Standard Versus Continuous Administration of Capecitabine in Metastatic Breast Cancer (GEICAM/2009-05): A Randomized, Noninferiority Phase II Trial With a Pharmacogenetic Analysis

Abstract

Background. The approved capecitabine regimen as monotherapy in metastatic breast cancer (MBC) is 1,250 mg/m 2 twice daily for 2 weeks on and 1 week off (Cint). Dose modifications are often required because of severe hand-foot syndrome (HFS). We tested a continuous regimen with a lower daily dose but a similar cumulative dose in an attempt to reduce the severity of adverse events (AEs) while maintaining efficacy. Methods. We randomized 195 patients with HER-2/neunegative MBC to capecitabine 800 mg/m 2 twice daily throughout the 21-day cycle (Ccont) or to Cint to assess noninferiority in the percentage of patients free of progression at 1 year. Secondary endpoints included efficacy and safety. Associations between polymorphisms in capecitabine metabolismrelated genes and drug response were assessed. Results. The percentage of patients free of progression at 1 year was 27.3% with Cint versus 25.3% with Ccont (difference of 22.0%; 95% confidence interval: 215.5% to 11.5%, exceeding the 15% deemed noninferior). Differences regarding other efficacy variables were also not found. Grade 3-4 HFS was the most frequent AE (41.1% in Cint vs. 42.3% in Ccont). Grade 3-4 neutropenia, thrombocytopenia, diarrhea, and stomatitis were more frequent with Cint. A 59 untranslated region polymorphism in the carboxylesterase 2 gene was associated

The efficacy and toxicity profile of metronomic chemotherapy for metastatic breast cancer: A meta-analysis

“…Reasons for exclusion were: 2 studies did not pertain solely to MCT; data of interest was not reported in 4 studies; the total data of 2 trials had been presented in 4 papers [ 25 – 28 ] (so all of the articles were included with trial number adjusted only); 9 papers presented overlapping data with other studies included in the meta-analysis; and 3 trials presented data from MCT combined with immunotherapy (the results of which could not be explained by the two newly-emerging anti-cancer methods [ 29 – 31 ]). Lastly, two additional studies that met the inclusion criteria were identified from the reference of articles [ 32 , 33 ].…”

“…Subgroup analysis showed serious polarized heterogeneity for MCT (Q = 98.8, P<0.001, I 2 = 90.9) and combination schemes (Q = 5.3, P = 0.379, I 2 = 5.9). Sensitivity analysis demonstrated that a total or subgroup of heterogeneity could be attributed primarily to one clinical trial [ 32 ] compared to others. After removing the data from that trial, we observed a trend showing a lower AEs rate favoring MCT used alone as compared to the combined schemes (24.4% vs. 33.6%, respectively, P = 0.070).…”

Changing breast cancer prognosis

“…• **Капецитабин 650 мг/м 2 внутрь 2 раза в день постоянно, длительно [202] • **Капецитабин 1500 мг в день внутрь постоянно, длительно [203] • **Капецитабин 800 мг/м 2 внутрь 2 раза в день постоянно, длительно [204] **Циклофосфамид (50 мг/сутки внутрь ежедневно длительно) + **метотрексат (2,5 мг два раза в сутки в 1 и 2 дни еженедельно) = 19% Рм в группе 63 больных распространенным РМЖ, клинически значимый эффект (Рм + стабилизация) -39%; выживаемость 1 год без прогрессирования -26%. Токсичность минимальная [212], [213].…”

Single Nucleotide Polymorphisms as Biomarkers for Drug Response and Toxicity in the Management of Colorectal Cancer

“…A randomized noninferiority phase II trial with a pharmacogenetic analysis in 195 metastatic breast cancer patients found that the presence of two polymorphisms in TP gene (rs 11479 and rs131804) found to increase the overall survival (OS) with capecitabine treatment (Figure 2) [20]. Glutathione S-transferase (GST): Oxaliplatin is detoxified in the body through glutathione conjugation (GSH) reaction mediated by glutathione S-transferase enzyme (GST) and later excreted out through kidneys.…”