Randomized, optimal dose-finding, phase II study of tri-weekly nab-paclitaxel in patients with metastatic breast cancer (ABROAD).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1070-1070
Author(s):  
Fumikata Hara ◽  
Masahiro Kitada ◽  
Masato Takahashi ◽  
Yuichiro Kikawa ◽  
Hiroaki Kato ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Low Dose ◽  
Medical Information ◽  
Objective Response ◽  
Metastatic Breast ◽  
Optimal Dose ◽  
University Hospital ◽  
Controlled Study ◽  
Grade 3

1070 Background: Although nab-paclitaxel (nab-PTX) has shown superior efficacy compared to conventional paclitaxel in metastatic breast cancer (MBC), chemotherapy induced peripheral neuropathy (CIPN) was more frequently observed in nab-PTX. In a single arm Phase 2 trail (CA002-0LD), low dose nab-PTX (175mg/m2) every 3 weeks (q3w) demonstrated a good objective response rate (39.5%) without grade 3 or higher CIPN. Herein, we conducted multicenter randomized controlled study to evaluate optimal dose of nab-PTX comparing lower dose (LD or MD) to standard dose (SD). Methods: This study compared three different doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2) in patients with HER2 negative metastatic breast cancer. Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses are estimated by the logistic regression. Optimal dose was selected by 2 step selection. At first, if hazard ratio (HR) for PFS was less than 0.75 or more than 1.33, the inferior dose was dropped. Then, if estimated incidence rate of grade 3/4 neurotoxicity exceed10%, that dose was also dropped. This trial is registered with the University Hospital Medical Information Network (UMIN), Japan (protocol ID C000012429). Results: In this study, 141 patients were randomly assigned to SD (n = 47), MD (n = 46) or LD (n = 48). Median PFS was 6.66 vs 7.34 vs 6.82 months, respectively. HR was 0.73 (95% confidence interval (CI): 0.42-1.28) in MD vs SD. SD was dropped due to inferiority to MD. HR was 0.77 (95%CI 0.47-1.28) in LD vs SD, and 0.96 (95%CI 0.56-1.66) in LD vs MD. LD and MD were carried over to next step due to equivalence. Overall survival was not different among all dose arms. Rate of dose reduction by treatment course was significantly higher in SD arm. Estimated incidence of grade 3/4 neurotoxicity rate was 29.5% in SD, 14.0% in MD and 5.9% in LD. Final selected dose was LD 180mg/m2. HR-QOL results will be presented. Conclusions: Low dose nab-PTX at 180 mg/m2/3 weeks could be an optimal dose with good clinical efficacy and tolerability for patients with MBC. Clinical trial information: C000012429.

Multicenter study of weekly trastuzumab, paclitaxel and carboplatin followed by a week of rest every 28 days in patients with HER2+ metastatic breast cancer (MBC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1083-1083
Author(s):  
M. Ruiz ◽  
J. Salvador ◽  
J. Bayo ◽  
M. Lomas ◽  
A. Moreno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Objective Response ◽  
Neoadjuvant Treatment ◽  
Growth Control ◽  
Metastatic Breast ◽  
Tolerability Profile ◽  
Combination Methods ◽  
Duration Of Response ◽  
Grade 3

