bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capecitabine (X) in elderly patients (pts) with hormone-refractory metastatic breast cancer (MBC)
Authors: Messina C. G. , Longo F. , Seri M. Di , Restuccia M. , Zivi A. , Proietti E. , Russillo M. , Cerbone L. , Bianco V. , Speranza I. , Basile G. M. L. , De Filippis L. 
Published: March 2020

1080 Background: X has demonstrated consistently high single-agent activity and good tolerability in pretreated and chemonaive MBC, and extends survival when added to docetaxel. High activity, minimal myelosuppression and no alopecia make X interesting in elderly pts with hormone-refractory disease. Methods: Between Feb 2004 and Oct 2006, 36 elderly (>65 years) MBC pts previously treated with adjuvant therapy and at least one previous hormonal therapy for advanced disease received X 1,000 mg/m2 twice daily, days 1–14 every 3 weeks. Study objectives were to assess efficacy, safety, and impact on quality of life (QoL), assessed by Clinical Benefit Response (CBR) every third cycle. Results: Median age was 70 years (range 68–73), median ECOG PS was 1 (range 0–2). All pts had visceral metastasis and 19 (53%) had ≥2 metastatic sites. A total of 284 cycles were administered (median 6 cycles per pt). After 3 cycles, 10 pts (28%) showed a partial response, 16 (44%) had stable disease (SD), and 2 (6%) had a minor response, resulting in a disease control rate of 78%. Biochemical response (CEA and/or CA 15.3 reduction) was observed in 20 (56%) pts. SD was maintained in 22 pts (61%) after 6 cycles, 10 pts (28%) after 9 cycles and 2 pts (6%) after 12 cycles. Treatment was well tolerated, the most common grade 3 events being mucositis (6%) and hand-foot syndrome (6%). There were no grade 3/4 hematologic toxicities. All adverse events were easily managed with dose adjustments and supportive therapies as required. As a result, all pts (100%) complied with appreciable benefits in terms of QoL (positive CBR in 56% of pts). Conclusions: These preliminary data indicate that this X dose is active and well tolerated in elderly pts with hormone-refractory MBC. This regimen also warrants study as first-line treatment in pts with less aggressive MBC who might not be suitable for combination therapy. No significant financial relationships to disclose.
Cost-effectiveness of docetaxel compared to paclitaxel in metastatic breast cancer: A UK health economic analysis
Authors: Jones S. E. , Benedict A. , Cameron D. , Jourdan S. 
Published: March 2020

1081 Background: Docetaxel was shown to be superior to paclitaxel in OS and TTP (median OS: 1.28 vs 1.06 yr, HR=1.41; median TTP: 0.47 vs 0.30 yr, HR= 1.64) for the treatment of patients with metastatic breast cancer progressing after an anthracycline-based regimen (Jones et al. J Clin Oncol. 2005;23:5542). A cost-effectiveness analysis based on this head-to-head comparison was performed considering clinical effectiveness, quality-adjusted life-years, and direct medical costs in the UK. Methods: A probabilistic Markov model was developed to examine results over a 10-yr long time-horizon. Patient level data were available on PFS and OS, treatment cycles and doses, number of cycles affected by adverse events, G-CSF use and post-failure treatment. Generalized gamma regression, fitting patient-level data best were used to model baseline PFS and OS in the paclitaxel arm. HRs adjusting for all covariates were applied to the baseline hazards to generate the docetaxel arm. Resource use and utility values for health states were obtained from published literature and practicing UK oncologists. Unit costs came from 2005 NHS reference costs; drug costs from the British National Formulary 2006 without hospital discount. Costs and benefits were discounted at 3.5%. A Monte-Carlo simulation and extensive 1-way sensitivity analyses were conducted. Results: Docetaxel is more costly (£13,500 vs £10,600), but yields higher health benefits than paclitaxel (2.01 vs 1.48 LYs and 1.18 vs 0.85 QALYs for docetaxel and paclitaxel, respectively) over a 10-yr time horizon. The discounted Incremental Cost-Effectivness Ratio (ICER) of docetaxel vs paclitaxel 3-weekly was estimated to be £5,532/LY gained (95% CI 2,250–12,700) and £8,741/QALY gained (95% CI 3,400–17,300). The ICER was most sensitive to the HR for PFS, OS and the cost of docetaxel and paclitaxel. However, ICERs remained below £20,000/QALY at extreme values of the parameters. Conclusions: Compared with paclitaxel 3-weekly, over a 10-yr time horizon docetaxel provides survival and quality-adjusted survival benefit to metastatic breast cancer patients failing anthracycline regimens at an acceptable cost in a UK setting. Docetaxel is cost-effective compared to paclitaxel. No significant financial relationships to disclose.
Trastuzumab with taxanes in HER2-ECD(+), IHC/CISH(-) advanced and heavily pretreated, chemotherapy-refractory breast cancer patients: Findings from a case series
Authors: Ardavanis A. , Kountourakis P. , Malliou S. , Kyriakou F. , Koumna S. , Kardara E. , Garoufalli A. , Yioti I. , Rigatos G. 
Published: March 2020

