Biomedical subjects

Stefania Cosio

Publications and source records attributed to Stefania Cosio.

14 recordsLinked to original sources

PubMed2006

Old and new perspectives in the pharmacological treatment of advanced or recurrent endometrial cancer: Hormonal therapy, chemotherapy and molecularly targeted therapies.

Hormonal therapy and chemotherapy play a major role in the management of advanced or recurrent endometrial cancer. Progesterone therapy obtains overall response rates ranging from 11% to 25% in patients with endometrioid-type tumours, and oral medroxyprogesterone acetate 200mg daily appears to be a reasonable therapeutic option for those lesions that are well differentiated and/or have a high progesterone receptor (PgR) content. However, the activity of progestins is often compromised by the down-regulation of PgR within the target tissues, and therefore therapeutic strategies designed to enhance PgR expression are warranted. Little data are currently available about the new aromatase inhibitors and selective estrogen receptor modulators. As for chemotherapy, the combination of doxorubicin [DOX]+cisplatin [CDDP] achieves overall response rates ranging from 34% to 60%, and the addition of paclitaxel (TAX) seems to improve response rates, progression-free survival and overall survival, but to worsen toxicity profile. A phase III study is currently comparing TAX+DOX+CDDP versus the less toxic combination of TAX+carboplatin. Chemotherapy is active against both endometrioid-type carcinoma and uterine serous papillary carcinoma. However, this latter endometrial malignancy is less chemosensitive than the histologically similar high-grade serous ovarian carcinoma. Interesting fields of research are represented by investigational agents directed against specific intracellular signal transduction pathways involved in the proliferation, invasiveness and metastatic spread of endometrial cancer. Mammalian target of the rapamycin (mTOR) inhibitors, epidermal growth factor receptor inhibitors (gefitinib, erlotinib, lapatinib, the monoclonal antibody cetuximab), imatinib, the monoclonal antibody trastuzumab, and the Clostridium perfrigens enterotoxin are currently under evaluation as molecularly targeted therapies for endometrial cancer. Further investigations addressed to better understand the signal transduction pathways that are disregulated in endometrial carcinogenesis could identify novel biological targets suitable for tailored therapies.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Consolidation and maintenance treatments for patients with advanced epithelial ovarian cancer in complete response after first-line chemotherapy: a review of the literature.

Most patients with advanced epithelial ovarian cancer experience objective responses to paclitaxel/platinum-based chemotherapy, but responses are generally short-lived and the clinical outcome is still unsatisfactory. Therefore, the strategy to consolidate and to prolong the duration of response is very attractive. Different consolidation or maintenance treatments have been attempted, such as whole abdomen radiotherapy, intraperitoneal chromic phosphate, radioimmunotherapy, intraperitoneal chemotherapy, high-dose chemotherapy with haematopoietic support, prolonged administration of the first-line regimen, second-line single-agent chemotherapy, and biological agents. Clinical studies have given conflicting, inconclusive, and generally disappointing results. A recent US randomised trial appeared to show that the prolonged administration of single-agent paclitaxel (175 mg/m2 every 3 weeks) significantly improved the progression-free survival of complete responders to paclitaxel/platinum-based chemotherapy. Alternative less toxic, and probably more effective schedules of administration of chemotherapy (i.e. weekly paclitaxel) might assure a better balance between quality of life and anti-tumor activity in patients previously exposed to chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Relationship between time interval from primary surgery to the start of taxane- plus platinum-based chemotherapy and clinical outcome of patients with advanced epithelial ovarian cancer: results of a multicenter retrospective Italian study.

