Phase-II trial of rebeccamycin analog, a dual topoisomerase-I and -II inhibitor, in relapsed "sensitive" small cell lung cancer

Anita Schwandt, Tarek Mekhail, Balazs Halmos, Timothy O'Brien, Patrick C. Ma, Pingfu Fu, Percy Ivy, Afshin Dowlati

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Relapsed small cell lung cancer (SCLC) carries a poor prognosis. Topoisomerase I and II inhibitors and DNA-damaging agents are considered among the most active agents against SCLC. Rebeccamycin analog (RA, Becatecarin) is an antitumor antibiotic with inhibitory activity against both topoisomerase I and II, and DNA-intercalating properties. We performed a phase-II trial of RA in relapsed, sensitive SCLC with the primary end point of response rate. Patients with previously treated SCLC who relapsed more than 60 days after the completion of first-line chemotherapy were treated with RA-administered intravenously at a dose of 140 mg/m on days 1 to 5 of 21-day cycles for a maximum of six cycles. Eligibility included Eastern Cooperative Oncology Group performance status 0 to 2 and adequate organ function. A two-stage design was employed. Twenty evaluable patients were enrolled. Median age was 61 years. Two patients (10%) had a partial response and six had stable disease. The clinical benefit rate was 40% (95% confidence interval [CI], 23-64%). The median progression-free survival was 2 months (95% CI, 1.2-5.2 months). The median survival was 6.7 months (95% CI, 3.3-8.0 months). No treatment-related deaths occurred. Grade-4 neutropenia and thrombocytopenia occurred in 23% and 14% of the patients, respectively. In conclusion, RA has single-agent activity in relapsed, sensitive SCLC with manageable toxicities but is unlikely to provide any superiority compared to existing agents for this disease.

Original languageEnglish (US)
Pages (from-to)751-754
Number of pages4
JournalJournal of Thoracic Oncology
Volume7
Issue number4
DOIs
StatePublished - Apr 2012
Externally publishedYes

Fingerprint

Topoisomerase I Inhibitors
Topoisomerase II Inhibitors
Small Cell Lung Carcinoma
becatecarin
Confidence Intervals
Type II DNA Topoisomerase
Type I DNA Topoisomerase
DNA
Neutropenia
Disease-Free Survival
rebeccamycin
Anti-Bacterial Agents
Drug Therapy
Survival

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Phase-II trial of rebeccamycin analog, a dual topoisomerase-I and -II inhibitor, in relapsed "sensitive" small cell lung cancer. / Schwandt, Anita; Mekhail, Tarek; Halmos, Balazs; O'Brien, Timothy; Ma, Patrick C.; Fu, Pingfu; Ivy, Percy; Dowlati, Afshin.

In: Journal of Thoracic Oncology, Vol. 7, No. 4, 04.2012, p. 751-754.

Research output: Contribution to journalArticle

Schwandt, Anita ; Mekhail, Tarek ; Halmos, Balazs ; O'Brien, Timothy ; Ma, Patrick C. ; Fu, Pingfu ; Ivy, Percy ; Dowlati, Afshin. / Phase-II trial of rebeccamycin analog, a dual topoisomerase-I and -II inhibitor, in relapsed "sensitive" small cell lung cancer. In: Journal of Thoracic Oncology. 2012 ; Vol. 7, No. 4. pp. 751-754.
@article{91eaf25d8d7f4dbe98ec35c68d94d2c2,
title = "Phase-II trial of rebeccamycin analog, a dual topoisomerase-I and -II inhibitor, in relapsed {"}sensitive{"} small cell lung cancer",
abstract = "Relapsed small cell lung cancer (SCLC) carries a poor prognosis. Topoisomerase I and II inhibitors and DNA-damaging agents are considered among the most active agents against SCLC. Rebeccamycin analog (RA, Becatecarin) is an antitumor antibiotic with inhibitory activity against both topoisomerase I and II, and DNA-intercalating properties. We performed a phase-II trial of RA in relapsed, sensitive SCLC with the primary end point of response rate. Patients with previously treated SCLC who relapsed more than 60 days after the completion of first-line chemotherapy were treated with RA-administered intravenously at a dose of 140 mg/m on days 1 to 5 of 21-day cycles for a maximum of six cycles. Eligibility included Eastern Cooperative Oncology Group performance status 0 to 2 and adequate organ function. A two-stage design was employed. Twenty evaluable patients were enrolled. Median age was 61 years. Two patients (10{\%}) had a partial response and six had stable disease. The clinical benefit rate was 40{\%} (95{\%} confidence interval [CI], 23-64{\%}). The median progression-free survival was 2 months (95{\%} CI, 1.2-5.2 months). The median survival was 6.7 months (95{\%} CI, 3.3-8.0 months). No treatment-related deaths occurred. Grade-4 neutropenia and thrombocytopenia occurred in 23{\%} and 14{\%} of the patients, respectively. In conclusion, RA has single-agent activity in relapsed, sensitive SCLC with manageable toxicities but is unlikely to provide any superiority compared to existing agents for this disease.",
author = "Anita Schwandt and Tarek Mekhail and Balazs Halmos and Timothy O'Brien and Ma, {Patrick C.} and Pingfu Fu and Percy Ivy and Afshin Dowlati",
year = "2012",
month = "4",
doi = "10.1097/JTO.0b013e31824abca2",
language = "English (US)",
volume = "7",
pages = "751--754",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "4",

}

TY - JOUR

T1 - Phase-II trial of rebeccamycin analog, a dual topoisomerase-I and -II inhibitor, in relapsed "sensitive" small cell lung cancer

AU - Schwandt, Anita

AU - Mekhail, Tarek

AU - Halmos, Balazs

AU - O'Brien, Timothy

AU - Ma, Patrick C.

AU - Fu, Pingfu

AU - Ivy, Percy

AU - Dowlati, Afshin

PY - 2012/4

Y1 - 2012/4

N2 - Relapsed small cell lung cancer (SCLC) carries a poor prognosis. Topoisomerase I and II inhibitors and DNA-damaging agents are considered among the most active agents against SCLC. Rebeccamycin analog (RA, Becatecarin) is an antitumor antibiotic with inhibitory activity against both topoisomerase I and II, and DNA-intercalating properties. We performed a phase-II trial of RA in relapsed, sensitive SCLC with the primary end point of response rate. Patients with previously treated SCLC who relapsed more than 60 days after the completion of first-line chemotherapy were treated with RA-administered intravenously at a dose of 140 mg/m on days 1 to 5 of 21-day cycles for a maximum of six cycles. Eligibility included Eastern Cooperative Oncology Group performance status 0 to 2 and adequate organ function. A two-stage design was employed. Twenty evaluable patients were enrolled. Median age was 61 years. Two patients (10%) had a partial response and six had stable disease. The clinical benefit rate was 40% (95% confidence interval [CI], 23-64%). The median progression-free survival was 2 months (95% CI, 1.2-5.2 months). The median survival was 6.7 months (95% CI, 3.3-8.0 months). No treatment-related deaths occurred. Grade-4 neutropenia and thrombocytopenia occurred in 23% and 14% of the patients, respectively. In conclusion, RA has single-agent activity in relapsed, sensitive SCLC with manageable toxicities but is unlikely to provide any superiority compared to existing agents for this disease.

AB - Relapsed small cell lung cancer (SCLC) carries a poor prognosis. Topoisomerase I and II inhibitors and DNA-damaging agents are considered among the most active agents against SCLC. Rebeccamycin analog (RA, Becatecarin) is an antitumor antibiotic with inhibitory activity against both topoisomerase I and II, and DNA-intercalating properties. We performed a phase-II trial of RA in relapsed, sensitive SCLC with the primary end point of response rate. Patients with previously treated SCLC who relapsed more than 60 days after the completion of first-line chemotherapy were treated with RA-administered intravenously at a dose of 140 mg/m on days 1 to 5 of 21-day cycles for a maximum of six cycles. Eligibility included Eastern Cooperative Oncology Group performance status 0 to 2 and adequate organ function. A two-stage design was employed. Twenty evaluable patients were enrolled. Median age was 61 years. Two patients (10%) had a partial response and six had stable disease. The clinical benefit rate was 40% (95% confidence interval [CI], 23-64%). The median progression-free survival was 2 months (95% CI, 1.2-5.2 months). The median survival was 6.7 months (95% CI, 3.3-8.0 months). No treatment-related deaths occurred. Grade-4 neutropenia and thrombocytopenia occurred in 23% and 14% of the patients, respectively. In conclusion, RA has single-agent activity in relapsed, sensitive SCLC with manageable toxicities but is unlikely to provide any superiority compared to existing agents for this disease.

UR - http://www.scopus.com/inward/record.url?scp=84858784067&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84858784067&partnerID=8YFLogxK

U2 - 10.1097/JTO.0b013e31824abca2

DO - 10.1097/JTO.0b013e31824abca2

M3 - Article

VL - 7

SP - 751

EP - 754

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

SN - 1556-0864

IS - 4

ER -