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.

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.

Gemcitabine and cisplatin in metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1084-1084 ◽  
Author(s):  
G. L. Moura ◽  
R. Pasquini ◽  
A. Frare ◽  
K. Vianna ◽  
L. Albini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Metastatic Breast ◽  
Synergistic Activity ◽  
Adjuvant Setting ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3 ◽  
Gemcitabine And Cisplatin

1084 Background: Gemcitabine plus cisplatin have synergistic activity and have been tested in several schedules and doses in metastatic breast cancer. Our objectives were to assesss the efficacy and toxicity of gemcitabine and cisplatin in pretreated patients. Methods: Measurable disease and at least two prior anthracycline and /or taxane-containing regimen in either metastatic or adjuvant setting was required. Treatment consisted of gemcitabine 700mg/m(2) IV infusion over 30 min plus cisplatin 30mg(2) given on day1 and 8 every 3 weeks. Results: Seventy four patients with median age of 48 years (range 26- 73) were recruited. A median of six cycles of the study treatment was delivered. The overal response rate was 30% (95% confidence interval, 12–53%). Median time to progreesion was 30.6 weeks (95%CI, 12.6–44 weeks). Median survival was 73.2 weeks (95% CI, 47.1–93.2 weeks). Toxicities included grade 3 and 4 leukopenia in 27(36.4%), anemia in 19 (25.6%) and oral mucositis in 4 (5.4%). No grade 3 or 4 peripheral neurophaty, hepatic or renal dysfunction was observed. No treatment-related death ocurred. Conclusions: Gemcitabine plus cisplatin is a well tollerated and active treatment in heavily pretreated patients with metastatic breast cancer. No significant financial relationships to disclose.

Real-world effectiveness of eribulin in heavily pretreated patients with metastatic breast cancer in China: A multicenter retrospective study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13057-e13057
Author(s):  
Yannan Zhao ◽  
Ning Xie ◽  
Wei Li ◽  
Wenyan Chen ◽  
Zheng Lv ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real World ◽  
Objective Response ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Combination Regimen ◽  
Real World Data ◽  
Heavily Pretreated ◽  
Pretreated Patients

e13057 Background: Eribulin is a nontaxane microtubule inhibitor approved in China for patients with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxane. The aim of this study was to evaluate the efficacy and safety profile of eribulin and explore potential predictive factors for the efficacy of eribulin among Chinese women with metastatic breast cancer (MBC) in real-world practice. Methods: A total of 272 consecutive MBC patients who were treated with eribulin from November 2019 to October 2020 in 9 institutions nationwide were included in this study. Eribulin was administered intravenously at a dose of 1.4 mg/m2 on days 1 and 8 of a 21-day cycle. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Adverse events (AEs) were graded according to The National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0. Results: Eribulin showed a median PFS of 3.9 months (95% confidence interval [CI] 3.3–4.3); however, the OS data were immature. The ORR was 16.2%, and the CBR was 21.7%. A total of 51.8% of patients received eribulin monotherapy, and 48.2% of patients were treated with eribulin combine with targeted therapy or other chemotherapy. The number of metastatic sites, duration of previous taxane treatment for MBC, and combination regimen with bevacizumab were significant in Cox multivariate analysis (p=0.048, p=0.039, and p=0.045, respectively) and were significantly associated with PFS of eribulin. The most common AEs with eribulin treatment were hematological toxicities, including neutropenia, leukopenia, and anemia. Conclusions: This is the first cohort of eribulin real-world data base on retrieval currently after eribulin launched in China. Eribulin was effective with a manageable toxicity profile in clinical practice. Furthermore, when prescribed in combination with other agents, eribulin did not increase the toxic effects of each agents. Eribulin monotherapy or combine with other agents is alternative for the heavily pretreated patients with MBC. [Table: see text]

Paclitaxel activity in heavily pretreated breast cancer: a National Cancer Institute Treatment Referral Center trial.

