Project description:We compared the results of randomised trials comparing taxane-containing chemotherapy regimens with regimens not containing a taxane in women with metastatic breast cancer. The specialised register of the Cochrane Breast Cancer Group was searched in March 2004. Eligibility was assessed and data extracted from eligible studies by two reviewers. Hazard ratios (HR) were derived for time-to-event outcomes, and a fixed-effect model was used for meta-analysis. Tumour response rates were analysed as dichotomous variables. Of 21 eligible trials, 16 had published some results and 12 data on overall survival. An estimated 2621 deaths among 3643 women suggest a significant difference in overall survival in favour of taxane-containing regimens (HR 0.93, 95% confidence interval (CI) 0.86-1.00, P=0.05). The treatment effect on survival was similar if only trials of first-line chemotherapy were included, although not statistically significant. There appeared to be an advantage for taxanes in time to progression (HR 0.92, 95% CI 0.85-0.99, P=0.02) and overall response (odds ratio (OR) 1.34, 95% CI 1.18-1.52, P<0.001). There was significant heterogeneity across the trials (P<0.001), partly because of the varying efficacy of the comparator regimens. Taxane-containing regimens improved overall survival in women with metastatic breast cancer. Taxane-containing regimens are more effective than some, but not all, nontaxane-containing regimens.
Project description:BackgroundApproximately one-fifth of women who develop early breast cancer have HER2-positive tumours, which if untreated, have a worse prognosis than HER2-negative tumours. Trastuzumab is a selective treatment targeting the HER2 pathway. Although the results on efficacy seem to support its use, there are potential cardiac toxicities which need to be considered, especially for women at lower risk of recurrence, or those at increased cardiovascular risk.ObjectivesTo assess the evidence on the efficacy and safety of therapy with trastuzumab, overall and in relation to its duration, concurrent or sequential administration with the standard chemotherapy regimen in patients with HER2-positive early breast cancer.Search methodsWe searched the Cochrane Breast Cancer Group's (CBCGs) Specialised Trials Register, and used the search strategy developed by the CBCG to search for randomised controlled trials (RCTs) in CENTRAL, MEDLINE, EMBASE, BIOSIS, TOXNET, and the WHO ICTRP search portal (up to February 2010).Selection criteriaRCTs comparing the efficacy and safety of trastuzumab alone, or in combination with chemotherapy, or no treatment, or standard chemotherapy alone, in women with HER2-positive early breast cancer including women with locally advanced breast cancer.Data collection and analysisWe collected data from published and unpublished trials. We used hazard ratios (HRs) for time-to-event outcomes and risk ratio (RRs) for binary outcomes. Subgroup analyses included duration (less or greater than six months) and concurrent or sequential trastuzumab administration.Main resultsWe included eight studies involving 11,991 patients. The combined HRs for overall survival (OS) and disease-free survival (DFS) significantly favoured the trastuzumab-containing regimens (HR 0.66; 95% confidence interval (CI) 0.57 to 0.77, P < 0.00001; and HR 0.60; 95% CI 0.50 to 0.71, P < 0.00001, respectively). Trastuzumab significantly increased the risk of congestive heart failure (CHF: RR 5.11; 90% CI 3.00 to 8.72, P < 0.00001); and left ventricular ejection fraction decline (LVEF: RR 1.83; 90% CI 1.36 to 2.47, P = 0.0008). For haematological toxicities, risks did not differ. The two small trials that administered trastuzumab for less than six months did not differ in efficacy from longer studies, but found fewer cardiac toxicities. Studies with concurrent administration gave similar efficacy and toxicity results to sequential studies.Authors' conclusionsTrastuzumab significantly improves OS and DFS in HER2-positive women with early and locally advanced breast cancer, although it also significantly increases the risk of CHF and LVEF decline. The available subgroup analyses are limited by the small number of studies. Studies that administered trastuzumab concurrently or sequentially did not differ significantly in efficacy. Shorter duration of therapy may reduce cardiotoxicity and maintain efficacy, however there is insufficient evidence at present to conclude this due to small numbers of patients in these trials.
