Dose escalation study on oxaliplatin and capecitabine (Xeloda) in patients with advanced solid tumors.
OBJECTIVE
Capecitabine (CAP) and oxaliplatin (OX) have shown interesting activity in a wide range of solid tumors. A phase I study was conducted in order to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of their combination in patients with refractory solid tumors.


METHODS
Thirty-three pretreated patients with histologically confirmed inoperable neoplasms were enrolled. The patients' median age was 64 years, 21 were males, and 27 had a WHO performance status of 0-1. OX was administered on days 1 and 8, as a 3-hour intravenous infusion, at escalated doses ranging from 50 to 70 mg/m(2). CAP was administered orally for 14 consecutive days, at escalated doses ranging from 1,200 to 2,100 mg/m(2)/day. Treatment was repeated every 3 weeks.


RESULTS
At the dose of 2,100 mg/m(2) (Xeloda) and 70 mg/m(2) (OX), all 3 enrolled patients presented DLT (grade 3 diarrhea, grade 3 asthenia and grade 3 neurotoxicity, respectively), and, thus, the recommended MTD for future phase II studies are 2,000 mg/m(2) for CAP and 70 mg/m(2 )for OX. A total of 145 treatment cycles were administered. Toxicity was very mild. Grade 2/3 neutropenia was observed in 4 (3%) treatment cycles. The main nonhematologic toxicities were grade 2/3 nausea/vomiting (7 cycles; 5%), grade 2/3 neurotoxicity (10 cycles; 7%), grade 2/3 asthenia (8 cycles; 5.5%) and grade 2/3 diarrhea (6 cycles; 4%). There was no treatment-related death. One (4%) complete remission, 2 (8%) partial remissions, and 9 (36%) cases of stable disease were observed among 25 evaluable patients.


CONCLUSIONS
The results demonstrate that CAP and OX can be safely combined at clinically relevant doses and that this regimen merits further evaluation.
Kakolyris
S
S
Department of Medical Oncology, University General Hospital of Alexandroupolis, Crete, Greece.
Souglakos
J
J
Kouroussis
C
C
Androulakis
N
N
Samonis
G
G
Vardakis
N
N
Amarantidis
K
K
Agelaki
S
S
Mavroudis
D
D
Xenidis
N
N
Georgoulias
V
V
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001247:Asthenia / Q000139:chemically induced; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
D000964:Antimetabolites, Antineoplastic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil