A dose escalation study of docetaxel plus capecitabine in combination with oxaliplatin in patients with advanced solid tumors.
OBJECTIVE
Capecitabine (CAP), Oxaliplatin (OX) and Docetaxel (DOC) have shown considerable 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 toxicities (DLTs) of their combination in patients with advanced solid tumors.


METHODS
Twenty-one patients were enrolled. The patient's median age was 68 years, 15 were male, and 12 were chemo-naïve. DOC was administered on day 1 as an 1-hour (iv) infusion at a standard dose of 50 mg/m(2). OX was administered on day 1 as a 2-hour (iv) infusion at escalating doses ranging from 70-80 mg/m(2). CAP was administered orally on days 1 to 7 at escalating doses ranging from 2,000-2,750 mg/m(2) given as two daily divided doses. Treatment was repeated every two weeks.


RESULTS
Six different dose-levels were examined. At dose-level VI, two of three enrolled patients presented DLTs (one patient diarrhea and asthenia grade 3 and another grade 3 diarrhea), and thus, the recommended MTD for future phase II studies is CAP 2,750 mg/m(2) , DOC 50 mg/m(2) and OX 75 mg/m(2). A total of 121 treatment cycles were administered. Grade 3 neutropenia was observed in six (5%) treatment cycles and grade 3 thrombocytopenia in one (1%). There was no febrile episode. Grade 3 asthenia was observed in three (14%) patients, grade 3 diarrhea in four (19%), grade 3 neuropathy in one (5%), and grade 1/2 hand-foot syndrome in three (14%). Other toxicities were uncommon. There was no treatment related death. Four (29%) PRs and seven (50%) SD were observed among 14 evaluable patients. Responses were seen in patients with renal (n = 1), gastric (n = 2) and pancreatic (n = 1) cancer.


CONCLUSIONS
These results demonstrate that CAP, DOC and OX can be safely combined at clinically relevant doses and this regimen merits further evaluation.
Department of Medical Oncology, University General Hospital of Alexandroupolis, Dragana 68100, Alexandroupolis, Greece.
Kyriakos
K
Amarantidis
Nikolaos
N
Xenidis
Leonidas
L
Chelis
Anestis
A
Chiotis
Apostolos
A
Tentes
Ekaterini
E
Chatzaki
Alexandros
A
Kortsaris
A
A
Polychronidis
Petros
P
Karakitsos
Stylianos
S
Kakolyris
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; 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; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
D009944:Organoplatinum Compounds; D043823:Taxoids; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D005472:Fluorouracil