Primary chemotherapy for inoperable ovarian, fallopian tube, or primary peritoneal cancer with or without delayed debulking surgery.

OBJECTIVE: To describe the outcome of primary chemotherapy for women with advanced-stage epithelial ovarian or primary peritoneal cancer and delayed surgery when optimal debulking surgery cannot be achieved at diagnosis. METHODS: Between 1998 and 2006, we retrospectively reviewed the overall survival and examined prognostic markers in consecutive patients who were not suitable for initial radical surgery because of the extent of disease and/or poor performance status. They were treated with a policy of primary platinum-based chemotherapy, followed whenever possible in responding patients by debulking surgery. RESULTS: A total of 171 patients received least one cycle of chemotherapy. Eighty-six patients proceeded to surgery and 53 (31% of 171 and 62% of 86) had optimal (<1 cm) residual disease. Eighty-five patients did not undergo surgery because they remained unfit or had not responded sufficiently to chemotherapy. The median overall survival was 18.7 months (95% confidence interval [CI], 16.5-24.2). The median OS in the surgical group for optimal and suboptimal surgery was 40.8 (95% CI, 32.5-50.0) and 22.5 (95% CI, 17.7-37.1) months (P = 0.005). On multivariate analysis, interval surgery and optimal surgery were the only independent prognostic factors (hazard ratios, 0.45 and 0.43, respectively; P = 0.009). In the nonsurgical group, CA125 response was an independent prognostic factor (hazard ratio, 0.34; P = 0.001) with an OS of 21.7 months (95% CI, 14.0-35.4) in women with a normal CA125 after treatment compared with 6.7 (95% CI, 4.5-7.8) months. CONCLUSIONS: In one third of the women, the tumor was optimally debulked after primary chemotherapy and their median survival was 40.8 months. Suboptimal debulking surgery after primary chemotherapy did not result in a better survival than that achieved after a chemotherapy response alone, suggesting that surgery may be avoided when imaging after chemotherapy demonstrates residual disease that cannot be optimally debulked.

Cardiotoxicity induced by tyrosine kinase inhibitors.

BACKGROUND: Cardiotoxicity is a serious side effect of drugs used to treat cancer patients. Older chemotherapy drugs such as the anthracyclins and new targeted therapies, mainly trastuzumab, have been implicated in causing clinically significant cardiac dysfunction, which may be irreversible for many patients. The advent of a new category of drugs, the tyrosine kinase inhibitors has revolutionized the treatment of chronic myeloid leukemia, gastrointestinal stromal tumors and renal cancer, while their indications include a variety of other types of tumors. METHODS: Assessment of the incidence and severity of cardiac toxicity caused by the tyrosine kinase inhibitors and discussion on the molecular mechanisms and mode of diagnosis based on recent clinical trials. Review of related literature. RESULTS: Cardiac toxicity can be caused by the tyrosine kinase inhibitors imatinib mesylate, dasatinib, nilotinib, sunitinib, sorafenib and lapatinib, while gefitinib and erlotinib have not been related to toxic effect on the heart. Although targeted therapies are considered less toxic and better tolerated by patients compared with classic chemotherapy drugs, certain complications can be very serious and as these agents have been in use for a limited period of time, the exact profile of side effects will be better defined in the years to come. Cardiac toxicity may range from asymptomatic subclinical abnormalities such as electrocardiographic changes and left ventricular ejection fraction decline to life threatening events like congestive heart failure and acute coronary syndromes. For patients with severe side effects, discontinuation of treatment is warranted. CONCLUSIONS: Careful cardiac monitoring and assessment by a cardiologist throughout the course of treatment with those TKIs that exert cardiac toxic effect is of primary importance.

Prostate-specific antigen in the cerebrospinal fluid: a marker of local disease.

Leptomeningeal involvement from prostate cancer is a rare complication with dismal prognosis. Prostate-specific antigen in the cerebrospinal fluid may be found elevated and can be used as a marker for local disease. We present the case of a patient with prostate cancer and leptomeningeal metastases who had high levels of prostate-specific antigen in the cerebrospinal fluid.

