Bortezomib and capecitabine in patients with metastatic breast cancer previously treated with taxanes and/or anthracyclines: Final results of a phase I/II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1072-1072 ◽  
Author(s):  
P. Schmid ◽  
A. Regierer ◽  
P. Kiewe ◽  
W. Schippinger ◽  
R. Greil ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Antitumour Activity ◽  
Metastatic Breast ◽  
26S Proteasome ◽  
Breast Cancer Patients ◽  
Hand Foot Syndrome ◽  
Heavily Pretreated ◽  
Grade 3

1072 Background: Capecitabine has shown substantial activity in taxane and/or anthracycline pretreated breast cancer patients. Bortezomib, a 26S proteasome inhibitor, has been shown to increase sensitivity to chemotherapy. This phase I/II trial was initiated to evaluate the combination of capecitabine and bortezomib in heavily pretreated patients with metastatic breast cancer. Methods: Patients with metastatic breast cancer and prior taxane and/or anthracycline therapy were treated with bortezomib (1.0–1.3 mg/m2; days 1, 4, 8 & 11) and capecitabine (1,500–2,500 mg/m2, days 1–14) in 3-weeks intervals for up to 8 cycles. Primary endpoints were to determine the optimal doses for the combination (phase I) and the tumor response rate (RR) (phase II). Secondary endpoints included safety, time to progression (TTP), duration of response (DR), and overall survival (OS). Results: A total of 35 patients were enrolled and 29 patients were assessable for response. The majority of patients had received 2 or 3 lines of chemotherapy (69% and 14%, respectively) prior to the study. The maximum tolerated doses (MTD) were bortezomib 1.3 mg/m2 and capecitabine 2500 mg/m2. Dose limiting toxicities were Grade 3 stomatitis in 1 out of 6 patients at 1.0/2,000 and Grade 3 diarrhea in 1 out of 6 patients at 1.3/2,500. Myelosuppression was low. Non-hematological toxicities were generally mild to moderate with no G4 toxicity being observed. Most common side effects were thrombocytopenia (Grade 3/4 27% of patients), diarrhea (18%), hand-foot syndrome (12%), peripheral neuropathy (12%), leucopenia (9%) and asthenia (9%). The overall RR was 17.2% and an additional 31% of patients had stable disease (31%; 4 unconfirmed). In the 21 patients treated at the MTD, RR was 17.6% and 47% of patients had SD. Median TTP and OS were 3.5 months (95% CI 1.9–4.4) and 7.5 months (95% CI 5.6–14.6), respectively. Median DR was 4.4 months. Conclusions: The combination of bortezomib and capecitabine is well tolerated and has moderate antitumour activity in heavily pretreated breast cancer. [Table: see text]

Study of lapatinib (T) in combination with trastuzumab (T) in women heavily pretreated with HER2-positive metastatic breast cancer (MBC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11577-e11577 ◽  
Author(s):  
Javier Salvador ◽  
Manuel Ruiz Borrego ◽  
Maria Valero ◽  
Juan L. Bayo ◽  
Luis De La Cruz-Merino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Benefit ◽  
Kinase Inhibitor ◽  
Antitumour Activity ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Heavily Pretreated ◽  
Grade 3

e11577 Background: The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer.In heavily pre-treated pts, L+T is associated with improved outcomes compared to L alone and significantly improved progression-free survival (PFS), offering a chemotherapy-free option for patients with heavily pretreated human epidermal growth factor. (Kimberly L et al, 2012 JCO). Methods: We evaluated the safety and efficacy of L+T in patients with 1-4 prior (Median 3) lines of chemotherapy (CT) for HER2+ MBC.: 20 Pts with measurable, HER2+ MBC were eligible. Pts received every 3 weeks T (8 mg/kg loading then 6 mg/Kg) and daily L 1000 mg. Results: The characteristic of the all of pts included (20) are: median age 51.4 (32-68) Total number of cycles administered was 141. The median cycles administered per pts was 6 (range 1-18). Median follow-up was 6 months. Of the 18 pts with response assessment, the clinical benefit obtained was: 76,1% (5,9% PR + and 70,6% disease stabilization) with 95% CI 71.3%-80.9%. Disease progression was 17,6%. Of the 20 pts with a median follow up of 13,32 m (3-32), median PFS for these pts was 6 m. The one year OS % was 64,70% (56,7-72,7). All pts had received al least one line lapatinib prior (1-3). Toxicity was generally manageable. No major cardiac dysfunctions ocurred. Grade 3/4 treatment-related toxicities were uncommon (grade 3 diarrhea, 18%; grade 3 hepatic 7%. All others < 3 %). Conclusions: L+T is an active regimen in HER2+ MBC. L+T showed high clinical benefit with manageable safety profile. Dual inhibition of HER2 might be a valid approach to treatment of Her-2 positive metastatic breast cancer.

