A Phase I Study of the Oral Platinum Agent Satraplatin in Combination with Oral Vinorelbine in Patients with Advanced Solid Malignancies

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/m²/day, days 1–5) and V (mg/m²/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.

Advances in oral delivery of anti-cancer prodrugs

“…Satraplatin entered into clinical trials in 1992, because of its similar anticancer activity to parentally administered cisplatin or carboplatin in in vivo murine models and relatively mild toxicity profile with dose limiting myelosuppression. Several clinical studies (phase I, II and III) have been conducted to evaluate the various pharmacokinetics parameters, maximum tolerable dose (MTD), anticancer efficacy and toxicity profile of satraplatin as its monotherapy as well as in combination with other chemotherapeutic drugs such as prednisone [40], bevacizumab [41], vinorelbine [42] and docetaxel [43]. Table 1 shows the key clinical studies conducted for establishing oral deliverability and anticancer efficacy of satraplatin.…”