1083 Background: The addition of Carboplatin to Trastuzumab and Paclitaxel improves the efficacy in HER2+ metastatic breast cancer (MBC). We have conducted a multicenter Phase II study to investigate the efficacy and safety of this combination given weekly × 3 followed by 1 week of rest. Primary endpoint was objective response rate and secondary endpoints were time to progression, overall survival and to study the toxicity profile of the combination. Methods: Between August 2003 and April 2006, 40 patients with HER2+ MBC (IHC 3+ or FISH+) have been included in the study. Pats received Trastuzumab (loading dose of 4 mg/kg/wk and 2 mg/kg/d following wks), Paclitaxel (80 mg/m2) and Carboplatin (AUC 2) all given weekly × 3 followed by 1 week of rest. Treatment was given until disease progression or unacceptable toxicity. Results: 40 pats had baseline data available. Median age was 54 yrs (range 29–75). 38 (95%) pats received prior adjuvant or neoadjuvant treatment. 11 (27,5%) pats have received one prior CT line for metastatic disease. 87,5% pats had PS 0 or 1 at study entry. Disease sites were liver 16 (40%), bone 12 (30%), lymph nodes 13 (32,5%) and lung 8 (20%). 19 (47,5%) had = 2 lesions. 97,5% had measurable disease. 36 pats have been evaluated for response: 11 CR (31%, 95% CI: 15–46%), 11 PR (31%, 15- 36%), 9 SD (25%, 9–36%), 5 PD (14%, 2–26%) and 4 NE resulting in an ORR of 61% (95% CI: 45–77%) and tumor growth control rate (RR+SD) of 86% of patients (95% CI: 75–97%). Median TTP was 12.1 mo (95% CI: 8.8–19.9 mo) and median duration of response and OS have not been reached yet. For a time of observation of 35 mo, the OS is 80,6%. 37 patients have received 194 cycles with a median of 5 cycles. Grade 3–4 toxicities/pats were: 3(7.5%) anaemia, 2 (5%) leucopenia, 8(20%) neutropenia, 1 (2,5%) febrile neutropenia, 1 (2,5%) trombopenia, 2(5%) asthenia, 2(5%) diarrhea, 3(7.5%) nausea, 2(5%) vomiting, 3(7.5%) mucositis Conclusions: This interim analysis shows an interesting activity with this regimen. One week of rest may be of better convenience for the patient and hospital but also may improve the tolerability profile and efficacy of the combination. Further results would be available for presentation. No significant financial relationships to disclose.

Real world experience of palbociclib in hormone receptor-positive metastatic breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18094-e18094 ◽  
Author(s):  
Faizan Malik ◽  
Naveed Ali ◽  
Syed Imran Mustafa Jafri ◽  
Mark L. Sundermeyer ◽  
Michael Jeffrey Seidman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Side Effects ◽  
Real World ◽  
Hormone Receptor ◽  
Objective Response ◽  
Metastatic Breast ◽  
Hormone Receptor Positive ◽  
Her 2 ◽  
Grade 3

e18094 Background: Palbociclib has been approved as a first line therapy in hormone-receptor positive (HR+) and HER-2 negative metastatic breast cancer(MBC) manifesting significant improvement in progression free survival (PFS). We studied this drug in a community setting. The endpoints were estimated PFS, objective response, toxicities and patient outcomes. Methods: This was a single-center, retrospective study of HR+MBC patients receiving palbociclib after its FDA approval. 22 patients were selected Results: A total of 22 patients were included (Male = 2, Female = 20). Median age was 60-years (range, 49-84). About 90% patients had received at least one previous therapy and the median number was 1.5. 13% patients were on fulvestrant, 86% on letrozole and 4.5% on exemestane. About 64% of patients had ECOG status of ≥ 1. Median duration of palbociclib treatment was 5-months, therefore, an estimated PFS at 18-months was 50%. 4.5% patients attained complete response. 22% patients achieved partial response, 22% had stable disease and 50% patients demonstrated disease progression. 72% patients had neutropenia, of which 45% were grade ≥ 3. Thrombocytopenia and anemia were common (63% and 58%, respectively) but grade ≥ 3 thrombocytopenia or anemia was not observed. 50% patients required dose reductions and 18% required drug cessation owing to side effects. Conclusions: PFS was much lower as compared to actual trials in our real-world experience. Despite, several interesting observations were good objective response rates in males and HER-2+ patients underscoring its potential clinical efficacy in these subsets. Furthermore, apart from myelosuppressive side effects, pneumonitis was observed in one patient necessitating vigilance in clinical practice

scholarly journals A randomized phase II trial evaluating the addition of low dose, short course sunitinib to docetaxel in advanced solid tumours

