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Phase I study of cisdiamminedichloroplatinum in combination with azidothymidine in the treatment of patients with advanced malignancies.

Publication ,  Journal Article
Morgan, RJ; Newman, EM; Sowers, L; Scanlon, K; Harrison, J; Akman, S; Leong, L; Margolin, K; Niland, J; Raschko, J; Somlo, G; Carroll, M ...
Published in: Cancer Chemother Pharmacol
June 2003

PURPOSE: Azidothymidine (AZT, zidovudine) has been shown to reverse cisplatin resistance in cell culture. This phase I study was performed to determine the maximally tolerated dose (MTD) and dose-limiting toxicities of AZT when administered by continuous intravenous infusion in combination with cisplatin (CDDP), and to evaluate the pharmacokinetics of AZT in this setting. PATIENTS AND METHODS: Entered in the study were 61 patients with advanced, histologically confirmed malignancies which were unresponsive to or for which no "standard" chemotherapeutic regimen existed. AZT was administered as a 72-h infusion on days 1-3 and 14-16 of a 28-day cycle at dose levels from 400 through 14,364 mg/m(2) per day. CDDP at dose levels of 30, 45, or 60 mg/m(2) was administered at hour 36 of each AZT infusion. The plasma pharmacokinetics of AZT were determined in patients treated at representative dose levels. RESULTS: Of the 61 patients who completed 125 courses of therapy, 21 had stable disease for a median of four cycles (range two to eight), 33 progressed on therapy, and 7 were not assessable for response. The major observed toxicity was myelosuppression. The MTD of AZT was 8135 mg/m(2) per day when administered on this schedule. Escalation of CDDP did not result in additive toxicity. The mean steady-state level of AZT at the MTD was 44 microM (range 35-51 microM). CONCLUSIONS: Steady-state concentrations of AZT increased with dose. The plasma levels achieved at the MTD exceeded those required for drug resistance reversal in vitro. The administration of CDDP had no effect on AZT steady-state levels. The dose-limiting toxicity of this drug combination is myelosuppression. AZT may be useful in further studies utilizing combination therapy to achieve increased chemotherapy effectiveness.

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Published In

Cancer Chemother Pharmacol

DOI

ISSN

0344-5704

Publication Date

June 2003

Volume

51

Issue

6

Start / End Page

459 / 464

Location

Germany

Related Subject Headings

  • Zidovudine
  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Male
  • Humans
  • Female
  • Drug Resistance, Neoplasm
  • Cisplatin
  • Antineoplastic Combined Chemotherapy Protocols
 

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Morgan, R. J., Newman, E. M., Sowers, L., Scanlon, K., Harrison, J., Akman, S., … Doroshow, J. H. (2003). Phase I study of cisdiamminedichloroplatinum in combination with azidothymidine in the treatment of patients with advanced malignancies. Cancer Chemother Pharmacol, 51(6), 459–464. https://doi.org/10.1007/s00280-003-0605-0
Morgan, Robert J., Edward M. Newman, Lawrence Sowers, Kevin Scanlon, Jonathan Harrison, Steven Akman, Lucille Leong, et al. “Phase I study of cisdiamminedichloroplatinum in combination with azidothymidine in the treatment of patients with advanced malignancies.Cancer Chemother Pharmacol 51, no. 6 (June 2003): 459–64. https://doi.org/10.1007/s00280-003-0605-0.
Morgan RJ, Newman EM, Sowers L, Scanlon K, Harrison J, Akman S, et al. Phase I study of cisdiamminedichloroplatinum in combination with azidothymidine in the treatment of patients with advanced malignancies. Cancer Chemother Pharmacol. 2003 Jun;51(6):459–64.
Morgan, Robert J., et al. “Phase I study of cisdiamminedichloroplatinum in combination with azidothymidine in the treatment of patients with advanced malignancies.Cancer Chemother Pharmacol, vol. 51, no. 6, June 2003, pp. 459–64. Pubmed, doi:10.1007/s00280-003-0605-0.
Morgan RJ, Newman EM, Sowers L, Scanlon K, Harrison J, Akman S, Leong L, Margolin K, Niland J, Raschko J, Somlo G, Carroll M, Chow W, Tetef M, Hamasaki V, Yen Y, Doroshow JH. Phase I study of cisdiamminedichloroplatinum in combination with azidothymidine in the treatment of patients with advanced malignancies. Cancer Chemother Pharmacol. 2003 Jun;51(6):459–464.
Journal cover image

Published In

Cancer Chemother Pharmacol

DOI

ISSN

0344-5704

Publication Date

June 2003

Volume

51

Issue

6

Start / End Page

459 / 464

Location

Germany

Related Subject Headings

  • Zidovudine
  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Male
  • Humans
  • Female
  • Drug Resistance, Neoplasm
  • Cisplatin
  • Antineoplastic Combined Chemotherapy Protocols