Gemcitabine monotherapy as salvage chemotherapy in heavily pretreated metastatic breast cancer

SummaryPurposes We evaluated the efficacy and tolerability of gemcitabine monotherapy in heavily pretreated, breast cancer patients as salvage chemotherapy.Methods A weekly infusion of gemcitabine at 850 mg/m2for 30 min, for 3 of every 4 weeks, was introduced in advanced breast cancer patients who had failed previous doxorubicin and taxane based chemotherapy. There was no dose modification, and the treatment was delayed until the leukopenia was recovered with G-CSF support. The efficacy was evaluated every three cycles and the treatment was continued until either disease progression or 12 cycles.Results Of 41 enrolled patients, 38 were evaluable with a median age of 47. Total 178 cycles of gemcitabine was administered and the relative dose intensity was 89. The toxicity was mild with 12 of grade III neutropenia and 14 of grade III/IV thrombocytopenia without clinical symptoms. The response rate was 20 (8/38), comprising two complete and six partial responses. The median response duration and overall survival were 9 (2–25) and 11 months, respectively. The overall survival of 12 months was better in the third line patients than the 7 months in the fourth line treatment group.Conclusion Gemcitabine monotherapy is effective and safe as salvage treatment in heavily pretreated, breast cancer patients.     

Intermittent capecitabine monotherapy with lower dose intensity in heavily pretreated patients with metastatic breast cancer

AIMS AND BACKGROUND: The purpose of the present retrospective study was to evaluate efficacy and safety of a lower dose-intensity capecitabine monotherapy regimen in heavily pretreated patients with metastatic breast cancer. METHODS: Patients with metastatic breast cancer who had been administered capecitabine monotherapy between June 2003 and August 2004 at our hospital were retrospectively reviewed. Oral capecitabine (828 mg/m2) was given twice daily for three weeks followed by a one-week rest period; this was repeated every four weeks. RESULTS: One-hundred and two patients were assessed. Median follow-up of patients was 16.4 months. One hundred patients (98%) had been pretreated with either anthracyclines or taxanes, 81 patients (79%) with both anthracyclines and taxanes. Response rate was 17% (95% CI, 9-24%), and clinical benefit rate was 41% (95% CI, 32-51%). Median time-to-treatment failure was 4.9 months, and median overall survival time was 24.3 months. This regimen was well tolerated. The most frequent grade 3 or 4 adverse event was hand-foot syndrome (6%). Other grade 3 or 4 adverse events were seen in only 1%-3% of patients. CONCLUSIONS: Intermittent capecitabine monotherapy with lower dose intensity achieved a high tumor control rate with low toxicity in heavily pretreated metastatic breast cancer patients.     

Weekly ixabepilone administration in heavily pretreated metastatic breast cancer patients

Ixabepilone 40 mg/m(2) administered on an every 3-week schedule is approved for use in metastatic breast cancer (MBC) as monotherapy, or in combination with capecitabine in anthracycline/taxane resistant tumors. Because the mechanism of action and toxicity profile is similar to the taxanes, it has been suggested that weekly administration (15-20 mg/m(2) on days 1, 8, 15 for 28 days/cycle) may provide a therapeutic advantage while minimizing toxicity. We report 24 MBC patients treated with weekly ixabepilone. Demographics, ER/PR/HER-2/neu, ECOG performance status (PS), sites of metastatic disease, lines of previous therapy, dosage, treatment duration, dose reductions/interruptions, hematologic/non-hematologic toxicities, growth factor use, reasons for discontinuation, time to progression (TTP), and response rate were recorded. Median age was 61 years (33-79). 0-1 ECOG PS was 54%. Sixty-seven percent of patients received ≥ 4 previous chemotherapy regimens. Median treatment duration was 1.4 months (0.5-10.8). Median dose was 16 mg/m(2) (15-20). In 37.5% of patients, the dose was held due to toxicities with median missed dose of 2. Partial response and stable disease were 4 and 48%. Median TTP was 2.1 months (0.9-16.4). Majority of patients discontinued therapy due to disease progression (84%). Grade 3-4 neutropenia and neuropathy were 4% and 8%. It is not yet clear whether the weekly administration of ixabepilone impacts the risk/benefit profile. There are clinical data to suggest that weekly ixabepilone is efficacious and tolerable. Upcoming clinical trials will continue to inform the question. Our data suggest that weekly ixabepilone is well tolerated with a manageable side-effect profile in this small, heavily pretreated population.     

