In vitro phase II comparison of the cytotoxicity of a novel platinum analog, nedaplatin (254-S), with that of cisplatin and carboplatin against fresh, human ovarian cancers

David S Alberts, Paul T. Fanta, Kelli L. Running, Laurence P. Adair, Dava J. Garcia, Rosa Liu-Stevens, Sydney E. Salmon

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Purpose: To compare the in vitro cytotoxicity of nedaplatin, an investigational platinum analog, with that of the standard platinum agents, cisplatin and carboplatin, against fresh human, epithelial ovarian cancers. Methods: The Hamburger-Salmon human tumor colony-forming assay (HTCA) was used to measure the chemosensitivity of 36 fresh tumor samples obtained during initial exploratory laparotomy from patients with newly diagnosed stage III-IV epithelial ovarian cancer who had received no prior chemotherapy or radiation therapy. Tumor samples were exposed to the platinum analogs for I h at concentrations of 10 and 100 μg/ml of nedaplatin and cisplatin and 100 and 1000 μg/ml of carboplatin. The resulting survival data were used to estimate the IC50 (drug concentration associated with 50% inhibition of tumor colony forming units, TCFUs) of each of the platinum analogs for each of the tumor samples, as well as the estimated survival following exposure to clinically achievable drug levels (i.e. the ultrafiltrable platinum area under the plasma disappearance curve, AUC, achieved in cancer patients following administration of standard or phase II doses). Results: At the lowest concentration tested (i.e. 10 μg/ml nedaplatin and cisplatin and 100 μg/ml carboplatin) the percentages of tumor samples which were sensitive (as defined by 50% or less survival of TCFUs as compared with controls) were 42, 50, and 40% for nedaplatin, cisplatin and carboplatin, respectively. The median IC50 values were 28.5, 12 and 121 μg/ml for nedaplatin, cisplatin and carboplatin, respectively. The estimated percentage of tumors sensitive to clinically achievable dose levels was 42% for nedaplatin and 36% for cisplatin and carboplatin. Nedaplatin and carboplatin proved relatively crossresistant with cisplatin in vitro; of the Is tumor samples which were resistant to cisplatin, only 5 (28%) were sensitive to nedaplatin and 3 of 17 (18%) were sensitive to carboplatin. Conclusion: Nedaplatin was associated with cytotoxicity similar to cisplatin and carboplatin in this study. Although nedaplatin appears to be crossresistant with cisplatin, its high rate of in vitro cytotoxicity, relative lack of neurotoxicity and nephrotoxicity, and large in vivo bioavailability establish nedaplatin as a promising platinum analog for further clinical development as a salvage and primary chemotherapeutic agent for patients with advanced ovarian cancer.

Original languageEnglish (US)
Pages (from-to)493-497
Number of pages5
JournalCancer Chemotherapy and Pharmacology
Volume39
Issue number6
DOIs
StatePublished - 1997

Fingerprint

Carboplatin
Cytotoxicity
Platinum
Ovarian Neoplasms
Cisplatin
Tumors
Neoplasms
Inhibitory Concentration 50
Survival
nedaplatin
In Vitro Techniques
Stem Cells
Salvaging
Chemotherapy
Salmon
Radiotherapy
Proxy
Pharmaceutical Preparations
Laparotomy
Biological Availability

Keywords

  • Chemotherapy
  • Nedaplatin
  • Ovarian cancer
  • Platinum analog

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

In vitro phase II comparison of the cytotoxicity of a novel platinum analog, nedaplatin (254-S), with that of cisplatin and carboplatin against fresh, human ovarian cancers. / Alberts, David S; Fanta, Paul T.; Running, Kelli L.; Adair, Laurence P.; Garcia, Dava J.; Liu-Stevens, Rosa; Salmon, Sydney E.

In: Cancer Chemotherapy and Pharmacology, Vol. 39, No. 6, 1997, p. 493-497.