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yvonne L. E. Ang ◽  
Gwo Fuang Ho ◽  
Ross A. Soo ◽  
Raghav Sundar ◽  
Sing Huang Tan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Low Dose ◽  
Negative Impact ◽  
Objective Response ◽  
Metastatic Breast ◽  
Solid Tumours ◽  
Breast Cancer Patients ◽  
Short Course ◽  
Grade 3

Abstract Background We previously reported that low-dose, short-course sunitinib prior to neoadjuvant doxorubicin-cyclophosphamide (AC) normalised tumour vasculature and improved perfusion, but resulted in neutropenia and delayed subsequent cycles in breast cancer patients. This study combined sunitinib with docetaxel, which has an earlier neutrophil nadir than AC. Methods Patients with advanced solid cancers were randomized 1:1 to 3-weekly docetaxel 75 mg/m2, with or without sunitinib 12.5 mg daily for 7 days prior to docetaxel, stratified by primary tumour site. Primary endpoints were objective-response (ORR:CR + PR) and clinical-benefit rate (CBR:CR + PR + SD); secondary endpoints were toxicity and progression-free-survival (PFS). Results We enrolled 68 patients from 2 study sites; 33 received docetaxel-sunitinib and 35 docetaxel alone, with 33 breast, 25 lung and 10 patients with other cancers. There was no difference in ORR (30.3% vs 28.6%, p = 0.432, odds-ratio [OR] 1.10, 95% CI 0.38–3.18); CBR was lower in the docetaxel-sunitinib arm (48.5% vs 71.4%, p = 0.027 OR 0.37, 95% CI 0.14–1.01). Median PFS was shorter in the docetaxel-sunitinib arm (2.9 vs 4.9 months, hazard-ratio [HR] 2.00, 95% CI 1.15–3.48, p = 0.014) overall, as well as in breast (4.2 vs 5.6 months, p = 0.048) and other cancers (2.0 vs 5.3 months, p = 0.009), but not in lung cancers (2.9 vs 4.1 months, p = 0.597). Median OS was similar in both arms overall (9.9 vs 10.5 months, HR 0.92, 95% CI 0.51–1.67, p = 0.789), and in the breast (18.9 vs 25.8 months, p = 0.354), lung (7.0 vs 6.7 months, p = 0.970) and other cancers (4.5 vs 8.8 months, p = 0.449) subgroups. Grade 3/4 haematological toxicities were lower with docetaxel-sunitinib (18.2% vs 34.3%, p = 0.132), attributed to greater discretionary use of prophylactic G-CSF (90.9% vs 63.0%, p = 0.024). Grade 3/4 non-haematological toxicities were similar (12.1% vs 14.3%, p = 0.792). Conclusions The addition of sunitinib to docetaxel was well-tolerated but did not improve outcomes. The possible negative impact in metastatic breast cancer patients is contrary to results of adding sunitinib to neoadjuvant AC. These negative results suggest that the intermittent administration of sunitinib in the current dose and schedule with docetaxel in advanced solid tumours, particularly breast cancers, is not beneficial. Trial registration The study was registered (NCT01803503) prospectively on clinicaltrials.gov on 4th March 2013.

scholarly journals A Prospective, Randomized, Placebo-Controlled Study of a Combination of Simvastatin and Chemotherapy in Metastatic Breast Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Hiba Alarfi ◽  
Lama A. Youssef ◽  
Maher Salamoon
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Controlled Trial ◽  
Performance Status ◽  
Objective Response ◽  
Metastatic Breast ◽  
High Sensitivity ◽  
Controlled Study ◽  
Ecog Performance Status ◽  
Baseline Values

