Search

Objective: Febrile neutropenia (FN) is a common toxic side effect of myelosuppressive chemotherapy. The cost-effectiveness of primary prophylaxis (PP) of FN with granulocyte colony stimulating growth factor (G-CSF) filgrastim for six or eleven days was compared to single dose pegfilgrastim in patients with early breast cancer receiving chemotherapy (>or= 20 % FN risk) as simulated in a model., Methods: Based on a decision-analytical model we conducted a cost-effectiveness analysis (CEA) and a cost-utility analysis (CUA) from the perspective of the Statutory Health Insurance (SHI) in Germany. The model simulated three clinical alternatives being built on each other, that pegfilgrastim and filgrastim had differential impact on (1) the risk of FN, (2) on FN-related mortality, and (3) on the achieved chemotherapy relative dose intensity (RDI) leading to gain in long-term survival., Results: Assuming a 5.5 % lower risk of FN for PP with pegfilgrastim than an 11-day course of filgrastim provided - from the perspective of the SHI - a cost saving of Euro 2,229. A gain of 0.039 quality-adjusted life-years (QALY) resulted when the third alternative was used. Assuming a 10.5 % lower risk of FN for PP with pegfilgrastim than a 6-day filgrastim course, the third alternative showed an incremental cost-effectiveness ratio (ICER) of Euro 17.165 per life-year gained (LYG) and Euro 18.324 per QALY with 0.074 QALYs gained., Conclusion: These results indicate that PP with pegfilgrastim is cost saving compared to 11-day use of filgrastim and cost-effective compared to 6-day use of filgrastim in patients with breast cancer treated in Germany.

High-risk situations in early breast cancer concern patients with less than 3 involved lymph nodes but additional risk factors as well as patients with more than 3 involved lymph nodes. For the first group, new risk assessment methods to better identify the need for chemotherapy with or without a taxane or with a taxane instead of an anthracycline are needed. For the second group, further improvement of anthracycline- or taxane-containing chemotherapy regimens is warranted. Current approaches include the sequential or simultaneous use of these groups of agents, the combination with antimetabolites, antibodies or small molecules, the neoadjuvant use of chemotherapy as well as dose-dense and dose-escalated chemotherapy regimens., (Copyright 2008 S. Karger AG, Basel.)

The Organgruppe Mamma der Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) conducted a nationwide 3-phase analysis of the care structure and standard of therapy given to patients with breast cancer from 2002 (4th quarter) to 2004 (4th quarter). The analysis includes 1069 patients from 257 institutions; 34% with early breast cancer and 66% with metastatic disease. No reliable data on the pattern of care of these patients have been published to date in Germany. The extent to which national and international therapy recommendations were implemented in routine clinical practice was unclear. Evaluation of the data shows that treatment based on the guidelines is now being implemented very reliably in certain sectors. This is of particular relevance to the pattern of adjuvant treatment in early breast cancer. At that time 68 % of the patients received an anthracyclin based chemotherapy and in addition 18% received an anthracycline and taxane based chemotherapy. Participation in clinical trials peaked with 30% in the neoadjuvant setting. The problem with metastatic breast cancer is the complexity of the interdisciplinary treatment involved. The present analysis conducted by the AGO was the first attempt to analyse the treatment given to metastatic patients and to systematise the approach to treatment. The fundamental problem remains, irrespective of the stage of the tumour, namely that too few patients are treated in randomised clinical studies.

Neoadjuvant chemotherapy provides today a valid option for many patients with primary breast cancer. For evaluation of treatment response as well as for biomarker studies for prediction of response, an efficient collaboration between pathologists and gynaecological oncologists is essential. This report reflects aims and indication according to the current opinion, describes advantages and disadvantages in comparison to the conventional adjuvant approach and provides guidelines on how to conduct the whole treatment concept of neoadjuvant therapy. Current and projected study concepts of preoperative and following postsurgical treatments in Germany are introduced. While the basic principles of histopathological evaluation of tumour specimens from neo-adjuvant breast cancer studies are similar to conventional surgical therapy, some aspects of histopathological management are of special importance in these studies.

