Antonella Surbone

Paclitaxel and recombinant human granulocyte colony-stimulating factor as initial chemotherapy for metastatic breast cancer.

PURPOSE A phase II study of Taxol (paclitaxel; Bristol-Myers Squibb Co, Princeton, NJ) as initial chemotherapy for metastatic breast cancer was conducted. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was used to ameliorate myelosuppression, the anticipated dose-limiting toxicity. PATIENTS AND METHODS Twenty-eight patients with bidimensionally measurable breast cancer who had not received prior chemotherapy for metastatic disease were treated. Taxol was administered at 250 mg/m2 as a continuous 24-hour intravenous (i.v.) infusion every 21 days. rhG-CSF was administered at 5 micrograms/kg/d subcutaneously on days 3 through 10. RESULTS Objective responses were observed in 16 of 26 assessable patients (62%; 95% confidence interval, 41% to 80%). There were three (12%) complete responses (CRs) and 13 (50%) partial responses (PRs). Ten of 16 patients (63%) who had received prior adjuvant chemotherapy responded, which included one CR and four PRs among eight patients who had received prior doxorubicin-containing therapy. Responses were observed in all sites of metastatic disease. The median time to first objective response was 5 weeks (range, 1 to 14). Administration of rhG-CSF was associated with a short duration of neutropenia (median, 2 days with absolute neutrophil count < 500 cells/microL). Eight of 26 patients (31%) who received more than one course received subsequent therapy without dose reduction. One hundred seventy-eight cycles of treatment were administered, with a median of six cycles per patient (range, one to 19). Eight courses (4.5%) were associated with admissions for neutropenic fever. Twenty-two patients (79%) did not require admission for neutropenic fever. Treatment was well tolerated. Adverse effects included generalized alopecia in all patients. Myalgias, arthralgias, and peripheral neuropathy were mild. No hypersensitivity reactions and no cardiac toxicity were observed. CONCLUSION Taxol is highly active as initial chemotherapy for metastatic breast cancer. Administration of rhG-CSF reduced the incidence, depth, and duration of neutropenia, compared with published prior experience. Further studies of Taxol in breast cancer, including combinations with other active agents, are clearly warranted.

Sequential Dose-Dense Doxorubicin, Paclitaxel, and Cyclophosphamide for Resectable High-Risk Breast Cancer: Feasibility and Efficacy

PURPOSE Dose-dense chemotherapy is predicted to be a superior treatment plan. Therefore, we studied dose-dense doxorubicin, paclitaxel, and cyclophosphamide (A-->T-->C) as adjuvant therapy. METHODS Patients with resected breast cancer involving four or more ipsilateral axillary lymph nodes were treated with nine cycles of chemotherapy, using 14-day intertreatment intervals. Doses were as follows: doxorubicin 90 mg/m2 x 3, then paclitaxel 250 mg/m2/24 hours x 3, and then cyclophosphamide 3.0 g/m2 x 3; all doses were given with subcutaneous injections of 5 microg/kg granulocyte colony-stimulating factor on days 3 through 10. Amenorrheic patients with hormone receptor-positive tumors received tamoxifen 20 mg/day for 5 years. Patients treated with breast conservation, those with 10 or more positive nodes, and those with tumors larger than 5 cm received radiotherapy. RESULTS Between March 1993 and June 1994, we enrolled 42 patients. The median age was 46 years (range, 29 to 63 years), the median number of positive lymph nodes was eight (range, four to 25), and the median tumor size was 3.0 cm (range, 0 to 11.0 cm). The median intertreatment interval was 14 days (range, 13 to 36 days), and the median delivered dose-intensity exceeded 92% of the planned dose-intensity for all three drugs. Hospital admission was required for 29 patients (69%), and 28 patients (67%) required blood product transfusion. No treatment-related deaths or cardiac toxicities occurred. Doxorubicin was dose-reduced in four patients (10%) and paclitaxel was reduced in eight (20%). At a median follow-up from surgery of 48 months (range, 3 to 57 months), nine patients (19%) had relapsed, the actuarial disease-free survival rate was 78% (95% confidence interval, 66% to 92%), and four patients (10%) had died of metastatic disease. CONCLUSION Dose-dense sequential adjuvant chemotherapy with doxorubicin, paclitaxel, and cyclophosphamide (A-->T-->C) is feasible and promising. Several ongoing phase III trials are evaluating this approach.

Childbearing issues in breast carcinoma survivors

The issue of the subsequent pregnancy after breast carcinoma treatment is of paramount importance to young survivors and their oncologists. Matters related to having children, whether biologic or not, are analyzed.

