A phase I study of the oral platinum agent satraplatin in combination with oral vinorelbine in patients with advanced solid malignancies

Onkologie. 2013;36(1-2):40-5. doi: 10.1159/000346671. Epub 2013 Jan 28.

Abstract

Background: The broad spectrum of antitumor activity of the oral platinum satraplatin (S) and vinorelbine (V) were the rationale for performing a phase I trial to define the maximum tolerated (MTD) and the recommended (RD) dose in adult patients with advanced solid tumors.

Patients and methods: 4 dose levels (DLs) of S (mg/m(2)/day, days 1-5) and V (mg/m(2)/day, days 1, 8, 15, and 22) every 28 days were explored: S60/V60 on days 1, 8 and 15 only; S60/V60; S70/V60; and S80/V60. Subsequently, 3 further DLs were evaluated with V omitted on day 22: S70/V60, S80/V60, and S80/V80.

Results: Treating 27 patients, the MTD was S80/V80 on days 1, 8, and 15, with 2 dose-limiting toxicities in 2 patients (nausea and vomiting grade (G) 3 with skipping of V on day 15, and neutropenia G4 with infection). The RD was S80/V60 on days 1, 8, and 15. The most frequent toxicities (any G) were nausea (70%), diarrhea (59%), anorexia (37%), vomiting (33%), asthenia (26%), constipation (26%), and paresthesia (18%). Partial responses were observed in 2 platinum-sensitive ovarian cancer patients and in 1 prostate cancer patient.

Conclusion: The combination of S and V is tolerable at a DL of S80/V60 on days 1, 8, and 15; further evaluations in platinum- and V-sensitive tumor types would be of interest.

Trial registration: ClinicalTrials.gov NCT01220284.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nausea / chemically induced*
  • Neoplasms / complications
  • Neoplasms / diagnosis
  • Neoplasms / drug therapy*
  • Organoplatinum Compounds / administration & dosage*
  • Organoplatinum Compounds / adverse effects*
  • Treatment Outcome
  • Vinblastine / administration & dosage
  • Vinblastine / adverse effects
  • Vinblastine / analogs & derivatives*
  • Vinorelbine
  • Vomiting / chemically induced*

Substances

  • Antineoplastic Agents
  • Drug Combinations
  • Organoplatinum Compounds
  • Vinblastine
  • satraplatin
  • Vinorelbine

Associated data

  • ClinicalTrials.gov/NCT01220284