Combination chemotherapy with gencitabine and cisplatin in anthracycline and taxane pretreated metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1108-1108 ◽  
Author(s):  
F. M. Peria ◽  
F. E. Zola ◽  
D. G. Tiezzi ◽  
H. H. Carrara ◽  
P. M. Philbert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Combination Chemotherapy ◽  
Performance Status ◽  
Single Agent ◽  
Metastatic Breast ◽  
Hematological Toxicity ◽  
Eligibility Criteria ◽  
Metastatic Sites ◽  
The Right

1108 Background: Metastatic breast cancer (MBC) anthracycline (A) and taxane (T) resistant has a complicated management.Combination chemotherapy, even in 2nd line, may have advantages over single agent therapy. Gencitabine (G) - cisplatin (C) combinations have been used as synergistic salvage therapy in MBC and it’s another option for patients with important symptoms and aggressive visceral disseminated disease. Methods: This trial analyses the safety and efficacy of G-C in A-T pretreated MBC. Eligibility criteria include: confirmatory pathological analyses; measurable disease; adequate performance status, organ and hematological functions. It was not allowed patients with exclusive bone metastasis. They received IV G 750mg/m2 and C 30mg/m2, both d1 and d8 every three weeks for 6 cycles up to a maximum of 9 cycles. Response evaluation was performed every third cycle and in the end of treatment. Results: From February 2005 through December 2006, 31 patients have been evaluated for response and toxicity from G-C combination. For 20/31 patients this treatment was 2nd line palliative chemotherapy. 26/31 received at least 3 or more cycles (medium 4 cycles) and no one treatment was discontinued due to toxicity. The most frequent site of metastasis was lung (20/31), followed by hepatic in 13 patients, bone in 11, skin in 10, lymph nodes in 7, brain metastasis in 3 and pericardium in only one. Each patient had at least lung or hepatic metastasis and medium of 2 different metastatic sites. According to RECIST criteria, partial response were observed in 8/31, stable disease in 17/31 (55%) and progressive disease in 6 patients. 90% of cycles were given at full dose and at the right time. Hematological toxicity was modest with grade 2–3 (NCI-CTC) leucopenia in 58/140 cycles, grade 1–2 anemia in 40/140, grade 1–2 thrombocytopenia in 27/140 and was none febrile neutropenia. Non hematological toxicity: grade 2 fatigue in 4 patients and grade 2 nausea in 6/31. Following 22 months, global survival was at mean 4.8 months. Conclusions: Combination chemotherapy with gencitabine 750mg/m2 and cisplatin 30mg/m2 both d1 and d8 is feasible and effective in A-T pretreated MBC and demonstrated good tolerance with low intensity of collateral effects. No significant financial relationships to disclose.

Phase III Trial of Sunitinib in Combination With Capecitabine Versus Capecitabine Monotherapy for the Treatment of Patients With Pretreated Metastatic Breast Cancer

2013 ◽  
Vol 31 (23) ◽  
pp. 2870-2878 ◽  
Author(s):  
John P. Crown ◽  
Véronique Diéras ◽  
Elzbieta Staroslawska ◽  
Denise A. Yardley ◽  
Thomas Bachelot ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Performance Status ◽  
Single Agent ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Phase Iii Trial ◽  
Free Survival

Purpose Metastatic breast cancer (MBC) remains an incurable illness in the majority of cases, despite major therapeutic advances. This may be related to the ability of breast tumors to induce neoangiogenesis, even in the face of cytotoxic chemotherapy. Sunitinib, an inhibitor of key molecules involved in neoangiogenesis, has an established role in the treatment of metastatic renal cell and other cancers and demonstrated activity in a phase II trial in MBC. We performed a randomized phase III trial comparing sunitinib plus capecitabine (2,000 mg/m2) with single-agent capecitabine (2,500 mg/m2) in patients with heavily pretreated MBC. Patients and Methods Eligibility criteria included MBC, prior therapy with anthracyclines and taxanes, one or two prior chemotherapy regimens for metastatic disease or early relapse after a taxane plus anthracycline adjuvant regimen, and adequate organ function and performance status. The primary end point was progression-free survival, for which the study had 90% power to detect a 50% improvement (from 4 to 6 months). Results A total of 442 patients were randomly assigned. Progression-free survival was not significantly different between the treatment arms, with medians of 5.5 months (95% CI, 4.5 to 6.0) for the sunitinib plus capecitabine arm and 5.9 months (95% CI, 5.4 to 7.6) for the capecitabine monotherapy arm (hazard ratio, 1.22; 95% CI, 0.95 to 1.58; one-sided P = .941). There were no significant differences in response rate or overall survival. Toxicity, except for hand-foot syndrome, was more severe in the combination arm. Conclusion The addition of sunitinib to capecitabine does not improve the clinical outcome of patients with MBC pretreated with anthracyclines and taxanes.

Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer.

1996 ◽  
Vol 14 (8) ◽  
pp. 2197-2205 ◽  
Author(s):  
P A Greenberg ◽  
G N Hortobagyi ◽  
T L Smith ◽  
L D Ziegler ◽  
D K Frye ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Complete Remission ◽  
Combination Chemotherapy ◽  
Alkylating Agent ◽  
Performance Status ◽  
Metastatic Breast ◽  
Second Primary ◽  
Treatment Protocols

PURPOSE To determine the long-term clinical course of patients with metastatic breast cancer (MBC) who achieved a complete remission with doxorubicin-alkylating agent-containing combination chemotherapy programs. PATIENTS AND METHODS To assess the long-term prognosis of MBC, we reviewed our experience with 1,581 patients treated on consecutive doxorubicin and alkylating agent-containing front-line treatment protocols between 1973 and 1982. Treatment was administered for a maximum duration of 2 years. Characteristics of long-term survivors were evaluated, and hazard rates for progression were calculated. RESULTS From this group, 263 (16.6%) achieved complete responses (CR) and 49 (3.1%) remained in CR for more than 5 years. After a median duration of 191 months, 26 patients remain in first CR, four patients died in CR at times ranging from 118 to 234 months, 18 patients died of breast cancer, and one is alive with metastatic disease. Compared with the overall CR and total patient populations, the long-term CR group had more premenopausal patients, a younger median age, a lower tumor burden, and better performance status. The hazard function shows a substantial drop in risk of progression after approximately 3 years from initiation of therapy. Ten long-term CR patients developed second primary cancers: breast (3), ovary (2), pancreas (1), endometrium (1), colon (1), head and neck (1), and lung (1). CONCLUSION Most patients with MBC treated with systemic therapies have only temporary responses to treatment, but some patients continue in CR following initial treatment. These data show that a small percentage of patients achieve long-term remissions with standard chemotherapy regimens. Remission consolidation strategies are needed.

Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer: a prospective randomized trial.

1998 ◽  
Vol 16 (12) ◽  
pp. 3720-3730 ◽  
Author(s):  
H Joensuu ◽  
K Holli ◽  
M Heikkinen ◽  
E Suonio ◽  
A R Aro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Combination Chemotherapy ◽  
Performance Status ◽  
Single Agent ◽  
Objective Response ◽  
Metastatic Breast ◽  
Distant Metastases ◽  
World Health ◽  
Second Line ◽  
Significant Difference

PURPOSE We report results of a randomized prospective study that compared single agents of low toxicity given both as the first-line and second-line chemotherapy with combination chemotherapy in advanced breast cancer with distant metastases. PATIENTS AND METHODS Patients in the single-agent arm (n = 153) received weekly epirubicin (E) 20 mg/m2 until progression or until the cumulative dose of 1,000 mg/m2, followed by mitomycin (M) 8 mg/m2 every 4 weeks, and those in the combination chemotherapy arm (n = 150) were first given cyclophosphamide 500 mg/m2, E 60 mg/m2, and fluorouracil 500 mg/m2 three times per week (CEF) followed by M 8 mg/m2 plus vinblastine (V) 6 mg/m2 every 4 weeks. Exclusion criteria included age greater than 70 years, World Health Organization (WHO) performance status greater than 2, prior chemotherapy for metastatic disease, and presence of liver metastases in patients younger than 50. RESULTS An objective response (complete [CR] or partial [PR]) was obtained in 55%, 48%, 16%, and 7% of patients treated with CEF, E, M, and MV, respectively. A response to CEF tended to last longer than a response to E (median, 12 v 10.5 months; P = .07). Treatment-related toxicity was less in the single-agent arm and quality-of-life (QOL) analysis favored the single-agent arm. No significant difference in time to progression or survival was found between the two arms. Similarly, no difference in survival was found when the patients who received both the planned first-and second-line treatments were compared or when survival was calculated from the beginning of the second-line therapy. CONCLUSION Patients treated with single-agent E followed by single-agent M had similar survival, but less treatment-related toxicity and better QOL as compared with those treated with CEF followed by MV.