Weekly ixabepilone administration in heavily pretreated metastatic breast cancer patients

Ixabepilone 40 mg/m² administered on an every 3-week schedule is approved for use in metastatic breast cancer (MBC) as monotherapy, or in combination with capecitabine in anthracycline/taxane resistant tumors. Because the mechanism of action and toxicity profile is similar to the taxanes, it has been suggested that weekly administration (15–20 mg/m² on days 1, 8, 15 for 28 days/cycle) may provide a therapeutic advantage while minimizing toxicity. We report 24 MBC patients treated with weekly ixabepilone. Demographics, ER/PR/HER-2/neu, ECOG performance status (PS), sites of metastatic disease, lines of previous therapy, dosage, treatment duration, dose reductions/interruptions, hematologic/non-hematologic toxicities, growth factor use, reasons for discontinuation, time to progression (TTP), and response rate were recorded. Median age was 61 years (33–79). 0–1 ECOG PS was 54%. Sixty-seven percent of patients received ≥4 previous chemotherapy regimens. Median treatment duration was 1.4 months (0.5–10.8). Median dose was 16 mg/m² (15–20). In 37.5% of patients, the dose was held due to toxicities with median missed dose of 2. Partial response and stable disease were 4 and 48%. Median TTP was 2.1 months (0.9–16.4). Majority of patients discontinued therapy due to disease progression (84%). Grade 3–4 neutropenia and neuropathy were 4% and 8%. It is not yet clear whether the weekly administration of ixabepilone impacts the risk/benefit profile. There are clinical data to suggest that weekly ixabepilone is efficacious and tolerable. Upcoming clinical trials will continue to inform the question. Our data suggest that weekly ixabepilone is well tolerated with a manageable side-effect profile in this small, heavily pretreated population.

     

Weekly ixabepilone administration in heavily pretreated metastatic breast cancer patients

Ixabepilone 40 mg/m² administered on an every 3-week schedule is approved for use in metastatic breast cancer (MBC) as monotherapy, or in combination with capecitabine in anthracycline/taxane resistant tumors. Because the mechanism of action and toxicity profile is similar to the taxanes, it has been suggested that weekly administration (15–20 mg/m² on days 1, 8, 15 for 28 days/cycle) may provide a therapeutic advantage while minimizing toxicity. We report 24 MBC patients treated with weekly ixabepilone. Demographics, ER/PR/HER-2/neu, ECOG performance status (PS), sites of metastatic disease, lines of previous therapy, dosage, treatment duration, dose reductions/interruptions, hematologic/non-hematologic toxicities, growth factor use, reasons for discontinuation, time to progression (TTP), and response rate were recorded. Median age was 61 years (33–79). 0–1 ECOG PS was 54%. Sixty-seven percent of patients received ≥4 previous chemotherapy regimens. Median treatment duration was 1.4 months (0.5–10.8). Median dose was 16 mg/m² (15–20). In 37.5% of patients, the dose was held due to toxicities with median missed dose of 2. Partial response and stable disease were 4 and 48%. Median TTP was 2.1 months (0.9–16.4). Majority of patients discontinued therapy due to disease progression (84%). Grade 3–4 neutropenia and neuropathy were 4% and 8%. It is not yet clear whether the weekly administration of ixabepilone impacts the risk/benefit profile. There are clinical data to suggest that weekly ixabepilone is efficacious and tolerable. Upcoming clinical trials will continue to inform the question. Our data suggest that weekly ixabepilone is well tolerated with a manageable side-effect profile in this small, heavily pretreated population.     

