Publication | Closed Access
Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothec in, a novel water-soluble derivative of camptothecin, against murine tumors.
412
Citations
0
References
1987
Year
Antitumor ActivityPathologyMurine TumorsPharmacotherapyMetronomic ChemotherapyPharmaceutical ChemistryTumor BiologyMedicinal ChemistryAnti-cancer AgentP388 LeukemiaRadiation OncologyChemotherapyCancer ResearchMedicineNew Water-soluble AnaloguesPharmacologyOncologyDrug DiscoveryNovel Water-soluble Derivative
Researchers sought water‑soluble camptothecin analogues with greater potency and reduced toxicity, leading to the creation of CPT‑11, a novel derivative. CPT‑11 exhibited potent antitumor activity across multiple murine tumor models, outperforming CPT and Adriamycin with high maximum life‑span increases, frequent cures, and minimal acute toxicity, indicating strong clinical potential.
The search for new water-soluble analogues of camptothecin (CPT) with higher activity and less toxicity has led to the development of a novel compound, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11), which showed significant antitumor activity against a broad spectrum of experimental tumor models by i.p., i.v., or oral administration. When its activity against L1210 was compared with that of CPT and known derivatives, CPT-11 was most effective, giving the highest maximum increase in life span (ILS) and showing good activity over a wide dose range. The antitumor activity of CPT-11 was shown against tumors not only in the ascites form but also in the solid form. Included among the more susceptible murine tumors are S180, Meth A fibrosarcoma, Lewis lung carcinoma, Ehrlich carcinoma, MH134 hepatoma, mammary carcinoma of C3H/HeN mice, L1210, and P388 leukemia. Probable cures of these tumors were induced frequently by CPT-11. The antitumor activity of CPT-11 against i.p.-implanted L1210 was superior to that of Adriamycin in maximum ILS, the number of cured mice, and the therapeutic ratio. CPT-11 at a dose of 100 mg/kg produced an ILS in excess of 300% with five of six mice surviving tumor free, and effected 100% tumor regression at 200 mg/kg, whereas the optimum dose of Adriamycin, 12.5-25 mg/kg, brought about 114-129% ILS with one of six mice surviving. The acute toxicity of CPT-11 was extremely low, particularly in the case of oral administration. CPT-11 is expected to be clinically useful.