Safety and Efficacy of Using a Single Agent or a Phase II Agent Before Instituting Standard Combination Chemotherapy in Previously Untreated Metastatic Breast Cancer Patients: Report of a Randomized Study—Cancer and Leukemia Group B 8642

1999 ◽  
Vol 17 (5) ◽  
pp. 1397-1397 ◽  
Author(s):  
Mary E. Costanza ◽  
Raymond B. Weiss ◽  
I. Craig Henderson ◽  
Larry Norton ◽  
Donald A. Berry ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Single Agent ◽  
Metastatic Breast ◽  
Response Rates ◽  
Breast Cancer Patients ◽  
Safety And Efficacy

PURPOSE: We undertook a prospective, randomized phase III trial to evaluate the safety and efficacy of using a phase II agent before initiating therapy with standard combination chemotherapy in metastatic breast cancer patients. PATIENTS AND METHODS: A total of 365 women with measurable metastatic breast cancer, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either immediate chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) or up to four cycles of one of five sequential cohorts of single-agent drugs: trimetrexate, melphalan, amonafide, carboplatin, or elsamitrucin, followed by CAF. RESULTS: The toxicity of each single agent followed by CAF was comparable to that of CAF alone. The cumulative response rates for the single agent followed by CAF were not statistically different from those of CAF alone (44% v 52%; P = .24). However, in the multivariate analysis, patients with visceral disease had a trend toward lower response rates on the phase II agent plus CAF arm (P = .078). Although survival and response duration also were not statistically significantly different between the two study arms (P = .074 and P = .069, respectively), there was a suggestion of benefit for the CAF-only arm. CONCLUSION: The brief use of a phase II agent, regardless of its efficacy, followed by CAF resulted in response rates, toxicities, durations of response, and survival statistically equivalent to those seen with the use of CAF alone. These findings support the use of a new paradigm for the evaluation of phase II agents in the treatment of patients with metastatic breast cancer.

High efficacy and low toxicity of the combination of vinorelbine and capecitabine as second line treatment in metastatic breast cancer previously treated with taxanes and/or anthracyclines

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10719-10719 ◽  
Author(s):  
G. Orphanos ◽  
A. Alexopoulos ◽  
G. Ioannidis ◽  
C. Kandylis ◽  
A. Ardavanis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Single Agent ◽  
Metastatic Breast ◽  
Line Treatment ◽  
Second Line ◽  
Previously Treated ◽  
Statistical Planning ◽  
Metastatic Sites ◽  
Ecog Ps

10719 Background: Capecitabine and Vinorelbine have shown considerable activity given as single agent or in combination with other drugs. The aim of this single institution ph.II study is to evaluate the response to the combination of Capecitabine and Vinorelbine given as second line treatment in patients with metastatic breast cancer previously treated with taxanes and/or anthracyclines. Methods: The regimen consists of Capecitabine 2000 mg/m2 D1-D14 and Vinorelbine 20 mg/m2 D1,D8 q 3 weeks for six cycles. Evaluation of response was accomplished with CT scan after the third and sixth cycle. Patients with disease progression after cycle 3 are taken off protocol. Patients with gr 2/3 granulocytopenia are given G-CSF for all subsequent cycles and there is a 20% dose reduction in both drugs for patients with gr 4 granulocytopenia. Results: 30 pts have been enrolled so far; according to statistical planning the total number of accrued pts should reach 63. Median age 55 yrs (30–76), median ECOG PS 1 (0–2), pre/postmenopausal 6/24. Number of metastatic sites: 1 in 6 pts, 2 in 15 pts, 3 in 6 pts and 4 in 3 pts. A total of 146 cycles was administered. Overall response rate 50% with CR in 2 (6.7%) pts, PR in 13 (43.3%) pts. Stable disease was observed in 4 (13.3%) pts, 8 (26.6%) pts had progressive disease and 3 (10%) were non evaluable. Toxicity: anemia gr 2 in 2 (6.7%) pts and gr 3 in 1 (3.3%) ptn, thrombocytopenia gr2 in 2 (6.7%) pts, granulocytopenia gr 2/3 in 17 (56.7%) pts and gr4 in 1 (3.3%) ptn. Gr 1/2 nausea or vomiting was observed in 5 (16.6%) pts and gr 3/4 in 2 (6.7%) pts. Vinorelbine induced phlebitis in 3 (10%) pts, gr1/2 diarrhea in 3 (10%) and fungal infection of the nail beds in 2 (6.7%) pts. Conclusions: Preleminary results suggest that the Capecitabine and Vinorelbine combination is an active and safe regimen for second line metastatic breast cancer treatment. The study remains open to achieve the planned patient accrual. No significant financial relationships to disclose.

scholarly journals Real-world survival outcomes of heavily pretreated patients with refractory HR+, HER2−metastatic breast cancer receiving single-agent chemotherapy—a comparison with MONARCH 1

