A Phase II trial of carboplatin (CBDCA) in small-cell and non-small-cell lung cancer with correlation to in vitro analysis of cytotoxicity

E. Dmitrovsky, E. J. Seifter, A. F. Gazdar, C. M. Tsai, M. Edison, P. Brantley, S. R. Veach, G. Batist, D. C. Ihde, J. L. Mulshine

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

A Phase II trial of carboplatin (CBDCA) was performed in 33 patients with advanced lung cancer, including 15 patients with inoperable Stage III non-small-cell (NSCLC) and 18 patients with relapsed small-cell (SCLC) lung cancer. Initial dosage was 320 mg/m2 infused over 24 h; in the absence of hematologic toxicity, subsequent doses were escalated to 400 mg/m2. Patients received a median of two cycles (range 1-13 for NSCLC and 1-5 for SCLC) of therapy. There were no complete or partial responses among the NSCLC patients. Among the SCLC patients, two had a partial response. In vitro analysis of the cytotoxicity of CBDCA and its parent compound cisplatin by two different methods for 20 NSCLC cell lines suggested that equivalent tumor cell kill is achieved by the two compounds, but this occurs at a log lower concentration of cisplatin than of CBDCA. The in vitro cytotoxicity against NSCLC of CBDCA at a concentration predicted to be in the range produced by the dose employed in this Phase II study correlated well with the resulting very modest in vivo benefit. In vitro, a continuous dose-response relationship exists for CBDCA, suggesting that if higher doses could be administered safely to patients, greater clinical benefit might occur. We conclude that single agent CBDCA in the dosage and schedule administered has less than 20% activity (95% confidence intervals 0-19%) in NSCLC and an 11% response rate in SCLC (95% confidence intervals 2-34%). Despite this outcome, in vitro data in human NSCLC cell lines suggest higher dosages should perhaps be evaluated before discounting a role for CBDCA in the management of NSCLC.

Original languageEnglish (US)
Pages (from-to)285-289
Number of pages5
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume13
Issue number4
StatePublished - 1990

Fingerprint

Carboplatin
Non-Small Cell Lung Carcinoma
Cisplatin
Confidence Intervals
Cell Line
In Vitro Techniques
Small Cell Lung Carcinoma
Lung Neoplasms
Appointments and Schedules

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A Phase II trial of carboplatin (CBDCA) in small-cell and non-small-cell lung cancer with correlation to in vitro analysis of cytotoxicity. / Dmitrovsky, E.; Seifter, E. J.; Gazdar, A. F.; Tsai, C. M.; Edison, M.; Brantley, P.; Veach, S. R.; Batist, G.; Ihde, D. C.; Mulshine, J. L.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 13, No. 4, 1990, p. 285-289.

Research output: Contribution to journalArticle

Dmitrovsky, E, Seifter, EJ, Gazdar, AF, Tsai, CM, Edison, M, Brantley, P, Veach, SR, Batist, G, Ihde, DC & Mulshine, JL 1990, 'A Phase II trial of carboplatin (CBDCA) in small-cell and non-small-cell lung cancer with correlation to in vitro analysis of cytotoxicity', American Journal of Clinical Oncology: Cancer Clinical Trials, vol. 13, no. 4, pp. 285-289.
Dmitrovsky, E. ; Seifter, E. J. ; Gazdar, A. F. ; Tsai, C. M. ; Edison, M. ; Brantley, P. ; Veach, S. R. ; Batist, G. ; Ihde, D. C. ; Mulshine, J. L. / A Phase II trial of carboplatin (CBDCA) in small-cell and non-small-cell lung cancer with correlation to in vitro analysis of cytotoxicity. In: American Journal of Clinical Oncology: Cancer Clinical Trials. 1990 ; Vol. 13, No. 4. pp. 285-289.
@article{c8f21cb63e694051882ac2e78e2b090c,
title = "A Phase II trial of carboplatin (CBDCA) in small-cell and non-small-cell lung cancer with correlation to in vitro analysis of cytotoxicity",
abstract = "A Phase II trial of carboplatin (CBDCA) was performed in 33 patients with advanced lung cancer, including 15 patients with inoperable Stage III non-small-cell (NSCLC) and 18 patients with relapsed small-cell (SCLC) lung cancer. Initial dosage was 320 mg/m2 infused over 24 h; in the absence of hematologic toxicity, subsequent doses were escalated to 400 mg/m2. Patients received a median of two cycles (range 1-13 for NSCLC and 1-5 for SCLC) of therapy. There were no complete or partial responses among the NSCLC patients. Among the SCLC patients, two had a partial response. In vitro analysis of the cytotoxicity of CBDCA and its parent compound cisplatin by two different methods for 20 NSCLC cell lines suggested that equivalent tumor cell kill is achieved by the two compounds, but this occurs at a log lower concentration of cisplatin than of CBDCA. The in vitro cytotoxicity against NSCLC of CBDCA at a concentration predicted to be in the range produced by the dose employed in this Phase II study correlated well with the resulting very modest in vivo benefit. In vitro, a continuous dose-response relationship exists for CBDCA, suggesting that if higher doses could be administered safely to patients, greater clinical benefit might occur. We conclude that single agent CBDCA in the dosage and schedule administered has less than 20{\%} activity (95{\%} confidence intervals 0-19{\%}) in NSCLC and an 11{\%} response rate in SCLC (95{\%} confidence intervals 2-34{\%}). Despite this outcome, in vitro data in human NSCLC cell lines suggest higher dosages should perhaps be evaluated before discounting a role for CBDCA in the management of NSCLC.",
author = "E. Dmitrovsky and Seifter, {E. J.} and Gazdar, {A. F.} and Tsai, {C. M.} and M. Edison and P. Brantley and Veach, {S. R.} and G. Batist and Ihde, {D. C.} and Mulshine, {J. L.}",
year = "1990",
language = "English (US)",
volume = "13",
pages = "285--289",
journal = "American Journal of Clinical Oncology",
issn = "0277-3732",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - A Phase II trial of carboplatin (CBDCA) in small-cell and non-small-cell lung cancer with correlation to in vitro analysis of cytotoxicity