1089 Background: The “invisible” potential of a tumor is responsible for the discrepancy sometimes observed between favourable initial pathological profile and aggressive clinical course. We describe a series of Breast Cancer patients with refractory to standard chemotherapy advanced tumors without HER2-amplification/overexpression treated with trastuzumab (TZB). Methods: Twenty five patients progressing under anthracyclines and taxanes were selected on the basis of increased HER2-ECD levels at entry (>16 ng/ml) and lack of HER2-amplification/overexpression in the primary tumor documentation. In 22/25, TZB 6 mg/m2 with either docetaxel 75 mg/m2 q3w or paclitaxel 90 mg/m2 weekly were administered for six courses or less if toxicicity or progression was documented; TZB alone had to be continued thereafter until progression. Serial HER2-ECD were performed during therapy. Results: No objective response was noted; however, in 5 and 11 pts minor response and stabilization respectively was noted. All minor responders and stabilized patients experienced subjective improvement. Toxicity was acceptable. Median time to progression has not yet been reached, actually 5+mos; in 9 patients the progression-free period is 12 months from start of therapy. Median HER2-ECD declined from 54ng/ml at baseline to 14.3ng/ml at 28 weeks from treatment start. Conclusion: Although the sample size of this case-series is small, our findings suggest that, in HER2 negative patients with clinical aggressive behaviour and refractoriness to standard chemotherapy, HER2 positivity should be assessed by serum ECD levels and the addition of trastuzumab may be a valuable therapeutic option. However, these findings should be confirmed in larger number of patients. No significant financial relationships to disclose.
EGFR, MAPK, and Akt status by immunohistochemistry (IHC) are not correlated with clinical outcome in HER2-positive (HER2+) metastatic breast cancer (MBC) patients (pts) treated with trastuzumab (T) with or without chemotherapy (CT)
Authors: Gori S. , Sidoni A. , Colozza M. , Ferri I. , Cioccoloni C. , Fenocchio D. , Mosconi A. , Anastasi P. , De Angelis V. , Crinò L. 
Published: March 2020

1090 Background: T alone or in combination with CT has been shown to be an active therapy in HER2-positive MBC pts. However, not all pts will benefit and mechanisms of resistance to T are still poorly understood. The aim of this study was to evaluate the IHC expression of EGFR and two downstream effectors of the EGFR family signaling pathway, MAPK and Akt and their correlation with clinical outcome in HER2-positive MBC pts treated with T ± CT. Methods: 133 consecutive HER2+ MBC pts were treated between 04/99 and 03/06 but tumor tissue was available for this analysis only from 45 pts. HER2 evaluated by CB11 was scored according to Herceptest. Tumors were considered EGFR positive if =1% positive tumor cells and MAPK positive and Akt positive if the percentage of positive tumor cells was =10%. Results: At median follow up of 57 months (range 5–229) from the start of T, 45 pts were evaluable for TTP and OS and 42 for response to T. Median age of pts was 53 years (23–77). Twenty seven objective responses (CR+PR) to T ± CT (64.28%) were observed; median TTP was 24 months (3.3–179.8). In 11 of the 27 responsive pts (40.7%), progression was observed in CNS ± other sites. Median OS from the start of T was 74 months. EGFR positive tumors were 10 (22.2%), MAPK positive tumors were 16 (35.5%) and Akt positive tumors were 23 (51.1%). We analyzed the correlation of HER2, EGFR, MAPK and Akt status with response to T, TTP and OS. HER2 was significantly correlated with response to T (p = 0.013): in HER2 3+ tumors we observed 22 (9 CR and 13 PR) out of 27 objective responses but, no significant correlation was found between HER2 status and TTP and OS. EGFR, MAPK and Akt status of tumor were not significantly associated with response to T, TTP and OS in this series of HER2+ MBC pts. Conclusions: We did not found any significant correlation between EGFR, MAPK, Akt status evaluated by IHC and clinical outcome in HER2+ MBC pts treated with T ± CT. Only HER2 status evaluated by IHC significantly correlated with response to T ± CT. No significant financial relationships to disclose.
Capecitabine (X) monotherapy as first-line chemotherapy (CT) for metastatic breast cancer (MBC): High efficacy regardless of prior therapy
Authors: Mauriac L. , Trainaud A. , Floquet A. , Donamaria C. , Durand M. , Brouste V. , Debled M. 
Published: March 2020

