Toxicities
DLTs are summarized in Table 2 . Three dosage levels were assessed in Stratum I. At dosage level 1 (50 mg/m2), 0/3 patients experienced a DLT. At dosage level 2 (75 mg/m2), there were no DLTs in the first 3 patients, prompting dose escalation. At dosage level 3 (95 mg/m2), there were 6 patients enrolled, 4 of which were evaluable (1 patient received less than the required amount of study agent due to progressive disease and 1 patient voluntarily withdrew after initiating protocol therapy). Two of the 4 patients developed grade 4 neutropenia. Hence the MTD was exceeded at dosage level 3, and a total of 9 additional patients were enrolled at dosage level 2. An MTD of 75 mg/m2 was established for Stratum I, with only 2/12 patients experiencing a DLT (Table 2 ).
We proceeded to Stratum II after establishing a MTD for Stratum I. Given concern for myelosuppression in the heavily pretreated patients, enrollment in Stratum II was started at 50 mg/m2 (1 dose level below the MTD of Stratum I). Four patients were enrolled at 50 mg/m2, all were evaluable with no DLTs. This prompted a dose increase to 75 mg/m2 where a total of 10 subjects were enrolled and 7 were evaluable for DLT assessment (2 patients progressed before receiving sufficient study drug and 1 patient withdrew prior to treatment initiation). No DLT was observed among the first 6 evaluable subjects. There was no intent of escalating beyond the MTD of Stratum I, so the cohort was expanded to include a total of 12 patients. However, slow accrual prompted closure of the study prior to completing enrollment. One of 7 evaluable patients experienced a DLT, establishing 75 mg/m2 as the MTD for both Stratum I and II.
Adverse events associated with palbociclib in Stratum I and II are outlined in Table 3 and Table 4 , respectively. Similar to the side effect profile in adults,18 the most common adverse events were related to myelosuppression with decrease in white blood cells, neutrophils, lymphocytes, and platelets being the most common.