A multicentre dose-escalating study of cabazitaxel (XRP6258) in combination with capecitabine in patients with metastatic breast cancer progressing after anthracycline and taxane treatment: a phase I/II study.

Most patients with metastatic breast cancer (MBC) progress after chemotherapy. Cabazitaxel (XRP6258) is a new taxoid that is active in chemotherapy-resistant tumour cell lines. The objectives of this phase I/II study were to assess the maximum tolerated dose (MTD), safety profile, pharmacokinetics, and activity of cabazitaxel plus capecitabine in patients with MBC who had been previously treated with taxanes and anthracyclines. In part I, we used a 3+3 dose-escalation scheme to assess the MTD of intravenous cabazitaxel (day 1) with oral capecitabine twice daily (days 1-14) every 3 weeks. In part II, we evaluated the objective response rate (ORR) at the MTD. Thirty-three patients were enrolled and treated (15 in part I; 18 in part II). Cabazitaxel 20mg/m(2) plus capecitabine 1000 mg/m(2) was the MTD. Pharmacokinetic analysis showed no apparent drug-drug interaction. In all patients, the main grade 3-4 toxicities were asthenia (n=5), hand-foot syndrome (n=5), neutropenia (n=21), neutropenic infection (n=1), and neutropenic colitis (n=1). One patient had febrile neutropenia. Antitumour activity was observed at all dose-levels with two complete responses, five partial responses (PRs), and 20 disease stabilisations (seven unconfirmed PR). At the MTD, 21 patients were evaluable for efficacy. The ORR was 23.8% (95% CI: 8.2-47.2%). The median response duration was 3.1 months (95% CI: 2.1-8.4 months), with four of five lasting for more than 3 months. Median time to progression was 4.9 months. Cabazitaxel combined with capecitabine is active, has a safety profile consistent with a taxane plus capecitabine combination and warrants further investigation in patients with MBC.

Villanueva C ，Awada A ，Campone M ，Machiels JP ，Besse T ，Magherini E ，Dubin F ，Semiond D ，Pivot X ... -  《-》

Phase II study of oral vinorelbine in combination with capecitabine as second line chemotherapy in metastatic breast cancer patients previously treated with anthracyclines and taxanes.

Jones A ，O'Brien M ，Sommer H ，Nowara E ，Welt A ，Pienkowski T ，Rolski J ，Pham ML ，Perraud K ，Trillet-Lenoir V ... -  《-》

A phase I study of vinflunine in combination with capecitabine in patients with metastatic breast cancer previously treated with anthracyclines and taxanes.

Campone M ，Isambert N ，Bourbouloux E ，Roché H ，Bonneterre J ，Milano G ，Fumoleau P ... -  《-》

Phase II study of capecitabine plus trastuzumab in human epidermal growth factor receptor 2 overexpressing metastatic breast cancer pretreated with anthracyclines or taxanes.

Schaller G ，Fuchs I ，Gonsch T ，Weber J ，Kleine-Tebbe A ，Klare P ，Hindenburg HJ ，Lakner V ，Hinke A ，Bangemann N ... -  《-》

Prospective study of vinorelbine and capecitabine combination therapy in Chinese patients with metastatic breast cancer pretreated with anthracyclines and taxanes.

This phase II study prospectively evaluated the feasibility of vinorelbine in combination with capecitabine in Chinese patients with metastatic breast cancer (MBC) pretreated with anthracyclines and taxanes. Vinorelbine (25 mg/m(2) intravenous infusion on days 1 and 8) and capecitabine (1,000 mg/m(2) b.i.d., days 1-14) were administered to eligible MBC patients previously treated with anthracyclines and taxanes every 3 weeks for up to 6 cycles, until disease progression or unacceptable toxicity. The primary endpoint was objective response. Seventy-two patients were enrolled. In total, 297 cycles were given (median 4 cycles, range 2-6). The overall response rate was 45.8% (95% CI 34.2-57.4%), including 5 complete (6.9%) and 28 partial responses (38.9%). With median follow-up of 22 months, median time to progression was 7.7 months (95% CI 5.5-10.0) and median survival was 26.1 months (95% CI 19.6-32.6). The response rate was 53.8% in patients resistant to anthracyclines and taxanes combination. The most common hematologic adverse events were leukopenia (81.9%) with grade 3/4 incidence of 41.7%; nausea was the most frequent non-hematologic toxicity (62.5%). Hand-foot syndrome occurred in 12.5% of patients, and diarrhea was rare. Capecitabine 1,000 mg/m(2) b.i.d. combined with vinorelbine 25 mg/m(2) is an effective and safe treatment for MBC patients, no matter if anthracycline and taxane pretreated or resistant.

Fan Y ，Xu B ，Yuan P ，Wang J ，Ma F ，Li Q ，Zhang P ，Li Q ，Cai R ... -  《-》