AU - Dmitrovsky, E.

AU - Seifter, E. J.

AU - Gazdar, A. F.

AU - Tsai, C. M.

AU - Edison, M.

AU - Brantley, P.

AU - Veach, S. R.

AU - Batist, G.

AU - Ihde, D. C.

AU - Mulshine, J. L.

PY - 1990

Y1 - 1990

N2 - A Phase II trial of carboplatin (CBDCA) was performed in 33 patients with advanced lung cancer, including 15 patients with inoperable Stage III non-small-cell (NSCLC) and 18 patients with relapsed small-cell (SCLC) lung cancer. Initial dosage was 320 mg/m2 infused over 24 h; in the absence of hematologic toxicity, subsequent doses were escalated to 400 mg/m2. Patients received a median of two cycles (range 1-13 for NSCLC and 1-5 for SCLC) of therapy. There were no complete or partial responses among the NSCLC patients. Among the SCLC patients, two had a partial response. In vitro analysis of the cytotoxicity of CBDCA and its parent compound cisplatin by two different methods for 20 NSCLC cell lines suggested that equivalent tumor cell kill is achieved by the two compounds, but this occurs at a log lower concentration of cisplatin than of CBDCA. The in vitro cytotoxicity against NSCLC of CBDCA at a concentration predicted to be in the range produced by the dose employed in this Phase II study correlated well with the resulting very modest in vivo benefit. In vitro, a continuous dose-response relationship exists for CBDCA, suggesting that if higher doses could be administered safely to patients, greater clinical benefit might occur. We conclude that single agent CBDCA in the dosage and schedule administered has less than 20% activity (95% confidence intervals 0-19%) in NSCLC and an 11% response rate in SCLC (95% confidence intervals 2-34%). Despite this outcome, in vitro data in human NSCLC cell lines suggest higher dosages should perhaps be evaluated before discounting a role for CBDCA in the management of NSCLC.

AB - A Phase II trial of carboplatin (CBDCA) was performed in 33 patients with advanced lung cancer, including 15 patients with inoperable Stage III non-small-cell (NSCLC) and 18 patients with relapsed small-cell (SCLC) lung cancer. Initial dosage was 320 mg/m2 infused over 24 h; in the absence of hematologic toxicity, subsequent doses were escalated to 400 mg/m2. Patients received a median of two cycles (range 1-13 for NSCLC and 1-5 for SCLC) of therapy. There were no complete or partial responses among the NSCLC patients. Among the SCLC patients, two had a partial response. In vitro analysis of the cytotoxicity of CBDCA and its parent compound cisplatin by two different methods for 20 NSCLC cell lines suggested that equivalent tumor cell kill is achieved by the two compounds, but this occurs at a log lower concentration of cisplatin than of CBDCA. The in vitro cytotoxicity against NSCLC of CBDCA at a concentration predicted to be in the range produced by the dose employed in this Phase II study correlated well with the resulting very modest in vivo benefit. In vitro, a continuous dose-response relationship exists for CBDCA, suggesting that if higher doses could be administered safely to patients, greater clinical benefit might occur. We conclude that single agent CBDCA in the dosage and schedule administered has less than 20% activity (95% confidence intervals 0-19%) in NSCLC and an 11% response rate in SCLC (95% confidence intervals 2-34%). Despite this outcome, in vitro data in human NSCLC cell lines suggest higher dosages should perhaps be evaluated before discounting a role for CBDCA in the management of NSCLC.

UR - http://www.scopus.com/inward/record.url?scp=0025172741&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025172741&partnerID=8YFLogxK

M3 - Article

VL - 13

SP - 285

EP - 289

JO - American Journal of Clinical Oncology

JF - American Journal of Clinical Oncology

SN - 0277-3732

IS - 4

ER -