Phase II study of BBR 3464 as treatment in patients with sensitive or refractory small cell lung cancer

Thomas A. Hensing, Nasser H. Hanna, Heidi H. Gillenwater, M. Gabriella Camboni, Cecilia Allievi, Mark A. Socinski

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

BBR 3464 is a novel triplatinum compound that has exhibited anti-tumor activity in both cisplatin-sensitive and cisplatin-resistant, as well as in p53 mutant tumor models. In phase I testing, the dose-limiting toxicities have included myelosuppression and diarrhea. Both an intermittent (day 1 every 21-28 days) and a continuous (daily×5 days) schedule have been studied, and the intermittent schedule has been chosen for further development. The primary objective of this study was to assess the efficacy of BBR 3464 administered at a dose of 0.9 mg/m i.v. over 1 h every 21 days in patients with small cell lung cancer who have progressed after first-line therapy. Pharmacokinetic analysis was also performed and will be reported. Patients were stratified based on prior response into resistant and sensitive (response duration 3 months or longer) subgroups. Thirty-seven patients were enrolled onto this multicenter study. The median number of cycles delivered was 2 in the resistant subgroup (range 1-12) and 3 in the sensitive subgroup (range 1-8). Most common grade 3/4 hematological toxicities included neutropenia (62%), febrile neutropenia (16%), anemia (10%), fatigue (5%) and hypokalemia (5%). Although no objective responses were seen in 34 evaluable patients, 11 patients (32%) had disease stabilization (four resistant/seven sensitive) with 23 patients (68%) experiencing continued disease progression (12 resistant/11 sensitive). Median time to progression was 53 days in the resistant subgroup [95% confidence interval (CI) 37-63] and 66 days in the sensitive subgroup (95% CI 51-136). The median and 1-year survival rate based on subgroup was 78 (resistant) (95% CI 56-165) versus 209 days (sensitive) (95% CI 83-296) and 6 (resistant) (95% CI 0-17) versus 20% (95% CI 2-38%), respectively. We conclude that the toxicity profile of BBR 3464 in this phase II trial is consistent with the phase I experience. The lack of activity in either patient subgroup, however, does not support further evaluation of this drug as a single agent in this disease.

Original languageEnglish (US)
Pages (from-to)697-704
Number of pages8
JournalAnti-Cancer Drugs
Volume17
Issue number6
DOIs
StatePublished - Jul 1 2006

Fingerprint

Small Cell Lung Carcinoma
Confidence Intervals
Cisplatin
Therapeutics
Appointments and Schedules
Febrile Neutropenia
Drug Evaluation
Hypokalemia
BBR 3464
Neutropenia
Multicenter Studies
Fatigue
Disease Progression
Anemia
Diarrhea
Neoplasms
Survival Rate
Pharmacokinetics

Keywords

  • BBR 3464
  • Relapsed
  • Second line
  • Small cell lung cancer

ASJC Scopus subject areas

  • Pharmacology
  • Cancer Research
  • Oncology

Cite this

Phase II study of BBR 3464 as treatment in patients with sensitive or refractory small cell lung cancer. / Hensing, Thomas A.; Hanna, Nasser H.; Gillenwater, Heidi H.; Gabriella Camboni, M.; Allievi, Cecilia; Socinski, Mark A.

In: Anti-Cancer Drugs, Vol. 17, No. 6, 01.07.2006, p. 697-704.

Research output: Contribution to journalArticle

Hensing, Thomas A. ; Hanna, Nasser H. ; Gillenwater, Heidi H. ; Gabriella Camboni, M. ; Allievi, Cecilia ; Socinski, Mark A. / Phase II study of BBR 3464 as treatment in patients with sensitive or refractory small cell lung cancer. In: Anti-Cancer Drugs. 2006 ; Vol. 17, No. 6. pp. 697-704.
@article{5df5a89f308d458f8642f2a8f99a6cbd,
title = "Phase II study of BBR 3464 as treatment in patients with sensitive or refractory small cell lung cancer",
abstract = "BBR 3464 is a novel triplatinum compound that has exhibited anti-tumor activity in both cisplatin-sensitive and cisplatin-resistant, as well as in p53 mutant tumor models. In phase I testing, the dose-limiting toxicities have included myelosuppression and diarrhea. Both an intermittent (day 1 every 21-28 days) and a continuous (daily×5 days) schedule have been studied, and the intermittent schedule has been chosen for further development. The primary objective of this study was to assess the efficacy of BBR 3464 administered at a dose of 0.9 mg/m i.v. over 1 h every 21 days in patients with small cell lung cancer who have progressed after first-line therapy. Pharmacokinetic analysis was also performed and will be reported. Patients were stratified based on prior response into resistant and sensitive (response duration 3 months or longer) subgroups. Thirty-seven patients were enrolled onto this multicenter study. The median number of cycles delivered was 2 in the resistant subgroup (range 1-12) and 3 in the sensitive subgroup (range 1-8). Most common grade 3/4 hematological toxicities included neutropenia (62{\%}), febrile neutropenia (16{\%}), anemia (10{\%}), fatigue (5{\%}) and hypokalemia (5{\%}). Although no objective responses were seen in 34 evaluable patients, 11 patients (32{\%}) had disease stabilization (four resistant/seven sensitive) with 23 patients (68{\%}) experiencing continued disease progression (12 resistant/11 sensitive). Median time to progression was 53 days in the resistant subgroup [95{\%} confidence interval (CI) 37-63] and 66 days in the sensitive subgroup (95{\%} CI 51-136). The median and 1-year survival rate based on subgroup was 78 (resistant) (95{\%} CI 56-165) versus 209 days (sensitive) (95{\%} CI 83-296) and 6 (resistant) (95{\%} CI 0-17) versus 20{\%} (95{\%} CI 2-38{\%}), respectively. We conclude that the toxicity profile of BBR 3464 in this phase II trial is consistent with the phase I experience. The lack of activity in either patient subgroup, however, does not support further evaluation of this drug as a single agent in this disease.",
keywords = "BBR 3464, Relapsed, Second line, Small cell lung cancer",
author = "Hensing, {Thomas A.} and Hanna, {Nasser H.} and Gillenwater, {Heidi H.} and {Gabriella Camboni}, M. and Cecilia Allievi and Socinski, {Mark A.}",
year = "2006",
month = "7",
day = "1",
doi = "10.1097/01.cad.0000215054.62942.7f",
language = "English (US)",
volume = "17",
pages = "697--704",
journal = "Anti-Cancer Drugs",
issn = "0959-4973",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Phase II study of BBR 3464 as treatment in patients with sensitive or refractory small cell lung cancer

