Lonidamine significantly increases the activity of epirubicin in patients with advanced breast cancer: results from a multicenter prospective randomized trial.

1996 ◽  
Vol 14 (4) ◽  
pp. 1165-1172 ◽  
Author(s):  
L Dogliotti ◽  
A Berruti ◽  
T Buniva ◽  
P Zola ◽  
M G Baù ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Randomized Trial ◽  
Response Rate ◽  
Single Agent ◽  
Advanced Breast ◽  
Prospective Randomized Trial ◽  
Significant Difference

PURPOSE Some evidence in vitro and in vivo shows that lonidamine (LND) can positively modulate the activity of doxorubicin and epirubicin (EPI). On this basis, a multicenter prospective randomized trial was performed in patients with advanced breast cancer (BC) to determine if the addition of LND to EPI could increase the response rate of EPI alone. PATIENTS AND METHODS From May 1991 to May 1993, 207 patients were enrolled onto this study and randomized to receive intravenous (IV) EPI (60 mg/m2 on days 1 and 2) alone or with LND (600 mg orally daily). EPI administration was repeated every 21 days until tumor progression or for a maximum of eight cycles. LND was administered continuously until chemotherapy withdrawal. RESULTS Response rate was significantly superior for the EPI plus LND scheme compared with the single-agent EPI either considering assessable patients (60.0% v 39.8%; P < .01) or including all registered patients according to an intention-to-treat analysis (55.3% v 37.5%; P < .02). The distribution of the response rate according to the site of disease did not show any significant difference between the treatment arms, except for the patient subgroup with liver metastases in which the combination EPI plus LND resulted in a significant improvement of responses than EPI alone. Toxicity was moderate, and except for myalgia, no adjunctive side effects were observed in the EPI plus LND arm. Overall survival and time to progression were similar in both groups. CONCLUSION This study confirms in vivo that the administration of EPI is enhanced by the concomitant LND administration.

Quinidine as a resistance modulator of epirubicin in advanced breast cancer: mature results of a placebo-controlled randomized trial.

1994 ◽  
Vol 12 (9) ◽  
pp. 1771-1777 ◽  
Author(s):  
G C Wishart ◽  
D Bissett ◽  
J Paul ◽  
D Jodrell ◽  
A Harnett ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Response Rate ◽  
Advanced Breast ◽  
Toxicity Profile ◽  
Survival Times ◽  
Double Blind ◽  
P Glycoprotein ◽  
Significant Difference

PURPOSE To evaluate the effect of quinidine, a putative modulator of P-glycoprotein-mediated drug resistance, on the response rate and toxicity profile of epirubicin in patients with advanced breast cancer. PATIENTS AND METHODS Between 1989 and 1992, 223 eligible patients were randomized in double-blind fashion to receive epirubicin 100 mg/m2 by intravenous (i.v.) bolus and prednisolone 25 mg orally twice daily, along with either placebo or quinidine (250 mg) capsules, taken for 4 days before and 2 days after chemotherapy. Treatment was continued for a maximum of eight courses. RESULTS Ten eligible patients did not complete the first cycle of treatment. Of the remaining patients, 106 in the placebo arm received 619 courses of treatment, and 107 in the quinidine arm received 612 courses. The median cumulative dose of epirubicin in both arms was 600 mg/m2. The median quinidine level (measured before epirubicin administration in 288 courses) was 5.5 mumol/L; at this concentration, the drug partially reverses anthracycline resistance in multidrug-resistant (MDR) breast carcinoma cells in vitro. There were no statistically significant differences in hematologic or gastrointestinal toxicity between the two arms. The response rate in the placebo arm was 44% (6% complete remission [CR], 38% partial remission [PR]), and in the quinidine arm was 43% (4% CR, 39% PR). Surviving patients have been monitored for a median time of 74 weeks, and there is no significant difference in the overall or progression-free survival between the two arms. The median survival times were 59 weeks for placebo and 47 weeks for quinidine patients. The estimated relative death rate (quinidine/placebo) was 1.2 (P = .247; 95% confidence interval [CI], 0.88 to 1.63). CONCLUSION Quinidine at this dose does not significantly alter the toxicity profile, response rate, or survival after epirubicin chemotherapy in patients with advanced breast cancer. This may be due to ineffective modulation of P-glycoprotein by quinidine or the lack of expression of mdr-1 in a sufficient proportion of cells in these tumors, or alternative mechanisms underlying resistance to epirubicin.

