Phase II study of oral capecitabine in patients with hormone-refractory prostate cancer.

BACKGROUND: Currently available treatment for hormone refractory prostate cancer is limited in efficacy and associated with significant toxicity. This phase II study was performed to assess the efficacy of the oral fluoropyrimidine capecitabine in advanced prostate cancer. PATIENTS AND METHODS: Patients who had a rising prostate-specific antigen (PSA) despite androgen withdrawal, but who remained free from cancer-related symptoms. In total, 14 patients received oral capecitabine 1250 mg/m2 twice daily for two weeks of a three-week cycle. Tumour response was assessed using serum PSA measurement at 3-weekly intervals and, where present, imaging of soft tissue metastases. RESULTS: One of 14 patients experienced a partial response as assessed by both PSA and imaging of liver metastases. In seven other patients (50%), treatment decreased the rate of PSA rise. The duration of PSA stabilisation was generally short, but in 5/14 patients (36%) was sustained beyond 18 weeks, and in one patient to 24 weeks. Toxicity was significant but manageable, the most common adverse events being nausea, mucositis and hand-foot syndrome, each occurring in 50% of patients. Other common side effects were diarrhoea and lymphopenia. All toxicities were grade 1 or 2, except for grade 3 hand-foot syndrome occurring in one patient, and no dose reduction was required because of toxicity. CONCLUSION: Capecitabine has limited activity as a single agent in prostate cancer, but appears to modulate tumour biology. Considering the added convenience of oral administration, these results support further evaluation of combinations containing capecitabine in hormone-refractory prostate cancer.

The role of positron emission tomography in the management of colorectal cancer.

Positron emission tomography (PET) is a functional imaging modality that has made the transition from the research environment to the clinical environment over the last 10 years. Its major role is in the field of oncology where it is being used increasingly in the management of several tumour types including colorectal cancer. This review aims to outline the current and future role of PET scanning in the field of colorectal cancer.

13. New biological therapies for breast cancer.

The exploitation of biological differences between normal and malignant cells is a logical approach to novel treatments for breast cancer. The potential targets for such therapy include the products of proto-oncogenes and oncogenes, inhibition of growth factor receptor signalling and the immunological exploitation of antigenic differences between normal and malignant cells. Monoclonal antibody technology was heralded as a potential 'magic bullet' for cancer therapy following its discovery in the mid-1970s, but it is only in the past few years that such technology has entered mainstream clinical practice. The humanised murine monoclonal antibody to HER2 (trastuzumab) has significant anti-tumour activity but with minimal toxicity, and has been licensed for use in patients with advanced breast cancer. A different approach has been the use of enzyme inhibitors to interfere with the signalling pathways downstream of growth factor receptors (e.g. farnesyl transferase inhibitors). It is likely that effective targets for such therapies will be identified in the next few years. There have been significant advances in our understanding of human immunology which have coincided with the identification of so-called tumour-associated antigens (TAA). These developments have resulted in a resurgence of interest in tumour immunotherapy. Peptides derived from these TAAs have been used to generate tumour-specific immune responses. An alternative strategy has been to immunise patients using viral vectors and plasmid cDNA encoding the TAA. In some studies, notably those in patients with advanced melanoma, significant clinical responses have been observed. Cell-based strategies including autologous tumour cell vaccines, allogeneic tumour cell vaccines and dendritic cell vaccines have been used, and significant responses have been reported in several studies. Few of these methods have so far been applied to breast cancer, but the possible benefits and drawbacks of such an approach will be discussed.

Update on HER-2 as a target for cancer therapy: HER2/neu peptides as tumour vaccines for T cell recognition.

During the past decade there has been renewed interest in the use of vaccine immunotherapy for the treatment of cancer. This review focuses on HER2/neu, a tumour-associated antigen that is overexpressed in 10-40% of breast cancers and other carcinomata. Several immunogenic HER2/neu peptides recognized by T lymphocytes have been identified to be included in cancer vaccines. Some of these peptides have been assessed in clinical trials of patients with breast and ovarian cancer. Although it has been possible to detect immunological responses against the peptides in the immunized patients, no clinical responses have so far been described. Immunological tolerance to self-antigens like HER2/neu may limit the functional immune responses against them. It will be of interest to determine whether immune responses against HER2/neu epitopes can be of relevance to cancer treatment.

