escalated for the subsequent 3 patients. If dose limiting toxicity occurs in 1 of 
the 3 additional patients, the maximum tolerated dosage (MTD) has been 
exceeded and 3 additional patients will be treated at the next lower dosage (if 
only 3 patients were treated previously at that dosage level). 
The MTD is defined as that dosage level immediately below the dosage level at 
which 2 patients of a cohort (of 3-6 patients) experience dose limiting toxicity. 
9.5 Patients with measurable disease will have serial measurement of such indicator 
lesions which will be considered for response according to the definitions below, 
at 6 weeks, and thereafter. 
9.5.1 Complete Response (CR) : Total disappearance of all measureable 
disease, M-l marrow status with restoration of normal hematopoiesis 
and normal performance status persisting at least 4 weeks. Onset of 
response will be appropriately noted and detailed, and duration noted. 
9.5.2 Very Good Partial Response (VGPR1: Regression 
of primary tumor (>90%), clearing of metastatic 
disease except for persistent bone scan positive 
lesions attained by and maintained through 
induction. 
9.5.3 Partial ResponsefPRl : Regression of <50% of all tumor. 
9.5.4 Stable Disease : Exists when a patient fails to qualify for either complete 
response, VGPR, partial response or progressive disease. 
9.5.5 Progressive Disease : Worsening of disease, evidenced by enlargement 
of existing tumors or apppearance of new disease. 
9.6 Statistical Considerations 
Since this is a Phase I study with exploratory investigation of several dosage 
quantities to define one dosage schedule for future Phase II studies at a level 
which is tolerable, toxicity to be evaluated will include skin, hematopoietic, renal, 
hepatic, gastrointestinal, and neurotoxicity, which will be compared among 
subjects at each dosage step. Qualitative and quantitative toxicities will be 
recorded for comparison among patients at each dosage step, with considerations 
for the time to recovery from various types of toxicity. A total of 12 patients will 
be studied with a predicted accrual time of two years. 
Recombinant DNA Research, Volume 15 