Salvage chemotherapy with gemcitabine and oxaliplatin in heavily pretreated patients with metastatic breast cancer: a multicenter phase II study

PURPOSE: It was the aim of this study to evaluate the activity and tolerance of gemcitabine and oxaliplatin in pretreated metastatic breast cancer patients. METHODS: Thirty-one patients who had disease relapse or progression after completion of an anthracycline- and/or taxane-based front-line regimen were treated with gemcitabine 1,500 mg/m(2) on days 1 and 8 as a 30-min intravenous infusion and oxaliplatin 130 mg/m(2) on day 8 as a 4-hour intravenous infusion, in cycles of 21 days. RESULTS: Complete response occurred in 1 patient (3%) and partial response in 4 patients (13%) (overall response rate 16%; 95% confidence interval 3.2-29.1). Nine patients (29%) had stable disease and 17 (55%) progressive disease. Three partial responses (13%) were achieved among 23 patients receiving the regimen as third-line treatment. The median duration of response was 6 months (range 3-44.8), the median time to tumor progression 4.6 months (range 0.8-43.8), and the median survival 14.4 months (range 2.1-44.8). Grade 3 and 4 neutropenia occurred in 14 patients (45%), grade 3 and 4 thrombocytopenia in 6 patients (20%), and grade 2 and 3 asthenia in 4 patients (13%). There was no episode of febrile neutropenia. CONCLUSION: The gemcitabine-oxaliplatin combination is a relatively active and well-tolerated salvage regimen in patients with heavily pretreated metastatic breast cancer.     

Thalidomide is inactive in heavily pretreated patients with metastatic breast cancer

Experimental studies have demonstrated that thalidomide has anti-tumor activity mediated by blockage of angiogenesis, with clinical efficacy in multiple myeloma, glioblastoma multiforme, and renal cell cancer. We investigated the therapeutic activity and toxicity of thalidomide in patients with progressive metastatic breast cancer pretreated with chemotherapy. Inclusion criteria were metastatic breast cancer in progression of disease after at least two lines of chemotherapy, age > or = 18 years, performance status < or = 2, and adequate hematologic, renal, and hepatic functions. Twelve patients entered the study, eight of whom were pretreated with three or more lines of chemotherapy (66.7%). Thalidomide was well tolerated: the most common side effects were constipation and somnolence (58.3% of patients). No objective response or durable stable disease was observed. Median time to progression and median overall survival were 8 weeks (range, 4-10 weeks) and 16 weeks (range, 8-54 weeks), respectively. In conclusion, thalidomide is an ineffective treatment in patients with progressive metastatic breast cancer heavily pretreated with chemotherapy.     

Gemcitabine and cisplatin salvage regimen in heavily pretreated metastatic breast cancer: a Brazilian experience

Gemcitabine and cisplatin combination (Gem–Cis) is a commonly used regimen in metastatic breast cancer (MBC), with proven activity in phase II trials. It is mostly used as a salvage regimen for progressive disease refractory to anthracyclines and taxanes, and when liver dysfunction secondary to liver metastasis precludes these drugs. Retrospective review of medical charts was conducted for patients treated with Gem–Cis for MBC in a single institution in Brazil between January 2004 and July 2007. The purpose of this study was to evaluate the outcomes and toxicity of Gem–Cis in a broad indication, including patients with deteriorated performance status (PS) and liver dysfunction, which were excluded from clinical trials. Fifty-six patients were included. Median age was 52 years, 46.4% were hormone–receptor negative, 57.2% received 3 or more prior chemotherapy lines, and 34 had liver metastasis. The median overall survival (OS) was 7.6 months, the median progression-free survival was 3.3 months, and the response rate was 21.2%. In variable analysis, PS was significantly associated with OS, even after adjusting to other factors. Toxicities included grades 3 or 4 anemia in 19.3%, neutropenia in 21.1%, and thrombocytopenia in 12.3%. Gem–Cis was a relatively active combination in this population that typically carries a poor prognosis. The subgroup of patients with favorable PS experienced longer survival, even when liver metastasis and hepatic dysfunction were a concern. Toxicity was manageable and it was not correlated with PS or liver dysfunction.