Metastatic eccrine porocarcinoma: response to docetaxel (Taxotere) chemotherapy.

BACKGROUND: Eccrine porocarcinoma is an uncommon neoplasm of the intra-epidermal sweat gland duct. PATIENTS AND METHODS: A case of eccrine porocarcinoma in a female renal transplant patient aged 45 years is described with a review of pertinent literature. RESULTS: The primary tumour was highly pleomorphic. In places large and small cells merged and focally the former component infiltrated the epidermis in a manner akin to Paget's disease of the breast. The majority of the tumour was high grade; using the modified Bloom and Richardson grading system, usually applied to mammary ductal carcinomas, the tumour graded as 3. Metastatic disease developed nine months following primary surgical treatment. The metastatic eccrine porocarcinoma was resistant to epirubicin but responded to docetaxel chemotherapy. CONCLUSIONS: There are no data to support the use of adjuvant therapy in the management of eccrine porocarcinoma. The use of the modified Bloom and Richardson grading system may define cases at high risk of relapse in which adjuvant therapy might be considered. Metastatic eccrine porocarcinoma has proven resistant to many chemotherapeutic agents. We report the first use of docetaxel in the management of this disease. The treatment was well tolerated and resulted in marked symptomatic and radiological responses. Treatment with docetaxel should be considered in future cases of this rare tumour.

Breast cancer and the immune system: opportunities and pitfalls.

The identification of tumor-associated antigens, and advances in our understanding of human immunology, have resulted in renewed interest in tumor immunology. A variety of approaches have been utilized in recent years against different tumor types. The results from some of these studies have been encouraging, but it is not yet clear whether they will be applicable to patients with breast cancer.

Management of Merkel cell carcinoma.

Merkel cell carcinoma is an uncommon cutaneous malignancy. Although it is rare, Merkel cell carcinoma has been described as the most malignant primary skin tumor. It is therefore important that once diagnosed, Merkel cell carcinoma is treated appropriately. The aim of this short review is to provide a summary of the available literature to guide clinicians in the future management of such patients. Inevitably in such a rare disease, there are no randomized trials of therapy. The treatment of individual patients will rely on opinion as much as the 'evidence'.

Risk of complications from bone metastases in breast cancer. implications for management.

A retrospective analysis of 859 patients who developed bone metastases from breast cancer between 1975 and 1991 was performed in order to identify factors that predict for complications from skeletal disease. The patients were divided into four groups based on the sites of disease at diagnosis of skeletal metastases: bone disease only; bone and soft tissue disease; bone and pleuro-pulmonary disease; bone and liver disease. Patients with metastatic disease confined to the skeleton were most likely to develop a pathological fracture. The time to long bone fracture was similar for all groups, but the least number of such fractures occurred in patients with bone and liver metastases since their survival was shortest (median: 5.5 months; P<0.001). Patients with bone metastases only were most likely to require radiotherapy to painful osseous deposits (P=0.0001) and most rapidly developed spinal cord compression (P=0.01, data not shown). The results suggest that patients with disease confined to the skeleton at the diagnosis of bone metastases are most likely to develop skeletal-related complications from advanced breast cancer. Such patients may benefit most from treatment with bisphosphonates.

Coexistence of acanthosis nigricans and the sign of Leser-Trélat in a patient with gastric adenocarcinoma: a case report and literature review.

The association of acanthosis nigricans (AN) with the sign of Leser-Trélat (LT) and gastric carcinoma is rare. Our patient was a 69-year-old man, who presented with hematemesis; a stage-IV poorly differentiated, diffuse-type, adenocarcinoma of the gastric antrum was diagnosed. The AN was striking, with florid cutaneous papillomatosis that also involved the mucous membranes of the mouth and eyelids, and keratoderma. AN and the sign of LT predated tumor detection by 6 months and regressed after chemotherapy in parallel with reduction of the tumor load, demonstrating the dermatoses as paraneoplastic phenomena. The patient died 7 months after completion of chemotherapy. The coexistence of AN and the sign of LT should prompt a search for underlying malignancy. The pathogenesis of both dermatoses is discussed.

