European Organization for Research and Treatment of Cancer (EORTC) 08957 phase II study of topotecan in combination with cisplatin as second-line treatment of refractory and sensitive small cell lung cancer

Andrea Ardizzoni, Christian Manegold, Channa Debruyne, Rabab Gaafar, Erika Buchholz, Egbert F. Smit, Pilar Lianes, Guul Ten Velde, Lionel Bosquee, Catherine Legrand, Carlo Neumaier, Kathrine King, Giuseppe Giaccone

Research output: Contribution to journalArticle

Abstract

Purpose: The purpose of this study was to assess the activity and toxicity of a combined regimen of topotecan and cisplatin in "sensitive" (s) and "refractory" (r) small-cell lung cancer (SCLC) patients treated previously. Experimental Design: Patients with measurable SCLC and progressive disease after one first-line regimen were eligible for the study. Patients were enrolled in two separate groups: r group (patients who failed first-line treatment 2 on day 1, and topotecan was administered as a daily i.v. infusion at the dose of 0.75 mg/m2 from day 1 to 5, every 3 weeks. Results: A total of 110 eligible (68 s and 42 r) patients were enrolled from 24 institutions. The main patient characteristics were as follows: median age 60 (s) and 55 (r) years, median performance status 1 for both (s) and (r). Seventy-four percent (s) and 67% (r) had extensive stage disease, including 22% and 36%, respectively, with brain metastases. A total of 398 chemotherapy courses were administered [median 4 (s) and 3 (r) per patient]. The most frequent and serious toxicity was myelosuppression. Grade IV neutropenia occurred in 62% (s) and 49% (r) of patients, with a 19% (s) and 15% (r) incidence of febrile neutropenia, and grade IV thrombocytopenia in 54% (s) and 44% (r). Most of these toxicities occurred during the first chemotherapy course and led to topotecan dose reduction and/or delay in the following courses. Grade III-IV nonhematological toxicity was uncommon. Five deaths possibly related to toxicity occurred among s patients only. Objective responses have been documented in 20 s patients, 19 partial responses and 1 complete response, (29.4% response rate; 95% confidence interval, 19-42), whereas, among r patients, 10 partial responses have been observed (23.8% response rate; 95% confidence interval, 12-39). Median survival for s and r was 6.4 and 6.1 months, respectively. Conclusions: The combination of cisplatin and topotecan, at this dose and schedule, shows activity and promising results in patients with refractory SCLC, with reversible myelosuppression being the main side effect. Additional development of this regimen, using better-tolerated schedules, is warranted in patients with refractory SCLC.

Original languageEnglish
Pages (from-to)143-150
Number of pages8
JournalClinical Cancer Research
Volume9
Issue number1 I
Publication statusPublished - Jan 1 2003

Fingerprint

Topotecan
Small Cell Lung Carcinoma
Cisplatin
Research
Neoplasms
Therapeutics
Appointments and Schedules
Confidence Intervals
Drug Therapy
Febrile Neutropenia
Neutropenia
Thrombocytopenia

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

European Organization for Research and Treatment of Cancer (EORTC) 08957 phase II study of topotecan in combination with cisplatin as second-line treatment of refractory and sensitive small cell lung cancer. / Ardizzoni, Andrea; Manegold, Christian; Debruyne, Channa; Gaafar, Rabab; Buchholz, Erika; Smit, Egbert F.; Lianes, Pilar; Ten Velde, Guul; Bosquee, Lionel; Legrand, Catherine; Neumaier, Carlo; King, Kathrine; Giaccone, Giuseppe.

In: Clinical Cancer Research, Vol. 9, No. 1 I, 01.01.2003, p. 143-150.