1092 Background: X is one of the most active agents in pretreated MBC. Data on X monotherapy as first-line CT are limited, although a recent randomized phase III trial showed a survival benefit vs oral CMF (Stockler et al SABCS 2006). We retrospectively analyzed MBC pts receiving first-line X at our institution. Methods: Between 01/2002 and 09/2006, 167 pts received X (bid, days 1–14 q3w). Response classifications (improvement in disease [ID], stable disease [SD], or progressive disease [PD]) were as described by Hennessy et al (Ann Oncol 2005). Results: Median age was 68 years (range 34–91). Prior adjuvant therapy included CT in 47% and tamoxifen in 49% of pts. Median interval between initial surgery and MBC was 4.4 years (range 0–39). Before X, most pts (79%) had received endocrine therapy (ET) for MBC (median 2 lines, median duration 2.1 years). Median no. of metastatic sites was 2; bone and visceral metastases were each present in 60% of pts. The initial X dose was 1,500–2,500mg/d in 23%, 3,000mg/d in 47%, and 3,150–4,800mg/d in 29% of pts. ID was seen in 57% of pts (median duration 11.7 months [95% CI 3.8–28.6]). A further 20% had SD for =6 weeks. Median time to X failure (TTF) and OS were 9.0 [95% CI 7.1–11.0] and 25.8 months [95% CI 22.1–29.5], respectively. None of the following influenced TTF: age (<70/=70y), prior adjuvant CT (yes/no), prior ET for MBC (no/<12m/=12m), visceral disease (yes/no), initial dose (<3,000/3,000/>3,000mg). Toxicities were typical of X monotherapy. X was continued for =12 months in 46 pts without cumulative toxicity. Conclusions: X appears highly active as first-line CT for MBC pts, including those who had received ET for MBC and/or adjuvant CT. Long-term treatment is well tolerated. The safety profile is consistent with previous reports. High activity, oral administration, lack of alopecia, and low hematologic toxicity make X a very attractive first- line CT for slowly progressing disease and/or after ET failure. No significant financial relationships to disclose.
Capecitabine/cisplatin doublet in antracycline and taxane pre-treated patients with metastatic breast carcinoma
Authors: Oksuzoglu B. , Abali H. , Ozdemir N. , Budakoglu B. , Hayran M. , Zengin N. 
Published: March 2020

1093 Background: Treating heavily pretreated metastatic breast cancer patients is challenging. To evaluate the activity and toxicity of the combination of capecitabine and cisplatin (CapCisp) in antracycline and taxane pretreated metastatic breast carcinoma (MBC) patients was the aim of our study. Methods: Thirty-three female MBC patients, 20 to 61 years of age (median; 41) were included in the study. Patients received Cap 2x1000 mg/m2 on days 1–14, and Cisp 60 mg/m2 on day 1, repeated every 3 weeks. In the case of disease control without intolerable toxicity, single agent Cap was continued. Results: Infiltrative ductal carcinoma was the most common histology (88%). In 23 patients with assigned histological grade, 13% had grade 1, 48% grade 2, and 39% grade 3 disease. Estrogen receptor (ER), Progesteron receptor (PR), and c-ErbB2 were positive in 39%, 63%, and 42%, respectively. All patients were pretreated with antracycline and taxane on an adjuvant or palliative basis before CapCisp chemotherapy. Altogether were given 154 courses of CapCisp chemotherapy (range; 1–8 courses per patient, median; 5 courses). Disease control rate was 82% (complete response, n: 1; partial response, n:16, stable disease, n: 10, progressive disease, n: 6). Eleven patients continued with single agent Cap (median; 4, range; 3–6 cycles). Grade 1 and 2 nausea/vomiting (66.7%) and fatigue (60.6%) were the most frequently observed side effects. Grade 3 neutropenia was observed in 4 patients (12.1%). Median follow-up was 9.5 months or until death. Median duration of response was 5.1 months (3.2–6.9, %95 CI). Median time to disease progression was 6.3 months (3.8–8.8, %95 CI). Fifteen patients died, and median survival was 11.5 months (6.9–16.1, 95% CI). Conclusion: CapCispl doublet has an encouraging antitumor activity with acceptable and manageable toxicity in antracycline and taxane pretreated metastatic breast carcinoma patients. No significant financial relationships to disclose.
A retrospective review of breast cancer patients with central nervous nystem metastasis treated with capecitabine
Authors: Kurt M. , Aksoy S. , Hayran M. , Guler N. 
Published: March 2020