Overexpression of c-erbB2 is an independent marker of resistance to endocrine therapy in advanced breast cancer.

The present study investigated the interaction between c-erbB2 overexpression and the response to first-line endocrine therapy in patients with advanced breast cancer. The primary tumours of 241 patients who were treated at first relapse with endocrine therapy were assessed for overexpression of c-erbB2 by immunohistochemistry. c-erbB2 was overexpressed in 76 (32%) of primary breast cancers and did not correlate with any other prognostic factor. The overall response to treatment and time to progression were significantly lower in patients with c-erbB2-positive tumours compared to those that were c-erbB2-negative (38% vs 56%, P = 0.02; and 4.1 months vs 8.7 months, P < 0.001, respectively). In multivariate analysis, c-erbB2 status was the most significant predictive factor for a short time to progression (P = 0.0009). In patients with ER-positive primary tumours treated at relapse with tamoxifen (n = 170), overexpression of c-erbB2 was associated with a significantly shorter time to progression (5.5 months vs 11.2 months, P < 0.001). In conclusion, overexpression of c-erbB2 in the primary tumour is an independent marker of relative resistance to first-line endocrine therapy in patients with advanced breast cancer. In patients with ER-positive primary tumours, the overexpression of c-erbB2 defines a subgroup less likely to respond to endocrine therapy.

[In defense of intra-uterine inseminations]. / Plaidoyer pour les inséminations intra-utérines.

Intrauterine insemination (IUI) has been used for treatment of infertility for many years with discouraging results (8.3% in the analysis of Dorangeon and Quereux). A new approach of IUI, using ovarian stimulation, ovulation monitoring and sperm preparation has significantly improved the results. The obtained pregnancy rate (15 to 25%) are now comparable to those reported with IVF or GIFT. Therefore IUI should be offered to patients with patent tubes prior to their referral for the more invasive procedure FIV or GIFT.

The use of the antiprogestin RU486 (mifepristone) as an abortifacient in early pregnancy--clinical and pathological findings; predictive factors for efficacy.

RU486, a potent antiprogesterone steroid was administered to 124 women requesting therapeutic abortion. All were less than 49 days from their last menstrual period. Ten of these subjects (Group I) received high doses of RU486 in a decremental dose regimen (400, 300, 200 and 100 mg/day) over 4 successive days and 14 received 50 mg/day for 7 days (Group II). A further 50 subjects (Group III) received 100 mg/day for seven days and the remaining 50 subjects (Group IV) received 450 mg in a single dose. In the first three groups, half the daily dose was given in the morning and the remainder in the evening. Blood was collected before, and on Days 4 and 7 and then once a week after commencing therapy until disappearance of circulating beta HCG. In addition to beta HCG, estradiol-17 beta (E2), progesterone (P), cortisol, and various metabolic and hematological parameters were measured. Plasma RU486 concentrations were also assayed in Group II, III and IV subjects on Day 7 of therapy and in some cases on Days 14 and 21. Ultrasonography was performed in all cases on Day 1 and on Day 14. All the patients bled within five days following RU486 administration, for 1 to 21 days. A complete abortion occurred in 60% in Group I, 50% in Group II, 86% in Group III, and 80% in Group IV. The difference between the last two groups and the first two was significant at p less than 0.01. The non-responders were submitted to a uterine vacuum aspiration. A stepwise discriminant analysis was performed and indicated that the best predictors of the outcome of therapy were beta HCG values and the gestational sac diameter. With these criteria, the prediction was accurate in 86.4% of the cases. The best results were obtained in the cases where the ultrasonic measurement of gestational sac was under 10 mm in diameter and the initial beta HCG values under 15,000 mIU/ml. Among the observed side effects were moderate pelvic cramps (20.9%), nausea (27%), fainting (4.8%); 61.3% of the women complained of fatigue. Heavy bleeding occurred in 15.3% of the women but only one of them required blood transfusion. In the patients with complete abortion, beta HCG values decreased to below 500 mIU/ml by Day 14 (but in 11 cases values fell below 2,000 mIU/ml only by Day 21). Plasma estradiol and progesterone also fell. Cortisol levels increased during therapy especially in subjects of Group I, but returned to basal values after termination of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)