differences in % maximum fall in PEFR were found at four and eight hours postdosing, in favor of salmeterol. At 12 hours postdosing, no clear statistical inference was possible, owing to the presence of a statistical carry-over effect; however, significant differences in area under curve in favor of salmeterol were found at 4, 8, and 12 hours postdosing. CONCLUSION Salmeterol, 50 micrograms, dry powder inhalation had a protective effect against exercise-induced bronchoconstriction up to 12 hours postdosing, as compared with placebo. No adverse effects were identified.

O-87 Duration of chemotherapy and survival in advanced non-small cell lung cancer (NSCLC). A multicenter, prospective randomised study

Duration of chemotherapy and survival in advanced non-small cell lung cancer (NSCLC). A multicenter prospective randomised study.

O-57 Quality of life as related to duration of chemotherapy in advanced non-small cell lung cancer: A randomized study comprising 297 patients

Quality of life as related to duration of chemotherapy in advanced non-small cell lung cancer : a randomised study comprising 297 patients.