scholarly journals Phase I Study of Panobinostat (LBH589) and Letrozole in Postmenopausal Metastatic Breast Cancer Patients

2016 ◽  
Vol 16 (2) ◽  
pp. 82-86 ◽  
Author(s):  
Winston W. Tan ◽  
Jacob B. Allred ◽  
Alvaro Moreno-Aspitia ◽  
Donald W. Northfelt ◽  
James N. Ingle ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Cancer Patients ◽  
Phase I Study ◽  
Metastatic Breast ◽  
Breast Cancer Patients

Phase II Study of Temsirolimus (CCI-779), a Novel Inhibitor of mTOR, in Heavily Pretreated Patients With Locally Advanced or Metastatic Breast Cancer

2005 ◽  
Vol 23 (23) ◽  
pp. 5314-5322 ◽  
Author(s):  
Stephen Chan ◽  
Max E. Scheulen ◽  
Stephen Johnston ◽  
Klaus Mross ◽  
Fatima Cardoso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Dose Level ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3 ◽  
Time To Tumor Progression

Purpose In this study, two doses of temsirolimus (CCI-779), a novel inhibitor of the mammalian target of rapamycin, were evaluated for efficacy, safety, and pharmacokinetics in patients with locally advanced or metastatic breast cancer who had been heavily pretreated. Patients and Methods Patients (n = 109) were randomly assigned to receive 75 or 250 mg of temsirolimus weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, adverse events, and pharmacokinetics of temsirolimus. Results Temsirolimus produced an objective response rate of 9.2% (10 partial responses) in the intent-to-treat population. Median time to tumor progression was 12.0 weeks. Efficacy was similar for both dose levels but toxicity was more common with the higher dose level, especially grade 3 or 4 depression (10% of patients at the 250-mg dose level, 0% at the 75-mg dose level). The most common temsirolimus-related adverse events of all grades were mucositis (70%), maculopapular rash (51%), and nausea (43%). The most common, clinically important grade 3 or 4 adverse events were mucositis (9%), leukopenia (7%), hyperglycemia (7%), somnolence (6%), thrombocytopenia (5%), and depression (5%). Conclusion In heavily pretreated patients with locally advanced or metastatic breast cancer, 75 and 250 mg temsirolimus showed antitumor activity and 75 mg temsirolimus showed a generally tolerable safety profile.

Docetaxel: Standard Recommended Dose of 100 mg/m2 Is Effective But Not Feasible for Some Metastatic Breast Cancer Patients Heavily Pretreated With Chemotherapy—A Phase II Single-Center Study

1999 ◽  
Vol 17 (4) ◽  
pp. 1127-1127 ◽  
Author(s):  
E. Salminen ◽  
M. Bergman ◽  
S. Huhtala ◽  
E. Ekholm
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Dose Reduction ◽  
Cancer Patients ◽  
Dose Level ◽  
Metastatic Breast ◽  
Recommended Dose ◽  
Line Treatment ◽  
Breast Cancer Patients ◽  
Heavily Pretreated

PURPOSE: Patients with metastatic breast cancer, especially those with progression after several prior chemotherapy treatments, need efficient chemotherapy. This study investigates the efficacy and toxicity of docetaxel in metastatic breast cancer patients with previous chemotherapy for metastatic disease. PATIENTS AND METHODS: Thirty-one women (median age, 52 years; range, 40 to 65 years) treated for metastatic breast cancer with docetaxel were included. Eleven patients had one metastatic site, 10 patients had two, and 10 patients had three or more. The planned dose of docetaxel per course was the standard treatment of 100 mg/m2 (or 75 mg/m2 if liver enzyme levels were abnormal) every 3 weeks, given for six or eight cycles. RESULTS: The overall response rate was 48% (three complete responses [CR] and 11 partial responses [PR] ), and the median duration of response was 7 months (range, 2 to 16 months). Twenty patients (65%) experienced fatigue, and 27 patients (87%) had alopecia. Fifteen cases (48%) of grade 4 leukopenia were observed. Edema with a weight gain of 2 to 15 kg was seen in 12 patients (39%), and mucositis occurred in 20 patients (65%). Twenty-three patients (74%) interrupted treatment before reaching the planned number of courses, nine patients owing to progression of cancer and 14 owing to toxicity. Dose reduction was required in 18 (61%) of the patients. Only two patients were able to receive the planned eight courses without dose reduction. CONCLUSION: Docetaxel is highly active in metastatic breast cancer, even as a third-line treatment, and can be considered as an efficient standard option in second-line treatment. The standard recommended dose level of 100 mg/m2 is not feasible in heavily pretreated patients; therefore, for such patients, an initial dose level not exceeding 75 mg/m2 is recommended.

