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ARA-C analogs.

Antibiotics and Chemotherapy

|January 1, 1978

Summary

Anhydro-ara-5-fluorocytidine (AAFC) is a promising derivative of cytarabine (Ara-C) that shows significant activity against leukemias and solid tumors, including gastrointestinal adenocarcinomas, with manageable toxicity and less schedule dependence.

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Area of Science:

Oncology
Pharmacology
Cancer Therapeutics

Background:

Cytarabine (Ara-C) is a phase-specific antitumor agent rapidly inactivated by cytidine deaminase.
Developing Ara-C derivatives with enhanced resistance to deamination and longer serum half-life can prolong biological activity.
Cyclocytidine (cyclo-C), anhydro-ara-5-fluorocytidine (AAFC), and N4-acyl-derivatives are examples of such promising agents.

Purpose of the Study:

To evaluate the efficacy and toxicity of anhydro-ara-5-fluorocytidine (AAFC) as an anticancer agent.
To compare the clinical profile of AAFC with cytarabine (Ara-C) and cyclocytidine (cyclo-C).
To explore the potential of AAFC in treating various human leukemias and solid tumors.

Main Methods:

Clinical trials were conducted to assess AAFC's activity and tolerance.
Phase II trials specifically evaluated AAFC in gastrointestinal tract adenocarcinomas, breast cancer, and lung cancer.
Comparative assessments were made regarding side effects and schedule dependence relative to Ara-C and cyclo-C.

Main Results:

AAFC demonstrated significant activity in gastrointestinal tract adenocarcinomas (pancreas, stomach, colorectal).
Activity was also observed in breast cancer and anaplastic small cell lung carcinoma.
AAFC showed comparable efficacy to Ara-C in acute leukemias and potential activity in malignant lymphomas, with manageable myelodepression, nausea, and vomiting.

Conclusions:

AAFC is a well-tolerated derivative of Ara-C with significant activity in various solid tumors and leukemias.
Its reduced schedule dependence and favorable side effect profile (no parotid pain or hypotension) make it a viable alternative to Ara-C.
Further extensive clinical studies of AAFC and similar Ara-C analogs are warranted for various solid tumor types.

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