A dose escalating study of oxaliplatin and high dose weekly leucovorin and 5-Fluorouracil in patients with advanced solid tumors.
OBJECTIVE
To determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTD) of L-OHP plus 5-FU and LV in patients with advanced solid malignancies.


METHODS
Patients received escalated doses of L-OHP (starting dose 50 mg/m2) as a 2-hour IV infusion on Days 1 and 15, and LV (500 mg/m2 as a 2-hour IV infusion) followed by escalated doses of 5FU (starting dose 1,800 mg/m2) as a 22-hour continuous IV infusion on Days 1, 8, 15, 21 every 6 weeks. DLTs were evaluated in the first cycle.


RESULTS
Fifty-two patients [median age: 66 years; PS (ECOG) 0-1 in 90 percent] were treated on 12 dose-levels. Five (10 percent) patients had received 2 prior chemotherapy regimens, 24 (46 percent) one, and 23 (44 percent) were chemo-naïve. The DLT was reached at the dose of LOHP 100 mg/m2 and 5FU 2,200 mg/m2. Dose-limiting events were G3 diarrhea, G3 asthenia, G4 neutropenia, and G4 thrombocytopenia. Grade 3 diarrhea was observed in 6 (12 percent) patients and Grade 3 fatigue in 6 (12 percent). One (2 percent) patient developed Grade 4 neutropenia and another (2 percent) Grade 4 thrombocytopenia.


CONCLUSIONS
The MTD were L-OHP 95 mg/m2 on d1 and d15 and 5FU 2,200 mg/m2/week for 4 consecutive weeks every 6 weeks.
Souglakos
John
J
Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece.
Kakolyris
Stylianos
S
Vardakis
Nikolaos
N
Androulakis
Nikolaos
N
Mavroudis
Dimitrios
D
Vamvakas
Lambos
L
Kouroussis
Charalambos
C
Agelaki
Sophia
S
Saridaki
Zacharenia
Z
Georgoulias
Vassilis
V
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil