scholarly journals Prospective Evaluation of a Circulating Tumor Cell Sensitivity Profile to Predict Response to Cisplatin Chemotherapy in Metastatic Breast Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
I. E. de Kruijff ◽  
A. M. Sieuwerts ◽  
N. Beije ◽  
W. J. C. Prager - van der Smissen ◽  
L. Angus ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Circulating Tumor Cell ◽  
Molecular Characteristics ◽  
Breast Cancer Patients ◽  
Clinical Trial Registration ◽  
Heavily Pretreated ◽  
Sensitivity Profile

BackgroundCisplatin (cDDP) has regained interest for metastatic breast cancer (MBC) patients, given the platinum sensitivity in subtypes and better manageable toxicity. Here, the primary aim was to determine whether molecular characteristics of circulating tumor cells (CTCs) could identify patients responding to cDDP and to describe the outcomes to cDDP monotherapy in a large group of MBC patients pretreated with anthracycline- and taxane-based treatments.MethodsBased on cell line data, a CTC-cDDP-sensitivity profile was generated. Applying an A’Herns single-stage phase II design, further investigation was considered worthwhile if 5/10 patients with a favorable profile responded to cDDP. Patients received 70mg/m2 cDDP every three weeks, CTCs were enumerated and the CTC-cDDP-sensitivity profile was determined. In total, 65 heavily pretreated MBC patients (77% received ≥2 lines of previous chemotherapy for MBC) were eligible for the per-protocol analysis. Primary endpoint was response rate, secondary endpoints included best observed response, progression-free survival (PFS) and overall survival (OS).ResultsThe best observed response during cDDP therapy was a partial response in 7% and stable disease in 56% of the patients. None of the patients with a favorable CTC-cDDP-sensitivity profile had a response. The median baseline CTC count was 8 (range 0-3254). Patients with <5 CTCs had a better PFS and OS than patients with ≥5 CTCs (median PFS 4.5 months (95%CI 2.38-6.62) vs. 2.1 months [(95%CI 1.34-2.80)(p=0.009)] and median OS 13.1 months (95%CI 9.89-16.33) vs. 5.6 months [(95%CI 3.60-7.64)(p=0.003)]. No other factors than CTC count were associated with outcome to cDDP therapy, including triple-negative breast cancer versus ER-positive tumors.ConclusionsThe CTC-cDDP-sensitivity profile was unable to select patients responding to cDDP monotherapy. In an unselected group of heavily pretreated MBC patients, cDDP yields outcomes comparable to other chemotherapeutic regimens for heavily pretreated MBC patients. CTC count was the only factor associated with outcome in these patients.Clinical Trial Registration(https://www.trialregister.nl/trial/3885, identifier NTR4046)

Impressive survival data with semimetronomic oral chemotherapy with old agents in heavily treated metastatic breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1082-1082
Author(s):  
H. Mutlu ◽  
H. Bozcuk ◽  
M. Ozdogan ◽  
M. Artac ◽  
H. S. Coskun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Survival Data ◽  
Low Cost ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Oral Etoposide ◽  
Breast Cancer Patients ◽  
Difficult Patient ◽  
Heavily Pretreated

1082 Background: To assess the efficacy of semi-metronomic regimen metronomic cyclophosphomide with oral etoposide in heavily treated patients with metastatic breast cancer. Methods: Consecutive metastatic breast cancer (MBC) patients predominantly refractory to antracyclines, taxanes, and antimetabolites receiving semi-metronomic regimen of metronomic cyclophosphomide with oral etoposide were evaluated for clinical efficacy and toxicity. This novel regimen comprised of continuous oral cyclophosphomide 50 mg/day, and oral etoposide given as 2 x 50 mg/day for 5 days. Results: A total of 42 MBC patients received this treatment in 2.5 years (May 2005-October 2008). The median age was 51.5 (29–81), ER and/or PR receptor status was positive in 67%, and c-erb-B2 overexpression existed in 50%. The biologically favorable group, hormone responsive and c-erb-B2 negative comprised of 36% of cases. The portions of patients with visceral metastases, cranial metastases, and 2 or more organ involvement were 82%, 24%, and 65%, respectively. Subjects had received this treatment in the fourth or more advanced setting in 50% of cases (after a median of 2.5 cycles). The median overall and progression free survival figures were 25 and 10.5 months, respectively. No toxic mortality occurred, and the treatment was well tolerated. Toxicity and response data are being updated currently. Conclusions: Semi-metronomic treatment with metronomic cyclophosphomide and oral etoposide is a novel and effective strategy in heavily pretreated MBC patients. Survival data and low cost may make this regimen a highly preferable option in this difficult patient group. No significant financial relationships to disclose.

scholarly journals A Phase II, Single-Arm Study of Apatinib and Oral Etoposide in Heavily Pre-Treated Metastatic Breast Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Nanlin Hu ◽  
Anjie Zhu ◽  
Yiran Si ◽  
Jian Yue ◽  
Xue Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Metastatic Breast Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Oral Etoposide ◽  
Breast Cancer Patients ◽  
Clinical Trial Registration

IntroductionWe performed this clinical trial to evaluate the efficacy and safety of apatinib and oral etoposide in patients with HER2-negative locally advanced or metastatic breast cancer (MBC).MethodsPatients with HER2-negative MBC previously treated with anthracycline and taxanes and failed ≥1 prior chemotherapy regimens were recruited. The starting dose of apatinib was 500 and 425 mg in patients with ECOG scores of 0–1 and 2, respectively. The etoposide capsules were given at 50 mg/m2 on days 1 to 10 for 21 days. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety.ResultsThirty-one eligible patients were enrolled. The median follow-up time was 11 months. The median PFS for all patients was 6.9 months [95% confidence interval (CI) 6.0–7.9], and 6.9 months (95% CI 5.3–8.6) and 6.6 months (95% CI 1.4–11.7) for patients with apatinib 425 and 500mg once daily, respectively. The ORR was 35.5% (11/31). The DCR was 87.1% (27/31). The median OS was 20.4 months (95% CI 11.4–29.3). The median PFS of patients who had hypertension and proteinuria was longer than that for those without hypertension and proteinuria. The most common grade 3/4 treatment-related AEs were hypertension (12/31, 38.7%), fatigue (3/31, 9.7%), thrombocytopenia (3/31, 9.7%).ConclusionApatinib combined with etoposide capsules is effective and tolerable in heavily pretreated, metastatic HER2-negative breast cancer patients. A lower apatinib dose provide equivalent efficacy and reduced toxicity.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier NCT03535961.

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.

Activity of trastuzumab-based therapy beyond disease progression in heavily pretreated metastatic breast cancer patients—Single institution experience

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13159-13159
Author(s):  
P. Tokajuk ◽  
B. Czartoryska-Arlukowicz ◽  
M. Z. Wojtukiewicz
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Soft Tissues ◽  
Advanced Disease ◽  
Metastatic Breast ◽  
Second Line ◽  
Breast Cancer Patients ◽  
Heavily Pretreated ◽  
Her 2

