Table 1.
Planned dose levels and observed dose-limiting toxicities
| Dose levela | Paclitaxel (mg/m2) | Carboplatin (mg•min/mL) | Sunitinib (mg) | N (n evaluable for DLT) | DLTs |
|---|---|---|---|---|---|
| Schedule 2/1b | |||||
| 1 | 175 | 6 | 25 | 9 (7) | Grade 4 papilledema (n = 1) |
| 2 | 175 | 6 | 37.5 | 13 (10) | Grade 5 gastrointestinal hemorrhage (n = 1) |
| Grade 4 thrombocytopenia (n = 2) | |||||
| Grade 3 neutropenic infection (n = 1) | |||||
| 3 | 200 | 6 | 37.5 | 3 (3) | None |
| CDD schedulec | |||||
| A | 175 | 6 | 25 | 3 (3) | None |
| B | 175 | 6 | 37.5 | 9 (9) | None |
| Cd | 175 | 6 | 50 | 2 (2) | Grade 4 thrombocytopenia (n = 1) |
| B1d | 200 | 6 | 25 | 4 (4) | None |
CDD continuous daily dosing; DLT dose-limiting toxicity
Patients started sunitinib on day 3 and chemotherapy on day 1 of cycle 1. During subsequent cycles, patients started both chemotherapy and sunitinib on day 1
If 0/3 patients experienced a DLT during cycle 1, subjects were enrolled onto the next dose level
If 1/3 subjects experienced a DLT during cycle 1, the cohort was expanded to a total of n = 6 patients. If 1/6 subjects experienced a DLT, then dose escalation continued and subjects were enrolled in the next dose level
If ≥ 2 subjects in any cohort experienced a DLT during cycle 1, then the MTD had been exceeded and cohorts in preceding dose levels could be expanded to a total of n = 6 patients until the MTD was identified
If there was interest in further exploring the toxicity profile observed at a specific dose level and 2 DLTs were observed in the initial 6 patients enrolled, an additional 3 patients could be enrolled. If no additional DLTs were observed, dose escalation could continue after discussion between the sponsors and investigators
On Schedule 2/1, the MTD was determined as sunitinib 25 mg/day plus paclitaxel 175 mg/m2 and carboplatin AUC 6 mg•min/mL
MTD was not determined on the CDD schedule
Patients were enrolled concurrently onto doses C and B1