Randomised, phase II trial comparing oral capecitabine (Xeloda®) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines

Abstract

Capecitabine, an oral fluoropyrimidine carbamate, was designed to generate 5-fluorouracil preferentially at the tumour site. This randomised, phase II trial evaluated the efficacy and safety of capecitabine or paclitaxel in patients with anthracyclinepretreated metastatic breast cancer. Outpatients with locally advanced and/or metastatic breast cancer whose disease was unresponsive or resistant to anthracycline therapy were randomised to 3-week cycles of intermittent oral capecitabine (1255 mg m 72 twice daily, days 1 -14, (22 patients)) or a reference arm of i.v. paclitaxel (175 mg m 72 , (20 patients)). Two additional patients were initially randomised to continuous capecitabine 666 mg m 72 twice daily, but this arm was closed following selection of the intermittent schedule for further development. Overall response rate was 36% (95% CI 17 -59%) with capecitabine (including three complete responses) and 26% (95% CI 9 -51%) with paclitaxel (no complete responses). Median time to disease progression was similar in the two treatment groups (3.0 months with capecitabine, 3.1 months with paclitaxel), as was overall survival (7.6 and 9.4 months, respectively). Paclitaxel was associated with more alopecia, peripheral neuropathy, myalgia and neutropenia, whereas typical capecitabine-related adverse events were diarrhoea, vomiting and hand -foot syndrome. Twenty-three per cent of capecitabine-treated patients and 16% of paclitaxel-treated patients achieved a 510% improvement in Karnofsky Performance Status. Oral capecitabine is active in anthracycline-pretreated advanced/ metastatic breast cancer and has a favourable safety profile. Furthermore, capecitabine provides a convenient, patientorientated therapy.

Capecitabine in hormone-resistant metastatic prostatic carcinoma – a phase II trial

“…Capecitabine has demonstrated consistently high single-agent activity and a favourable safety profile in taxane and anthracycline pretreated metastatic breast cancer (Blum et al, 1999(Blum et al, , 2001Fumoleau et al, 2001;Talbot et al, 2002) and improved overall survival when added to docetaxel in the anthracycline-failure setting (O'Shaughnessy et al, 2002). In addition, randomised phase III trials comparing the efficacy and tolerability of 3-weekly intermittent capecitabine with i.v.…”

Nucleoside anticancer drugs: the role of nucleoside transporters in resistance to cancer chemotherapy

“…Capecitabine has shown activity in metastatic colorectal cancer that is comparable to that of 5-fluorouracil combined with leucovorin (Hoff et al, 2001). Capecitabine has activity against metastatic breast cancer that has progressed after docetaxel or anthracyclines (Blum et al, 1999;Talbot et al, 2002).…”

Capecitabine Monotherapy: Safe and Effective Treatment for Metastatic Breast Cancer

“…A phase II RCT by Talbot et al [42] compared the safety profile of single-agent capecitabine with that of singleagent paclitaxel in patients who had failed or were resistant to anthracycline-based therapy and/or who had undergone 19 (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) All regimens used twice daily dosing, 2 weeks on/1 week off, unless otherwise noted.…”

“…In one randomized phase II clinical trial [42], 22 patients received oral capecitabine at a dose of 1,255 mg/m 2 bid for 2 weeks on/1 week off for two cycles, and 19 patients received parenteral paclitaxel at a dose of 175 mg/m 2 every 3 weeks. The CR rate and ORR were greater in the capecitabine group than in the paclitaxel group (14% vs. 0% and 36% vs. 26%, respectively), but these differences were not significant (p = .24 and p = .52).…”