PURPOSE: To assess whether the interval from primary surgery to the start of taxane- plus platinum-based chemotherapy has any impact on the clinical outcome of advanced ovarian cancer patients. PATIENTS AND METHODS: The study was conducted on 313 patients who underwent surgery followed by taxane- plus platinum-based chemotherapy. The median follow-up of survivors was 30.7 months (range, 6 to 109 months). RESULTS: The 25%, 50%, and 75% quantiles of intervals from surgery to the start of chemotherapy were 11, 21, and 31 days, respectively. After the sixth cycle, 102 patients achieved a pathologic complete response at second-look surgery and 98 obtained a clinical complete response but were not submitted to second-look surgery. Taking into consideration the best assessed response, a complete (either clinical or pathologic) response was found in 200 patients. Residual disease (< or = 1 v > 1 cm; P < .0001) and ascites (absent v present; P = .003) were independent predictive factors for achieving a complete response, whereas residual disease (P = .001) and stage (IIc to III v IV; P = .04) were independent prognostic variables for survival. Conversely, statistical analyses failed to detect significant differences in complete response rates and survival among patients with an interval from surgery to chemotherapy shorter than 11 days, 12 to 21 days, 22 to 31 days, and longer than 31 days. CONCLUSION: The interval from surgery to the start of taxane- plus platinum-based chemotherapy seems to have neither a predictive value for response to treatment nor a prognostic relevance for survival of advanced ovarian cancer patients.

Adult↗

PubMed2004

Serum tumor markers in the management of ovarian, endometrial and cervical cancer.

CA 125 is the most reliable serum marker for ovarian carcinoma. Whereas its role in the screening of the malignancy is controversial, serum CA 125 assay is very useful for both the differential diagnosis of ovarian masses, particularly in postmenopause, and the monitoring of the response to chemotherapy and follow-up of patients with histologically proven ovarian carcinoma. Tumor-associated antigens other than CA 125, such as CA 19.9, CA 15.3 and TAG.72, firstly identified in gastro-intestinal or breast malignancies, have been detected also in tissue and serum samples from patients with ovarian carcinoma. In particular CA19.9 offers the advantage of high sensitivity for mucinous histotype, which often fails to express CA 125. Serum CA 125 correlates with the clinical course of disease better than the other antigens, and in patients with positive CA 125 assay at diagnosis the concomitant evaluation of CA 19.9 or CA 72.4 or CA 15.3 does not offer any additional benefit for monitoring ovarian carcinoma. Conversely, the serial measurements of these other antigens may represent an interesting biochemical tool for the management of patients with negative CA 125 assay. Serum alphaFP and betaHCG are very useful in the preoperative evaluation and management of nondysgerminomatous ovarian germ cell tumors, whereas elevated serum inhibin levels can be detected in patients with granulosa cell tumors of the ovary. As for endometrial carcinoma, preoperative serum CA 125 levels correlate with stage, depth of myometrial invasion, histologic grade, cervical invasion, peritoneal cytology, lymph node status and clinical outcome. Moreover, serial CA 125 assay is a good indicator of disease activity and a useful biochemical tool for post-treatment surveillance of patients with endometrial carcinoma. SCC is the most reliable serum marker for squamous cell cervical carcinoma, and in patients with this malignancy pretreatment SCC levels are related to tumor stage, tumor size, depth of cervical invasion, lymph-vascular space involvement, lymph node status and clinical outcome. Serial SCC measurements parallel the response to radiotherapy and chemotherapy as well as the clinical course of disease after the completion of treatment. Serum CYFRA 21.1 seems to be less sensitive than serum SCC for squamous cell cervical carcinoma. Elevated CA 125 levels can be often detected in patients with cervical adenocarcinoma. The future for tumor marker research is represented by the emerging technologies of transcriptional profiling and proteomics.

Animals↗

PubMed2004

The predictive and prognostic value of serum CA 125 half-life during paclitaxel/platinum-based chemotherapy in patients with advanced ovarian carcinoma.

