................... 29 3.1.1 Dose Limiting Toxicity ................................ ................................ ............................... 30 3.1.2 Dose De -Escalation ................................ ................................ ................................ ....30 3.2 ADMINISTRATION AND DURATION OF TREATMENT ................................ ............................. 33 3.3 DOSE DELAY OR DISCONTINUATION ................................ ................................ ................... 33 3.4 DOSE MODIFICATIONS ................................ ................................