13159 Background: Benefits from continuing trastuzumab-based (TZB) therapy beyond disease progression in HER-2-overexpressing metastatic breast cancer (MBC) patients (pts) remain obscure. Methods: A retrospective analysis was undertaken to assess activity of TZB therapy for MBC pts treated in our institution from 2002 to 2005 outside clinical trials. Results: 27 pts were evaluated. Median age: 52 years (range, 33–62). 9 pts (33.3%) were premenopausal. Hormonal receptors status: 9 pts ER(+), 4 pts PgR (+), 2 unknown. HER-2 overexpression was determined by IHC staining (3+ score) in all pts. Metastases location: 18 pts soft tissues/bone, 18 pts visceral disease. Median number of metastatic sites: 2 (range: 1–4). 9 pts (33.3%) had metastases in < 2 locations. 16 pts (59.2%) received neo/adjuvant chemotherapy: 11 pts doxorubicin, 8 pts CMF, 2 pts docetaxel, 4 pts other. Median previous chemotherapy lines for advanced disease: 2 (range: 0–6). 16 pts received doxorubicin/epirubicin, 14 pts docetaxel, 13 pts vinorelbine as a part of advanced disease chemotherapy regimen. Trastuzumab was administered at standard doses and combined with docetaxel, vinorelbine, cisplatin, capecitabine, etoposide, gemcitabine or administered as monotherapy. Response for the first-line TZB therapy was as follows: CR 5/27 pts (18.5%); PR 10/27 pts (37%). Median TTP was 5.8 months (range: 0–22). 14/27 pts (51.8%) received a second-line TZB therapy beyond disease progression. Response for the second-line therapy: CR 2/14 pts (14.3%); PR 5/14 pts (35.7%). Median TTP was 5.1 months (range: 0–24). 6/14 pts received a third-line and subsequent lines (up to five lines) of TZB therapy. PR for subsequent lines of therapy was observed in 4 pts. Median survival has not been reached. Pts who received ≥2 of TZB regimens survived significantly longer than pts who had received only 1 regimen (P = 0,02 logrank). Pts with metastasis in 1 location survived significantly longer than pts with metastasis in ≥2 sites (P = 0,01 logrank). Conclusions: Trastuzumab-based therapy seems to be active in MBC pts beyond disease progression even in heavily pretreated population. Durable responses were observed in some cases. No significant financial relationships to disclose.

Methallotionein expression and outcome in patients with metastatic breast cancer (MBC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1085-1085
Author(s):  
Jorge Arturo Rios-Perez ◽  
Sameem Abedin ◽  
Margaret Quinn Rosenzweig ◽  
Su Yon Jung ◽  
Rohit Bhargava ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancer Diagnosis ◽  
Rank Test ◽  
Cancer Tissue ◽  
Breast Cancer Patients ◽  
Development Of Resistance ◽  
Bivalent Metal Ions

1085 Background: Platinum-based agents are important components of therapy of metastatic breast cancer (MBC) and triple negative breast cancer. Their use can be limited by development of resistance. Metallothioneins (MT) are low molecular weight proteins believed to bind bivalent metal ions such as platinum and zinc. MT expression has been associated with decreased survival in breast cancer patients. A proposed mechanism confers resistance to platinum-based agents by their inactivation or limitation of their activity by MT binding. Methods: MT expression in 99 women with MBC (selected at random from our database of 800 women with MBC) was determined from primary breast cancer tissue (n=80) or metastatic tissue n=19). MT expression was determined by immunohistochemistry, and graded as negative, weak, moderate or strong. Clinical data was obtained through our database and supplemented by chart review. Overall survival from breast cancer diagnosis (OS), progression free survival for first metastastic regimen (PFS), and time from first metastasis to death or last update (metastatic survival, MS), were calculated through December 2011 using the log rank test. Results: Consistent with prior studies, moderate to strong MT expression was associated with decreased 5-year OS (p=.03). There was no correlation between MT expression and PFS or MS in this cohort. Surprisingly, MT expression at any degree was strongly associated with better MS in patients with MBC that received carboplatin-based regimens in the first line (n=25, p=.0005) or at any line (n=41, p=.0437). Conclusions: Consistent with prior studies, MT expression was associated with decreased survival in patients with MBC. Surprisingly, MT expression was associated with longer MS in patients with MBC that received carboplatin. These findings are inconsistent with the hypothesis that MT expression causes chemoresistance to platinum based agents in patients with metastatic breast cancer. Further studies are needed to elucidate the mechanisms behind these findings.

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