CD4+CD25+ regulatory T-cell frequency in HER-2/neu (HER)-positive and HER-negative advanced-stage breast cancer patients.

PURPOSE: CD4(+)CD25(bright) regulatory T cells (Tregs) are increased in patients with several malignancies and correlate with disease stage and prognosis. Breast cancer patients represent a heterogeneous population with unpredictable disease progression even at advanced stages. Circulating Tregs in correlation with HER-2/neu (HER) status and treatment with chemotherapy, either alone or in combination with trastuzumab therapy, were monitored in advanced-stage breast cancer patients. EXPERIMENTAL DESIGN: Circulating Treg frequency and absolute counts of 46 HER(+) and 28 HER(-), stage III and IV, breast cancer patients before therapy and during trastuzumab therapy and/or chemotherapy have been compared with 24 healthy donors and correlated with plasma HER extracellular domain concentration and clinical outcome. RESULTS: Treg frequency in HER(+) patients was significantly increased compared with both HER(-) patients and healthy donors. Trastuzumab therapy, with or without combined chemotherapy, resulted in a progressive decrease of circulating Tregs. Percentage change in Tregs statistically correlated with percentage change in plasma HER extracellular domain. Furthermore, decrease in Tregs correlated with either objective clinical response or stable disease, whereas increased Treg frequency during trastuzumab therapy coincided with disease progression. No statistically significant change in Treg frequency following chemotherapy was observed in HER(-) patients. CONCLUSIONS: Treg cell frequency does not directly correlate with clinical stage in breast cancer, as stage III and IV HER(+) and HER(-) patients exhibit significantly different Treg profiles. Trastuzumab therapy, either alone or combined with chemotherapy, results in decreased Treg frequency in HER(+) advanced patients with an objective clinical response.

Systemic sclerosis associated with rectal cancer. Case report and a brief review of the literature.

Autoimmune diseases may appear as paraneoplastic syndromes during the course of a neoplastic disease, the most common being dermatomyositis/ polymyositis. The association of systemic sclerosis and cancer is not clear. The case of a 56-year-old male with rectal cancer and systemic sclerosis where the coexistence of the two diseases was closely related, so that scleroderma was considered a paraneoplastic syndrome rather than a concomitant morbid condition, is presented.

Salvage treatment with single-agent capecitabine in patients with heavily pretreated advanced colorectal cancer.

BACKGROUND: Refractory and/or relapsing advanced colorectal cancer (ACRC) requires frequent and prolonged hospitalisations, with a negative impact on the patients' quality of life (QoL). The aim of this single-centre, phase II study was to investigate the efficacy and safety of capecitabine (C) as salvage therapy in patients (pts) with ACRC, heavily pretreated with various chemotherapeutic regimens, as well as radiotherapy. PATIENTS AND METHODS: A total of 28 pts were enrolled, with the following characteristics: 16 male and 12 female, median age 60 years (36-70) and median ECOG PS 1 (0-2). All pts had previously received at least 2 regimens of standard chemotherapy, including 5-FU/leucovorin, oxaliplatin and irinotecan in various combinations, while 8 pts had been offered radiotherapy. Four pts had already been treated with C. The treatment was administered at home and consisted of C at a dose of 1250 mg/m2 twice daily on days 1-14, every 3 weeks, until disease progression (PD) and for a maximum of 9 cycles. Since grade (G) 3 gastrointestinal (GI) toxicity was observed among the first 7 pts, a daily dose of 2 g/m2 was adopted in the subsequent enrolment. RESULTS: The disease control (DC) rate was 53% (95% CI: 33.8%-72.5%): partial response in 2 pts and disease stabilization in 13 pts. Three out of 4 pts previously exposed to C showed stable disease. A significant symptom improvement was demonstrated in all 4pts with non-measurable baseline disease. The median time to progression was 4 months (range: 2-7). Nine pts had PD while on treatment. The median overall survival times for pts with DC and PD were 6 months and 3 months, respectively. Various types of G3 haematological toxicity were observed in 4/28 pts, G3 hand-foot syndrome in 6/28 pts and G3 GI toxicity in 8/28 pts. Nevertheless, the patients' QoL and the regimen's safety profile were satisfactorily preserved. CONCLUSION: Despite its methodological limitations, our trial suggests that salvage treatment of heavily pretreated ACRC with single-agent C may be considered a safe and cost-effective alternative to best supportive care.

