Chemotherapy under cachectic conditions and the possibility of cachexia-controlled chemotherapy.
We studied the role of chemotherapy in cancer cachexia, which is well known to lower QOL and responsiveness to chemotherapy. In BALB/c mice we used two clones derived from the murine colon 26 adenocarcinoma cell line; clone 5, a non-cachexigenic tumor and clone 20, a cachexigenic tumor, in which IL-6 mRNA was selectively detected. While maximum tolerated dose (MTD) of CPM and CPT-11 showed significantly smaller tumor weight and higher survival than 1/2 MTD in both drug groups with clone 5, the results were reversed with clone 20. The tumor weights with MTD of CPM or CPT-11 in combination with anti-IL-6 antibody treatment, which decreases serum IL-6 level and improves cachexia status, were significantly smaller than those in the MTD treatment-alone group with clone 20, but not with clone 5. From these results, we suggest that lower dose chemotherapy or cachexia-controlled chemotherapy, such as some chemotherapeutic agents with neutralizing cachexia-related cytokine effects, elicit anti-tumor effects in cachectic individuals that are superior to conventional MTD chemotherapy.
Takahashi
Yutaka
Y
Department of Surgical Oncology, Cancer Research Institute, Kanazawa University, 13-1 Takaramachi, Kanazawa 920-8641, Japan. takahasi@kenroku.kanazawa-u.ac.jp
Yasumoto
Kazuo
K
Mai
Masayoshi
M
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002100:Cachexia / Q000503:physiopathology*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D000077146:Irinotecan; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D000906:Antibodies; D000970:Antineoplastic Agents; D015850:Interleukin-6; D000077146:Irinotecan; D003520:Cyclophosphamide; D002166:Camptothecin