1098 Background: In all of the major studies on the effects of capecitabine in metastatic breast cancer (MBC) patients with central nervous system (CNS) metastasis were categorically excluded, understandably due to the poor outcome associated with such advanced disease, and as a consequence, the data are limited on such cases. The aim of this study was to evaluate the effectiveness and toxicity of capecitabine in breast cancer patients with CNS metastasis. Methods: The records of all patients with MBC presenting to the Department of Medical Oncology at Hacettepe University Hospital, Ankara, Turkey, for treatment between December 2001 and December 2005 were evaluated. Patients who recieved capecitabine as a sole agent for MBC with CNS metastasis were included in the study. All patients recieved capecitabine at a dose of 2,500mg/m2/day for 14 days at 3 weeks intervals. Results: Twenty patients were included in this retrospective analysis. All were female with a median age of 38 years (range, 20–58) at the diagnosis and the median time to brain metastasis was 3.9 years (range, 0.5–19.6). Three patients had undergone surgery for CNS metastasis, and all patients had recieved whole brain radiotherapy before the capecitabine treatment. A total of 159 cycles of chemotherapy were introduced and for each patient median number of chemotherapy cycles were 6.5 (range 1–28 cycles). Nine of them were given capecitabine as first-line chemotherapy after brain metastasis. There were 2 (10%) complete (one patient had metastasectomy for brain metastasis), and 7 (35%) partial responses with 6 (30%) patients having stable disease. Progressive disease was observed in 5 (25%) patients. Overall response rate was 45%. Median progression free survival time was 7.3 months (range 1.8–26.7). Adverse effects were seen in 13 patients, with grade 3 hand food syndrome occuring in 5 patients resulting in dose reduction. Grade II neutropenia was observed in 1 patient. Conclusions: Capecitabine is effective and well tolerated in the treatment of breast cancer patients with CNS metastases. No significant financial relationships to disclose.
Randomized phase II study of biweekly gemcitabine (gem)-paclitaxel (pac), gem-carboplatin (carb) and gem-cisplatin (cis) as first-line treatments in metastatic breast cancer (MBC) after anthracycline failure
Authors: Xu B. , Jiang Z. , Kim S. , Yu S. , Feng J. , Malzyner A. , Giglio A. Del , Chung H. , Yu M. , Serrano A. 
Published: March 2020

1099 Background: Biweekly gem-pac and gem-cis regimens have shown promising activity and safety in different tumor types. In MBC biweekly gem-pac is active and well tolerated. The aim of this multi-country study is to evaluate the efficacy and safety of gem in combination with pac, carb or cis on a biweekly schedule in patients (pts) with MBC. Methods: Major eligibility criteria included: tissue diagnosis of stage IV breast carcinoma; prior anthracycline therapy; ECOG performance status (PS) of 0 or 1; and written informed consent. Pts were randomized to receive gem 2500 mg/m2 in combination with pac 150 mg/m2 (Arm A), carb AUC 2.5 (Arm B) or cis 50 mg/m2 (Arm C) on day 1 of 2-week cycles. The primary endpoint was response rate, with safety a secondary endpoint. Results: This interim analysis was planned to occur when patient enrollment had reached 50% (75/150 pts), at which point there were 26 pts in Arm A, 25 in Arm B and 24 in Arm C, with 12 pts still on treatment. The baseline characteristics were similar in the three arms, including mean age (Arm A 50.2 yr, Arm B 46.1, Arm C 47.3); ECOG PS (PS 0: 50.0%, 64.0%, 54.2%); mean number of sites of tumor involvement (2.9, 2.6, 2.7); dominant type of metastasis (visceral: 73.1%, 80.0%, 79.2%); and disease-free interval (<24 mo: 53.8%, 60.0%, 41.7%). The mean number of cycles was 6.4, 6.0 and 5.8. There was a partial response in 5/26 efficacy qualified pts (19.2%), 5/25 pts (20.0%) and 2/23 pts (8.7%) in Arms A, B and C, respectively, stable disease in 10 pts (38.5%), 9 pts (36.0%) and 9 pts (39.1%), and progressive disease in 5 pts (19.2%), 6 pts (24.0%) and 6 pts (26.1%). There were no treatment-related deaths. Conclusions: The three regimens appear to show activity and have manageable toxicity when given on a biweekly schedule. [Table: see text] No significant financial relationships to disclose.
Impact of trastuzumab on the pathological complete response (pCR) rates in primary systemic therapy for breast cancer
Authors: Mizuta N. , Nakajima H. , Sakaguchi K. , Hachimine Y. , Fujiwara I. 
Published: March 2020

