Background: S is a novel, oral platinum (P) analogue with a preclinical safety and activity profile comparable to carboplatin. C is an oral pro-drug of 5'-DFUR approved as single agent or in combination with other cytotoxic agents for the treatment of breast and colon cancer. A sequential administration schedule of S and C was assessed in an open-label phase Ib study in adult patients (pts) with advanced solid tumours. Methods: S was given QD to fasting pts from d1 to 5, C BID from d8 to 21 of a 4-week cycle. The starting daily doses were S 60 mg/m2 and C 1,650 mg/m2 (825 BID). Prophylactic oral 5HT 3 antagonists and steroids were given 30-60 min before S. Three to six pts were entered per dose level (DL). The maximum tolerated dose (MTD) was one dose level below the dose at which >2 of 3 or >2 of 6 pts experienced dose-limiting toxicities (DLTs). Eligibility criteria included ECOG PS <2, adequate renal/liver function, <2 lines of prior chemotherapies (CTs) for advanced disease, lack of resistance to approved P and/or fluoropyrimidine compounds, absence of clinical situations significantly affecting oral absorption. Results: 38 pts with a variety of solid tumours (20 prostate, 7 ovarian, 4 gastrointestinal, 7 other) entered the study at 4 Swiss centres (SAKK-SENDO phase I network). All pts but 1 (hormone-resistant prostate cancer) had received prior CTs, including P compounds in 13 pts. Dose-limiting thrombocytopenia G3-4 occurred in 2/6 pts at DL S 80 mg/m2 and C 1,650 mg/m2. The MTD and thus the RD was determined at S 70 mg/m2 and C 2,000 mg/m2, with DLT nausea G3 and long-lasting moderate neutropenia in 1/6 pts. Main non-haematological toxicities were nausea, anorexia, diarrhoea and mild to moderate fatigue. In 24 pts evaluated, 2 confirmed partial responses (PR) were seen in P-sensitive ovarian cancer, 1 PR and 4 stable diseases (SD) in prostate cancer pts. Conclusions: The phase II RD of the sequential combination has been defined at S 70 mg/m2 and C 2,000 mg/m2 (1,000 BID). Preliminary results suggest that the sequential administration of S and C represents a well tolerated and convenient oral treatment for pts with advanced solid tumours.