A randomised pilot Phase II study of doxorubicin and cyclophosphamide (AC) or epirubicin and cyclophosphamide (EC) given 2 weekly with pegfilgrastim (accelerated) vs 3 weekly (standard) for women with early breast cancer

Accelerated (dose-dense) chemotherapy, in which the frequency of administration is increased without changing total dose or duration, may increase the efficacy of cancer chemotherapy. We performed a randomised Phase II study to assess the safety and relative toxicity of AC (doxorubicin; cyclophosphamide) vs E(epirubicin)C given by conventional or accelerated schedules as neoadjuvant or adjuvant chemotherapy for early breast cancer. Furthermore, the relative toxicity of doxorubicin and epirubicin remains uncertain. Patients were randomised to one of four arms; four courses of standard 3 weekly cyclophosphamide 600 mg m−2 in combination with doxorubicin 60 mg m−2 (AC) vs epirubicin 90 mg m−2 (EC) 3 weekly vs the same regimens administered every 2 weeks with pegfilgrastim (G-CSF). A total of 126 patients were treated, 42 with standard AC, 42 with accelerated AC, 19 with standard EC and 23 with accelerated EC. Significantly more grade 3/4 day one neutropenia was seen with standard (6/61, 10%) compared to accelerated (0/65,) regimens (P=0.01). A trend towards more neutropenic sepsis was seen in the combined standard and accelerated AC arms (12/84, 14%) compared to the combined EC arms (1/42, 2%), P=0.06. Falls in left ventricular ejection fraction were not increased with accelerated treatment. Accelerated AC and EC with pegfilgrastim are safe and feasible regimens in the treatment of early breast cancer with less neutropenia than conventional 3 weekly schedules

Dose-dense adjuvant chemotherapy for primary breast cancer

Adjuvant chemotherapy has been proven to reduce significantly the risk for relapse and death in women with operable breast cancer. Nevertheless, the prognosis for patients presenting with extensive axillary lymph node involvement remains suboptimal. In an attempt to improve on the efficacy of existing chemotherapy, a phase III intergroup trial led by the Cancer and Leukemia Group B (CALGB 97-41) was designed, which tested a mathematical model of tumor growth based on the Norton–Simon hypothesis. This hypothesis, developed about 3 decades ago, and the kinetic model derived from it, created the basis of the concepts of dose density and sequential therapy, both of which were tested in CALGB 97-41. This large prospective randomized trial demonstrated that shortening the time interval between each chemotherapy cycle while maintaining the same dose size resulted in significant improvements in disease-free and overall survival in patients with node-positive breast carcinoma. This finding is highly relevant and has immediate implications for clinical practice

Incidence of chemotherapy-induced amenorrhea associated with epirubicin, docetaxel and navelbine in younger breast cancer patients

<p>Abstract</p> <p>Background</p> <p>The rates of chemotherapy-induced amenorrhea (CIA) associated with docetaxel-based regimens reported by previous studies are discordant. For navelbine-based chemotherapies, rates of CIA have seldom been reported.</p> <p>Methods</p> <p>Of 170 premenopausal patients recruited between January 2003 and September 2008, 78 were treated with fluorouracil plus epirubicin and cyclophosphamide (FEC), 66 were treated with docetaxel plus epirubicin (TE), and 26 were treated with navelbine plus epirubicin (NE). Patient follow-up was carried up every 3-4 months during the first year, then every 9-12 months during subsequent years.</p> <p>Results</p> <p>In univariate analysis, the rates of CIA were 44.87% for the FEC regimen, 30.30% for the TE regimen and 23.08% for the NE regimen (<it>P </it>= 0.068). Significant differences in the rates of CIA were not found between the FEC and TE treatment groups (<it>P </it>> 0.05), but were found between the FEC and NE treatment groups (<it>P </it>< 0.05). Furthermore, no significant differences were found between the TE and NE regimens (<it>P </it>> 0.05). Tamoxifen use was a significant predictor for CIA (<it>P </it>= 0.001), and age was also a significant predictor (<it>P </it>< 0.001). In multivariate analysis, age (<it>P </it>< 0.001), the type of chemotherapy regimens (<it>P </it>= 0.009) and tamoxifen use (<it>P </it>= 0.003) were all significant predictors.</p> <p>Conclusions</p> <p>Age and administration of tamoxifen were found to be significant predictive factors of CIA, whereas docetaxel and navelbine based regimens were not associated with higher rates of CIA than epirubicin-based regimen.</p