2020 ◽  
Vol 184 (1) ◽  
pp. 161-172
Author(s):  
Hope S. Rugo ◽  
Veronique Dieras ◽  
Javier Cortes ◽  
Debra Patt ◽  
Hans Wildiers ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real World ◽  
Single Agent ◽  
Metastatic Breast ◽  
Clinical Context ◽  
Eligibility Criteria ◽  
The Real ◽  
Heavily Pretreated ◽  
Single Agent Chemotherapy

Abstract Purpose In MONARCH 1 (NCT02102490), single-agent abemaciclib demonstrated promising efficacy activity and tolerability in a population of heavily pretreated women with refractory HR+, HER2− metastatic breast cancer (MBC). To help interpret these results and put in clinical context, we compared overall survival (OS) and duration of therapy (DoT) between MONARCH 1 and a real-world single-agent chemotherapy cohort. Methods The real-world chemotherapy cohort was created from a Flatiron Health electronic health records-derived database based on key eligibility criteria from MONARCH 1. The chemotherapies included in the cohort were single-agent capecitabine, gemcitabine, eribulin, or vinorelbine. Results were adjusted for baseline demographics and clinical differences using Mahalanobis distance matching (primary analysis) and entropy balancing (sensitivity analysis). OS and DoT were analyzed using the Kaplan–Meier method and Cox proportional hazards regression. Results A real-world single-agent chemotherapy cohort (n = 281) with eligibility criteria similar to the MONARCH 1 population (n = 132) was identified. The MONARCH 1 (n = 108) cohort was matched to the real-world chemotherapy cohort (n = 108). Median OS was 22.3 months in the abemaciclib arm versus 13.6 months in the matched real-world chemotherapy cohort with an estimated hazard ratio (HR) of 0.54. The median DoT was 4.1 months in MONARCH 1 compared to 2.9 months in the real-world chemotherapy cohort with HR of 0.76. Conclusions This study demonstrates an approach to create a real-world chemotherapy cohort suitable to serve as a comparator for trial data. These exploratory results suggest a survival advantage and place the benefit of abemaciclib monotherapy in clinical context.

Safety and efficacy of capecitabine (C) plus bevacizumab (B) as first-line in metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1013-1013 ◽  
Author(s):  
G. Sledge ◽  
K. Miller ◽  
C. Moisa ◽  
W. Gradishar
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Performance Status ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Primary Objective ◽  
First Line ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Grade 3

1013 Background: C alone has good activity and tolerability in metastatic breast cancer (MBC) and when combined with docetaxel improves response and survival. C combined with B in heavily pretreated MBC improved the response rate but not PFS. In untreated MBC, the addition of B to chemotherapy significantly improves progression-free survival (PFS) which suggests that B, is most effective in early disease. Methods: Primary objective of this single-arm, 2-phase study, is to evaluate PFS in MBC patients receiving first-line treatment with C 1,000 mg/m2 twice daily on days 1–15 (28 doses) and B 15 mg/kg on day 1. Treatment was repeated every 21 days until progression. Eligibility criteria included HER2-negative MBC previously untreated for metastatic disease; ECOG performance status =1; no prior anti-angiogenic or oral fluoropyrimidine therapy. A sample size of 109 patients (including dropouts) was required to give 90% power to test an improvement from 4 months median PFS to 5.6 months with the two-sided test (a 5%) Results: At data cut-off, 103 patients had received study medication. Present results are based on 103 patients (ITT population), except tumor response which is based on 91 patients who had response evaluation. The average # of cycles received in first phase is 6.8. 84 pts.are alive at this time. 38.5% (35/91) pts. have had a response: complete response 5.5%; partial response 33.0%. Stable disease is 42.9% with 81.4% clinical benefit. Planned dose received is 77.7 % for C and 99.0 % for B. The majority of adverse events (AEs) were mild or moderate. The most common grade 3 AEs were hand-foot syndrome (13%) and pain (10%); grade 4 pulmonary embolism occurred in 2% in the first phase of the study. Conclusions: Updated results with longer follow-up including toxicity, TTP and PFS will be presented at the meeting. It appears that in first-line C+B is active for MBC and is well tolerated, with few grade 3/4 toxicities. [Table: see text]