5-Year Results of Dose-Intensive Sequential Adjuvant Chemotherapy for Women With High-Risk Node-Positive Breast Cancer: A Phase II Study

PURPOSE We conducted a phase II pilot study of dose-intensive adjuvant chemotherapy with doxorubicin followed sequentially by high-dose cyclophosphamide to determine the safety and feasibility of this dose-dense treatment and to estimate the disease-free and overall survival in breast cancer patients with four or more involved axillary lymph nodes. PATIENTS AND METHODS Seventy-three patients received adjuvant treatment with four cycles of doxorubicin 75 mg/m(2) as an intravenous bolus every 21 days, followed by three cycles of cyclophosphamide 3,000 mg/m(2) every 14 days with granulocyte colony-stimulating factor support. RESULTS Seventy-one patients were assessable, and all but two completed all planned chemotherapy. There was no treatment-related mortality. The most common toxicity was neutropenic fever, which occurred in 39% of patients. Median disease-free survival is 66 months (95% confidence interval, 34 to 98 months), and median overall survival has not yet been reached. At 5 years of follow-up, the disease-free survival is 51.7%, and overall survival is 60.0%. There is no long-term treatment-related toxicity, and no cases of acute myelogenous leukemia or myelodysplastic syndrome have been observed. CONCLUSION Our pilot study of doxorubicin followed by cyclophosphamide demonstrates the safety and feasibility of the sequential dose-dense plan. Long-term follow-up, although noncomparative, is promising. However, this regimen is associated with a higher incidence of toxicity (and also higher costs) than the standard dose and schedule of doxorubicin and cyclophosphamide, and therefore it should not be used as conventional therapy in the absence of demonstrated improvement of outcome. Randomized trials testing the dose-dense approach have been completed but not yet reported. Because the sequential plan can decrease overlapping toxicities, it is an appropriate platform for the addition of newer active agents, such as taxanes or monoclonal antibodies.

Ethical implications of genetic testing for breast cancer susceptibility

The identification of gene mutations involved in hereditary breast cancer is a major recent scientific discovery, enabling us to identify women at very high risk, and also providing the means to understand the biology of breast cancer and to explore novel preventive strategies. Yet, it carries medical, psychological, ethical and social implications. This paper is a review of all the ethical implications of genetic testing for breast cancer predisposition, as well as an attempt to discuss the more philosophical questions of women facing BRCA testing. To what extent does the individual benefit from genetic knowledge? Some women look with trepidation upon the potential of planning their life in view of a risk, while others believe that only through knowledge and awareness we can improve control of our life. The risk of breast cancer may be qualitatively so important to justify all the potential risks of finding out about it.

Autotransplantation in Lymphoma: Better Therapy or Healthier Patients?

Although some persons with large-cell lymphoma are cured with chemotherapy, most are not. In persons failing to achieve an initial remission and in those relapsing, rescue is generally attempted wi...

New Challenges in Communication with Cancer Patients

New challenges in communication with cancer patients / , New challenges in communication with cancer patients / , کتابخانه دیجیتال جندی شاپور اهواز

Pregnancy after breast cancer. The relationship of pregnancy to breast cancer development and progression

6. The safety of pregnancy after breast cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 6.1. Published clinical data on subsequent pregnancy . . . . . . . . . . . . . . . . . . . . . . . 173 6.2. Influence of pregnancy on subclinical breast cancer . . . . . . . . . . . . . . . . . . . . . 173 6.3. Limitations of published literature on subsequent pregnancy . . . . . . . . . . . . . . . . 173 6.4. The ‘healthy mother effect’ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174 6.5. Theoretical concerns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174 6.6. Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174

Truth‐telling, Risk, and Hope

If truth-telling is difficult in the face of the established reality of a disease, it becomes a real quandary when dealing with risk. Yet, in medicine we often face risks more than certainties, and to present them to and discuss them with our patients pose tremendous problems. In many cultures and societies, risks are seldom discussed. In the name of beneficence, doctors most often evaluate risks without involving the patient, and then act according to what appears to be in the patient’s best interest, for the patient’s good. In most Western countries, however, the patient as an autonomous agent, responsible for decisions regarding his or her health, is entitled to full disclosure of the risks involved in any medical or surgical procedure, as well as in any therapeutic measure. Moreover, both patients and healthy individuals should be able to gather information on the risks involved in certain lifestyles (the subject of preventive medicine). Finally, it seems that now all persons should be entitled to inquire about their genetic risks. Far from aiming at a philosophical discussion of risk and hope, I shall offer some elements of consideration that are drawn from my practice and thus quite limited to a Western reality. I am well aware that genetic predisposition, for instance, exists for all human kind, but not all have the luxury of living in a society in which genetic research is available and feasible. What constitutes risk and hope might be quite different in different contexts.

Phase II trial of carboplatin and etoposide in metastatic breast cancer

Background. High‐dose chemotherapy with hematopoietic support produces high rates of response in metastatic breast cancer. To facilitate new high‐dose regimens there is a need to identify active agents with toxicity limited to hematopoietic suppression. Cisplatin/etoposide is a highly active regimen in metastatic breast cancer, but cisplatin dose‐escalation is limited by nonhematologic toxicity. Carboplatin is active in breast cancer and has marrow‐dominant toxicity. Demonstration of activity for the combination of carboplatin and etoposide would facilitate their inclusion in high‐dose programs.