     

Gemcitabine and cisplatin salvage regimen in heavily pretreated metastatic breast cancer: a Brazilian experience

Gemcitabine and cisplatin combination (Gem-Cis) is a commonly used regimen in metastatic breast cancer (MBC), with proven activity in phase II trials. It is mostly used as a salvage regimen for progressive disease refractory to anthracyclines and taxanes, and when liver dysfunction secondary to liver metastasis precludes these drugs. Retrospective review of medical charts was conducted for patients treated with Gem-Cis for MBC in a single institution in Brazil between January 2004 and July 2007. The purpose of this study was to evaluate the outcomes and toxicity of Gem-Cis in a broad indication, including patients with deteriorated performance status (PS) and liver dysfunction, which were excluded from clinical trials. Fifty-six patients were included. Median age was 52 years, 46.4% were hormone-receptor negative, 57.2% received 3 or more prior chemotherapy lines, and 34 had liver metastasis. The median overall survival (OS) was 7.6 months, the median progression-free survival was 3.3 months, and the response rate was 21.2%. In variable analysis, PS was significantly associated with OS, even after adjusting to other factors. Toxicities included grades 3 or 4 anemia in 19.3%, neutropenia in 21.1%, and thrombocytopenia in 12.3%. Gem-Cis was a relatively active combination in this population that typically carries a poor prognosis. The subgroup of patients with favorable PS experienced longer survival, even when liver metastasis and hepatic dysfunction were a concern. Toxicity was manageable and it was not correlated with PS or liver dysfunction.     

Gemcitabine and cisplatin salvage regimen in heavily pretreated metastatic breast cancer: a Brazilian experience

Gemcitabine and cisplatin combination (Gem–Cis) is a commonly used regimen in metastatic breast cancer (MBC), with proven activity in phase II trials. It is mostly used as a salvage regimen for progressive disease refractory to anthracyclines and taxanes, and when liver dysfunction secondary to liver metastasis precludes these drugs. Retrospective review of medical charts was conducted for patients treated with Gem–Cis for MBC in a single institution in Brazil between January 2004 and July 2007. The purpose of this study was to evaluate the outcomes and toxicity of Gem–Cis in a broad indication, including patients with deteriorated performance status (PS) and liver dysfunction, which were excluded from clinical trials. Fifty-six patients were included. Median age was 52 years, 46.4% were hormone–receptor negative, 57.2% received 3 or more prior chemotherapy lines, and 34 had liver metastasis. The median overall survival (OS) was 7.6 months, the median progression-free survival was 3.3 months, and the response rate was 21.2%. In variable analysis, PS was significantly associated with OS, even after adjusting to other factors. Toxicities included grades 3 or 4 anemia in 19.3%, neutropenia in 21.1%, and thrombocytopenia in 12.3%. Gem–Cis was a relatively active combination in this population that typically carries a poor prognosis. The subgroup of patients with favorable PS experienced longer survival, even when liver metastasis and hepatic dysfunction were a concern. Toxicity was manageable and it was not correlated with PS or liver dysfunction.     

