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Continuous low-dose cyclophosphamide and methotrexate combined with celecoxib for patients with advanced cancer.

Khan OA, Blann AD, Payne MJ, Middleton MR, Protheroe AS, Talbot DC, Taylor M, Kirichek O, Han C, Patil M, Harris AL - Br. J. Cancer (2011)

Bottom Line: Median time to progression was 57 days.Among plasma markers, levels of tissue factor were higher in the SD group of patients at baseline, and levels of both angiopoietin-1 and matrix metalloproteinase-9 increased in the progressive disease group only.There were no changes in other plasma markers.

View Article: PubMed Central - PubMed

Affiliation: University of Oxford Department of Medical Oncology, Churchill Hospital, Oxford OX3 7LJ, UK.

ABSTRACT

Background: Combined therapy of metronomic cyclophosphamide, methotrexate and high-dose celecoxib targeting angiogenesis was used in a phase II trial.

Methods: Patients with advanced cancer received oral cyclophosphamide 50 mg o.d., celecoxib 400 mg b.d. and methotrexate 2.5 mg b.d. for two consecutive days each week. Response was determined every 8 weeks; toxicity was evaluated according to CTC version 2.0. Plasma markers of inflammation, coagulation and angiogenesis were measured.

Results: Sixty-seven of 69 patients were evaluable for response. Twenty-three patients had stable disease (SD) after 8 weeks, but there were no objective responses to therapy. Median time to progression was 57 days. There was a low incidence of toxicities. Among plasma markers, levels of tissue factor were higher in the SD group of patients at baseline, and levels of both angiopoietin-1 and matrix metalloproteinase-9 increased in the progressive disease group only. There were no changes in other plasma markers.

Conclusion: This metronomic approach has negligible activity in advanced cancer albeit with minimal toxicity. Analysis of plasma markers indicates minimal effects on endothelium in this trial. These data for this particular regimen do not support basic tenets of metronomic chemotherapy, such as the ability to overcome resistant tumours by targeting the endothelium.

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Related in: MedlinePlus

OS shown by treatment outcome. SD=stable disease; PD=progressive disease; NE=non-evaluable.
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fig1: OS shown by treatment outcome. SD=stable disease; PD=progressive disease; NE=non-evaluable.

Mentions: There were no objective responses, but 23 of 67 patients (34.3%) evaluable had SD at 12 weeks. The other 44 patients (65.7%) progressed. Best response by site of disease is shown in Table 3. The median TTP was 57 days (range: 2–338). Median OS was 226 days (range: 9–846). The TTP of breast cancer patients was longer than in the other groups (82 days) and the median OS of melanoma patients was shorter than in the other groups (139 days). Survival by response is shown in Figure 1. Patients with SD survived longer than those with PD, although this was not quite statistically significant (P=0.06).


Continuous low-dose cyclophosphamide and methotrexate combined with celecoxib for patients with advanced cancer.

Khan OA, Blann AD, Payne MJ, Middleton MR, Protheroe AS, Talbot DC, Taylor M, Kirichek O, Han C, Patil M, Harris AL - Br. J. Cancer (2011)

OS shown by treatment outcome. SD=stable disease; PD=progressive disease; NE=non-evaluable.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3111194&req=5

fig1: OS shown by treatment outcome. SD=stable disease; PD=progressive disease; NE=non-evaluable.
Mentions: There were no objective responses, but 23 of 67 patients (34.3%) evaluable had SD at 12 weeks. The other 44 patients (65.7%) progressed. Best response by site of disease is shown in Table 3. The median TTP was 57 days (range: 2–338). Median OS was 226 days (range: 9–846). The TTP of breast cancer patients was longer than in the other groups (82 days) and the median OS of melanoma patients was shorter than in the other groups (139 days). Survival by response is shown in Figure 1. Patients with SD survived longer than those with PD, although this was not quite statistically significant (P=0.06).

Bottom Line: Median time to progression was 57 days.Among plasma markers, levels of tissue factor were higher in the SD group of patients at baseline, and levels of both angiopoietin-1 and matrix metalloproteinase-9 increased in the progressive disease group only.There were no changes in other plasma markers.

View Article: PubMed Central - PubMed

Affiliation: University of Oxford Department of Medical Oncology, Churchill Hospital, Oxford OX3 7LJ, UK.

ABSTRACT

Background: Combined therapy of metronomic cyclophosphamide, methotrexate and high-dose celecoxib targeting angiogenesis was used in a phase II trial.

Methods: Patients with advanced cancer received oral cyclophosphamide 50 mg o.d., celecoxib 400 mg b.d. and methotrexate 2.5 mg b.d. for two consecutive days each week. Response was determined every 8 weeks; toxicity was evaluated according to CTC version 2.0. Plasma markers of inflammation, coagulation and angiogenesis were measured.

Results: Sixty-seven of 69 patients were evaluable for response. Twenty-three patients had stable disease (SD) after 8 weeks, but there were no objective responses to therapy. Median time to progression was 57 days. There was a low incidence of toxicities. Among plasma markers, levels of tissue factor were higher in the SD group of patients at baseline, and levels of both angiopoietin-1 and matrix metalloproteinase-9 increased in the progressive disease group only. There were no changes in other plasma markers.

Conclusion: This metronomic approach has negligible activity in advanced cancer albeit with minimal toxicity. Analysis of plasma markers indicates minimal effects on endothelium in this trial. These data for this particular regimen do not support basic tenets of metronomic chemotherapy, such as the ability to overcome resistant tumours by targeting the endothelium.

Show MeSH
Related in: MedlinePlus