A dose escalation study of the biweekly administration of paclitaxel, oxaliplatin and capecitabine in patients with advanced solid tumors.
OBJECTIVE
To determine the dose-limiting toxicities (DLTs) and the maximum-tolerated doses of the paclitaxel, oxaliplatin (LOHP) and capecitabine combination in patients with advanced solid tumors.


METHODS
Patients received escalating doses of paclitaxel (starting dose 100 mg/m2) and LOHP (starting dose 40 mg/m2) on days 1 and 15 and capecitabine (starting dose 800 mg/m2/day) on days 1-7 and 15-21 every 28 days. DLTs were evaluated in the first cycle.


RESULTS
Sixteen patients were treated at four dose-escalating levels. Eleven (68.7%) patients had received two or more prior chemotherapy regimens. The DLT level was reached at paclitaxel 110 mg/m2, LOHP 50 mg/m2 and capecitabine 1,000 mg/m2/day. DLTs due to grade 2-3 neutropenia resulted in treatment delays. No febrile neutropenia or treatment-related death occurred. Grade 2-3 neutropenia occurred in 3 (19%) patients each, grade 2-4 fatigue affected 6 (37.5%) patients, and grade 2-3 neurotoxicity was observed in 2 (12.5%) and 1 (6%) patients, respectively. Two partial responses and four disease stabilizations were achieved.


CONCLUSIONS
The recommended doses for phase II studies are paclitaxel 100 mg/m2 and LOHP 50 mg/m2 on days 1 and 15 and capecitabine 1,000 mg/m2/day on days 1-7 and 15-21 every 4 weeks. This regimen is well tolerated and merits further evaluation.
Saridaki
Zacharenia
Z
Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Greece.
Bozionelou
Vasiliki
V
Kentepozidis
Nikolaos
N
Kotsakis
Athanasios
A
Vardakis
Nikolaos
N
Kalykaki
Antonia
A
Gioulbasanis
Ioannis
I
Karampeazis
Athanasios
A
Karabeazis
Athanasios
A
Vamvakas
Lambros
L
Georgoulias
Vassilis
V
Mavroudis
Dimitris
D
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D009369:Neoplasms / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D017239:Paclitaxel / Q000008:administration & dosage
D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D017239:Paclitaxel