scholarly journals Ixabepilone as Monotherapy or in Combination with Capecitabine for the Treatment of Advanced Breast Cancer

2011 ◽  
Vol 5 ◽  
pp. BCBCR.S5331 ◽  
Author(s):  
Katherine H. Rak Tkaczuk
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Response Rate ◽  
Locally Advanced Breast Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Advanced Breast ◽  
Prior Exposure ◽  
Phase Iii ◽  
Overall Response

Breast Cancer is the most prevalent cancer in the world with 4.4 million survivors up to 5 years following the diagnosis. 1 In the US alone approximately forty thousand women die annually of metastatic breast cancer (MBC). Despite many effective systemic treatment options approximately 50% of women with MBC succumb to the disease within 24 months of the diagnosis. 2 Ixabepilone is a novel, first in class member of the epothilone class of antineoplastic agents. Ixabepilone is indicated as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and Capecitabine. Ixabepilone is also indicated in combination with Capecitabine for the treatment of patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated. Ixabepilone was extensively studied as a single agent in patients with MBC and was found to be effective and well tolerated with a predictable and manageable safety profile. Not surprisingly prior exposure to anthracyclines and taxanes affects significantly the potential for response to therapy with single agent Ixabepilone in metastatic setting. MBC patients with taxane resistant MBC have objective response rate (RR) of 12%, patients with prior low exposure to taxanes and/or resistance RR = 22%, Ixabepilone treatment after adjuvant anthracycline therapy exposure renders RR = 42% and in Taxane naïve patients RR = 57%. In two large phase III studies of Ixabepilone + Capecitabine versus Capecitabine alone, progression free survival (PFS) and overall response rates (RR) were higher in the combination treatment arms, but no survival advantage was seen overall. Treatment with Ixabepilone + Capecitabine in a phase II study resulted in an overall response rate (ORR) of 23% in ER/PR/HER2 negative, triple-negative breast cancer patients (TNBC) while ORR of 31% was seen in a preplanned pooled analysis of TNBC in the phase III trials of Ixabepilone + Capecitabine. Significantly prolonged median PFS was seen for TNBC treated with the combination of Ixabepilone + Capecitabine compared to Capecitabine alone 4.2 vs. 1.7 months respectively. Ixabepilone as single agent appears to show excellent antitumor activity in patients with TNBC MBC. Addition of Ixabepilone to Capecitabine results in approximately doubling in median PFS for TNBC versus Capecitabine alone. Single agent Ixabepilone is generally well tolerated, and its toxicity profile does not overlap with that of Capecitabine and therefore depending on prior exposure to chemotherapy both single agent Ixabepilone or in combination with Capecitabine can be used safely and effectively for treatment of advanced breast cancer.

Comparison of Fulvestrant Versus Tamoxifen for the Treatment of Advanced Breast Cancer in Postmenopausal Women Previously Untreated With Endocrine Therapy: A Multinational, Double-Blind, Randomized Trial

2004 ◽  
Vol 22 (9) ◽  
pp. 1605-1613 ◽  
Author(s):  
Anthony Howell ◽  
John F.R. Robertson ◽  
Paul Abram ◽  
Mikhail R. Lichinitser ◽  
Richard Elledge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Randomized Trial ◽  
Postmenopausal Women ◽  
Hormone Receptor ◽  
Hazard Ratio ◽  
Advanced Breast ◽  
Double Blind ◽  
Hormone Receptor Positive ◽  
Significant Difference

