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 cervical cancers

Bradley J. Monk, David S Alberts, Robert A. Burger, Paul T. Fanta, Alton V. Hallum, Kenneth D Hatch, Sydney E. Salmon

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Objective. To compare the in vitro cytotoxicity of nedaplatin, an investigational platinum analog, with that of cisplatin and carboplatin against fresh cervical cancers from untreated patients. Methods. Specimens were obtained prior to irradiation or radical surgery from 20 patients with locally invasive cervical carcinoma. Cytotoxicity was measured after single cell suspensions were grown in agar using colony counts and incorporation of [3H]thymidine. Nedaplatin and cisplatin were tested at 1 and 10 μg/ml dose levels while carboplatin was tested at 10 and 100 μg/ml dose levels continuously. When single hour exposures were used, drug doses were increased by 10-fold. Results. The median drug concentrations associated with a 50% inhibition of growth (IC50) for nedaplatin, cisplatin, and carboplatin were 0.435, 0.73, and 18.6 μg/ml, respectively. At 10 μg/ml for both cisplatin and nedaplatin and 100 μg/ml for carboplatin, cisplatin was the most active drug with 70% of tumors sensitive (≤50% survival relative to control plates) to cisplatin and 45 and 50% sensitive to nedaplatin and carboplatin, respectively (P= 0.015, P=0.074). Six of 20 (30%) tumors resistant to cisplatin were also resistant to nedaplatin and carboplatin. Conclusion. At doses approximating clinically achievable drug concentrations as defined by the mean plasma concentration time product, cisplatin appears more cytotoxic in vitro than either carboplatin or nedaplatin among chemotherapy-naive cervical cancers. However, nedaplatin and carboplatin are also active agents with similar activity. Since differences in drug sensitivity may be related to subtle differences in dose and schedule and the pharmacokinetics and safety profile of nedaplatin are favorable, clinical trials of nedaplatin are indicated.

Original languageEnglish (US)
Pages (from-to)308-312
Number of pages5
JournalGynecologic Oncology
Volume71
Issue number2
DOIs
StatePublished - Nov 1998
Externally publishedYes

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Carboplatin
Platinum
Uterine Cervical Neoplasms
Cisplatin
Pharmaceutical Preparations
nedaplatin
In Vitro Techniques
Thymidine
Inhibitory Concentration 50
Agar
Neoplasms
Suspensions
Appointments and Schedules
Pharmacokinetics
Clinical Trials
Carcinoma
Safety
Drug Therapy
Survival

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • 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 cervical cancers. / Monk, Bradley J.; Alberts, David S; Burger, Robert A.; Fanta, Paul T.; Hallum, Alton V.; Hatch, Kenneth D; Salmon, Sydney E.

In: Gynecologic Oncology, Vol. 71, No. 2, 11.1998, p. 308-312.

