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Clinical investigations of neocarzinostatin in Japan
Abstract:
Neocarzinostatin (NCS) is an antibiotic from streptomyces carzinostaticus which inhibits DNA synthesis. Clinical trials in Japan began in 1971. NCS is active against S-180, Ehrlich tumor, L1210, Yoshida sarcoma, and a range of ascitic hepatomas. In rabbit NCS is distributed at high concentrations in the kidney, skin, stomach, pancreas, lung, and muscles. The high distribution in the pancreas and the stomach suggested possible effectiveness in human tumors at these sites. In clinical studies NCS has been shown to be active against acute leukemia. As a single agent 9 out of 51 obtained a CR with 9 more achieving a PR. Anorexia, nausea, and vomiting were the most frequent side effects. NCS has been tried in combination with Ara-C, daunorubicin and prednisolone and CR was ssen in 11 out of 14. In stomach cancer responses of some kind were observed in 12 out of 141 cases, while in the case of pancreatic tumors there were 10 out of 68.
Insights
Neocarzinostatin (NCS), an antibiotic inhibiting DNA synthesis, shows activity against various tumors. Clinical trials indicate its effectiveness in treating acute leukemia and potential in stomach and pancreatic cancers, despite side effects like nausea.
Area of Science:
- Pharmacology
- Oncology
- Microbiology
Background:
- Neocarzinostatin (NCS) is an antibiotic derived from Streptomyces carzinostaticus.
- NCS functions by inhibiting DNA synthesis.
- Early clinical trials commenced in Japan in 1971.
Purpose of the Study:
- To evaluate the efficacy of Neocarzinostatin (NCS) against various tumor types.
- To investigate the distribution and potential therapeutic applications of NCS in specific human cancers.
- To assess the safety and side effect profile of NCS in clinical settings.
Main Methods:
- Assessing NCS activity against S-180, Ehrlich tumor, L1210, Yoshida sarcoma, and ascitic hepatomas.
- Pharmacokinetic studies in rabbits to determine NCS distribution.
- Clinical trials evaluating NCS as a single agent and in combination therapy for acute leukemia, stomach, and pancreatic cancers.
Main Results:
- NCS demonstrated activity against multiple preclinical tumor models.
- In rabbits, high NCS concentrations were observed in the kidney, skin, stomach, pancreas, lung, and muscles.
- As a single agent for acute leukemia, NCS achieved a CR in 9/51 patients and PR in 9/51. In combination therapy (with Ara-C, daunorubicin, prednisolone), 11/14 achieved CR.
- Responses were observed in 12/141 stomach cancer cases and 10/68 pancreatic tumor cases.
Conclusions:
- Neocarzinostatin (NCS) exhibits broad-spectrum antitumor activity.
- The drug's distribution suggests potential efficacy against stomach and pancreatic cancers.
- NCS shows promise in treating acute leukemia, particularly in combination therapy, though common side effects include anorexia, nausea, and vomiting.