Skin metastases from primary lung cancer. Report of three cases and a brief review.

Skin metastasis from lung cancer is an unusual event carrying an ominous prognosis. Three cases with non-small cell lung cancer (NSCLC) with skin involvement and rapidly fatal clinical course due to extensive CNS metastasis are reported. The eventual association of skin metastases and a phenotype with "CNS-predilection" or an aggressive phase of NSCLC are discussed.

Alveolar soft part sarcoma with breast metastases: a case report.

Alveolar soft part sarcoma (ASPS) is a rare mesenchymal tumor, accounting for <1 % of all soft tissue sarcomas. It appears mainly in young adults, has a female predominance and follows an indolent natural history. Like other sarcomas, it can metastasize to the lungs, liver, bones and the brain, but unusual sites have also been described, including the vagina, the orbit, colonic mucosa and the breast. This paper presents a case report of a 31-year-old patient with metastatic ASPS, who developed two highly vascular breast nodules that following an excisional biopsy, were shown to represent metastases from the patient's known sarcoma.

Targeting the HER2 receptor in metastatic breast cancer.

The advent of targeted therapies has revolutionized the treatment of certain types of cancer. Identification of molecular targets on cancer cells has led to the design of novel drugs, which either used as single agents or in combination with chemotherapy, has prolonged survival in metastatic disease, or contributed to curative treatment in the adjuvant setting. A literature review was conducted to identify and present current knowledge on the molecular function of the HER2 receptor, its role in the pathogenesis of breast cancer and anti-HER2 targeted drugs in use or under development. Many molecular targets have been identified in breast cancer, with the HER family of receptors being the ones most extensively studied. Trastuzumab and lapatinib target the HER2 receptor and are approved drugs for the treatment of metastatic breast cancer. Several other targeted agents, including T-DM1, pertuzumab, neratinib, afatinib and ertumaxomab, are currently being tested in vivo as well as in clinical studies. The use of targeted therapies in metastatic breast cancer has improved prognosis, increased survival and dramatically changed the way we treat breast cancer patients today.

Leptomeningeal metastases from prostate cancer: an emerging clinical conundrum.

Leptomeningeal metastases from solid tumors are relatively uncommon events with dismal prognosis. They can be seen mainly in patients with breast and lung cancer, and malignant melanoma, but have also been described in a variety of other tumor types. Leptomeningeal carcinomatosis from prostate cancer is an extremely rare complication, but as patients' survival is prolonged due to more effective treatments, it is expected that more patients will present with leptomeningeal involvement in advanced stages of the disease. In these cases high levels of prostate-specific antigen can be found in the cerebrospinal fluid. This comprehensive review presents the recent findings from the literature.

A Phase II trial of the combination of vinorelbine and capecitabine as second-line treatment in metastatic breast cancer previously treated with taxanes and/or anthracyclines.

PURPOSE: Survival time for metastatic breast cancer (MBC) can be substantially improved by combination chemotherapy in the adjuvant setting. Capecitabine and vinorelbine have shown considerable efficacy and favourable toxicity as single agents. The aim of this study is to evaluate the response to the combination of capecitabine and vinorelbine as second-line treatment in patients previously treated with taxanes and/or anthracyclines. PATIENTS AND METHODS: Thirty-nine patients with MBC, who received a combination of vinorelbine and capecitabine were included in the study. RESULTS: Overall response rate was 53.9% and disease progression rate was 28.2% for patients who received six cycles of therapy, rates significantly higher than the three-cycle group. The treatment was generally well tolerated and toxicity was mild. CONCLUSIONS: The combination of capecitabine and vinorelbine as salvage therapy in anthracycline- and/or taxane-pre-treated patients with MBC seems to be effective and safe, even more so as the number of treatment cycles increases.