阿帕替尼治疗多线治疗失败的转移性乳腺癌的疗效观察

目的 观察阿帕替尼治疗难治性乳腺癌的疗效及不良反应.方法 回顾性分析29例经多线治疗失败后进行阿帕替尼化疗的转移性乳腺癌患者的临床资料,分析阿帕替尼单药化疗和阿帕替尼联合化疗患者的无进展生存期(PFS)、客观有效率(ORR)和疾病控制率(DCR).结果 29例患者中,1例死亡,1例由于血小板降低而停止用药,可评价疗效的患者共27例.27例患者的中位PFS为3.1个月(1.0~6.1个月).阿帕替尼联合化疗患者的PFS为3.10个月,阿帕替尼单药化疗患者的中位PFS为3.46个月,差异无统计学意义(P>0.05).治疗后部分缓解3例,疾病稳定12例,疾病进展12例,ORR为11.11%,DCR为55.56%.多因素分析结果显示,既往化疗方案数是影响乳腺癌患者PFS的独立危险因素(P<0.05).化疗后患者的3~4级不良反应包括手足综合征2例(6.90%),高血压2例(6.90%),低血小板血症1例(3.45%).结论 阿帕替尼单药及联合化疗治疗转移性乳腺癌有一定疗效,值得进一步研究.     

Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer

BackgroundThere is no standard treatment after progression on second-line chemotherapy for metastatic breast cancer (MBC). We compared vinflunine with physician’s choice of alkylating agent (AA) for patients with heavily pretreated MBC.Patients and methodsIn this open-label phase III trial, patients with MBC were included if they had received at least two prior chemotherapy regimens for MBC and had received anthracycline, taxane, antimetabolite and vinca alkaloid therapy. Patients were no longer candidates for these chemotherapies because of resistance and/or intolerance. Patients were randomised to either vinflunine 280 mg/m² intravenously every 3 weeks (q3w) or AA monotherapy q3w. Stratification factors were performance status, number of prior chemotherapy lines for MBC, disease measurability and study site. The primary end point was overall survival (OS).ResultsA total of 594 patients were randomised (298 to vinflunine, 296 to AA). There was no difference between treatment arms in OS (hazard ratio 1.04, P = 0.67; median 9.1 months for vinflunine versus 9.3 months for AA), progression-free survival (hazard ratio 0.94, P = 0.49; median 2.5 versus 1.9 months, respectively) or overall response rate (6% versus 4%, respectively). However, the disease control rate was significantly higher with vinflunine than AA (44% versus 35%, respectively; P = 0.04). The most common adverse events (any grade) were haematological and gastrointestinal disorders and asthenia in both arms. The most common grade 3/4 adverse events were neutropenia (19% versus 11% with vinflunine versus AA, respectively) and asthenia (10% versus 4%).ConclusionsVinflunine 280 mg/m² q3w did not improve OS compared with the physician’s choice of AA as third- or later-line therapy for MBC. Vinflunine demonstrated an acceptable safety profile, suggesting that vinflunine 320 mg/m² merits evaluation.ClinicalTrials.govNCT01091168.     

Predictive factors for efficacy of capecitabine in heavily pretreated patients with metastatic breast cancer

Purpose  The purpose of the present study is to evaluate what clinical factors affect the efficacy, time to treatment failure (TTF), and overall survival (OS) of oral capecitabine monotherapy in heavily pretreated patients with metastatic breast cancer (MBC). Methods  A total of 102 consecutive patients with MBC who had been administered capecitabine monotherapy between June 2003 and August 2004 were retrospectively reviewed. Capecitabine (828 mg/m²) was given twice daily for 3 weeks followed by a 1-week rest period; this was repeated every 4 weeks. We evaluated the potential clinical factors for TTF and OS, using univariate analysis (log-rank test) and the multivariate Cox regression model. Median follow-up was 16.9 months. Results  A total of 100 patients (98%) had been pretreated with either anthracyclines or taxanes, and 81 patients (79%) with both anthracyclines and taxanes. Response rate was 17% and clinical benefit rate was 41%. Median TTF and OS were 4.9 and 24.3 months, respectively. Multivariate analysis demonstrated that no liver metastasis (P = 0.015), good performance status (P = 0.033), longer disease-free interval (P = 0.036), and hormone receptor-positive tumor (P = 0.038) were significant for TTF. No liver metastasis (P = 0.00012), objective response to capecitabine (P = 0.00084), and good performance status (P = 0.0011) were significant for OS. Conclusions  Capecitabine monotherapy is effective over the long term for heavily pretreated patients with MBC who have no liver metastasis, good performance status, longer disease-free interval, or hormone receptor-positive tumor. Patients who have no liver metastasis, who respond to capecitabine, or who have good performance status are expected to survive even longer.     