Purpose To evaluate the efficacy and tolerability of fulvestrant (Faslodex; AstraZeneca Pharmaceuticals LP, Wilmington, DE), a new estrogen receptor (ER) antagonist that downregulates ER and has no agonist effects, versus tamoxifen, an antiestrogen with agonist and antagonist effects, for the treatment of advanced breast cancer in postmenopausal women. Patients and Methods In this multicenter, double-blind, randomized trial, patients with metastatic/locally advanced breast cancer previously untreated for advanced disease were randomly assigned to receive either fulvestrant (250 mg, via intramuscular injection, once monthly; n = 313) or tamoxifen (20 mg, orally, once daily; n = 274). Patients' tumors were positive for ER (ER+) and/or progesterone receptor (PgR+), or had an unknown receptor status. Results At a median follow-up of 14.5 months, there was no significant difference between fulvestrant and tamoxifen for the primary end point of time to progression (TTP; median TTP, 6.8 months and 8.3 months, respectively; hazard ratio, 1.18; 95% CI, 0.98 to 1.44; P = .088). In a prospectively planned subset analysis of patients with known ER+ and/or PgR+ tumors (∼78%), median TTP was 8.2 months for fulvestrant and 8.3 months for tamoxifen (hazard ratio, 1.10; 95% CI, 0.89 to 1.36; P = .39). The objective response rate for the overall population was 31.6% with fulvestrant and 33.9% with tamoxifen, and 33.2% and 31.1%, respectively, in the known hormone receptor–positive subgroup. Both treatments were well tolerated. Conclusion In the overall population, between-group differences in efficacy end points favored tamoxifen, and statistical noninferiority of fulvestrant could not be demonstrated. However, in patients with hormone receptor–positive tumors, fulvestrant had similar efficacy to tamoxifen and was well tolerated.

scholarly journals A prospective randomized trial of doxorubicinversus idarubicin in the treatment of advanced breast cancer

Cancer ◽  
1989 ◽  
Vol 64 (12) ◽  
pp. 2431-2436 ◽  
Author(s):  
Massimo Lopez ◽  
Alma Contegiacomo ◽  
Patrizia Vici ◽  
Concetta Dello Ioio ◽  
Luigi Di Lauro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Randomized Trial ◽  
Advanced Breast ◽  
Prospective Randomized Trial

Randomized comparison of vinorelbine and melphalan in anthracycline-refractory advanced breast cancer.

1995 ◽  
Vol 13 (10) ◽  
pp. 2567-2574 ◽  
Author(s):  
S Jones ◽  
E Winer ◽  
C Vogel ◽  
L Laufman ◽  
L Hutchins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Failure ◽  
Advanced Breast Cancer ◽  
Randomized Trial ◽  
Disease Progression ◽  
Single Agent ◽  
Objective Response ◽  
Advanced Breast ◽  
Time To Treatment ◽  
Time To Treatment Failure

PURPOSE This prospective multicenter randomized trial was performed to compare the effectiveness and safety of intravenous (i.v.) vinorelbine tartrate (Navelbine [NVB]; Burroughs Wellcome Co, Research Triangle Park, NC) with i.v. melphalan (Alkeran [ALK]; Burroughs Wellcome Co) in a heavily pretreated population of patients with anthracycline-refractory advanced breast cancer (ABC). Efficacy end points included time to disease progression (TDP), time to treatment failure (TTF), survival, tumor response rates, and quality of life (QL) and relief of cancer-related symptoms. PATIENTS AND METHODS Between August 24, 1990, and December 1, 1992, 183 patients were randomized (2:1) to treatment with NVB (30 mg/m2 weekly) or ALK (25 mg/m2 every 4 weeks) i.v. Patients were stratified by measurable or nonmeasurable-assessable disease and by treatment center. RESULTS Time to disease progression was significantly longer with NVB than with ALK, with a median 12 weeks versus 8 weeks, respectively (P < .001). NVB patients also had significantly longer time to treatment failure than ALK patients, with a median 12 weeks versus 8 weeks, respectively (P < .001). The effect of NVB on survival was also statistically significant (P = .034): 1-year survival rates were 35.7% with NVB and 21.7% with ALK and the median survival rate was 35 weeks and 31 weeks, respectively. In total, 46.5% of NVB patients and 28.2% of ALK patients achieved an objective response or stabilization of disease (P = .06). No intergroup differences were noted in patient-assessed QL and cancer-related symptoms. The most common toxicities were hematologic, including granulocytopenia with NVB and thrombocytopenia and granulocytopenia with ALK. Both drugs were generally well tolerated, and no septic deaths were reported. CONCLUSION This randomized trial demonstrates a survival benefit in anthracycline-refractory ABC. NVB was well tolerated and demonstrated activity superior to ALK in anthracycline-refractory ABC, without compromising QL. Based on activity of single-agent NVB in this difficult-to-treat patient population, investigations of NVB in combination with other anticancer drugs are warranted.

Sign in / Sign up

Export Citation Format

Share Document