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Subsequent cohorts of patients were treated at intermediate dose levels of 170 and 200 mg m−2 in order to define a safe dose for phase 2 studies.
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An intermediate dose level of 85 mg was studied.
Responses were observed at the intermediate dose level of 15 mg/m daily × 10 days (150 mg/m/course).
Ingestion of the intermediate dose level of 2 mg/kg-day caused lesser degrees of toxicity, but no evidence of neoplasia.
These events suggested that 70 mg was poorly tolerated so an intermediate dose level of 60 mg was open for evaluation.
Provision was made in the protocol for intermediate dose levels or expansion of a dose cohort to define better the dose toxicity relationship of XR5944.14.
No significant haematological toxicity occurred at either of these intermediate dose levels.
A minimum of three patients were treated at each predefined dose level before dose escalation; depending on treatment-emergent toxicities, additional patients could have been entered as needed at any dose level, including intermediate dose levels.
Dose levels for the study were predefined as in Figure 1; however, intermediate dose levels were allowed.
Three further intermediate dose levels (L1b, L2b, L3b), are also provided in case MTD is reached.
However, the protocol was subsequently amended to include a dose level of 10 mg/m, an intermediate dose level between the recommended IV dose of 8.4 mg/m and the MTD of 12 mg/m.
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