Breast cancer, metastatic chemotherapy

Systemic chemotherapy is usually not indicated in non-colorectal liver metastases due to lack of response. The systemic administration of cytostatics (also in combination) possesses the status of palliative therapy. However, in metastatic neuroendocrine tumours, a combination of octreotide -i- IFN had a positive effect on the survival time. Systemic chemotherapy produced remission rates of up to 60%. (320) In metastatic breast cancer, systemic chemotherapy is indicated, usually in combination with hormonal and immune therapy. (316, 342) In metastatic gastric carcinoma, palliative chemotherapy can achieve a remission rate of up to 40%, with a slight extension of survival time. 

Determine appropriate indications for endocrine therapy, chemotherapy, and biologic therapy for patients with metastatic breast cancer. 

Evaluate available chemotherapy options for patients with metastatic breast cancer based on pertinent patient and disease-state characteristics. 

The taxanes (e.g., paclitaxel and docetaxel) are a newer class of agents that rival the anthracyclines in their activity in metastatic breast cancer, becoming (arguably) the most active class of chemotherapy for this disease. 

Cytotoxic chemotherapy is eventually required in most patients with metastatic breast cancer. Patients with hormone-receptor-negative tumors require chemotherapy as initial therapy of symptomatic metastases. Patients who respond initially to hormonal manipulations eventually cease to respond and go on to require chemotherapy. The median duration of response is 5 to 12 months, but some patients will have an excellent response to an initial course of chemotherapy and may live 5 to 10 years or longer without evidence of disease. In general, median survival of patients after treatment with commonly used drug combinations for metastatic breast cancer is 14 to 33 months. The median time to response has ranged from 2 to 3 months in most studies, but this period depends in large part on the site of measurable disease. The median time to appearance of response is between 3 and 6 weeks in patients whose disease is primarily in the skin and lymph nodes, 6 to 9 weeks in patients with metastatic lung involvement, 15 weeks in patients with hepatic involvement, and nearly 18 weeks in patients with bone involvement. Thus it is often the case that an immediate response to therapy is not... 

CA 15-3 serum tumor marker is intended to detect disease recurrence in stage II and stage III breast cancer patients. It has been reported that CA 15-3, together with other suitable markers, is preferred in measuring the effect of applied hormonal therapy or chemotherapy in metastatic disease. Studies have indicated that CA 15-3 assay values are frequently elevated in patients with breast cancer. These... 

Hydroxamic acid derivatives, which belong to a new class of NO donors, have been shown to inhibit the matrix metalloproteinases (MMPs) [112]. MMPs are a family of zinc-dependent endopeptidases, which play a critical role in multiple steps in the metastatic cascade and facilitate neoangiogenesis. Numerous hydroxamic acids, such as marimastat, have been developed, that bind the zinc atom in the active catalytic domain of MMPs. During a randomized Phase III trial, comparing marimastat with placebo in patients with metastatic breast cancer, marimastat was not associated with an improvement in progression-free survival or overall survival. Other studies also indicated no benefit for MMP inhibitors when used either in combination with chemotherapy or sequentially after first-line chemotherapy in a variety of cancers [113]. Currently, many pharmaceutical companies have suspended clinical development of this kind of agent. 

Human cancers vary widely in their ability to produce metastasis. At present, there are no reliable methods to predict metastatic potential. For optimum patient management, however, knowledge of the aggressiveness of a tumor is desirable when deciding which patients should receive adjuvant chemotherapy. This type of information is particularly important for axillary node-negative breast cancer and Dukes B colorectal cancer. 

Finally, one of fhe most recent and most interesting approvals of a new formulation of paclifaxel was fhe approval of the agent ABl-007 (Abraxane ) (Abraxis Oncology, Schaumburg, IL, U.S.A.) (paclifaxel protein-bound particles for injectable suspension [albumin-bmmd]). It is indicated for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated. The endpoint for that pivotal trial of Abraxane vs. paclitaxel was a... 

Slamon, D.J. et al.. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2, N. Engl.. Med., 344, 783-792, 2001. 

Tamoxifen is on oestrogen-receptor antagonist. It is used in post-menopousol women with oestrogen-receptor-positive metastatic breast cancer at a dose of 20 mg doily. It con also be used in combination with chemotherapy. Severe side-effects ore infrequent however, it is associated with a small risk of endometrial cancer. Patients should be informed and reassured that the benefits of the treatment at this dose outweigh the risk. 

Pronzato P. (2008) New therapeutic options for chemotherapy resistant metastatic breast cancer The epothilones. Drugs 68 139-146. 

Kaufman PA. Paclitaxel and anthracycline combination chemotherapy for metastatic breast cancer. Semin Oncol 1999 26(3 Suppl 8) 39-46. 

Kuerer HM, Newman LA, Buzdar AU, et al. Residual metastatic axillary lymph nodes following neoadj uvant chemotherapy predict disease-free survival in patients with locally advanced breast cancer. Am J Surg 1998 176 502-509. 

Initial phase I and II trials with trastuzumab were done in patients with metastatic breast cancer with documented HER-2 overexpression as measured by immunohis-tochemistry. The first phase Ell study reported by Baselga et al. (22) enrolled patients heavily pretreated with chemotherapy and demonstrated an objective response rate of 11%. Side effects were minimal and consisted of occasional fever and chills acutely... 

Pegram MD, Lipton A, Hayes DF, et al. Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-pl 85HER2/neu monoclonal antibody plus cisplatin in patients with HER2/ neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol 1998 16 2659-2671. 

Cobleigh M A, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 1999 17 2639-2648. 

Patients with metastatic breast cancer are incurable using conventional therapy such as hormonal manipulation or chemotherapy. However, as in most other neoplastic diseases the bulk of knowledge on drug treatment has been obtained in this stage of the disease. The median survival from the manifestation of metastasis is approximately 18-24 months. It is, however, important to realize that metastatic breast cancer is a heterogeneous disease and for some patients the disease can be controlled for many years with relatively good quality of life. 

J. Dose Schwarz, M. Bader, L. Jenicke, G. Hemminger, F. Janicke, N. Avril, Early prediction of response to chemotherapy in metastatic breast cancer using sequential F-FDG PET, J. Nucl. Med. 46(7) (2005) 1144-1150. 

Indications For treatment of patients with metastatic breast cancer whose tumors overexpress the HER2 protein and who have received one or more chemotherapy regimens for their metastatic disease. Trastuzumab in combination with pacli-taxel is also indicated for treatment of patients with metastatic breast cancer whose tumors overexpress HER2 protein and who have not received chemotherapy for their metastatic disease... 

G. Other applications Herceptin has been combined with cisplatin in the treatment of heavily pretreated metastatic breast cancer. Treatment of patients with ovarian cancer is under investigation. A recent study demonstrated that Herceptin increased the clinical benefits of first-line chemotherapy—doxorubicin (or epiru-bicin) and cyclophosphamide or pacli-taxel—in metastatic breast cancer that overexpressed HER2. 

Only 20% to 33% of metastatic breast carcinomas robustly express HER2, and tumors that do not overexpress the protein are unlikely to benefit from treatment. Hence demonstration of clinical benefit in unselected breast cancer patients was a challenging task [24]. The need to keep patients on other chemotherapies added to the complexity of clinical trials. Nevertheless, the decision to first demonstrate overexpression of HER2 antigen levels as one of the key clinical trial inclusion criteria, reached in consultation with the FDA, allowed the investigators to demonstrate efficacy (Table 14.2). 

---