Phase II clinical trial of didemnin B in previously treated small cell lung cancer

Dong M. Shin, Paul Y. Holoye, Arthur Forman, Rodger Winn, Roman Perez-Soler, Shaker Dakhil, Julian Rosenthal, Martin N. Raber, Waun Ki Hong

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Didemnin B (NSC 325319), a cyclic depsipeptide isolated from a Carribean sea tunicate, exhibited potent antitumor activity in preclinical studies. After determining the maximum tolerated dose in our previous phase I/II trial, we conducted a phase II study of this drug in patients with previously treated small cell lung cancer; the starting dose was 6.3 mg/m2 intravenously over 30 min every 28 days. The major side effects were in the neuromuscular system and included severe muscle weakness, myopathy and/or myotonia by electromyography, and elevation of creatine phosphokinase and aldolase levels. We also observed modest increases in bilirubin and alkaline phosphatase levels. There were minimal hematologic toxic effects. No response was observed among 15 evaluable patients, leading us to conclude that didemnin B was toxic but inactive in patients with previously treated small cell lung cancer at the stated dose and schedule. A review of the literature revealed no significant antitumor activity in cancers of the colon, breast, ovaries, cervix, or lung (non-small cell) or in renal cell carcinoma. Further clinical trials for didemnin B may not be warranted at the stated dose and schedule.

Original languageEnglish (US)
Pages (from-to)243-249
Number of pages7
JournalInvestigational New Drugs
Volume12
Issue number3
DOIs
StatePublished - Sep 1994
Externally publishedYes

Fingerprint

didemnins
Phase II Clinical Trials
Small Cell Lung Carcinoma
Poisons
Appointments and Schedules
Depsipeptides
Myotonia
Urochordata
Fructose-Bisphosphate Aldolase
Maximum Tolerated Dose
Muscle Weakness
Electromyography
Muscular Diseases
Creatine Kinase
Bilirubin
Renal Cell Carcinoma
Cervix Uteri
Oceans and Seas
Colonic Neoplasms
Alkaline Phosphatase

Keywords

  • didemnin B
  • myopathy
  • small cell lung cancer

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Shin, D. M., Holoye, P. Y., Forman, A., Winn, R., Perez-Soler, R., Dakhil, S., ... Hong, W. K. (1994). Phase II clinical trial of didemnin B in previously treated small cell lung cancer. Investigational New Drugs, 12(3), 243-249. https://doi.org/10.1007/BF00873966

Phase II clinical trial of didemnin B in previously treated small cell lung cancer. / Shin, Dong M.; Holoye, Paul Y.; Forman, Arthur; Winn, Rodger; Perez-Soler, Roman; Dakhil, Shaker; Rosenthal, Julian; Raber, Martin N.; Hong, Waun Ki.

In: Investigational New Drugs, Vol. 12, No. 3, 09.1994, p. 243-249.

Research output: Contribution to journalArticle

Shin, DM, Holoye, PY, Forman, A, Winn, R, Perez-Soler, R, Dakhil, S, Rosenthal, J, Raber, MN & Hong, WK 1994, 'Phase II clinical trial of didemnin B in previously treated small cell lung cancer', Investigational New Drugs, vol. 12, no. 3, pp. 243-249. https://doi.org/10.1007/BF00873966
Shin, Dong M. ; Holoye, Paul Y. ; Forman, Arthur ; Winn, Rodger ; Perez-Soler, Roman ; Dakhil, Shaker ; Rosenthal, Julian ; Raber, Martin N. ; Hong, Waun Ki. / Phase II clinical trial of didemnin B in previously treated small cell lung cancer. In: Investigational New Drugs. 1994 ; Vol. 12, No. 3. pp. 243-249.
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