Correlation of in vitro drug-sensitivity testing results with response to chemotherapy and survival in extensive-stage small cell lung cancer

A prospective clinical trial

Adi F. Gazdar, Seth M. Steinberg, Edward K. Russell, R. Ilona Linnoila, Herbert K. Oie, Bimal C. Ghosh, James D. Cotelingam, Bruce E. Johnson, John D. Minna, Daniel C. Ihde

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

We devised a novel clinical protocol for extensive-stage small cell lung cancer (SCLC), selecting chemotherapy whenever possible on the basis of in vitro drug-sensitivity testing (DST) of individual patients' tumor specimens. Most of the specimens were obtained from metastatic sites during routine staging procedures. Increase of tumor cell number by culture in selective media usually was required before DST could be performed. We used the Weisenthal dye exclusion assay to place the seven drugs in rank order and to select the in vitro best regimen (IVBR), a three-drug combination of proved efficacy in SCLC. After initial staging and specimen acquisition, patients received etoposide and cisplatin (primary therapy) and were restaged after 12 weeks. Patients with partial or no responses and those relapsing after a complete response to primary therapy were switched to the IVBR if DST data were available. If DST data were unavailable, an empiric combination, vincristine-doxorubicin-cyclophosphamide, was administered as secondary therapy. Tumor-containing specimens were collected from 60 of the 80 patients (75%). One or more cell lines were established from 28 patients, and DST data were available from 26 patients (33% of total). Several parameters of in vitro drug sensitivity were significantly associated [two-sided P (P2) < .05] with clinical response to primary therapy and also with response to the IVBR and were marginally associated with length of survival (.07 ≤ P2 ≤ .08). Sixteen patients (23%) received their IVBR as secondary therapy, and four of these (25%) attained a complete response, compared with three of 43 (7%) who received an empiric regimen (P2 = .16). We concluded that (a) selection of individualized chemotherapy is labor intensive but feasible in extensive-stage SCLC; (b) DST data are associated with clinical response to primary therapy and to secondary therapy with an IVBR; and (c) further observations will be required if we are to determine whether there is a modest therapeutic benefit to administering the IVBR as a secondary therapy.

Original languageEnglish (US)
Pages (from-to)117-124
Number of pages8
JournalJournal of the National Cancer Institute
Volume82
Issue number2
StatePublished - Jan 17 1990

Fingerprint

Small Cell Lung Cancer
Chemotherapy
Small Cell Lung Carcinoma
Clinical Trials
Drugs
Therapy
Cells
Drug Therapy
Testing
Survival
Pharmaceutical Preparations
Tumors
Tumor
Therapeutics
Cell culture
Cisplatin
In Vitro Techniques
Clinical trials
Lung cancer
Assays

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging

Cite this

Correlation of in vitro drug-sensitivity testing results with response to chemotherapy and survival in extensive-stage small cell lung cancer : A prospective clinical trial. / Gazdar, Adi F.; Steinberg, Seth M.; Russell, Edward K.; Linnoila, R. Ilona; Oie, Herbert K.; Ghosh, Bimal C.; Cotelingam, James D.; Johnson, Bruce E.; Minna, John D.; Ihde, Daniel C.

In: Journal of the National Cancer Institute, Vol. 82, No. 2, 17.01.1990, p. 117-124.

Research output: Contribution to journalArticle

Gazdar, Adi F. ; Steinberg, Seth M. ; Russell, Edward K. ; Linnoila, R. Ilona ; Oie, Herbert K. ; Ghosh, Bimal C. ; Cotelingam, James D. ; Johnson, Bruce E. ; Minna, John D. ; Ihde, Daniel C. / Correlation of in vitro drug-sensitivity testing results with response to chemotherapy and survival in extensive-stage small cell lung cancer : A prospective clinical trial. In: Journal of the National Cancer Institute. 1990 ; Vol. 82, No. 2. pp. 117-124.
@article{15d40ea5c8c0403d9942809864e001de,
title = "Correlation of in vitro drug-sensitivity testing results with response to chemotherapy and survival in extensive-stage small cell lung cancer: A prospective clinical trial",
abstract = "We devised a novel clinical protocol for extensive-stage small cell lung cancer (SCLC), selecting chemotherapy whenever possible on the basis of in vitro drug-sensitivity testing (DST) of individual patients' tumor specimens. Most of the specimens were obtained from metastatic sites during routine staging procedures. Increase of tumor cell number by culture in selective media usually was required before DST could be performed. We used the Weisenthal dye exclusion assay to place the seven drugs in rank order and to select the in vitro best regimen (IVBR), a three-drug combination of proved efficacy in SCLC. After initial staging and specimen acquisition, patients received etoposide and cisplatin (primary therapy) and were restaged after 12 weeks. Patients with partial or no responses and those relapsing after a complete response to primary therapy were switched to the IVBR if DST data were available. If DST data were unavailable, an empiric combination, vincristine-doxorubicin-cyclophosphamide, was administered as secondary therapy. Tumor-containing specimens were collected from 60 of the 80 patients (75{\%}). One or more cell lines were established from 28 patients, and DST data were available from 26 patients (33{\%} of total). Several parameters of in vitro drug sensitivity were significantly associated [two-sided P (P2) < .05] with clinical response to primary therapy and also with response to the IVBR and were marginally associated with length of survival (.07 ≤ P2 ≤ .08). Sixteen patients (23{\%}) received their IVBR as secondary therapy, and four of these (25{\%}) attained a complete response, compared with three of 43 (7{\%}) who received an empiric regimen (P2 = .16). We concluded that (a) selection of individualized chemotherapy is labor intensive but feasible in extensive-stage SCLC; (b) DST data are associated with clinical response to primary therapy and to secondary therapy with an IVBR; and (c) further observations will be required if we are to determine whether there is a modest therapeutic benefit to administering the IVBR as a secondary therapy.",
author = "Gazdar, {Adi F.} and Steinberg, {Seth M.} and Russell, {Edward K.} and Linnoila, {R. Ilona} and Oie, {Herbert K.} and Ghosh, {Bimal C.} and Cotelingam, {James D.} and Johnson, {Bruce E.} and Minna, {John D.} and Ihde, {Daniel C.}",
year = "1990",
month = "1",
day = "17",
language = "English (US)",
volume = "82",
pages = "117--124",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Correlation of in vitro drug-sensitivity testing results with response to chemotherapy and survival in extensive-stage small cell lung cancer