AU - Hensing, Thomas A.

AU - Hanna, Nasser H.

AU - Gillenwater, Heidi H.

AU - Gabriella Camboni, M.

AU - Allievi, Cecilia

AU - Socinski, Mark A.

PY - 2006/7/1

Y1 - 2006/7/1

N2 - BBR 3464 is a novel triplatinum compound that has exhibited anti-tumor activity in both cisplatin-sensitive and cisplatin-resistant, as well as in p53 mutant tumor models. In phase I testing, the dose-limiting toxicities have included myelosuppression and diarrhea. Both an intermittent (day 1 every 21-28 days) and a continuous (daily×5 days) schedule have been studied, and the intermittent schedule has been chosen for further development. The primary objective of this study was to assess the efficacy of BBR 3464 administered at a dose of 0.9 mg/m i.v. over 1 h every 21 days in patients with small cell lung cancer who have progressed after first-line therapy. Pharmacokinetic analysis was also performed and will be reported. Patients were stratified based on prior response into resistant and sensitive (response duration 3 months or longer) subgroups. Thirty-seven patients were enrolled onto this multicenter study. The median number of cycles delivered was 2 in the resistant subgroup (range 1-12) and 3 in the sensitive subgroup (range 1-8). Most common grade 3/4 hematological toxicities included neutropenia (62%), febrile neutropenia (16%), anemia (10%), fatigue (5%) and hypokalemia (5%). Although no objective responses were seen in 34 evaluable patients, 11 patients (32%) had disease stabilization (four resistant/seven sensitive) with 23 patients (68%) experiencing continued disease progression (12 resistant/11 sensitive). Median time to progression was 53 days in the resistant subgroup [95% confidence interval (CI) 37-63] and 66 days in the sensitive subgroup (95% CI 51-136). The median and 1-year survival rate based on subgroup was 78 (resistant) (95% CI 56-165) versus 209 days (sensitive) (95% CI 83-296) and 6 (resistant) (95% CI 0-17) versus 20% (95% CI 2-38%), respectively. We conclude that the toxicity profile of BBR 3464 in this phase II trial is consistent with the phase I experience. The lack of activity in either patient subgroup, however, does not support further evaluation of this drug as a single agent in this disease.

AB - BBR 3464 is a novel triplatinum compound that has exhibited anti-tumor activity in both cisplatin-sensitive and cisplatin-resistant, as well as in p53 mutant tumor models. In phase I testing, the dose-limiting toxicities have included myelosuppression and diarrhea. Both an intermittent (day 1 every 21-28 days) and a continuous (daily×5 days) schedule have been studied, and the intermittent schedule has been chosen for further development. The primary objective of this study was to assess the efficacy of BBR 3464 administered at a dose of 0.9 mg/m i.v. over 1 h every 21 days in patients with small cell lung cancer who have progressed after first-line therapy. Pharmacokinetic analysis was also performed and will be reported. Patients were stratified based on prior response into resistant and sensitive (response duration 3 months or longer) subgroups. Thirty-seven patients were enrolled onto this multicenter study. The median number of cycles delivered was 2 in the resistant subgroup (range 1-12) and 3 in the sensitive subgroup (range 1-8). Most common grade 3/4 hematological toxicities included neutropenia (62%), febrile neutropenia (16%), anemia (10%), fatigue (5%) and hypokalemia (5%). Although no objective responses were seen in 34 evaluable patients, 11 patients (32%) had disease stabilization (four resistant/seven sensitive) with 23 patients (68%) experiencing continued disease progression (12 resistant/11 sensitive). Median time to progression was 53 days in the resistant subgroup [95% confidence interval (CI) 37-63] and 66 days in the sensitive subgroup (95% CI 51-136). The median and 1-year survival rate based on subgroup was 78 (resistant) (95% CI 56-165) versus 209 days (sensitive) (95% CI 83-296) and 6 (resistant) (95% CI 0-17) versus 20% (95% CI 2-38%), respectively. We conclude that the toxicity profile of BBR 3464 in this phase II trial is consistent with the phase I experience. The lack of activity in either patient subgroup, however, does not support further evaluation of this drug as a single agent in this disease.

KW - BBR 3464

KW - Relapsed

KW - Second line

KW - Small cell lung cancer

UR - http://www.scopus.com/inward/record.url?scp=33747597058&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33747597058&partnerID=8YFLogxK

U2 - 10.1097/01.cad.0000215054.62942.7f

DO - 10.1097/01.cad.0000215054.62942.7f

M3 - Article

C2 - 16917215

AN - SCOPUS:33747597058

VL - 17

SP - 697

EP - 704

JO - Anti-Cancer Drugs

JF - Anti-Cancer Drugs

SN - 0959-4973

IS - 6

ER -