Phase I trial of an all-oral combination chemotherapy regimen: topotecan and capecitabine in solid tumor patients.
The objective of this phase I study was to investigate the safety of an all-oral combination chemotherapy regimen: topotecan and capecitabine. Topotecan was administered once a day for 5 consecutive days followed by 2 days of rest and was administered again for 5 consecutive days. The starting dose of topotecan was 0.5 mg/m2/d(-1). Capecitabine was administered concurrently at an oral dose of 1800 mg/m2/d(-1) divided twice daily for 14 concurrent consecutive days. Each cycle of treatment was 21 days. Topotecan pharmacokinetic studies were performed on day 1 of cycles 1 and 2. Nineteen patients with refractory cancer were treated. Dose-limiting toxicity (thrombocytopenia, diarrhea) was observed in 2 of 3 patients at a topotecan dose of 2.0 mg/m2/d(-1). A total of 10 patients were treated at the maximum-tolerated dose of topotecan (1.5 mg/m2/d(-1)) and only 1 treatment-related grade 3 nonhematologic toxic event was demonstrated; however, grade 3 hematologic toxicity was observed in 8 of 10 patients at the maximum-tolerated dose, although no correlated clinical sequela resulted. One patient achieved a partial response and 7 achieved stable disease for 4 months or longer. Measurement of plasma topotecan showed pharmacokinetics consistent with no alteration by capecitabine. In conclusion, we recommend further investigation of oral topotecan (1.5 mg/m2/d(-1)) on days 1 to 5 of each week for 2 weeks in combination with capecitabine (180 mg/m2 twice daily) on days 1 to 14 within a 21-day cycle.
Nemunaitis
John
J
Mary Crowley Medical Research Center, USA. JNemunaitis@mcmrc.com
Adams
Ned
N
Cunningham
Casey
C
Senzer
Neil
N
Graham
Sue
S
Barrera
David
D
Nugent
John
J
Stewart
Clinton
C
D000284:Administration, Oral; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000069287:Capecitabine; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011446:Prospective Studies; D019772:Topotecan / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
D003841:Deoxycytidine; D000069287:Capecitabine; D019772:Topotecan; D005472:Fluorouracil