Research output: Contribution to journalArticle

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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 cervical cancers",
abstract = "Objective. To compare the in vitro cytotoxicity of nedaplatin, an investigational platinum analog, with that of cisplatin and carboplatin against fresh cervical cancers from untreated patients. Methods. Specimens were obtained prior to irradiation or radical surgery from 20 patients with locally invasive cervical carcinoma. Cytotoxicity was measured after single cell suspensions were grown in agar using colony counts and incorporation of [3H]thymidine. Nedaplatin and cisplatin were tested at 1 and 10 μg/ml dose levels while carboplatin was tested at 10 and 100 μg/ml dose levels continuously. When single hour exposures were used, drug doses were increased by 10-fold. Results. The median drug concentrations associated with a 50{\%} inhibition of growth (IC50) for nedaplatin, cisplatin, and carboplatin were 0.435, 0.73, and 18.6 μg/ml, respectively. At 10 μg/ml for both cisplatin and nedaplatin and 100 μg/ml for carboplatin, cisplatin was the most active drug with 70{\%} of tumors sensitive (≤50{\%} survival relative to control plates) to cisplatin and 45 and 50{\%} sensitive to nedaplatin and carboplatin, respectively (P= 0.015, P=0.074). Six of 20 (30{\%}) tumors resistant to cisplatin were also resistant to nedaplatin and carboplatin. Conclusion. At doses approximating clinically achievable drug concentrations as defined by the mean plasma concentration time product, cisplatin appears more cytotoxic in vitro than either carboplatin or nedaplatin among chemotherapy-naive cervical cancers. However, nedaplatin and carboplatin are also active agents with similar activity. Since differences in drug sensitivity may be related to subtle differences in dose and schedule and the pharmacokinetics and safety profile of nedaplatin are favorable, clinical trials of nedaplatin are indicated.",
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N2 - Objective. To compare the in vitro cytotoxicity of nedaplatin, an investigational platinum analog, with that of cisplatin and carboplatin against fresh cervical cancers from untreated patients. Methods. Specimens were obtained prior to irradiation or radical surgery from 20 patients with locally invasive cervical carcinoma. Cytotoxicity was measured after single cell suspensions were grown in agar using colony counts and incorporation of [3H]thymidine. Nedaplatin and cisplatin were tested at 1 and 10 μg/ml dose levels while carboplatin was tested at 10 and 100 μg/ml dose levels continuously. When single hour exposures were used, drug doses were increased by 10-fold. Results. The median drug concentrations associated with a 50% inhibition of growth (IC50) for nedaplatin, cisplatin, and carboplatin were 0.435, 0.73, and 18.6 μg/ml, respectively. At 10 μg/ml for both cisplatin and nedaplatin and 100 μg/ml for carboplatin, cisplatin was the most active drug with 70% of tumors sensitive (≤50% survival relative to control plates) to cisplatin and 45 and 50% sensitive to nedaplatin and carboplatin, respectively (P= 0.015, P=0.074). Six of 20 (30%) tumors resistant to cisplatin were also resistant to nedaplatin and carboplatin. Conclusion. At doses approximating clinically achievable drug concentrations as defined by the mean plasma concentration time product, cisplatin appears more cytotoxic in vitro than either carboplatin or nedaplatin among chemotherapy-naive cervical cancers. However, nedaplatin and carboplatin are also active agents with similar activity. Since differences in drug sensitivity may be related to subtle differences in dose and schedule and the pharmacokinetics and safety profile of nedaplatin are favorable, clinical trials of nedaplatin are indicated.

AB - Objective. To compare the in vitro cytotoxicity of nedaplatin, an investigational platinum analog, with that of cisplatin and carboplatin against fresh cervical cancers from untreated patients. Methods. Specimens were obtained prior to irradiation or radical surgery from 20 patients with locally invasive cervical carcinoma. Cytotoxicity was measured after single cell suspensions were grown in agar using colony counts and incorporation of [3H]thymidine. Nedaplatin and cisplatin were tested at 1 and 10 μg/ml dose levels while carboplatin was tested at 10 and 100 μg/ml dose levels continuously. When single hour exposures were used, drug doses were increased by 10-fold. Results. The median drug concentrations associated with a 50% inhibition of growth (IC50) for nedaplatin, cisplatin, and carboplatin were 0.435, 0.73, and 18.6 μg/ml, respectively. At 10 μg/ml for both cisplatin and nedaplatin and 100 μg/ml for carboplatin, cisplatin was the most active drug with 70% of tumors sensitive (≤50% survival relative to control plates) to cisplatin and 45 and 50% sensitive to nedaplatin and carboplatin, respectively (P= 0.015, P=0.074). Six of 20 (30%) tumors resistant to cisplatin were also resistant to nedaplatin and carboplatin. Conclusion. At doses approximating clinically achievable drug concentrations as defined by the mean plasma concentration time product, cisplatin appears more cytotoxic in vitro than either carboplatin or nedaplatin among chemotherapy-naive cervical cancers. However, nedaplatin and carboplatin are also active agents with similar activity. Since differences in drug sensitivity may be related to subtle differences in dose and schedule and the pharmacokinetics and safety profile of nedaplatin are favorable, clinical trials of nedaplatin are indicated.

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