Primary systemic treatment today represents a new option for patients with operable breast cancer and is equally effective as conventional adjuvant chemotherapy. Improving surgical options is the most important indication for choosing this approach. The highest chance for breast conserving surgery can be obtained when a sequence of adriamycin and cyclophosphamide (AC) is followed by docetaxel. This has been shown in the Geparduo and NSABP-B27 trial. New approaches are considering individual tailoring of treatment according to either early response of the primary breast tumor (Gepartrio) or pharmacogenetic testing on the tumor tissue., (Copyright 2003 S. Karger GmbH, Freiburg)

Primary systemic therapy represents today the standard of care in patients with locally advanced breast cancer and becomes more and more an alternative to adjuvant postoperative chemotherapy in patients with operable breast cancer. In a subset of large randomized trials it could be shown that sequential schedules with more than 4 cycles can reach the highest rates of clinical and histopathological complete remissions. In two randomized trials (NSABP B-27, Geparduo) using 4 cycles of Adriamycin/Cyclophosphamide followed by 4 cycles of Docetaxel significant better results could be obtained in comparison with the referring control arm. New approaches try to further individualize chemotherapy, either using molecular biological tumor factors or the early effect of some chemotherapy cycles. In the Gepartrio study clinical response evaluation after 2 cycles can identify patients with a high or low chance for a histopathological complete remission and further treatment strategies can be developed for these different subgroups.

Purpose: To evaluate the potential of stereotactic vacuum breast biopsy in the histologic evaluation of suspicious mammographic findings ( BI-RADS IV)., Materials and Methods: In 221 patients with 227 probable mammographic lesions categorized as ( BI-RADS -IV), stereotactic biopsies were performed with an 11-gauge vacuum-assisted biopsy device (Mammotome). The evaluation included the histology of the specimens obtained with the Mammotome or with surgery, the time for the biopsy, the amount of bleeding, number of rotations and procured specimens, the extent of the resection and the complications., Results: The biopsies were technically successful in 214 of the 227 probable mammographic lesions, with 176 lesions mostly resected and 34 lesions removed more than 50 %. No representative tissue was obtained from 4 lesions. All biopsies were performed without any clinically relevant complications and terminated after adequate material was obtained (O 28 specimens, 2.58 rotations). The mean time needed for performing the biopsy was 40.2 minutes. The histologic findings were DCIS (42 lesions), ADH (7 lesions), LCIS (3 lesions), ID-Ca (14 lesions, IL-Ca (3 lesions), and IDL-Ca (1 lesion). In 28 of 42 lesions with the initial DCIS histology, the surgical histology was also DCIS (n=28) or no residual tumor (n=10). In 4 lesions with an initial DCIS-histology, the surgical histology was invasive ductal cancer (9.5 %). The late follow-up examinations (up to 3 years) did not find any evidence of a false negative biopsy., Conclusion: Stereotactic vacuum breast biopsy ideally complements existing breast biopsy methods. The method is minimal invasive with a low rate of mostly minor complications.

The standard primary therapy of advanced ovarian cancer consists of platinum derivatives in combination with paclitaxel. In a first report presented at this year's meeting of the American Society of Clinical Oncology (ASCO) docetaxel appeared to be as effective as paclitaxel in combination with carboplatin, while the toxicity profile present some advantages. The addition of a third drug to platinum-taxane-combination does not appear to improve the therapeutic index. According to the data of the ICON1- and ACTION-trial, carboplatin containing chemotherapies are associated with a significant benefit also in early ovarian cancer. Platinum-resistant disease remains a therapeutic challenge, since the available drugs display only limited activity of short duration. Some experimental data suggest evidence for a possible therapeutic role of small molecules that inhibit the epidermal growth factor receptor (OSI-774) or antisense oligonucleotides interfering with EGF-receptor signalling (ISIS 5132). Novel classes of chemotherapeutic agents, including the acylfulvenes and the epothilone-analogues warrant further study in this disease. Multimodal therapies combining cytotoxic agents with antibodies against CA 12-5 or metalloproteinase inhibitors have failed to demonstrate any survival benefit in patients with ovarian cancer. Despite significant progress in the last decade ovarian cancer remains the most lethal gynaecologic malignancy in women in most western countries. Further multicenter clinical studies are needed to better define new therapeutic options.

Objective: The German Adjuvant Breast Cancer Study Group (GABG) conducts trials of preoperative chemotherapy in patients with primary breast cancer using a combination of doxorubicin and docetaxel (ADoc). -, Patients and Methods: We conducted a parallel-grouped phase IIa-study with 42 patients with a conventionally dosed and a dose-dense ADoc-schedule (4 cycles of Doxorubicin 50 mg/m(2), Docetaxel 75 mg/m(2) i. v. day 1, q day 15 or 22; G-CSF day 3-15 only for the dose-dense schedule) and a randomized phase IIb-study (GEPARDO-Study) with 250 patients with ADoc +/- Tamoxifen. Biological factors were determined immunohistochemically on 197 core biopsies before treatment. A comparison to a sequential AC-Doc regimen including 913 patients has been completed recently. -, Results: ADoc can be applicated on schedule in 93 % of all patients. The dose-dense regimen shows a tendency to more toxicity but also to more efficacy. The rate of complete pathological remissions (pCR) was 9.7 %. No difference was found between chemo- and chemoendocrine treatment. Clinically negative lymphnodes and a negative estrogen receptor status is predictive for a higher pCR-rate. To date no differences in toxicity could be found between ADoc and AC-Doc. -, Conclusions: The dose-dense ADoc regimen is well tolerated and highly effective as preoperative therapy of breast cancer.