scholarly journals Phase I Study of Combination Therapy With Weekly Nanoparticle Albumin-bound Paclitaxel and Cyclophosphamide in Metastatic Breast Cancer Patients

2019 ◽  
Vol 39 (12) ◽  
pp. 6903-6907 ◽  
Author(s):  
DAISUKE OTA ◽  
SOTARO AKATSUKA ◽  
TSUNEHIRO NISHI ◽  
TAKAO KATO ◽  
MASASHI TAKEUCHI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Combination Therapy ◽  
Phase I ◽  
Cancer Patients ◽  
Phase I Study ◽  
Metastatic Breast ◽  
Breast Cancer Patients

Efficacy and Safety of Capecitabine Alone or in Combination in Advanced Metastatic Breast Cancer Patients Previously Treated with Anthracycline and Taxane: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 43 (12) ◽  
pp. 694-702
Author(s):  
Louai Alsaloumi ◽  
Shaima Shawagfeh ◽  
Abdikarim Abdi ◽  
Bilgen Basgut
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Efficacy And Safety ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
Hand Foot Syndrome

<b><i>Background:</i></b> Capecitabine is frequently used alone or combined with other chemotherapy agents for the treatment of metastatic breast cancer in relapsed patients. <b><i>Objective:</i></b> The objective of this meta-analysis is to evaluate the effectiveness and safety of capecitabine monotherapy versus combination in the treatment of metastatic breast cancer patients pretreated with anthracycline and taxane. <b><i>Methods:</i></b> Eligible randomized controlled trials examining the efficacy and safety of capecitabine alone compared to capecitabine combination were systematically searched. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grades 3–4 drug-related adverse events were the outcomes assessed. <b><i>Results:</i></b> A total of 6,714 patients of 9 trials were involved in the pooled analysis. Our findings demonstrated that capecitabine combination is significantly superior to capecitabine monotherapy in improving PFS (hazard ratio [HR] 1.32, 95% CI 1.13–1.54, <i>p</i> &#x3c; 0.0001) and ORR (risk ratio [RR] 0.67, 95% CI 0.54–0.83, <i>p</i> &#x3c; 0.001), but it was insignificant in OS (HR 1.09, 95% CI 0.98–1.22, <i>p</i> = 0.12). On the other hand, the incidence of non-hematological adverse events such as hand-foot syndrome and diarrhea was lower in capecitabine combination compared to capecitabine monotherapy. <b><i>Conclusion:</i></b> Capecitabine-based combination chemotherapy showed superiority over capecitabine monotherapy in terms of PFS and ORR, with no significant difference in OS. Non-hematological adverse effects such as hand-foot syndrome were fewer with a combination regimen. However, hematological adverse events were fewer with capecitabine monotherapy regimen.

A phase II study of mitoxantrone, etoposide, and thiotepa with autologous marrow support for patients with relapsed breast cancer.

1990 ◽  
Vol 8 (11) ◽  
pp. 1782-1788 ◽  
Author(s):  
R Wallerstein ◽  
G Spitzer ◽  
F Dunphy ◽  
S Huan ◽  
G Hortobagyi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Poor Response ◽  
High Dose ◽  
Significant Activity ◽  
Heavily Pretreated ◽  
Grade 3

To further improve the effect of high-dose chemotherapy in the treatment of locally advanced and metastatic breast cancer, we sought to develop a second active high-dose noncross-resistant regimen to use in tandem with our customary high-dose regimen of cyclophosphamide, etoposide, and cisplatin (CVP). We performed a phase II trial of high-dose mitoxantrone 30 mg/m2, etoposide 200 mg/m2 every 12 hours x 6, and thiotepa 250 mg/m2 x 3 days (MVT) in 31 patients with heavily pretreated metastatic breast cancer and one with locally advanced chemotherapy-refractory breast cancer. These patients were ineligible for high-dose CVP chemotherapy because of the amount of prior treatment and poor-response status. Of the 32 patients, 14 responded to cycle 1, did not experience any grade 4 toxicity, and received a second cycle of MVT. Overall, seven of 31 patients achieved a complete response (CR; 23%). Four of the 14, who were partial responders to the first cycle, achieved a CR after the second cycle. The overall response rate was 19 of 31 (61%) with an overall median freedom from progression of 4 to 5 months and an overall median survival of 9 months. Toxicity consisted primarily of mucositis (grade 3 or 4 in 69%). The results indicate that high-dose MVT produces significant activity, even in heavily pretreated patients. Administration of a second cycle of high-dose therapy with MVT increased the CR rate, and the morbidity and mortality from the second cycle were not greater than that for the first cycle. Because of the high incidence of grade 3 or 4 mucositis with this regimen, we are currently completing a follow-up study of high-dose mitoxantrone and thiotepa alone.

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