11000 Background: Various regimens of primary systemic therapy (PST) have been performed to patients with locally advanced breast cancer to decrease the size of the primary tumor and allow for effective local and distant control. In terms of pathological complete response (pCR) rate, however, satisfactory results were not obtained. Therefore, in this study, we have tried to determine whether the addition of trastuzumab on PST could increase pCR rate. Methods: Two prospective nonrandomized studies were performed that used different regimens as PST, followed by breast conserving surgery. Group-A ; Eighty-fore HER2-negative patients with operable breast cancer were assigned to 4 cycles of epirubicin and cyclophosphamide followed by 12 cycles of weekly paclitaxel. GroupB; Eighteen HER2-positive patients were assigned to 4 cycles of epirubicin and cyclophosphamide followed by 12 cycles of weekly paclitaxel and trastuzumab. Results: A total of 102 assessable patients were enrolled, and all the patients have completed the above 2 regimens of PST. Pathological complete response (pCR) rates were 12% in Group-A and 61.1% in Group-B, respectively. Following the PST, 75% of Group-A and all of Group-B patients were able to be subjected to breast conserving surgery. All the toxicities happened in both groups were well controlled in grade 1 or 2. Conclusion: These results indicate that both the PST regimens were safely performed in women with locally advanced breast cancer and allow breast conserving surgery in a high fraction of patients (90%). In addition, significantly high rates of pCR were obtained in patients with use of trastuzumab (p<0.01). No significant financial relationships to disclose.
Association between standard clinical and pathological breast cancer characteristics and the 21-gene recurrence score: A population-based study
Authors: Wolf I. , Ben-Baruch N. , Shapira-Frommer R. , Rizel S. , Goldberg H. , Yaal-Hahoshen N. , Klein B. , Geffen D. B. , Kaufman B. 
Published: March 2020

11002 Background: The 21-gene recurrence score (RS) aims to quantify chemotherapy benefit in lymph node-negative, estrogen receptor (ER)-positive breast cancer (BC) patients. We aimed to elucidate the association between the RS and clinical-pathological features in a population-based Israeli cohort. Methods: Study population included all Israeli BC female patients referred to the RS assay from October 2004 until October 2006. Clinical and pathology data were collected upon referral, RS risk was categorized as previously defined (low < 18, intermediate 18–30, high = 31) and chemotherapy benefit was also assessed for each patient using NCCN guidelines, St. Gallen recommendations and Adjuvant! Online. Results: 300 patients were referred to the assay by 70 physicians from 16 institutions. Low, intermediate and high RS were noted in 109 (36 %), 134 (45 %) and 57 (19%) of the patients respectively, compared to 54%, 21% and 25% respectively, in the validation study (JCO;24:3726). Median age was 54 and median tumor size was 1.6 cm. Similar age distribution, tumor size and ER staining intensity were noted in all risk categories. Interestingly, no association has been identified between the RS and the presence of lymph nodes micrometastases. High tumor grade was noted in 15%, 20% and 56%; progesterone expression in 88% 72% 43%; non-infiltrative ductal carcinoma (IDC) 24%, 12% and 6%; and Her2 expression in 2%, 3% and 19% of the low, intermediate and high risk categories respectively (p<0.0001 for all variables). Risk assessment according to clinical guidelines or Adjuvant! Online correlated poorly with the RS. Conclusions: Risk stratification of referred Israeli patients differs from that of the validation study population. Moreover, the RS did not correlate with age, tumor size and ER intensity. The RS correlated with histology, grade, PR and Her2 expression and may be predicted, in specific subsets of patients, using these features. However, RS categorization cannot be predicted by commonly-used clinical predicting tools. No significant financial relationships to disclose.