OBJECTIVES: Serum CA 125 kinetics during early chemotherapy has a strong predictive and prognostic relevance for patients with advanced ovarian carcinoma who received a first-line platinum-based regimen, whereas the ability of serum CA 125 assay to reflect the response to paclitaxel-based chemotherapy has not yet been defined. The aim of the present paper is to calculate the serum CA 125 half-life during first-line paclitaxel/platinum-based chemotherapy in patients with advanced ovarian carcinoma and to correlate this kinetic parameter with the response to treatment, progression-free survival and overall survival. METHODS: This retrospective investigation assessed 71 patients with stages IIc-IV ovarian carcinoma who underwent initial surgery followed by paclitaxel/platinum-based chemotherapy and who had serum CA 125 > 35 U/ml before the first cycle of chemotherapy. Only epithelial ovarian cancers were included. RESULTS: The 25%, 50%, and 75% quantiles of serum CA 125 half-life during early chemotherapy were 10, 14, and 20 days, respectively. Taking the value corresponding to the 50% quantile (i.e., 14 days) as cutoff limit, serum CA 125 half-life was an independent prognostic factor for the chance of achieving a complete response to treatment as well as for progression-free survival and overall survival. In detail, patients with serum antigen half-life <== 14 days had a 3.362 times as great probability to achieve a complete response and a 3.113 times as low probability to die when compared to those with a longer half-life. CONCLUSIONS: Serum CA 125 assay represents a reliable biochemical tool for the management of advanced ovarian carcinoma patients who receive a first-line paclitaxel/platinum-based chemotherapy.

Adult↗

PubMed2004

Use of estrogen antagonists and aromatase inhibitors in breast cancer and hormonally sensitive tumors of the uterine body.

The new anti-estrogens, including the selective estrogen receptor modulators (e.g., toremifene, droloxifene, idoxifene, raloxifene and arzoxifene), the selective estrogen receptor downregulators (e.g., fulvestrant), and the new steroidal (e.g., exemestane) and non-steroidal (anastrozole and letrozole) aromatase inhibitors have been investigated in the treatment of breast cancer and hormonally sensitive tumors of the uterine body. In postmenopausal women, anastrozole, letrozole and exemestane appear to have superior efficacy and an improved toxicity profile than tamoxifen, and fulvestrant seems to be at least as effective as anastrozole in patients in whom tumors have progressed after prior endocrine treatment. Preliminary data showed a high response rate and a favorable toxicity profile for arzoxifene in endometrial cancer, whereas letrozole could represent a new interesting therapeutic tool for endometrial cancer as well as for low-grade endometrial stromal sarcoma.

Aromatase Inhibitors↗

PubMed2003

Human telomerase reverse transcriptase mRNA expression assessed by real-time reverse transcription polymerase chain reaction predicts chemosensitivity in patients with ovarian carcinoma.

PURPOSE: To evaluate in vivo whether the expression of the human telomerase reverse transcriptase (hTERT) gene, the catalytic subunit of the telomerase complex, is predictive of response to chemotherapy in ovarian cancer patients. PATIENTS AND METHODS: Fifty-nine advanced-stage ovarian cancer patients who were treated with platinum-based chemotherapy were studied. hTERT levels were evaluated by real-time reverse transcriptase polymerase chain reaction (RT-PCR) on tumor specimens obtained before the treatment. Variables were analyzed by the chi(2) and Fisher's exact tests. Logistic regression analysis was also performed to account for the effects of all the covariates investigated (residual disease, stage, histotype, and grade). RESULTS: Twenty-eight (47%) of the 59 tumors showed low hTERT levels, whereas 31 (53%) tumors displayed high hTERT levels. Seventy-five percent of complete responders showed high levels of hTERT expression, whereas 66% of partial responders or nonresponders exhibited low hTERT levels (P =.002). Only residual disease and hTERT expression were independent predictors of response (odds ratios, 13.455 and 7.586, respectively). The combination of these two parameters provides powerful predictive information: 18 of the 20 patients with residual disease more than 2 cm and low hTERT levels were partial responders or nonresponders, whereas 11 of the 12 patients with residual disease less than 2 cm and high hTERT levels showed a complete response (chi(2) = 21,416; P <.00001). CONCLUSION: Our data indicate that hTERT expression, measured by real-time RT-PCR, is a possible independent marker of response to platinum-based therapy in advanced stage ovarian cancer patients. Prospective validation of this marker will be required to further define its predictive value.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Renal impairment in patients with ovarian cancer.

