ANTICANCER CHEMOSENSITIVITY CHANGES BETWEEN THE ORIGINAL AND RECURRENT TUMORS AFTER SUCCESSFUL CHEMOTHERAPY SELECTED ACCORDING TO THE SENSITIVITY ASSAY

Objective The authors compare and characterize the changes in chemosen sitivity between the original tumors before chemotherapy and recurrent tumors after responses. Summary Background Data The drug resistance i n clinical chemotherapy appears to be different from that in experimen tal chemotherapy, and the profile and mechanisms of clinical drug resi stance in recurrent tumors, especially after successful chemotherapy h as scarcely been studied. Methods Applied chemotherapies were selected out of four agents, cisplatin (CDDP), adriamycin (ADR), mitomycin-C ( MMC) and 5-fluorouracil (5-FU), singly or in combinations by a DNA syn thesis inhibition assay, by which the sensitivity of recurrent tumors was assessed. Responses were defined according to the standard criteri a, acid successful chemotherapy indicates complete response (CR) or pa rtial response (PR) for solid tumors and complete disappearance for ma lignant effusion. Results In 37 patients, the effectiveness of four ag ents were compared between before chemotherapy and after recurrence, a nd the response lasted between 2 and 26 months (mean +/- SD; 7.7 +/- 5 .5). The results suggest that locally recurred tumors may become resis tant to the agents previously administered; by contrast, distantly rec urred tumors may not necessarily become resistant to the agents admini stered. The recurrent tumors are suggested to be sensitive to the agen ts as follows. locally recurrent solid tumors, 5-FU; distantly recurre nt solid tumors, 5-FU and CDDP; locally recurrent effusion, CDDP; dist antly recurrent eff usion, ADR. Twenty-three of 37 recurrent tumors we re re-treated with chemotherapies selected according to the sensitivit y assay, singly or in combination with a biologic response modifier (B RM)-a streptococcal preparation, OK-432, or interferon-alpha. Response s were seen in 1 of 13 solid recurrent tumors and in 6 of 10 recurrent effusions. Responses were seen only when the patients were treated wi th a combination of chemotherapy and BRM. Conclusion There may be a no table differences in the basic biologic characteristics of tumor cells with respect to local versus distant recurrences, and between effusio n versus solid recurrences. Various approaches, including a combinatio n of chemotherapy and BRM, therefore, may have to be applied to overco me these drug resistances in practical chemotherapies for recurrent tu mors.