Preclinical studies support the anticancer activity of statins; however, the existing clinical evidence is inconsistent and not definitive. Our study aimed at evaluating a postulated cancer chemo-sensitizing effect of statin (simvastatin) in a cohort of metastatic breast cancer (MBC) patients. We designed a prospective, single-centered, randomized, double blinded, placebo-controlled trial that encompassed MBC patients with an ECOG Performance Status Scale ≤2 and scheduled to be treated with a chemotherapy regimen consisting of carboplatin and vinorelbine every 3 weeks at Al-Baironi Hospital, Damascus, Syria. Patients were enrolled between August 2011 and July 2012 and randomly allocated to receive a 15-day course of either simvastatin (40 mg) or placebo seven days prior to the first day of each chemotherapy cycle and then continued for eight days in each individual cycle. Primary endpoints were objective response rate (ORR) and toxicity, and the secondary endpoint was overall survival (OS). Eighty-two patients met the inclusion criteria and consented. ORR (35% vs. 32.5%) and predominant toxicity and grade ≥3 neutropenia (occurred in 30% vs. 40% of the patients) were not significantly different between simvastatin and placebo groups, respectively. Over a median follow-up of 44 months (range, 10–60), median OS was 15 months in the simvastatin group and 17 the in placebo group (hazard ratio (HR) = 1.16, 95% CI (0.70–1.91), P=0.57). Elevated baseline values of high-sensitivity C-reactive protein (hsCRP >10 mg/l), lactate dehydrogenase (LDH >480 U/L), and chemotherapy being ≥2nd line were significantly associated with shorter OS for the total cohort in both Univariate and multivariate analyses. Our data prove a safe profile of simvastatin at 40 mg per day combined with carboplatin and vinorelbine in MBC patients but without any beneficial increase of tumor sensitivity to chemotherapy. Moreover, we demonstrated a strong clinical advantage of baseline values of hsCRP and LDH as useful prognostic tools in MBC patients. This trial is registered with ISRCTN12964275.

A multicenter phase I-II trial of weekly paclitaxel and carboplatin plus bevacizumab in women with triple-negative metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1045-1045
Author(s):  
Emmanouil S. Saloustros ◽  
Aristidis Polyzos ◽  
Charalampos Christophyllakis ◽  
Nikolaos K. Kentepozidis ◽  
Lampros Vamvakas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Objective Response Rate ◽  
Triple Negative ◽  
Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Primary Objective ◽  
Dna Breaks ◽  
Grade 3

1045 Background: Triple-negative breast cancer cells are unable to repair double stranded DNA breaks and hence have sensitivity to platinum agents. The combination of carboplatin and paclitaxel administered weekly is active and well tolerated. Bevacizumab when added to paclitaxel prolonged progression-free survival in metastatic breast cancer (MBC). We investigated the activity and toxicity of paclitaxel plus carboplatin and bevacizumab in triple-negative MBC. Methods: The study’s primary objective was to estimate the objective response rate [complete (CR) + partial remission (PR)] and toxicity of the combination in women with triple negative MBC who had no prior chemotherapy for metastatic disease. The study followed the Simon's two-stage optimal design with 16 patients initially evaluated for response and toxicity and then expanding to a total of 46 patients. The null hypothesis that the objective response rate is ≤40% could be rejected if the number of CR/PR was ≥23. Paclitaxel 90mg/m2and Carboplatin AUC 2 were administered on days 1, 8, and 15 every 4 weeks, preceded by bevacizumab 10 mg/kg on days 1 and 15. Results: 45 women with triple negative MBC have been recruited thus far. Of them, 12 were premenopausal and 27 had prior (neo-)adjuvant chemotherapy. The median cycles administered were 5 (range 1-8). Of 38 evaluable patients we observed 7 CR, 22 PR’s for an objective response rate 76%. Seven patients achieved stable disease, while two had disease progression. Median duration of response was 8.1 months with median time to progression 9.2 months. Neutropenia grade 3 and 4 was experienced by 13 and 6 patients, respectively, with one toxic death due to febrile neutropenia. Other grade 3 toxicities included anemia/neurotoxicity (n=2), thrombocytopenia/diarrhea (n=1). Conclusions: Although still ongoingthe study has achieved the primary objective of demonstrating clinical activity for weekly carboplatin and paclitaxel in combination with bevacizumab in triple negative MBC. We believe that this triplet combination merits further evaluation in this patient population for whom there is no standard treatment. Clinical trial information: NCT00691379.

