Phase I/II trial of topotecan given as continuous infusion in combination with oxaliplatin in 5-FU-pretreated patients with colorectal cancer.
BACKGROUND
Oxaliplatin and topotecan are novel options for a variety of neoplasms. Topotecan has shown fewer side effects and higher efficacy when given as a continuous i.v. infusion compared to single doses, but this regimen has not yet been combined with oxaliplatin.


METHODS
This phase I/II trial was designed to establish the dose-limiting toxicity of a combination of oxaliplatin (85-130 mg/m2 on day 1) and a continuous infusion of topotecan (initial 0.9 mg/m2 over 72-120 h). Eligible patients with metastatic colorectal cancer had progressive disease during, or within 12 weeks after, palliative fluoropyrimidine-based chemotherapy or in whom intolerable 5-FU toxicity had developed.


RESULTS
The study included 21 patients. Subjectively the treatment was well tolerated but haematological toxicity was observed with the initial treatment schedule of oxaliplatin 85 mg/m2 on day 1 and topotecan 0.9 mg/m2 on days 1-5. Reducing topotecan to 0.9 mg/m2 on days 1-3 resulted also in acceptable haematological toxicity. In patients completing three or more therapy cycles, median progression-free survival was 5 months, and 50% had stable disease or showed a partial response.


CONCLUSIONS
The recommended dose of this combination for further testing is oxaliplatin 85 mg/m2 on day 1 and topotecan 0.9 mg/m2 per day as a continuous infusion on days 1-3.
Hütter
G
G
Medizinische Klinik III-Haematology, Oncology and Transfusion Medicine, Charité-Universitaetsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Germany. gero.h@gmx.de
Szélenyi
H
H
Deckert
P M
PM
Keilholz
U
U
Thiel
E
E
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004351:Drug Resistance; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D019772:Topotecan; D005472:Fluorouracil