OBJECTIVE: To investigate the prevalence of renal impairment in patients with ovarian cancer at the time of the diagnosis. STUDY DESIGN: Creatinine clearance was estimated according to Cockcroft and Gault (C&G Ccr), glomerular filtration rate (GFR) was determined as renal clearance of 99mTc-DTPA, and renal ultrasound was performed in 60 consecutive patients with newly diagnosed ovarian cancer. RESULTS: A 28% of the total population studied had a GFR <60 ml/min/1.73 m(2). A moderate/severe dilation of the upper urinary tract was found in 12% of patients. The length of kidneys ranged between 9.0 and 13.5 cm, and a statistically significant correlation was found between kidney length and values of GFR. CONCLUSION: A reduction in renal function and a moderate to severe dilation of upper urinary tract frequently occur in patients with ovarian cancer at the time of the diagnosis.

Adult↗

PubMedDate not supplied

Intratumoral microvessel density, response to chemotherapy and clinical outcome of patients with advanced ovarian carcinoma.

BACKGROUND: The aim of this study was to assess intratumoral microvessel density (IMD) in tissue samples from primary ovarian carcinomas, and to correlate this angiogenic parameter with the common clinico-pathological variables, response to chemotherapy and prognosis of patients with this malignancy. PATIENTS AND METHODS: The investigation was conducted on 64 patients who underwent initial surgery for FIGO stages I-IV ovarian carcinoma. Paraffin-embedded sections of primary tumor specimens were analyzed for IMD by immunohistochemistry using anti-CD34 antibodies. In detail, we assessed the 49 patients with advanced (FIGO stages II-IV) disease. Postoperative chemotherapy consisted of paclitaxel/platinum-based chemotherapy in 36 (73.5%) patients and platinum-based chemotherapy in 13. RESULTS: The IMD ranged from 6 to 115 microvessels/field, with a median value of 40, and correlated with none of the common clinico-pathological variables of ovarian carcinoma. As for the patients with advanced disease, women with elevated IMD (> or = 40 microvessels/field) had a higher chance of achieving a complete response to chemotherapy when compared to those with lower IMD (p = 0.0068). Multiple logistic regression showed that IMD was an independent predictor of complete response to chemotherapy (p = 0.0094). By log-rank test, patients with elevated IMD had a better progression-free survival (p = 0.0039) and a better overall survival (p = 0.0365) when compared to those with lower IMD. The Cox model showed that IMD was the only independent prognostic variable for both progression-free survival (p = 0.0112) and overall survival (p = 0.0296). DISCUSSION: The present retrospective analysis seems to show a positive association between IMD, response to chemotherapy, mainly represented by a paclitaxel/platinum-based regimen, and clinical outcome of patients with advanced ovarian carcinoma.

Adult↗

PubMedDate not supplied

The management of malignant nondysgerminomatous ovarian germ cell tumors.

Nondysgerminomatous ovarian germ cell tumors are always unilateral and predominantly occur in children, adolescents and young women. Conservative surgery should be the standard approach for most patients regardless of tumor stage. The role of adjuvant chemotherapy in stage I disease is questionable. Platinum-based chemotherapy is the standard postoperative treatment for all patients with advanced nondysgerminomatous ovarian germ cell malignancies. In immature teratoma patients with peritoneal spreading, chemotherapy is not required for grade 0 or 1 implants, is of uncertain significance for grade 2 lesions, but is warranted for grade 3 implants. In recent series, in which most patients received conservative surgery often followed by platinum-based chemotherapy, 5-year survival rates range from 82% to 100%. There have been several cases reported of normal babies delivered following treatment of ovarian germ cell tumors. In women previously treated conservatively for these malignancies, miscarriages are in the expected range whereas the malformation rate seems to be slightly higher than in the general population. In conclusion, the current therapeutic strategies are able to save the large majority of patients with nondysgerminomatous ovarian germ cell tumors and to preserve their reproductive potential.