International Guidelines for Management of Metastatic Breast Cancer: Combination vs Sequential Single-Agent Chemotherapy

Compared with treatment options for early-stage breast cancer, few data exist regarding the optimal use of chemotherapy for metastatic breast cancer (MBC). The choice of using a combination of cytotoxic chemotherapies vs sequential single agents is controversial. At the 6th European Breast Cancer Conference, the European School of Oncology Metastatic Breast Cancer Task Force convened an open debate on the relative benefits of combination vs sequential therapy. Based on the available data, the Task Force recommends sequential monotherapy as the preferred choice in advanced disease, in the absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control. Patient- and disease-related factors should be used to choose between combination and sequential single-agent chemotherapy for MBC. Additional research is needed to determine the impact of therapy on patient-rated quality of life and to identify predictive factors that can be used to guide therapy

Utilisation of primary and secondary G-CSF prophylaxis enables maintenance of optimal dose delivery of standard adjuvant chemotherapy for early breast cancer: An analysis of 1655 patients

Optimal outcome for early breast cancer patients receiving adjuvant chemotherapy requires adequate dose delivery, commonly defined as >85% of planned dose of chemotherapy agents. Outside the clinical trial setting, reports from community oncology centres have demonstrated that a significant proportion of patients fail to receive this dose intensity, with neutropenia being the most commonly cited reason for sub-optimal treatment. Data collected prospectively on 1655 patient treated in a single breast cancer centre demonstrates that patients at risk of sub-optimal dose delivery can be identified by routine assessment of neutropenic events during the first cycle. The uniform administration of secondary G-CSF for all subsequent cycles enables dose delivery ≥85%, which was shown to lead to improved survival outcomes when compared with those patients who received <85%

Use of zidovudine-sparing HAART in pregnant HIV-infected women in Europe: 2000-2009.

BACKGROUND: Increasing numbers of women in resource-rich settings are prescribed zidovudine (ZDV)-sparing highly active antiretroviral therapy (HAART) in pregnancy. We compare ZDV-sparing with ZDV-containing HAART in relation to maternal viral load at delivery, mother-to-child transmission (MTCT) of HIV, and congenital abnormality. METHODS: This is an analysis of data from the National Study of HIV in Pregnancy and Childhood and the European Collaborative Study. Data on 7573 singleton births to diagnosed HIV-infected women between January 2000 and June 2009 were analyzed. Logistic regression models were fitted to estimate adjusted odds ratios (AORs). RESULTS: Overall, 15.8% (1199 of 7573) of women received ZDV-sparing HAART, with increasing use between 2000 and 2009 (P < 0.001). Nearly a fifth (18.4%) of women receiving ZDV-sparing HAART in pregnancy had a detectable viral load at delivery compared with 28.6% of women on ZDV-containing HAART [AOR 0.90; 95% confidence interval (CI): 0.72 to 1.14, P = 0.4]. MTCT rates were 0.8% and 0.9% in the ZDV-sparing and ZDV-containing groups, respectively (AOR 1.81; 95% CI: 0.77 to 4.26, P = 0.2). The congenital abnormality rate was the same in both groups (2.7%, AOR 0.98; 95% CI: 0.66 to 1.45, P = 0.9), with no significant difference between the groups in a subanalysis of pregnancies with first trimester HAART exposure (AOR 0.79; 95% CI: 0.48 to 1.30, P = 0.4). CONCLUSIONS: We found no difference in risk of detectable viral load at delivery, MTCT, or congenital abnormality when comparing ZDV-sparing with ZDV-containing HAART. With increasing use of ZDV-sparing HAART, continued monitoring of pregnancy outcomes and long-term consequences of in utero exposure to these drugs is required