Background: Symptomatic brain metastases occur in approximately 10-15% of patients suffering from breast cancer and are linked to a clear deterioration of the patient's condition. Although radiotherapy is recommended as a primary therapy, the optimal management remains controversial. To evaluate the role of topotecan as a primary chemotherapy for brain metastases, we performed a pilot study in patients with metastatic breast cancer., Patients and Methods: 24 patients with newly diagnosed, bidimensionally measurable brain metastases received topotecan, 1.5 mg/m(2) day, 30-min infusion for 5 days every 3 weeks. A total of 93 courses of therapy were administered (range 1-11, median 3 courses per patient). Prior radiotherapy was excluded. Most of the patients had received prior adjuvant or palliative chemotherapy., Results: 3/24 patients were withdrawn from the study for various reasons, 16/24 patients could be evaluated in terms of their response to therapy; 1 and 5 patients showed complete and partial response to therapy, respectively, and 5 patients had a stable condition. The median time of survival was 6.25 months. Hematologic toxicity was the major side effect, nonhematologic side effects occurred rarely and were tolerable., Conclusions: Our results demonstrate that primary chemotherapy with topotecan is an effective and well-tolerated treatment for patients with breast cancer and CNS metastases. Based on this pilot study, future clinical protocols should be developed including multimodal treatment strategies (i.e. radiotherapy)., (Copyright 2001 S. Karger GmbH, Freiburg)

Breast cancer metastastic to sites beyond regional axillary lymph nodes represents a historically incurable condition despite the judicious use of various hormonal manipulations and surgical and radiotherapeutic interventions, and the application of active cytotoxic chemotherapeutic agents for hormone-refractory disease. The systemic management of patients with hormone refractory breast cancer is classically characterized by the thoughtful, stepwise administration of cytotoxic chemotherapeutic agents. At various junctures in the continuum of care, a patient/physician analysis of the potential risks and benefits of chemotherapy may lead to the decision to proceed with subsequent systemic therapy, to consider an investigational strategy like new active agents or high dose therapy, or to opt for supportive care alone.

Preoperative chemotherapy represents the standard procedure in inflammatory breast cancer. However, only recently it could be demonstrated that preoperative chemotherapy is beneficial even for patients with operable primary breast cancer. The number of breast conserving surgeries could be increased significantly. Furthermore this in vivo chemosensitivity assay can provide important prognostic as well as predictivy informations. Preoperative chemotherapy is not associated with an increased risk for the patients as outcome is similar to patients with conventional adjuvant treatment. We investigated new regimens to improve this type of chemotherapy and reached a remission rate of 93% with a combination of adriamycin and docetaxel (ADoc). A randomized study (GEPARDO-study) comparing ADoc with ADoc + tamoxifen has recently been started in Germany by the German Adjuvant Breast Cancer Study Group (GABG).

Clinical Results: Docetaxel is a taxan which has proven high efficacy in the treatment of breast cancer. The results are consistent throughout all phases of clinical evaluation. High response rates have been observed especially for women after failure of anthracyclins or with liver metastases. Response rates are superior to doxorubicin, while the extent of the side effects is comparable., Conclusion: Due to the different toxicity profile a combination of docetaxel and anthracyclins is feasible and has already been demonstrated in early clinical trials. The role of the combinatory treatments in first line or adjuvant setting is currently under investigation.

In 120 patients suffering from carcinoma of the endometrium of a wide variety of histological types, conventional clinical and morphological criteria of prognosis were compared with the DNA index (DI) and the S-phase fraction. The cellular kinetics parameters were obtained via flow cytophotometry. Adenocarcinomas (n = 101) were more frequently DNA diploid and had a lower S-phase share (less than 5%) than adenoacanthomas, clear-cell carcinomas and malignant Müller's mixed tumors. There are close correlations between the conventional prognostic factors such as FIGO stage, relative tumor invasion depth, grading and oestrogen or progesteron receptor content and the DNA content or S-phase fraction. Carcinomas with a DI less than or equal to 1.1 (n = 83) and the S-phase fraction less than 5% (n = 77), have a significantly longer survival time and recurrence-free interval than DNA-aneuploid tumors with a high S-phase fraction. The studies underline the need to use flow cytophotometry in the prognostic assessment of the carcinoma of the endometrium. The method is superior to histological grading, since the results obtained can be objectively assessed.