Responsiveness to Chemotherapy of Mice With L1210 Lymphoid Leukemia Implanted in Various Anatomic Sites

Abstract

Eighteen anticancer agents were tested against the L1210 leukemia implanted into (BALB/c × DBA)F, mice iv, intracerebrally (ic), ip, sc, im, and intrathoracically (ith). Percentage increase in life-span (ILS) data showed that the responsiveness of tumor-bearing animals to chemotherapy depended on the anatomic location of the tumor. For weakly (30–59% ILS) active compounds (nitrogen mustard, actinomycin D, chlorambucil, hexamethylmelamine, 5-fluorodeoxyuridine, and procarbazine), only the iv or ip sites were responsive to treatment; for the moderately active (60–154% ILS) compounds (methotrexate, thio-TEPA, melphalan, 5-fluorouracil, hydroxyurea, and 5-azacytidine), the relative order of sensitivity of anatomic sites to chemotherapy was: iv>(ip and ith)>(im and sc)>ic. For highly active (≥155% ILS) compounds [Cytoxan, cytosine arabinoside, 1,3-cis(2-chloroethyl)-1-nitrosourea (CCNU), methyi-CCNU, isophosphamide, and 1,3- bis(2-chloroethyl)-1-nitrosourea), the relative order of sensitivity of anatomic sites was: (iv, sc, ith, and ip)>(ic and im). Experimental data indicated that the responses to weakly active compounds were more susceptible to change with the site of tumor implantation than were those of highly active compounds; the iv and ip sites were more critical for the detection of weakly active compounds than highly or moderately active compounds.