A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics

Abstract

The European Lung Cancer Working Party (ELCWP) designed a 3-arm phase III randomised trial to determine the role of accelerated chemotherapy in extensive-disease (ED) small-cell lung cancer (SCLC). Eligible patients were randomised between the 3 following arms: (A) Standard chemotherapy with 6 courses of EVI (epirubicin 60 mg m−2, vindesine 3 mg m−2, ifosfamide 5 g m−2; all drugs given on day 1 repeated every three weeks. (B) Accelerated chemotherapy with EVI administered every 2 weeks and GM-CSF support. (C) Accelerated chemotherapy with EVI and oral antibiotics (cotrimoxazole). Primary endpoint was survival. 233 eligible patients were randomised. Chemotherapy could be significantly accelerated in arm B with increased absolute dose-intensity. Best response rates, in the population of evaluable patients, were, respectively for arm A, B and C, 59%, 76% and 70%. The response rate was significantly higher in arm B in comparison to arm A (P = 0.04). There was, however, no survival difference with respective median duration and 2-year rate of 286 days and 5% for arm A, 264 days and 6% for arm B and 264 days and 6% for arm C. Severe thrombopenia occurred more frequently in arm B but without an increased rate of bleeding. Non-severe infections were more frequent in arm B and severe infections were less frequent in arm C. Our trial failed to demonstrate, in ED-SCLC, a survival benefit of chemotherapy acceleration by using GM-CSF support. http://www.bjcancer.com

Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group

“…19 In extensive small-cell lung cancer, accelerated chemotherapy similarly improved the response rate without affecting median survival or 2-year survival. 20 The Children's Oncology Group recently completed a single-arm prospective study testing accelerated chemotherapy in patients with high-risk rhabdomyosarcoma, and results are pending. Some other dose-dense approaches have reduced doses with decreased intervals, maintaining (rather than increasing) dose-intensity.…”

Validation and comparison of several published prognostic systems for patients with small cell lung cancer

“…We collected data on a total of 693 patients, 204 from ELCWP 1922 [9], 233 from ELCWP 1923 [8] and 256 from the ongoing trial (ELCWP 1994). There was an intersection between institutions having recruited patients for the derivation series and the institutions contributing to the trials used for the present validation series.…”

“…Two of these studies are closed and the results have been published (ELCWP 1923 [8] and ELCWP 1922 [9]), while one is still ongoing (ELCWP 1994). The data on the patients registered in these studies were not included in the database used for derivation of our prognostic classification [4].…”

“…Small cell lung cancer had to be histologically proven and untreated; patients had to have normal haematological, hepatic and renal functions, have a Karnofsky performance status of o60, have provided informed consent and be accessible for follow-up. The definition of limited disease was a disease confined to primary site, mediastinum and homolateral subclavicular lymph nodes without malignant pleural effusion in one trial [8]. In the other two studies, it was defined as a disease that could be treated in one radiotherapy field.…”

“…In the first two published trials that we used for constructing our validation series, we failed to identify any survival benefit between the arms [8,9]. For the third, ongoing trial, we did not look at survival comparison between arms.…”