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.

Fluorouracil and high-dose leucovorin in previously treated patients with metastatic breast cancer.

1989 ◽  
Vol 7 (7) ◽  
pp. 890-899 ◽  
Author(s):  
S M Swain ◽  
M E Lippman ◽  
E F Egan ◽  
J C Drake ◽  
S M Steinberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Objective Response ◽  
Metastatic Breast ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Tumor Biopsy ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3

The efficacy and toxicity of leucovorin 500 mg/m2 administered intravenously (IV) over 30 minutes daily for five days followed in one hour by fluorouracil (5-FU) 375 mg/m2 administered IV daily for five days, each given every 3 weeks, was assessed in 54 previously treated patients with metastatic breast cancer. An overall objective response rate of 24% was achieved (95% confidence interval, 13% to 38%), with an additional 56% of patients maintaining stable disease. Eleven of 12 patients who responded had received previous 5-FU therapy. Toxicity of this regimen included grade 3 diarrhea in 13%, grade 3 or 4 mucositis in 33%, grade 3 or 4 granulocytopenia in 65%, and grade 3 or 4 thrombocytopenia in 19%. Delay of treatment was required for hematologic toxicity in 44 patients. Thirty-eight patients required dose reductions due to toxicity. Biochemical evaluation of tumor biopsy specimens obtained from 17 patients used as their own controls with and without leucovorin was performed. These studies reveal an increased stabilization of the 5-fluorodeoxyuridylate (FdUMP)-thymidylate synthase (TS) folate ternary complex with the addition of leucovorin. There was a 71% +/- 14% occupancy or inhibition of the enzyme with the use of both 5-FU and leucovorin, v 30% +/- 13% for 5-FU alone (P2 less than .037). The percent TS bound in responding patients was substantially higher than in those patients with progressive disease. Finally, the mean total tumor TS pre-therapy in seven patients was 31 fmol/mg compared with a mean of 81 fmol/mg in these same seven patients 24 hours after therapy. This 2.6-fold increase suggests that there is an induction of the enzyme, TS, with 5-FU treatment.

scholarly journals Paclitaxel, Epirubicin and Capecitabine (TEX) as First-Line Treatment for Metastatic Breast Cancer: A Pilot Phase I/II Feasibility Study

2008 ◽  
Vol 2 ◽  
pp. CMO.S1027
Author(s):  
Z. Einbeigi ◽  
D. Bergström ◽  
T. Hatschek ◽  
M. Malmberg
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Objective Response ◽  
Metastatic Breast ◽  
Line Treatment ◽  
Pilot Phase ◽  
Time To Progression ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

Thirteen patients with untreated metastatic breast cancer received epirubicin 60 mg/m2, paclitaxel 155 mg/m2 (both day 1) and capecitabine 665 mg/m2 twice daily (days 1-14) every 21 days, with intra-patient dose escalation/reduction. Grade 3/4 events were infrequent. Nine patients (69%) achieved an objective response. Median time to progression and overall survival were 6.6 and 23.5 months, respectively.

scholarly journals A Prospective, Randomized, Placebo Controlled Study of a Combination of Simvastatin and Chemotherapy in Metastatic Breast Cancer

2020 ◽  
Author(s):  
Hiba Alarfi ◽  
Lama A. Youssef ◽  
Maher Salamoon
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Controlled Trial ◽  
Performance Status ◽  
Objective Response ◽  
Metastatic Breast ◽  
High Sensitivity ◽  
Controlled Study ◽  
Ecog Performance Status ◽  
Baseline Values

