Chronomodulated oxaliplatin plus Capecitabine (XELOX) as a first line chemotherapy in metastatic colorectal cancer: A Phase II Brunch regimen study.
OBJECTIVE
The aim of this study was to evaluate safety and toxicity of chronomodulated capecitabine administered in the morning and at noon according to a specific time schedule (Brunch Regimen: Breakfast and Lunch) as a part of first-line XELOX chemotherapy in patients with metastatic colorectal cancer.


METHODS
A total of 30 treatment-naïve colorectal cancer patients with metastatic disease were included. Oxaliplatin 130 mg/m(2) on day 1 plus chronomodulated oral capecitabine 2000 mg/m(2) per day were administered (50 % dose at 8:00 a.m. and 50 % dose at 12:00 noon on days 1-14, every 21 days). All adverse events, treatment responses and survival were evaluated. In addition, pharmacokinetic profile of capecitabine was examined in a subset of 5 patients.


RESULTS
Median age was 57.1 years (range 32-77 years). Median follow-up was 19 months (range 3-36 months). Three patients (10 %) had complete response, 13 patients (43.3 %) had partial response and 4 patients (13.3 %) had stabile disease. Ten patients had progressive disease at their first evaluation (33.3 %). The median progression-free survival (PFS) was 10 months (range 2-36 months). There were no grade 4 toxicities. One patient (3.3 %) had grade 3 neutropenia. Hand-foot syndrome developed in three patients (10 %): 6.6 %, grade 1 and 3.3 %, grade 2.


CONCLUSIONS
Chronomodulated XELOX seems to represent a promising therapeutic option in the first-line treatment of metastatic colorectal carcinoma due to good tumor control and favorable toxicity profile. Phase III randomized trials are required to assess the actual clinical efficacy and side effect profile of this regimen.
Department of Medical Oncology, Haseki Education and Research Hospital, Istanbul, Turkey.
Kezban Nur
KN
Pilancı
Department of Medical Oncology, Istanbul Bilim University, Istanbul, Turkey. saglam@istanbul.edu.tr.|Gayrettepe Florence Nigtingale Hastanesi, Cemil Arslan Guder Sok. No: 8, Besiktas, 34349, Istanbul, Turkey. saglam@istanbul.edu.tr.
Sezer
S
Saglam
Department of Pharmacology, Istanbul University Faculty of Pharmacy, Istanbul, Turkey.
Alper
A
Okyar
Department of Radiation Oncology, Acıbadem University, Istanbul, Turkey.
Serap
S
Yucel
Department of Pharmacology, Istanbul University Faculty of Pharmacy, Istanbul, Turkey.
Zeliha
Z
Pala-Kara
Department of Medical Oncology, Istanbul Bilim University, Istanbul, Turkey.
Cetin
C
Ordu
Department of Medical Oncology, Istanbul Bilim University, Istanbul, Turkey.
Esat
E
Namal
Medical Oncology Department, Bakirkoy Dr Sadi Konuk Education and Research Hospital, Istanbul, Turkey.
Rumeysa
R
Ciftci
Department of Medical Oncology, Istanbul Bilim University, Istanbul, Turkey.
Ulkuhan
U
Iner-Koksal
Institute of Oncology, Department of Radiation Oncology, Istanbul University, Istanbul, Turkey.
Esra
E
Kaytan-Saglam
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010071:Oxaloacetates; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D010071:Oxaloacetates; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil
Capecitabine; Chronomodulated chemotherapy; Metastatic colorectal cancer; Pharmacokinetics; Treatment-naïve