(Glycolate-o,o') diammineplatinum (II) (254-S) is one of the platinum derivatives showing high activity against rodent solid tumors and lack of renal toxicity. We have used a human tumor clonogenic assay (HTCA) as a disease-oriented drug screening model for new antitumor drugs, in order to test the antitumor activity of 254-S against non-small cell lung carcinoma (NSCLC) and to compare its activity with that of cisplatin (CDDP) and of carboplatin (CBDCA). The overall in vitro response rate (defined as less than 50% survival of tumor colony forming units) for 254-S was observed in 10/29 and 20/30 evaluable specimens isolated freshly from NSCLC patients with continuous exposure at 1 and 10 micrograms/ml, respectively, indicating a positive dose-response relationship. Dose dependent cytotoxicity was also confirmed in 4 human tumor cell lines derived from NSCLC patients. The antitumor activity of 254-S was 3.6-fold that of CBDCA, but two-fifths that of CDDP. A comparison of these in vitro results with the toxic properties of 254-S such as low nephrotoxicity suggests that 254-S is a promising new drug against NSCLC.

Antineoplastic Agents↗

PubMedDate not supplied

In vitro antitumor activity of teniposide against carcinoma of the lung in human tumor clonogenic assay.

The antitumor activity of teniposide (VM26) on carcinoma of the lung was tested by comparing it with its congener, etoposide (VP16) in an in vitro soft agar clonogenic assay system (HTCA). Of 56 tumor biopsies placed in culture, 40 tumors were evaluable for drug sensitivity information (i.e., greater than or equal to 30 colonies in the control plate). The overall in vitro response rate (defined as less than or equal to 50% survival of TCFU) at the standard dose (10% peak plasma concentration) was 35%, which is higher than that of VP16 (28%). In cell lines derived from human carcinoma of the lung, VM26 showed 50% inhibition against colony formation of PC-7 cells at 0.45 microgram/ml which is less than that of VP16. A superior antitumor activity of VM26 on PC-9 cells was also observed. VM26 was observed to act faster than VP16 thus indicating its possible superior antitumor activity in vivo.

Adenocarcinoma↗

PubMedDate not supplied

Evaluation of novel platinum complexes, inhibitors of topoisomerase I and II in non-small cell lung cancer (NSCLC) sublines resistant to cisplatin.

We determined the in vitro cytotoxicities of promising new platinum complexes, an inhibitor of topoisomerase I, and novel anthracycline derivatives, and examined using clonogenic assay whether these compounds are cross-resistant in CDDP-resistant sublines derived from human non-small cell lung cancer (NSCLC) cell lines. Cytotoxicities were evaluated by means of the relative antitumor activity (RAA = peak plasma concentration/IC50 values), which we reported previously as a model for predicting antitumor activity. Of the CDDP analogues tested, including carboplatin (CBDCA), [(glycolate-0,0') diammineplatinum (II) (254-S)], ormaplatin [tetrachloro-(d,1-trans)- 1,2-diaminocyclohexaneplatinum (IV) (OP)] and oxaliplatin [oxalato (trans-1-1,2-diaminocyclohexane) platinum (II) (1-OHP)], no agent showed superior antitumor activity compared to CDDP. ME2303 [7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl) adriamycinone-14-O -pimelate], a new anthracycline derivative, showed higher antitumor activity than adriamycin (ADM). The CDDPresistant sublines, PC-9/CDDP and PC-14/CDDP, were 18.3- and 7.7-fold more resistant to CDDP compared to the respective parent cell lines. The CDDP analogues were all cross-resistant to CDDP and the order of relative resistance values was CBDCA > 254-S > 1-OHP > OP for PC9/CDDP and 254-S > CBDCA > 1-OHP > OP for PC-14/CDDP. Although OP showed cross-resistance to CDDP, OP was the most active against the CDDP-resistant sublines with relative resistance values of 3.8 and 1.6 for PC-9/CDDP and PC-14/CDDP, respectively. ME2303 and CPT-11, [7-ethyl-10-(4-[1-piperidino]-1-piperidino) carbonyloxycamptothecin], an inhibitor of topoisomerase I, was active against CDDP-resistant human NSCLC cell lines. These results suggest that OP, ME2303 and CPT-11 could be active in patients with, NSCLC clinically resistant to CDDP.

Adenocarcinoma↗