Research output: Contribution to journalArticle

Alberts, David S ; Fanta, Paul T. ; Running, Kelli L. ; Adair, Laurence P. ; Garcia, Dava J. ; Liu-Stevens, Rosa ; Salmon, Sydney E. / In vitro phase II comparison of the cytotoxicity of a novel platinum analog, nedaplatin (254-S), with that of cisplatin and carboplatin against fresh, human ovarian cancers. In: Cancer Chemotherapy and Pharmacology. 1997 ; Vol. 39, No. 6. pp. 493-497.
@article{a5c8f5b7baff422a86e4873f1e2a807b,
title = "In vitro phase II comparison of the cytotoxicity of a novel platinum analog, nedaplatin (254-S), with that of cisplatin and carboplatin against fresh, human ovarian cancers",
abstract = "Purpose: To compare the in vitro cytotoxicity of nedaplatin, an investigational platinum analog, with that of the standard platinum agents, cisplatin and carboplatin, against fresh human, epithelial ovarian cancers. Methods: The Hamburger-Salmon human tumor colony-forming assay (HTCA) was used to measure the chemosensitivity of 36 fresh tumor samples obtained during initial exploratory laparotomy from patients with newly diagnosed stage III-IV epithelial ovarian cancer who had received no prior chemotherapy or radiation therapy. Tumor samples were exposed to the platinum analogs for I h at concentrations of 10 and 100 μg/ml of nedaplatin and cisplatin and 100 and 1000 μg/ml of carboplatin. The resulting survival data were used to estimate the IC50 (drug concentration associated with 50{\%} inhibition of tumor colony forming units, TCFUs) of each of the platinum analogs for each of the tumor samples, as well as the estimated survival following exposure to clinically achievable drug levels (i.e. the ultrafiltrable platinum area under the plasma disappearance curve, AUC, achieved in cancer patients following administration of standard or phase II doses). Results: At the lowest concentration tested (i.e. 10 μg/ml nedaplatin and cisplatin and 100 μg/ml carboplatin) the percentages of tumor samples which were sensitive (as defined by 50{\%} or less survival of TCFUs as compared with controls) were 42, 50, and 40{\%} for nedaplatin, cisplatin and carboplatin, respectively. The median IC50 values were 28.5, 12 and 121 μg/ml for nedaplatin, cisplatin and carboplatin, respectively. The estimated percentage of tumors sensitive to clinically achievable dose levels was 42{\%} for nedaplatin and 36{\%} for cisplatin and carboplatin. Nedaplatin and carboplatin proved relatively crossresistant with cisplatin in vitro; of the Is tumor samples which were resistant to cisplatin, only 5 (28{\%}) were sensitive to nedaplatin and 3 of 17 (18{\%}) were sensitive to carboplatin. Conclusion: Nedaplatin was associated with cytotoxicity similar to cisplatin and carboplatin in this study. Although nedaplatin appears to be crossresistant with cisplatin, its high rate of in vitro cytotoxicity, relative lack of neurotoxicity and nephrotoxicity, and large in vivo bioavailability establish nedaplatin as a promising platinum analog for further clinical development as a salvage and primary chemotherapeutic agent for patients with advanced ovarian cancer.",
keywords = "Chemotherapy, Nedaplatin, Ovarian cancer, Platinum analog",
author = "Alberts, {David S} and Fanta, {Paul T.} and Running, {Kelli L.} and Adair, {Laurence P.} and Garcia, {Dava J.} and Rosa Liu-Stevens and Salmon, {Sydney E.}",
year = "1997",
doi = "10.1007/s002800050604",
language = "English (US)",
volume = "39",
pages = "493--497",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",
number = "6",

}

TY - JOUR

T1 - In vitro phase II comparison of the cytotoxicity of a novel platinum analog, nedaplatin (254-S), with that of cisplatin and carboplatin against fresh, human ovarian cancers

AU - Alberts, David S

AU - Fanta, Paul T.

AU - Running, Kelli L.

AU - Adair, Laurence P.

AU - Garcia, Dava J.

AU - Liu-Stevens, Rosa

AU - Salmon, Sydney E.

