CYCLIN-EPENDENT KINASES 4/6 INHIBITORS IN COMBINATION WITH AROMATASE INHIBITORS IN TREATMENT OF METASTATIC BREAST CANCER (clinical observation)

2020 ◽  
pp. 39-41
Author(s):  
M. V. Sadchikova ◽  
L. V. Syniavina ◽  
N. M. Otchenash

It is known that a complete recovery in patients with generalized tumor is impossible, but the use of effective treatment regimens can significantly inhibit the development of the disease. The main goal of treatment of metastatic breast cancer is to increase overall survival, time to disease progression, improvethe quality of life, to prevent serious complications. In recent years, the standard of first−line hormone therapy in postmenopausal patients has been the use of aromatase inhibitors. Recently, a new class of drugs has emerged that can increase the effectiveness of hormone therapy, which significantly strengthens the position of this method in metastatic breast cancer. A clinical trial of PALOMA−2 and its findings are presented: the palbociclib + letrozole protocol as first−line therapy in postmenopausal patients with estrogen−positive Her2 new negative advanced breast cancer improves the objective response rate and clinical efficacy compared to letrozole monotherapy. The overall incidence of adverse responses was higher in patients treated with palbociclib + letrozole compared with placebo + letrozole. This clinical case demonstrates the possibility of long−term effective disease control in metastatic breast cancer. Literature data and personal experience show high efficacy of the combined protocol of hormone therapy and inhibitors of cyclin−dependent kinases 4/6. The use of such protocols is advisable in patients with multiple bone metastases, while achieving an effective reduction of pain. The use of such regimens is possible in patients with a low ECOG score who cannot tolerate chemotherapy with more severe toxicity. Key words: metastatic breast cancer, aromatase inhibitors, palbociclib.

1994 ◽  
Vol 12 (2) ◽  
pp. 336-341 ◽  
Author(s):  
A Romero ◽  
M G Rabinovich ◽  
C T Vallejo ◽  
J E Perez ◽  
R Rodriguez ◽  
...  

PURPOSE A phase II trial was performed to evaluate the efficacy and toxicity of vinorelbine (VNB) as first-line chemotherapy for metastatic breast carcinoma. PATIENTS AND METHODS Between August 1991 and February 1993, 45 patients with metastatic breast cancer were entered onto the study. Therapy consisted of VNB 30 mg/m2 diluted in 500 mL of normal saline administered as a 1-hour intravenous infusion. Injections were repeated weekly until evidence of progressive disease (PD) or severe toxicity developed. RESULTS One patient was considered not assessable for response. An objective response (OR) was observed in 18 of 44 patients (41%; 95% confidence interval, 26% to 56%). Three patients (7%) had a complete response (CR) and 15 (34%) had a partial response (PR). The median time to treatment failure for the entire group was 6 months (range, 1 to 15), and the median duration of response was 9 months (range, 1 to 15). The median survival duration has not been reached yet. There were no treatment-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (78%) and was grade 3 or 4 in 16 (36%). Phlebitis was observed in 19 of 29 patients (66%) who did not have central implantable venous systems. Fifteen patients (33%) developed peripheral neurotoxicity. Myalgia occurred in 20 patients (44%). CONCLUSION VNB is an active drug against metastatic breast cancer with moderate toxicity, which justifies further evaluation in association with other agents.


2007 ◽  
Vol 25 (23) ◽  
pp. 3415-3420 ◽  
Author(s):  
Henri Roché ◽  
Louise Yelle ◽  
Francesco Cognetti ◽  
Louis Mauriac ◽  
Craig Bunnell ◽  
...  

PurposeThere is a need for new agents to treat metastatic breast cancer (MBC) in patients for whom anthracycline therapy has failed or is contraindicated. This study was conducted to assess the efficacy and safety of the novel antineoplastic, the epothilone B analog ixabepilone, in patients with MBC previously treated with an adjuvant anthracycline.Patients and MethodsPatients were age ≥ 18 years and had received a prior anthracycline-based regimen as adjuvant treatment. Ixabepilone as first-line metastatic chemotherapy was administered as a 40 mg/m2intravenous infusion during 3 hours every 3 weeks. The primary efficacy end point was objective response rate (ORR). Secondary efficacy end points included duration of response, time to response, time to progression, and survival.ResultsAll 65 patients were assessable for response. Their median age was 52 years (range, 33 to 80 years). ORR was 41.5% (95% CI, 29.4% to 54.4%), median duration of response was 8.2 months (95% CI, 5.7 to 10.2 months), and median time to response was 6 weeks (range, 5 to 17 weeks). Median survival was 22.0 months (95% CI, 15.6 to 27.0 months). Treatment-related adverse events were manageable and mostly grades 1/2: the most common of these (other than alopecia) was mild to moderate neuropathy, which was primarily sensory and mostly reversible in nature.ConclusionIxabepilone is efficacious and has a predictable and manageable safety profile in women with MBC previously treated with an adjuvant anthracycline.


2002 ◽  
Vol 7 (5) ◽  
pp. 410-417 ◽  
Author(s):  
Mohammad Jahanzeb ◽  
Joanne E. Mortimer ◽  
Furhan Yunus ◽  
David H. Irwin ◽  
James Speyer ◽  
...  

1993 ◽  
Vol 11 (3) ◽  
pp. 461-466 ◽  
Author(s):  
J E Perez ◽  
M Machiavelli ◽  
B A Leone ◽  
A Romero ◽  
M G Rabinovich ◽  
...  

PURPOSE A phase II trial was performed to evaluate the efficacy and toxicity of a combination of ifosfamide (IFX) and mitoxantrone (MXN) as first-line chemotherapy for metastatic breast carcinoma. PATIENTS AND METHODS Between January 1990 and August 1991, 48 patients with metastatic breast cancer were entered onto the study. Therapy consisted of IFX 2 g/m2 given as a 1-hour intravenous (IV) infusion on days 1 to 3; mesna 400 mg/m2 as an IV bolus immediately before and 4 hours after IFX administration and 2,000 mg orally 8 hours after IFX administration on days 1 to 3; and MXN 12 mg/m2 as an i.v. bolus on day 3. Cycles were repeated every 21 days until progressive disease (PD) or severe toxicity developed. RESULTS One patient was considered not assessable for response. Objective regression (OR) was observed in 28 of 47 patients (60%; 95% confidence interval, 46% to 74%). Six patients (13%) had a complete response (CR) and 22 (47%) had a partial response (PR). The median time to treatment failure for the whole group was 9 months (range, 1 to 28); median survival was 19 months (range, 2 to 28). There were no treatment-related deaths. The limiting toxicity was myelosuppression. Leukopenia occurred in 37 patients (77%) and was grade 3 or 4 in 19 patients (40%). Nausea and vomiting were observed in 38 patients (80%), mucositis in 16 patients (33%), and grade 2 hematuria in two patients (4%). Eight patients (16%) developed mild neurotoxicity. CONCLUSION The combination of IFX plus MXN is an active regimen against metastatic breast cancer with moderate toxicity that deserves further evaluation.


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