1995 ◽  
Vol 13 (8) ◽  
pp. 2056-2065 ◽  
Author(s):  
J S Abrams ◽  
D A Vena ◽  
J Baltz ◽  
J Adams ◽  
M Montello ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Progressive Disease ◽  
Overall Response Rate ◽  
Metastatic Breast ◽  
Investigational Drug ◽  
Single Institution ◽  
Doxorubicin Treatment ◽  
Heavily Pretreated ◽  
Pretreated Patients

PURPOSE To provide paclitaxel, an investigational drug at the inception of this study, to women with chemotherapy-refractory metastatic breast cancer and to evaluate response and toxicity in these patients. PATIENTS AND METHODS Two hundred sixty-seven patients with progressive disease (PD) following at least two chemotherapy regimens for metastatic breast cancer and a contraindication to further doxorubicin treatment received paclitaxel either at 175 mg/m2 intravenously (IV) over 24 hours or at 135 mg/m2 if they had prior irradiation to 30% of marrow-bearing bone or a cumulative dose of mitomycin > or = 20 mg/m2. RESULTS In a subgroup of patients (n = 172) with measurable disease, four complete responses (CRs) and 36 partial responses (PRs) occurred, for an overall response rate of 23% (95% confidence interval [CI], 17% to 30%). No differences in response rates were noted according either to the number of prior chemotherapy regimens received or to whether patients were considered refractory to doxorubicin. The dose and schedule used in this trial resulted in febrile neutropenia in 45% of patients and a hospitalization rate of 49%. CONCLUSION Paclitaxel's activity in this multiinstitutional trial in heavily pretreated patients confirms the encouraging results attained in single-institution trials. Although at this dose and schedule paclitaxel may be considered too myelosuppressive for palliative care, supportive measures such as colony-stimulating factors and antibiotics were not used prophylactically. Current research efforts are focusing on whether paclitaxel's activity against breast cancer is dose- and/or schedule-dependent, and on what role it has in patients with less advanced disease.

Randomized Phase II Trial of First-Line Trastuzumab Plus Docetaxel and Capecitabine Compared With Trastuzumab Plus Docetaxel inHER2-Positive Metastatic Breast Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 976-983 ◽  
Author(s):  
Andrew M. Wardley ◽  
Xavier Pivot ◽  
Flavia Morales-Vasquez ◽  
Luis M. Zetina ◽  
Maria de Fátima Dias Gaui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Her2 Positive ◽  
Grade 3

PurposeTo evaluate trastuzumab (H) and docetaxel (T) with or without capecitabine (X) as first-line combination therapy for human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.Patients and MethodsPatients with HER2-positive locally advanced or metastatic breast cancer were randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75 mg/m2in HTX arm, 100 mg/m2in HT arm, every 3 weeks) with or without X (950 mg/m2twice per day on days 1 to 14 every 3 weeks). The primary end point was overall response rate (ORR).ResultsIn 222 patients, median follow-up was approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7% with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4% with HT. HTX demonstrated significantly longer progression-free survival: median 17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045), which translates to a gain of around 5 months. Two-year survival probability was 75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade 3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment-related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%) occurred more commonly with HTX than HT. One case of congestive heart failure occurred in each arm.ConclusionHTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids.

Intermittent Capecitabine Monotherapy with Lower Dose Intensity in Heavily Pretreated Patients with Metastatic Breast Cancer

2007 ◽  
Vol 93 (2) ◽  
pp. 129-132 ◽  
Author(s):  
Tomo Osako ◽  
Yoshinori Ito ◽  
Shunji Takahashi ◽  
Nahomi Tokudome ◽  
Takuji Iwase ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Dose Intensity ◽  
Heavily Pretreated ◽  
Pretreated Patients

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.

Vinorelbine as a 96-Hour Continuous Infusion in Heavily Pretreated Patients with Metastatic Breast Cancer: A Cooperative Study by the GEICAM Group

2003 ◽  
Vol 3 (6) ◽  
pp. 399-404 ◽  
Author(s):  
Carlos Jara-Sánchez ◽  
Miguel Martín ◽  
Jose A. García-Sáenz ◽  
Agustí Barnadas ◽  
Antonio Fernández-Aramburo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Continuous Infusion ◽  
Metastatic Breast ◽  
Cooperative Study ◽  
Heavily Pretreated ◽  
Pretreated Patients
Sign in / Sign up

Export Citation Format

Share Document