PY - 1997

Y1 - 1997

N2 - Purpose: To compare the in vitro cytotoxicity of nedaplatin, an investigational platinum analog, with that of the standard platinum agents, cisplatin and carboplatin, against fresh human, epithelial ovarian cancers. Methods: The Hamburger-Salmon human tumor colony-forming assay (HTCA) was used to measure the chemosensitivity of 36 fresh tumor samples obtained during initial exploratory laparotomy from patients with newly diagnosed stage III-IV epithelial ovarian cancer who had received no prior chemotherapy or radiation therapy. Tumor samples were exposed to the platinum analogs for I h at concentrations of 10 and 100 μg/ml of nedaplatin and cisplatin and 100 and 1000 μg/ml of carboplatin. The resulting survival data were used to estimate the IC50 (drug concentration associated with 50% inhibition of tumor colony forming units, TCFUs) of each of the platinum analogs for each of the tumor samples, as well as the estimated survival following exposure to clinically achievable drug levels (i.e. the ultrafiltrable platinum area under the plasma disappearance curve, AUC, achieved in cancer patients following administration of standard or phase II doses). Results: At the lowest concentration tested (i.e. 10 μg/ml nedaplatin and cisplatin and 100 μg/ml carboplatin) the percentages of tumor samples which were sensitive (as defined by 50% or less survival of TCFUs as compared with controls) were 42, 50, and 40% for nedaplatin, cisplatin and carboplatin, respectively. The median IC50 values were 28.5, 12 and 121 μg/ml for nedaplatin, cisplatin and carboplatin, respectively. The estimated percentage of tumors sensitive to clinically achievable dose levels was 42% for nedaplatin and 36% for cisplatin and carboplatin. Nedaplatin and carboplatin proved relatively crossresistant with cisplatin in vitro; of the Is tumor samples which were resistant to cisplatin, only 5 (28%) were sensitive to nedaplatin and 3 of 17 (18%) were sensitive to carboplatin. Conclusion: Nedaplatin was associated with cytotoxicity similar to cisplatin and carboplatin in this study. Although nedaplatin appears to be crossresistant with cisplatin, its high rate of in vitro cytotoxicity, relative lack of neurotoxicity and nephrotoxicity, and large in vivo bioavailability establish nedaplatin as a promising platinum analog for further clinical development as a salvage and primary chemotherapeutic agent for patients with advanced ovarian cancer.

AB - Purpose: To compare the in vitro cytotoxicity of nedaplatin, an investigational platinum analog, with that of the standard platinum agents, cisplatin and carboplatin, against fresh human, epithelial ovarian cancers. Methods: The Hamburger-Salmon human tumor colony-forming assay (HTCA) was used to measure the chemosensitivity of 36 fresh tumor samples obtained during initial exploratory laparotomy from patients with newly diagnosed stage III-IV epithelial ovarian cancer who had received no prior chemotherapy or radiation therapy. Tumor samples were exposed to the platinum analogs for I h at concentrations of 10 and 100 μg/ml of nedaplatin and cisplatin and 100 and 1000 μg/ml of carboplatin. The resulting survival data were used to estimate the IC50 (drug concentration associated with 50% inhibition of tumor colony forming units, TCFUs) of each of the platinum analogs for each of the tumor samples, as well as the estimated survival following exposure to clinically achievable drug levels (i.e. the ultrafiltrable platinum area under the plasma disappearance curve, AUC, achieved in cancer patients following administration of standard or phase II doses). Results: At the lowest concentration tested (i.e. 10 μg/ml nedaplatin and cisplatin and 100 μg/ml carboplatin) the percentages of tumor samples which were sensitive (as defined by 50% or less survival of TCFUs as compared with controls) were 42, 50, and 40% for nedaplatin, cisplatin and carboplatin, respectively. The median IC50 values were 28.5, 12 and 121 μg/ml for nedaplatin, cisplatin and carboplatin, respectively. The estimated percentage of tumors sensitive to clinically achievable dose levels was 42% for nedaplatin and 36% for cisplatin and carboplatin. Nedaplatin and carboplatin proved relatively crossresistant with cisplatin in vitro; of the Is tumor samples which were resistant to cisplatin, only 5 (28%) were sensitive to nedaplatin and 3 of 17 (18%) were sensitive to carboplatin. Conclusion: Nedaplatin was associated with cytotoxicity similar to cisplatin and carboplatin in this study. Although nedaplatin appears to be crossresistant with cisplatin, its high rate of in vitro cytotoxicity, relative lack of neurotoxicity and nephrotoxicity, and large in vivo bioavailability establish nedaplatin as a promising platinum analog for further clinical development as a salvage and primary chemotherapeutic agent for patients with advanced ovarian cancer.

KW - Chemotherapy

KW - Nedaplatin

KW - Ovarian cancer

KW - Platinum analog

UR - http://www.scopus.com/inward/record.url?scp=0031037594&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031037594&partnerID=8YFLogxK

U2 - 10.1007/s002800050604

DO - 10.1007/s002800050604

M3 - Article

C2 - 9118460

AN - SCOPUS:0031037594

VL - 39

SP - 493

EP - 497

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 6

ER -