Τίτλος:
Dose selection trial of metronomic oral vinorelbine monotherapy in
patients with metastatic cancer: a hellenic cooperative oncology group
clinical translational study
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background: Metronomic chemotherapy is considered an anti-angiogenic
therapy that involves chronic administration of low-dose chemotherapy at
regular short intervals. We investigated the optimal metronomic dose of
oral vinorelbine when given as monotherapy in patients with metastatic
cancer.
Methods: Patients with recurrent metastatic breast (BC), prostate (PC)
or non-small cell lung cancer (NSCLC) and adequate organ functions were
randomly assigned to 30, 40 or 50 mg vinorelbine, taken orally three
times a week. Treatment continued until disease progression,
unacceptable toxicity, withdrawal of consent or maximum 24 months.
Primary endpoint was time-to-treatment failure (TTF) and secondary were
progression-free survival (PFS), toxicity, changes in blood
concentrations of angiogenesis-associated biomarkers and
pharmacokinetics.
Results: Seventy-three patients were enrolled. Four-month TTF rate did
not differ between the three arms: 25.9% (11.1%-46.2% 95% Confidence
Interval), 33.3% (15.6%-55.3%) and 18.2% (5.2%-40.3%) for the 30
mg, 40 mg and 50 mg arms (p-value = 0.56). Objective response was seen
in 2 patients with NSCLC (treated at 30 and 50 mg respectively), one
with BC (at 40 m g) and one with PC (at 50 mg) and lasted from 4 to 100
weeks, with maximum response duration achieved at 50 mg. Adverse events
were mild and negligible and did not differ between the three arms.
Blood levels of vinorelbine reached steady state from the second week of
treatment and mean values for the 30, 40 and 50 mg were respectively 1.8
ng/ml (SD 1.10), 2.2 ng/ml (SD 1.87) and 2.6 ng/ml (SD 0.69). Low
pre-treatment blood concentrations of FGF2 and IL8 predicted favorable
response to therapy (p values 0.02 and 0.006, respectively), while high
levels of TEK gene transcript predicted treatment resistance.
Conclusions: Considering the antitumor activity and response duration,
the negligible toxicity of the highest dose investigated and the lack of
drug accumulation over time, we suggest that 50 mg given three times a
week is the optimal dose for metronomic oral vinorelbine. Further
investigation of metronomic oral vinorelbine (MOVIN) at this dose is
warranted in combination with conventional chemotherapy regimens and
targeted therapies.
Trial registration: Clinicaltrials.gov NCT00278070
Συγγραφείς:
Briasoulis, Evangelos
Aravantinos, Gerasimos
Kouvatseas, George
and Pappas, Periklis
Biziota, Eirini
Sainis, Ioannis and
Makatsoris, Thomas
Varthalitis, Ioannis
Xanthakis, Ioannis and
Vassias, Antonios
Klouvas, George
Boukovinas, Ioannis and
Fountzilas, George
Syrigos, Kostantinos N.
Kalofonos, Haralambos
and Samantas, Epaminontas
Λέξεις-κλειδιά:
Metronomic-chemotherapy; Antiangiogenic; Vinorelbine; Cancer
DOI:
10.1186/1471-2407-13-263
