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activity acute acute lymphocytic leukemia adriamycin alkylating agents anticancer drugs antineoplastic antitumor Ara-C beneﬁt bleomycin bone marrow breast cancer Cancer Chemother Cancer Chemotherapy Cancer Philadelphia Cancer Res chemotherapeutic agents clearance combination chemotherapy cure cyclophosphamide Daunomycin DAYS POSTIMPLANT deﬁned deﬁnitions disease dogs dose drug treatment effects evaluation excretion experimental exponential ﬁrst Frei Freireich Gompertzian Guarino human increase individual tumor inﬂuence initial large animals leukemia liver lymphoma M. D. Anderson Hospital major MEDIAN LIFE SPAN metabolism metabolites methotrexate MG/KG mice monkey Muggia neoplastic number of patients pharmacokinetic Pharmacol pharmacologic Phase I studies Phase I trial physician PR rates predictive prednisone Procarbazine randomized clinical trial ratios renal response rate Schabel Schein scientiﬁc shark signiﬁcant signiﬁcantly solid tumors species speciﬁc Table tD_5 testing therapeutic therapy tion tissue toxicity toxicologic tumor tumor cells tumor regression urine variables vincristine