Xeloda + Taxotere
 Xeloda (capecitabine) plus docetaxel combination therapy in locally advanced/metastatic breast cancer: latest results.
Vukelja SJ et al. San Antonio 2001
Background: Xeloda (X) is a thymidine phosphorylase (TP)-activated oral fluoropyrimidine with high single-agent activity in metastatic breast cancer. Docetaxel (D) is highly active in breast cancer and upregulates TP, leading to synergistic activity with X. Methods: 511 patients with anthracycline-pretreated locally advanced/metastatic breast cancer were randomized to 21-day cycles of either combination therapy (X 1250mg/m2 bid, d1-14 plus D 75mg/m2, d1; n=255) or monotherapy (D 100mg/m2, d1; n=256). The primary efficacy endpoint is TTP. In the first report of this trial [O'Shaughnessy et al SABCS 2000:A381] overall survival was significantly superior with X+D, with median survival of 13.7 vs 11.1 months, respectively. We report here the latest results. Results: Minimum follow-up is now 15 months. X+D resulted in significantly superior OS (HR=0.775 [95% CI: 0.63-0.95], p=0.0126, median 14.5 vs 11.5m with monotherapy), TTP (HR=0.652 [95% CI: 0.54-0.77], p=0.0001, median 6.1 vs 4.2m), and RR (42 vs 30%, p=0.006). Treatment-related adverse events (AE) occurred in 98% and 94% of the X+D and D arms, respectively. Patients receiving X+D experienced a higher incidence of gastrointestinal AE and hand-foot syndrome, whereas there was more neutropenic fever, arthralgia and pyrexia in the monotherapy group. Grade 4 AE were less common with X+D (25% vs 30%, due to neutropenic fever in the D arm). Grade 3 AE were more common in the X+D arm, primarily owing to hand-foot syndrome in the second cycle. X+D AE were effectively managed with appropriate medical intervention, treatment interruption and if necessary, dose reduction. Conclusions: X+D therapy offers the unique benefit of superior OS, with a manageable safety profile. It is a highly effective new combination chemotherapy for the treatment of advanced disease.
Adding Xeloda (capecitabine) to docetaxel significantly improves survival and does not compromise quality of life in patients with metastatic breast cancer.
Twelves C, et al. San Antonio 2001
Background: A phase III trial demonstrated that Xeloda (X) 1250mg/m2 bid, d1-14 plus docetaxel (D) 75mg/m2, d1 q21d (XD) significantly increased overall survival (OS) compared with D 100mg/m2 alone, d1 q21d, in patients (pts) with anthracycline-pretreated BC. Methods: We compared quality of life (QoL) in pts receiving XD or D using the EORTC QLQ-C30 (v2) and BC module BR23. Questionnaires were completed before treatment administration at baseline, q6 wks during therapy, and at study end. Global health score was the predefined primary parameter for inferential statistical testing at wk 18 (Van der Waerden test applied to change from baseline using last observation carried forward methods for imputation of missing data). Results: 454 pts (224 XD, 230 D) completed a questionnaire at least once at baseline or during therapy. Decreased functional scale score indicates decline in QoL. Change from baseline scores of the functional scale global health at wk 18 and wk 30 (XD -3.7, -3.4; D -4.0, -4.4, respectively; p=0.8303 wk 18) showed no clinically meaningful change. Analysis of raw (non-imputed) scores showed a trend in favor of XD towards a clinically meaningful difference between XD and D at wk 30 (change from baseline: -2.3 and -12.1, respectively). There was no difference in other domains including physical, cognitive, role, and social functioning scales and systemic therapy side effects. Conclusions: QoL was similar with XD and D. This is a valuable outcome in the palliative setting,
Xeloda + epirubicin + docetaxel
 Capecitabine in association with epirubicin and docetaxel as a first line treatment in advanced breast cancer. A multicenter phase II study.
Rosso R, et al. San Antonio Breast Conference 2001
The combination of Epirubicin and Taxotere (ET), both drugs given at 75 mg/m2 day 1 q. 21 days, is widely used in the treatment of advanced breast cancer. We previously reported a phase I study which indicated that Capecitabine 2000 mg/m2/day for 14 consecutive days could be safely combined with full doses of ET. Among 23 patients treated 21 (91%), responded to the treatment. On these premises, we undertook a multicenter phase II trial to confirm the activity of the this regimen (Taxotere 75 mg/m2 IV bolus on day 1, Epirubicin 75 mg/m2 IV bolus on day 1, Capecitabine 2000 mg/m2/day for 14 consecutive days, q. 21 days). From March 2000 to February 2001, six Italian Centers enrolled 67 advanced breast cancer patients (pts), with measurable disease. To date, 65 pts have been evaluated. The median age was 53 years (range 31-68); 33 pts (51%) had locally advanced disease, 32 pts (49%) distant metastasis and 17 (26 %) of them had two or more metastatic sites. Severe non-hematological toxicity was rarely reported. Only one patient experienced a grade 4 non-hematological toxicity (mucositis). Grade 3 non-hematological toxicities were: asthenia 4 pts (6%), mucositis 3 pts (5%), hand-foot syndrome 2 pts (3%), nausea and vomiting 6 pts (9%), diarrhea 2 pts (3%), allergy 1 pt (2%), dyspnea 1 pt (2%), venous thrombosis 1 pt (2%). A mild or moderate increase of ALT and bilirubin was observed in 17 pts (26%), and 7 pts (11%), respectively. Thrombocytopenia was seldom reported: two (3%) pts suffered from it of grade 3. Grade 3/4 anemia was observed in 2 pts (3%). Neutropenia was the predominant toxicity. Forty-six percent of pts had grade 3/4 neutropenia. Ten pts (15%) had febrile neutropenia. Preliminary data on 50 evaluable pts showed an objective response (CR+PR) in 21/26 (81%) locally advanced pts and 17/24 (71%) metastatic pts. These data confirmed that Capecitabine can be incorporated with full doses of ET and that this new regimen is highly active in advanced breast cancer. Based on these data, a large multicenter randomized Phase III trial is ongoing