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Phase II study on 9-nitrocamptothecin (RFS 2000) in patients with advanced or metastatic urothelial tract tumors
M J A de Jonge1, J P Droz, L Paz-Ares
1Daniel den Hoed Cancer Center/Erasmus Medical Center, Rotterdam, The Netherlands. m.dejonge@erasmusmc.nl
Objective:
To investigate the antitumor activity and the safety of RFS2000, an oral topoisomerase I inhibitor, in patients with advanced or metastatic urothelial tract tumors refractory to one prior chemotherapy regimen.
Patients And Methods:
Eligible patients were to have failed first line treatment for advanced or metastatic disease. Patients received RFS2000 as one daily oral intake at the dose of 1.5 mg/m(2)/day according to a "5 days on/2 days" off schedule continuously. One cycle was arbitrarily defined as a 3 week period. Sufficient oral fluid intake to prevent cystitis previously described in phase I trials with RFS2000 was recommended. Gehan design was used for sample size determination. Anti-tumor activity was evaluated according to the RECIST criteria and toxicity according to CTC version 2.
Results:
Twenty patients received a total of 57 cycles (range 1-8). Grade 3-4 toxicity was observed in 10 patients requiring dose or schedule modifications. Hematological grade 3-4 toxicity was observed in 16% of the cycles. Only one patient experienced a partial response.
Conclusions:
RFS2000 could be administered orally as a "5 days on/2 days off" schedule continuously with a median dose intensity of 90.6% with an acceptable toxicity profile. However, RFS2000 did not exert significant activity in patients with advanced/metastatic urothelial tract tumors failing prior chemotherapy. The results of this study do not suggest further investigation of RFS2000 at the present dose and schedule for the treatment of urothelial tract tumors in this refractory population.
Insights
RFS2000, an oral topoisomerase I inhibitor, showed acceptable toxicity in patients with advanced urothelial tract tumors. However, it did not demonstrate significant antitumor activity in this refractory population.
Area of Science:
- Oncology
- Pharmacology
Background:
- Advanced or metastatic urothelial tract tumors often become refractory to standard chemotherapy.
- Topoisomerase I inhibitors represent a therapeutic strategy for various cancers.
Purpose of the Study:
- To evaluate the antitumor activity and safety of RFS2000, an oral topoisomerase I inhibitor.
- To assess RFS2000 in patients with urothelial tract tumors refractory to prior chemotherapy.
Main Methods:
- A phase II study administered RFS2000 orally at 1.5 mg/m(2)/day on a "5 days on/2 days off" schedule.
- Tumor response was assessed using RECIST criteria, and toxicity was graded per CTC version 2.
- Twenty patients with advanced/metastatic urothelial tract tumors refractory to first-line treatment were enrolled.
Main Results:
- RFS2000 was administered for a median of 57 cycles (range 1-8) with a median dose intensity of 90.6%.
- Grade 3-4 toxicity occurred in 10 patients, necessitating dose or schedule adjustments.
- Only one patient achieved a partial response, indicating limited efficacy.
Conclusions:
- RFS2000 can be administered orally with an acceptable toxicity profile in this patient population.
- RFS2000 did not show significant antitumor activity in advanced urothelial tract tumors resistant to prior chemotherapy.
- Further investigation of RFS2000 at the current dose and schedule for urothelial tract tumors is not recommended.
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