Abstract Preclinical studies support anticancer activity of statins, however, the existing clinical evidence are inconsistent and not definitive. Our study aimed at evaluating a postulated cancer chemo sensitizing effect of statin (simvastatin) in a cohort of metastatic breast cancer (MBC) patients. We designed a prospective, single-centered, randomized, double blinded, and placebo controlled trial that encompassed MBC patients with an ECOG Performance Status scale ≤2 and scheduled to be treated with a chemotherapy regimen consisting of carboplatin and vinorelbine every 3 weeks at Al-Baironi Hospital, Damascus, Syria. Patients were enrolled between August 2011 and July 2012, and randomly allocated to receive a 15-day course of either simvastatin (40 mg) or placebo seven days prior to the first day of each chemotherapy cycle, and then continued for eight days in each individual cycle. Primary endpoints were objective response rate (ORR) and toxicity, and secondary endpoint was overall survival (OS).Eighty-Two patients met the inclusion criteria and consented. ORR (35% vs. 32.5%) and predominant toxicity; grade≥3 neutropenia (occurred in 30% vs. 40% of the patients) were not significantly different between simvastatin and placebo groups, respectively. Over a median follow-up of 44 months (range, 10-60), median OS was 15 months in simvastatin group and 17 in placebo group (Hazard ratio (HR)=1.16, 95% CI (0.70-1.91), P=0.57). Elevated baseline values of high-sensitivity C-reactive protein (hsCRP >10 mg/l), lactate dehydrogenase (LDH >480 U/L) and chemotherapy being ≥2nd line significantly associated with shorter OS for the total cohort in both Univariate and multivariate analyses. Our data prove a safe profile of simvastatin at 40 mg per day combined with carboplatin and vinorelbine in MBC patients, but without any beneficial increase of tumor sensitivity to chemotherapy. Moreover, we demonstrated a strong clinical advantage of baseline values of hsCRP and LDH as useful prognostic tools in MBC patients.Trial registration: ISRCTN12964275. Retrospectively registered.

Phase II Study of Docetaxel, Doxorubicin, and Cyclophosphamide as First-Line Chemotherapy for Metastatic Breast Cancer

2001 ◽  
Vol 19 (2) ◽  
pp. 314-321 ◽  
Author(s):  
J. M. Nabholtz ◽  
J. R. Mackey ◽  
M. Smylie ◽  
A. Paterson ◽  
D. R. Noël ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Metastatic Breast ◽  
Fluid Retention ◽  
First Line ◽  
Grade 3 ◽  
Line Chemotherapy

PURPOSE: This pilot phase II study investigated the efficacy and toxicity of docetaxel with doxorubicin and cyclophosphamide (TAC) as first-line chemotherapy for anthracycline-naive patients with metastatic breast cancer. PATIENTS AND METHODS: Fifty-four patients received a total of 359 courses consisting of docetaxel 75 mg/m2 given intravenously (IV) over 1 hour, preceded by IV doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 for a maximum of eight 3-week cycles. RESULTS: After an independent panel review, the overall objective response rate was 77% (complete response, 6%). Overall objective response rates in patients with visceral, bone, and liver involvement were 82%, 82%, and 80%, respectively. Median duration of response was 52 weeks, and median time to progression was 42 weeks. With a median follow-up of 32 months, the median survival had not yet been reached, whereas the 2-year survival was 57%. The main toxicities were hematologic (neutropenia grade 3/4 in 100% of patients and 95% of cycles; febrile neutropenia in 34% of patients and 9% of cycles). Documented grade 3 infection was seen in one patient (2%) in one cycle, and no toxic death was reported. Severe acute or chronic nonhematologic adverse events were infrequent, and docetaxel-specific toxicities (such as fluid retention and nail changes) were mild, with only one patient being discontinued for fluid retention. Congestive heart failure was seen in two patients (4%). CONCLUSION: TAC is an active and manageable regimen that has been chosen as the basis of five randomized phase III trials, including two pivotal studies comparing TAC to fluorouracil plus doxorubicin and cyclophosphamide in the metastatic and adjuvant treatment of breast cancer.

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