Project description:Platinum-based chemotherapy regimens are frequently used in patients with triple-negative breast cancer (TNBC). The aim of the current study was to assess whether or not platinum-based chemotherapy is associated with an increased time to progression when compared with non-platinum-based regimens in TNBC and non-TNBC. A retrospective analysis was conducted within a cohort of patients with metastatic breast cancer who received platinum-based chemotherapy at a single institution. Data were collected for up to three lines of treatment for metastatic disease. Time to progression was determined for platinum-based chemotherapy and non-platinum-based regimens for each line of treatment. Adjusted hazard ratios (HRs), together with 95% confidence intervals (CIs) were estimated comparing the time to progression associated with the use of platinum-based chemotherapy versus non-platinum-based regimens. A total of 159 patients were included in the analysis, with 58 diagnosed with TNBC. Among the patients with TNBC, compared with non-platinum-based chemotherapy, no correlation was identified between platinum-based chemotherapy and an improved time to progression [first line: HR, 0.97 (95% CI, 0.40-2.35); second line: HR, 0.91 (95% CI, 0.42-2.01); and third line: HR, 2.83 (95% CI, 0.73-11.03)]. By contrast, patients with non-TNBC appeared to improve with non-platinum-based chemotherapy [first line: HR, 2.57 (95% CI, 1.11-5.99); second line: HR, 1.91 (95% CI, 1.00-3.63); and third line: HR, 1.08 (95% CI, 0.53-2.18)]. Although the present study was limited by the sample size and its observational nature, the results indicated that platinum-based chemotherapy does not offer a discernible or distinct advantage compared with standard regimens in patients with TNBC, and is perhaps less efficacious in patients with non-TNBC.
Project description:Despite the available prevention and early detection strategies, squamous-cell carcinoma of the uterine cervix is still diagnosed as locally advanced disease in a considerable proportion of patients. As a potent sensitizer of cancer cells, cisplatin has been the "traditional partner" of external beam irradiation in this setting for more than two decades. Induction chemotherapy strategies followed by concurrent chemoradiation or surgery and preoperative concurrent chemoradiation have been recently implemented in clinical trials in an effort to optimize local control and to minimize the risk of distant metastases. In this context, cisplatin has been combined with a number of other potential radiosensitizers, including 5-fluorouracil, capecitabine, and gemcitabine. In patients resistant or intolerant to platinum compounds, numerous non-platinum-containing regimens have been developed, implementing various antimetabolites, taxanes, antineoplastic antibiotics, and topoisomerase II inhibitors. More recently, molecular agents targeting critical pathways in cervical malignant transformation are being assessed in early clinical trials in combination with external-beam irradiation. In the current work, we review the evolving role of cisplatin and other platinum compounds, either alone or in combination regimens, in the context of other potent radiosensitizers. The emerging role of molecular targeted agents, as candidate partners of external beam irradiation, is also discussed.
Project description:BackgroundCapecitabine-based chemotherapy (CBC) presents potential value in patients with liver metastasis; platinum-based chemotherapy (PBC) has shown promising benefit in patients with triple-negative breast cancer (TNBC). For TNBC patients with liver metastasis, which treatment strategy is better remains to be further studied. The aim of this study was to report the first real-world data evaluating the efficacy and safety of PBC versus CBC in the first-line treatment in Chinese TNBC patients with liver metastasis.MethodsTNBC patients with liver metastasis pretreated with anthracyclines/taxanes in 4 institutions of China between January 2010 and December 2019 were included. Objective response rate (ORR), overall survival, treatment pattern, and toxicity profile were assessed between PBC and CBC groups.ResultsA total of 59 TNBC patients with liver metastasis were identified. Among these, 33 were treated with PBC and 26 were treated with CBC. The ORR was higher in the CBC group than in the PBC group (57.7% versus 30.3%, P=0.035). Median overall survival was also greatly improved (19.2 versus 14.4 months, P=0.041). Docetaxel/cisplatin was more likely to be used for PBC, and paclitaxel/capecitabine was the main regimen for CBC. Multivariable Cox regression analysis indicated that CBC was an independent predictor for overall survival after adjustment for baseline factors including age, tumor size, nodal status, prior anthracyclines/taxanes use, and tumor grade (odds ratio =0.51; 95% confidence interval, 0.27-0.98; P=0.042). Adverse events were not different except gastrointestinal tract toxicities, hand-foot syndrome and hematologic toxicity.ConclusionsFor TNBC patients with liver metastasis, capecitabin-based chemotherapy might be more suitable than the platinum-based regimen in the first-line treatment, as measured by objective response rate and overall survival. Further large-scale studies are warranted.
