Study Chairman:  Claire Verschraegen, MD
Study Sponsor:  SuperGen Pharmaceuticals
Research Nurse:  Monique Vincent, RN

Treatment schedule:
Cisplatin on day 1 of week, every 4 weeks.
Rubetican 1 dose/day x 5 days for 3 weeks.
Different groups of patients will receive slightly different doses of each drug. 

STUDY RATIONALE: Excerpted from the protocol abstract.

CPT and its analogs are the only well-studied group of naturally-occuring topoisomerase-I inhibitors. Topoisomerase-I relaxes supercoiled DNA by creating single-strand DNA breaks which are necessary for DNA and RNA synthesis. Re-sealing of DNA is prevented by the binding of CPT or its analogs to the DNA-enzyme complex resulting in the accumulation of reversible enzyme-DNA cleavable complexes. An intact E (lactone) ring is necessary for maximal activity of the camptothecins. Opening of the E-ring to form the carboxylate reduces the activity and appears to increase toxicity of the molecule. Substitutions at C-9 or C-10 enhance activity while substitutions at C-12 eliminate activity. The S-isomer is the most biologically active form.

Cisplatin causes DNA damage which employs topoisomerase repair. Because of the inhibition of topoisomerase by RFS 2000, an additive and synergistic effect is expected.

Inclusion:

Patients must be at least 10 years old with recurrent or refractory cancer who have failed standard chemotherapy regimens for their disease.

Patients must have adequate blood tests and sign informed consent.

Exclusion:

To be posted shortly.