Research output: Contribution to journalArticle

Ardizzoni, A, Manegold, C, Debruyne, C, Gaafar, R, Buchholz, E, Smit, EF, Lianes, P, Ten Velde, G, Bosquee, L, Legrand, C, Neumaier, C, King, K & Giaccone, G 2003, 'European Organization for Research and Treatment of Cancer (EORTC) 08957 phase II study of topotecan in combination with cisplatin as second-line treatment of refractory and sensitive small cell lung cancer', Clinical Cancer Research, vol. 9, no. 1 I, pp. 143-150.
Ardizzoni, Andrea ; Manegold, Christian ; Debruyne, Channa ; Gaafar, Rabab ; Buchholz, Erika ; Smit, Egbert F. ; Lianes, Pilar ; Ten Velde, Guul ; Bosquee, Lionel ; Legrand, Catherine ; Neumaier, Carlo ; King, Kathrine ; Giaccone, Giuseppe. / European Organization for Research and Treatment of Cancer (EORTC) 08957 phase II study of topotecan in combination with cisplatin as second-line treatment of refractory and sensitive small cell lung cancer. In: Clinical Cancer Research. 2003 ; Vol. 9, No. 1 I. pp. 143-150.
@article{c0e1e0c71904477499069f96395022b3,
title = "European Organization for Research and Treatment of Cancer (EORTC) 08957 phase II study of topotecan in combination with cisplatin as second-line treatment of refractory and sensitive small cell lung cancer",
abstract = "Purpose: The purpose of this study was to assess the activity and toxicity of a combined regimen of topotecan and cisplatin in {"}sensitive{"} (s) and {"}refractory{"} (r) small-cell lung cancer (SCLC) patients treated previously. Experimental Design: Patients with measurable SCLC and progressive disease after one first-line regimen were eligible for the study. Patients were enrolled in two separate groups: r group (patients who failed first-line treatment 2 on day 1, and topotecan was administered as a daily i.v. infusion at the dose of 0.75 mg/m2 from day 1 to 5, every 3 weeks. Results: A total of 110 eligible (68 s and 42 r) patients were enrolled from 24 institutions. The main patient characteristics were as follows: median age 60 (s) and 55 (r) years, median performance status 1 for both (s) and (r). Seventy-four percent (s) and 67{\%} (r) had extensive stage disease, including 22{\%} and 36{\%}, respectively, with brain metastases. A total of 398 chemotherapy courses were administered [median 4 (s) and 3 (r) per patient]. The most frequent and serious toxicity was myelosuppression. Grade IV neutropenia occurred in 62{\%} (s) and 49{\%} (r) of patients, with a 19{\%} (s) and 15{\%} (r) incidence of febrile neutropenia, and grade IV thrombocytopenia in 54{\%} (s) and 44{\%} (r). Most of these toxicities occurred during the first chemotherapy course and led to topotecan dose reduction and/or delay in the following courses. Grade III-IV nonhematological toxicity was uncommon. Five deaths possibly related to toxicity occurred among s patients only. Objective responses have been documented in 20 s patients, 19 partial responses and 1 complete response, (29.4{\%} response rate; 95{\%} confidence interval, 19-42), whereas, among r patients, 10 partial responses have been observed (23.8{\%} response rate; 95{\%} confidence interval, 12-39). Median survival for s and r was 6.4 and 6.1 months, respectively. Conclusions: The combination of cisplatin and topotecan, at this dose and schedule, shows activity and promising results in patients with refractory SCLC, with reversible myelosuppression being the main side effect. Additional development of this regimen, using better-tolerated schedules, is warranted in patients with refractory SCLC.",
author = "Andrea Ardizzoni and Christian Manegold and Channa Debruyne and Rabab Gaafar and Erika Buchholz and Smit, {Egbert F.} and Pilar Lianes and {Ten Velde}, Guul and Lionel Bosquee and Catherine Legrand and Carlo Neumaier and Kathrine King and Giuseppe Giaccone",
year = "2003",
month = "1",
day = "1",
language = "English",
volume = "9",
pages = "143--150",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "1 I",

}

TY - JOUR

T1 - European Organization for Research and Treatment of Cancer (EORTC) 08957 phase II study of topotecan in combination with cisplatin as second-line treatment of refractory and sensitive small cell lung cancer

AU - Ardizzoni, Andrea

AU - Manegold, Christian

AU - Debruyne, Channa

AU - Gaafar, Rabab

AU - Buchholz, Erika

AU - Smit, Egbert F.