Project description:PurposeBased on improvement in pathologic complete response (pCR) in the NeoSphere and TRYPHAENA studies, the FDA approved neoadjuvant pertuzumab for HER2+ localized breast cancer. These studies demonstrated high pCR rates with THP (docetaxel + HP), FEC (5-fluorouracil, epirubicin, and cyclophosphamide)-THP, and TCHP (docetaxel, carboplatin + HP). However, in the United States, doxorubicin/cyclophosphamide (AC) is favored over FEC despite no data comparing neoadjuvant AC-THP with AC-TH or TCHP. Here we report outcomes for patients with localized HER2+ breast cancer treated with pertuzumab-containing neoadjuvant regimens and AC-TH.MethodsWe reviewed clinicopathological characteristics of patients with HER2+ breast cancer (Stage I-III) treated with either a neoadjuvant pertuzumab-containing regimen or dose-dense (dd) AC-TH, from 2011 to 2016 at a large academic medical institution and two affiliated community sites. pCR was defined as ypT0/is ypN0. Fisher's exact test and logistic regression analysis were used for statistical analysis.ResultsIn this study (N = 121), pCR was numerically higher with pertuzumab-based regimens, including ddAC-THP (60%), TCHP (63%), THP (55%), as compared with ddAC-TH (46%). THP resulted in significantly less cycle delays due to toxicity compared to the other regimens (p = 0.02). THP also resulted in the least dose reductions, lowest rate of hospitalization, and lowest rate of treatment discontinuation.ConclusionsPertuzumab-based regimens, including THP, resulted in higher pCR rates as compared to ddAC-TH, with the THP regimen associated with the best tolerability among patients with localized HER2+ breast cancer. Given the various neoadjuvant regimens, additional studies are needed to determine optimal treatment sequencing and escalation/de-escalation strategies to personalize neoadjuvant regimens for localized HER2+ breast cancer.
Project description:Upon its establishment for the treatment of metastatic breast cancer (mBC), continuing trastuzumab beyond disease progression was an important paradigm shift that became the recommendation by major guidelines. However, data supporting continuation of human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab beyond the second-line setting are limited, resulting in a lack of approval of, or access to, this therapeutic strategy in many countries. This study aimed to provide additional data on the continued use of trastuzumab and trastuzumab-based therapies in combination with chemotherapy (CT) as third-line treatment for patients with mBC. This open-cohort, retrospective, observational study used deidentified patient-level data from an electronic health record-derived database that included patients with mBC who initiated third-line treatment with trastuzumab-based therapy combined with CT (Tras + CT; n = 288) or CT alone (CT; n = 49). Patients who received Tras + CT had a longer weighted median overall survival vs those who received CT only: 20.6 months (95% CI, 18.3-26.4 months) vs 10.1 months (95% CI, 7.8-12.3 months), respectively (hazard ratio [HR], 0.29; 95% CI, 0.16-0.53). This study provides additional support for maintaining trastuzumab-based therapies for patients with HER2+ mBC beyond second-line treatment. This treatment option should be available for all patients with mBC worldwide.