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Phase I study of weekly kahalalide F as prolonged infusion in patients with advanced solid tumors

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Abstract

Purpose

Kahalalide F (KF) is a dehydroaminobutyric acid-containing peptide from marine origin with activity against several human malignant cell lines. This dose-escalating phase I clinical trial evaluated the maximum tolerated dose (MTD), and the recommended dose for further phase II studies (RD) of weekly KF given as a prolonged (3- to 24-h) intravenous (i.v.) infusion.

Methods

Eligible patients with advanced solid tumors and adequate performance status, hematologic, renal, and hepatic function were recruited into this study.

Results

A total of 106 patients were treated with KF at four different weekly schedules: 3-h (n = 40), 24-h (n = 59), and two transitional schedules [6-h (n = 4) and 12-h (n = 3)]. For the 3-h weekly schedule, the MTD was 1,200 μg/m2 and the RD was 1,000 μg/m2. For the 24-h weekly schedule, the MTD was reached (6,650 μg/m2), but the RD could not be confirmed. Asymptomatic and reversible grade 3/4 transaminase increase was the most common dose-limiting toxicity in both schedules. Fatigue, paresthesia, pruritus, nausea, vomiting, and rash were the most common KF-related adverse events. No major deviations from linearity were detected in the pharmacokinetic (PK) profiles of both schedules, which showed a narrow distribution and short body residence. Prolonged disease stabilization (≥3 months) occurred in eight patients: two with the 3-h schedule and six with the 24-h schedule.

Conclusions

Administration of KF as prolonged weekly infusion appears feasible, with 3-h and 24-h infusion times having an acceptable safety profile.

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Conflict of interest

Josep Tabernero has participated in advisory boards of Pharma Mar, and his institution has received research funding from Pharma Mar to conduct clinical trials. Cinthya Coronado, Arturo Soto Matos-Pita, Bernardo Miguel-Lillo, Martin Cullell-Young, and Jorge Luis Iglesias Dios are currently PharmaMar employees. All other authors declare no conflicts of interest.

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Authors and Affiliations

  1. Instituto Catalán de Oncología, Ctra. Gran Vía, 08907 s/n. L’Hospitalet de Llobregat, Barcelona, Spain

    R. Salazar, B. Pardo, C. Cuadra & M. García

  2. Hospital Universitario Doce de Octubre, Madrid, Spain

    H. Cortés-Funes, A. López-Martín, C. Coronado & L. Paz-Ares

  3. Hospital Vall d’Hebron, University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain

    E. Casado & J. Tabernero

  4. Pharma Mar, S.A. Sociedad Unipersonal, Colmenar Viejo, Madrid, Spain

    A. Soto Matos-Pita, B. Miguel-Lillo, M. Cullell-Young & J. L. Iglesias Dios

Authors
  1. R. Salazar
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  2. H. Cortés-Funes
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  3. E. Casado
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  4. B. Pardo
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  5. A. López-Martín
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  6. C. Cuadra
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  7. J. Tabernero
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  8. C. Coronado
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  9. M. García
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  10. A. Soto Matos-Pita
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  11. B. Miguel-Lillo
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  12. M. Cullell-Young
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  13. J. L. Iglesias Dios
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  14. L. Paz-Ares
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Corresponding author

Correspondence to R. Salazar.

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Salazar, R., Cortés-Funes, H., Casado, E. et al. Phase I study of weekly kahalalide F as prolonged infusion in patients with advanced solid tumors. Cancer Chemother Pharmacol 72, 75–83 (2013). https://doi.org/10.1007/s00280-013-2170-5

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  • DOI: https://doi.org/10.1007/s00280-013-2170-5

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