T2 - A prospective clinical trial

AU - Gazdar, Adi F.

AU - Steinberg, Seth M.

AU - Russell, Edward K.

AU - Linnoila, R. Ilona

AU - Oie, Herbert K.

AU - Ghosh, Bimal C.

AU - Cotelingam, James D.

AU - Johnson, Bruce E.

AU - Minna, John D.

AU - Ihde, Daniel C.

PY - 1990/1/17

Y1 - 1990/1/17

N2 - We devised a novel clinical protocol for extensive-stage small cell lung cancer (SCLC), selecting chemotherapy whenever possible on the basis of in vitro drug-sensitivity testing (DST) of individual patients' tumor specimens. Most of the specimens were obtained from metastatic sites during routine staging procedures. Increase of tumor cell number by culture in selective media usually was required before DST could be performed. We used the Weisenthal dye exclusion assay to place the seven drugs in rank order and to select the in vitro best regimen (IVBR), a three-drug combination of proved efficacy in SCLC. After initial staging and specimen acquisition, patients received etoposide and cisplatin (primary therapy) and were restaged after 12 weeks. Patients with partial or no responses and those relapsing after a complete response to primary therapy were switched to the IVBR if DST data were available. If DST data were unavailable, an empiric combination, vincristine-doxorubicin-cyclophosphamide, was administered as secondary therapy. Tumor-containing specimens were collected from 60 of the 80 patients (75%). One or more cell lines were established from 28 patients, and DST data were available from 26 patients (33% of total). Several parameters of in vitro drug sensitivity were significantly associated [two-sided P (P2) < .05] with clinical response to primary therapy and also with response to the IVBR and were marginally associated with length of survival (.07 ≤ P2 ≤ .08). Sixteen patients (23%) received their IVBR as secondary therapy, and four of these (25%) attained a complete response, compared with three of 43 (7%) who received an empiric regimen (P2 = .16). We concluded that (a) selection of individualized chemotherapy is labor intensive but feasible in extensive-stage SCLC; (b) DST data are associated with clinical response to primary therapy and to secondary therapy with an IVBR; and (c) further observations will be required if we are to determine whether there is a modest therapeutic benefit to administering the IVBR as a secondary therapy.

AB - We devised a novel clinical protocol for extensive-stage small cell lung cancer (SCLC), selecting chemotherapy whenever possible on the basis of in vitro drug-sensitivity testing (DST) of individual patients' tumor specimens. Most of the specimens were obtained from metastatic sites during routine staging procedures. Increase of tumor cell number by culture in selective media usually was required before DST could be performed. We used the Weisenthal dye exclusion assay to place the seven drugs in rank order and to select the in vitro best regimen (IVBR), a three-drug combination of proved efficacy in SCLC. After initial staging and specimen acquisition, patients received etoposide and cisplatin (primary therapy) and were restaged after 12 weeks. Patients with partial or no responses and those relapsing after a complete response to primary therapy were switched to the IVBR if DST data were available. If DST data were unavailable, an empiric combination, vincristine-doxorubicin-cyclophosphamide, was administered as secondary therapy. Tumor-containing specimens were collected from 60 of the 80 patients (75%). One or more cell lines were established from 28 patients, and DST data were available from 26 patients (33% of total). Several parameters of in vitro drug sensitivity were significantly associated [two-sided P (P2) < .05] with clinical response to primary therapy and also with response to the IVBR and were marginally associated with length of survival (.07 ≤ P2 ≤ .08). Sixteen patients (23%) received their IVBR as secondary therapy, and four of these (25%) attained a complete response, compared with three of 43 (7%) who received an empiric regimen (P2 = .16). We concluded that (a) selection of individualized chemotherapy is labor intensive but feasible in extensive-stage SCLC; (b) DST data are associated with clinical response to primary therapy and to secondary therapy with an IVBR; and (c) further observations will be required if we are to determine whether there is a modest therapeutic benefit to administering the IVBR as a secondary therapy.

UR - http://www.scopus.com/inward/record.url?scp=0025125820&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025125820&partnerID=8YFLogxK

M3 - Article

VL - 82

SP - 117

EP - 124

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 2

ER -