AU - Lianes, Pilar

AU - Ten Velde, Guul

AU - Bosquee, Lionel

AU - Legrand, Catherine

AU - Neumaier, Carlo

AU - King, Kathrine

AU - Giaccone, Giuseppe

PY - 2003/1/1

Y1 - 2003/1/1

N2 - Purpose: The purpose of this study was to assess the activity and toxicity of a combined regimen of topotecan and cisplatin in "sensitive" (s) and "refractory" (r) small-cell lung cancer (SCLC) patients treated previously. Experimental Design: Patients with measurable SCLC and progressive disease after one first-line regimen were eligible for the study. Patients were enrolled in two separate groups: r group (patients who failed first-line treatment 2 on day 1, and topotecan was administered as a daily i.v. infusion at the dose of 0.75 mg/m2 from day 1 to 5, every 3 weeks. Results: A total of 110 eligible (68 s and 42 r) patients were enrolled from 24 institutions. The main patient characteristics were as follows: median age 60 (s) and 55 (r) years, median performance status 1 for both (s) and (r). Seventy-four percent (s) and 67% (r) had extensive stage disease, including 22% and 36%, respectively, with brain metastases. A total of 398 chemotherapy courses were administered [median 4 (s) and 3 (r) per patient]. The most frequent and serious toxicity was myelosuppression. Grade IV neutropenia occurred in 62% (s) and 49% (r) of patients, with a 19% (s) and 15% (r) incidence of febrile neutropenia, and grade IV thrombocytopenia in 54% (s) and 44% (r). Most of these toxicities occurred during the first chemotherapy course and led to topotecan dose reduction and/or delay in the following courses. Grade III-IV nonhematological toxicity was uncommon. Five deaths possibly related to toxicity occurred among s patients only. Objective responses have been documented in 20 s patients, 19 partial responses and 1 complete response, (29.4% response rate; 95% confidence interval, 19-42), whereas, among r patients, 10 partial responses have been observed (23.8% response rate; 95% confidence interval, 12-39). Median survival for s and r was 6.4 and 6.1 months, respectively. Conclusions: The combination of cisplatin and topotecan, at this dose and schedule, shows activity and promising results in patients with refractory SCLC, with reversible myelosuppression being the main side effect. Additional development of this regimen, using better-tolerated schedules, is warranted in patients with refractory SCLC.

AB - Purpose: The purpose of this study was to assess the activity and toxicity of a combined regimen of topotecan and cisplatin in "sensitive" (s) and "refractory" (r) small-cell lung cancer (SCLC) patients treated previously. Experimental Design: Patients with measurable SCLC and progressive disease after one first-line regimen were eligible for the study. Patients were enrolled in two separate groups: r group (patients who failed first-line treatment 2 on day 1, and topotecan was administered as a daily i.v. infusion at the dose of 0.75 mg/m2 from day 1 to 5, every 3 weeks. Results: A total of 110 eligible (68 s and 42 r) patients were enrolled from 24 institutions. The main patient characteristics were as follows: median age 60 (s) and 55 (r) years, median performance status 1 for both (s) and (r). Seventy-four percent (s) and 67% (r) had extensive stage disease, including 22% and 36%, respectively, with brain metastases. A total of 398 chemotherapy courses were administered [median 4 (s) and 3 (r) per patient]. The most frequent and serious toxicity was myelosuppression. Grade IV neutropenia occurred in 62% (s) and 49% (r) of patients, with a 19% (s) and 15% (r) incidence of febrile neutropenia, and grade IV thrombocytopenia in 54% (s) and 44% (r). Most of these toxicities occurred during the first chemotherapy course and led to topotecan dose reduction and/or delay in the following courses. Grade III-IV nonhematological toxicity was uncommon. Five deaths possibly related to toxicity occurred among s patients only. Objective responses have been documented in 20 s patients, 19 partial responses and 1 complete response, (29.4% response rate; 95% confidence interval, 19-42), whereas, among r patients, 10 partial responses have been observed (23.8% response rate; 95% confidence interval, 12-39). Median survival for s and r was 6.4 and 6.1 months, respectively. Conclusions: The combination of cisplatin and topotecan, at this dose and schedule, shows activity and promising results in patients with refractory SCLC, with reversible myelosuppression being the main side effect. Additional development of this regimen, using better-tolerated schedules, is warranted in patients with refractory SCLC.

UR - http://www.scopus.com/inward/record.url?scp=12244253729&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12244253729&partnerID=8YFLogxK

M3 - Article

C2 - 12538462

AN - SCOPUS:12244253729

VL - 9

SP - 143

EP - 150

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 1 I

ER -