Efficacy of S-1 in heavily pretreated patients with metastatic breast cancer: cross-resistance to capecitabine

Background  It is not clear what the optimal treatment of chemotherapy is for patients with heavily treated metastatic breast cancer (MBC). We have retrospectively examined the efficacy and safety of S-1 in patients with MBC who had been previously treated with anthracycline, taxane, and capecitabine. Methods  Patients with MBC who had been administered S-1, an oral modulated compound containing a fluoropyrimidine derivative, between November 2001 and June 2003 at the Cancer Institute Hospital were retrospectively reviewed. S-1 at a standard dose of 50 mg/body was administered twice daily for four weeks, followed by a two-week rest period. This was repeated every six weeks until disease progression or unacceptable toxicity. Results  Thirty-five patients were assessed. The patients were heavily pretreated with anthracycline (100%), taxane (paclitaxel or docetaxel) (100%), capecitabine (100%), vinorelbine (71%), and mitomycin (69%). Median follow-up time of patients was 9.6 months (range, 1.2–26.6). ORR was 3% (95% confidence interval: 0–9%), and CBR was 20% (95% confidence interval: 6–33%). Time to treatment failure was 2.8 months. Overall survival was 21.4 months. Grade 1 or 2 adverse events were observed in 17% and 13%, respectively. Grade 3 events occurred as anorexia (9%), nausea (9%), vomiting (9%), diarrhea (14%), fatigue (3%), and elevation of AST/ALT (3%). No grade 3 was seen as hand-foot syndrome. Neither grade 3 nor 4 was observed in bone marrow suppression. Conclusions  S-1 was fairly well tolerated, but demonstrated very limited activity in capecitabine-pretreated patients who had already been exposed to anthracycline and taxane. It was suggested that S-1 clinically exhibited cross-resistance to capecitabine.     

A phase II study of eribulin in Japanese patients with heavily pretreated metastatic breast cancer

BackgroundEribulin mesylate is a non-taxane microtubule dynamics inhibitor that recently gained Food and Drug Administration approval for late-line metastatic breast cancer (MBC).Patients and methodsIn this single-arm, multicentre open-label phase II trial Japanese patients pretreated with an anthracycline and a taxane received 1.4 mg/m² eribulin mesylate (2- to 5-min i.v. infusion on days 1 and 8 of a 21-day cycle). The primary efficacy end point was overall response rate (ORR) by independent review.ResultsPatients (N = 80) had received a median of three prior chemotherapy regimens (range 1–5). ORR was 21.3% [95% confidence interval (CI) 12.9–31.8; all partial responses (PRs)], stable disease (SD) occurred in 30 patients (37.5%) and the clinical benefit rate (complete response + PR + SD ≥6 months) was 27.5% (95% CI 18.1–38.6). Median duration of response was 3.9 months (95% CI 2.8–4.9), progression-free survival was 3.7 months (95% CI 2.0–4.4) and overall survival was 11.1 months (95% CI 7.9–15.8). The most frequent treatment-related grade 3/4 adverse events were neutropenia (95.1%), leukopenia (74.1%) and febrile neutropenia (13.6%). Grade 3 peripheral neuropathy occurred in 3.7% of patients (no grade 4).ConclusionsEribulin exhibited efficacy and tolerability in Japanese patients with heavily pretreated MBC.