A pressing need exists for agents active against anthracycline- or taxane-refractory metastatic breast cancer (MBC), or both. Previous clinical trials suggested that irinotecan might have such activity. We conducted this multicenter phase II study to assess efficacy and tolerability of two irinotecan schedules.
MBC patients who experienced disease progression after one to three chemotherapy regimens, including at least one anthracycline- or taxane-based regimen, were randomly assigned to irinotecan in 6-week cycles comprising 100 mg/m(2) weekly for 4 weeks, then a 2-week rest (weekly) or 240 mg/m(2) every 3 weeks.
The weekly arm had 52 assessable patients; the every-3-weeks arm had 51 assessable patients. In the weekly arm, the objective response (complete regression [CR] + partial regression [PR]) rate was 23% (one CR, 11 PR; 95% CI, 13% to 37%). Median response duration was 4.9 months (range, 1.9 to 15.9 months), and median overall survival was 9.7 months (95% CI, 8.0 to 14.2 months). In the every-3-weeks arm, the objective response rate was 14% (nine PR; 95% CI, 6% to 26%), median response duration was 4.2 months (range, 3.1 to 13.9 months), and median overall survival was 8.6 months (95% CI, 7.0 to 12.3 months). Treatment generally was well tolerated, especially in the weekly arm. Grade 3 to 4 adverse events with > or = 10% incidence included neutropenia (29%) and diarrhea (17%) in the weekly arm and neutropenia (36%), vomiting (20%), dyspnea (18%), nausea (16%), and diarrhea (12%) in the every-3-weeks arm.
Irinotecan is active with good tolerability in refractory MBC. Irinotecan (especially weekly) warrants additional study as monotherapy and in combination regimens in this setting.
"A phase II trial of vinorelbine in 40 patients with paclitaxelrefractory MBC demonstrated a median time to progression of 3 months and a median survival of 8 months with an objective response rate of 25% (Livingston et al, 1997). Moderate activity has been observed with irinotecan and pemetrexed yielding ORRs of 14 – 26% and 10 – 26%, respectively, in patients with MBC after anthracycline and/ or taxane exposure (Calvert, 2003; Heinemann, 2003; Perez et al, 2004). In a phase II trial with ixabepilone, 37 women with metastatic and locally advanced breast cancer who had received paclitaxel and/or docetaxel as prior neoadjuvant, adjuvant or metastatic therapy, the ORR was 22% and median duration of response 3.8 months; the median PFS was established at 2.8 months (Low et al, 2005). "
[Show abstract][Hide abstract] ABSTRACT: To evaluate the single agent activity, pharmacokinetics and tolerability of the novel tubulin targeted agent vinflunine (VFL) (320 mg m(-2) q 21 days) as second-line chemotherapy in patients with metastatic breast carcinoma (MBC). All patients had disease progression after anthracycline/taxane (A/T) therapy. They could have received a nonanthracycline adjuvant treatment and subsequently received a first-line A/T combination for advanced/metastatic disease; or relapsed >6 months after completion of adjuvant A/T therapy and were subsequently treated with the alternative agent; or relapsed within 6 months from an adjuvant A/T combination. Objective response was documented in 18 of 60 patients enrolled (RR: 30% (95% confidence interval (CI): 18.9-43.2%)). Among the responders, seven patients had relapsed during a period of <3 months from taxane-based regimen yielding a RR of 33.3%. The median duration of response was 4.8 months (95% CI: 4.2-7.2), median progression-free survival was 3.7 months (95% CI: 2.8-4.2) and median overall survival was 14.3 months (95% CI: 9.2-19.6). The most frequent adverse event was neutropenia (grade 3 in 28.3% and grade 4 in 36.7% of patients). No febrile neutropenia was observed. Fatigue (grade 3 in 16.7% of patients) and constipation (grade 3 in 11.7% of patients) were also common; these were non-cumulative and manageable permitting achievement of a good relative dose intensity of 93.5%. Vinflunine is an active agent with acceptable tolerance in the management of MBC patients previously treated with (A/T)-based regimens. These encouraging phase II results warrant further investigation of this novel agent in combination with other active agents in this setting or in earlier stages of disease.
British Journal of Cancer 12/2006; 95(9):1161-6. DOI:10.1038/sj.bjc.6603347 · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Topoisomerases are enzymes involved in the replication of DNA and they are the target of the topoisomerase inhibitors 1 and 2. This class of anticancer agents forms the backbone of chemotherapeutic regimens in several solid tumors including breast cancer. This review focuses on their role in the treatment of metastatic breast cancer. While anthracyclines (topoisomerase 2 inhibitors) are commonly used in metastatic breast cancer, other agents such as the topoisomerase 1 inhibitors and etoposide have reached some level of clinical development. New formulations of doxorubicin are frequently used in the clinic and a new formulation of irinotecan, and etirinotecan pegol, has recently reached phase 3 development. An overview of their mechanism of action, toxicity, and clinical use (single agent or combination settings) is provided.
Current Breast Cancer Reports 03/2013; 5(1). DOI:10.1007/s12609-012-0098-0
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.