Capecitabine maintenance therapy after docetaxel/capecitabine combination chemotherapy in patients with metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12018-e12018
Author(s):  
Pinar Gursoy ◽  
Zeki Gokhan Surmeli ◽  
Burcu Cakar ◽  
Cagatay Arslan ◽  
Baha Zengel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Maintenance Therapy ◽  
Single Agent ◽  
Objective Response ◽  
Metastatic Breast ◽  
Complete Response ◽  
Response To Treatment ◽  
Grade 3 ◽  
Metastatic Sites

e12018 Background: Addition of capecitabine to docetaxel improves survival outcomes compared with single agent docetaxel in metastatic breast cancer (MBC). In this study we analyzed efficacy of maintenance therapy with single agent capecitabine after six cycles of docetaxel/capecitabine chemotherapy in MBC patients. Methods: Patients with metastatic HER2 negative breast cancer were included. Six cycles of docetaxel (75mg/m2 q3wk) / capecitabine (1650mg/m2/day on days 1 to 14) followed by capecitabine (2000 mg/m2/day on days 1 to 14) were administered. Demographic features, progression free (PFS) and overall survival (OS) and response to treatment were recorded. Results: Fifty-four patients were included. Thirty-five patients (65%) were postmenopausal, and 40 (74%) were ER/PR positive. Median age was 53 (range 28 – 70). Number of metastatic sites was one in 23 patients, two in 21, three or more in 10 patients. Most common metastatic sites were bone (67%), lymph nodes (33%), lungs (30%), liver (13%); 13 patients (24%) had bone only disease. Forty-four (81.5%) patients received treatment in first-line, 10 (18.5%) received in second line setting. Median number of cycles applied (including docetaxel/capecitabine combination) was 9 (range 2 – 31, total 576). Median PFS was 9 months (10.4 for hormone receptor positive, 7.3 for negative patients) and median OS was 28 months. Objective response was assessable in 38 patients. Overall response rate (partial + complete response) was 42.6% (95% CI 29.6 – 55.6) with 1 complete response. Toxicities were evaluated in 41 patients; grade 3/4 neutropenia was observed in 10% and grade 3/4 hand-foot syndrome was observed in 24% of patients. Dose reduction was performed in capecitabine in 37%, and in docetaxel in 20% of patients. Conclusions: Maintenance with single agent capecitabine therapy after six cycles of docetaxel/capecitabine chemotherapy is an effective and tolerable treatment option for HER2 negative MBC patients.

Assessment of Molecular Markers of Clinical Sensitivity to Single-Agent Taxane Therapy for Metastatic Breast Cancer

2002 ◽  
Vol 20 (9) ◽  
pp. 2319-2326 ◽  
Author(s):  
Catherine Van Poznak ◽  
Lee Tan ◽  
Katherine S. Panageas ◽  
Crispinita D. Arroyo ◽  
Clifford Hudis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Markers ◽  
Metastatic Breast Cancer ◽  
Estrogen Receptors ◽  
Clinical Response ◽  
Performance Status ◽  
Single Agent ◽  
Progesterone Receptors ◽  
Metastatic Breast ◽  
Taxane Chemotherapy

PURPOSE: The taxanes affect tubulin polymerization and interfere with mitotic transition. A checkpoint blockade at the G1-S boundary would be expected to promote taxane-induced apoptotic cell death through a mechanism that may involve p27. Other proposed determinants of clinical taxane sensitivity/resistance include p53, members of the epidermal growth factor receptor (EGFR) superfamily (eg, HER2, EGFR), and estrogen receptors and progesterone receptors. These molecular markers and their correlation with clinical taxane sensitivity are investigated in this retrospective clinicopathologic study. PATIENTS AND METHODS: We performed immunohistochemistry (IHC) for estrogen receptors, progesterone receptors, HER2, EGFR, p53, and p27 on 144 breast tumor specimens from patients treated for metastatic breast cancer on a series of clinical trials of single-agent taxane chemotherapy for correlation with clinical response (complete or partial response). Patient characteristics that could influence response (ie, performance status, extent of disease, and prior therapy) were also examined. RESULTS: In univariate analysis, Karnofsky performance status ≥ 90% and no prior history of anthracycline therapy correlated with a good clinical response to single-agent taxane (P = .003 and P = .041, respectively). None of the IHC variables tested were predictive of clinical response to taxane therapy, although p27 negativity showed a trend toward significance (P = .075). Concordance between the polyclonal antibody with HercepTest (DAKO, Carpinteria, CA) and the monoclonal antibody CB-11 (BioGenex, San Ramon, CA) was noted (kappa = 0.943); however, neither univariate nor multivariate analysis demonstrated an association between HER2 status and response to taxane chemotherapy. CONCLUSION: The IHC biomarkers studied were not predictive of response to single-agent taxane chemotherapy in patients with metastatic breast cancer. Identification of molecular correlates of taxane response remains an important goal.

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