Adolescent↗

PubMedDate not supplied

Vascular endothelial growth factor (VEGF) expression in primary tumors and peritoneal metastases from patients with advanced ovarian carcinoma.

BACKGROUND: Several experimental and clinical data suggest that vascular endothelial growth factor (VEGF) is involved in ovarian carcinogenesis. However, there are no conclusive data about the prognostic value of tissue VEGF expression in this malignancy. The aim of the present investigation was to compare VEGF immunostaining in primary tumors and peritoneal metastases from patients with advanced ovarian carcinoma and to assess whether this parameter has a predictive or prognostic relevance. MATERIALS AND METHODS: The investigation was conducted on 45 patients who underwent initial surgery followed by platinum-based or paclitaxel/platinum-based chemotherapy for advanced ovarian carcinoma. Both primary tumors and peritoneal metastases were immunohistochemically analyzed for VEGF expression. Intense staining score was assigned if more than 75% of the cells stained positive. RESULTS: Intense VEGF immunostaining was detected in 14 and 36 (31.1% versus 80.0%, p < 0.0001), respectively, of primary tumors and peritoneal metastases. Twenty-six (57.8%) patients showed an increased VEGF immunostaining in metastatic lesions compared with primary tumors. VEGF immunostaining in primary tumors, VEGF immunostaining in peritoneal metastases and change in VEGF immunostaining from the primary tumor to peritoneal metastatic lesion were related neither to the response to chemotherapy nor to progression-free survival. CONCLUSION: In patients with advanced ovarian carcinoma, intense VEGF immunostaining was more often detected in peritoneal metastases than in primary tumors. VEGF immunostaining in primary as well as in metastatic lesions correlated neither with the response to chemotherapy nor with the clinical outcome. Therefore the immunohistochemical detection of VEGF in tissue samples collected during primary surgery failed to have a predictive or prognostic relevance for patients with advanced ovarian carcinoma.

Adult↗

PubMedDate not supplied

Chemotherapy with epirubicin and paclitaxel for breast cancer during pregnancy: case report and review of the literature.

BACKGROUND: Breast cancer diagnosed during pregnancy is a challenging clinical situation. Little data are currently available about chemotherapy in pregnant women with this malignancy. CASE REPORT: We report the case of a 36-year-old pregnant woman with a T2N1M0 breast cancer who received sequential chemotherapy including epirubicin (120 mg/m2 every three weeks for four cycles) and paclitaxel (175 mg/m2 every three weeks for three cycles) from the 14th to the 32nd week of gestation. The patient delivered a normal female baby by caesarean section at the 36th week. The immunohistochemical examination of the placenta showed a diffuse, strong P-glycoprotein expression. Thirty-six months after the delivery, the mother was disease-free and the infant showed normal development and growth. DISCUSSION: Sequential chemotherapy including epirubicin and paclitaxel should be taken into consideration as adjuvant treatment for pregnant women with high-risk breast cancer. The strong placental expression of P-glycoprotein may play a major role in limiting fetal exposure to anthracyclines and taxanes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

P53 gene status in patients with advanced serous epithelial ovarian cancer in relation to response to paclitaxel- plus platinum-based chemotherapy and long-term clinical outcome.

BACKGROUND: The aim of this retrospective study was to assess whether p53 gene status has any predictive or prognostic relevance in patients with advanced, poorly-differentiated serous epithelial ovarian cancer treated with paclitaxel- plus platinum-based chemotherapy. MATERIALS AND METHODS: The study was conducted on 46 patients who underwent surgery followed by paclitaxel- plus carboplatin-based chemotherapy. The tumor tissue samples were analyzed for p53 gene mutations. The median follow-up of survivors was 50.3 months. RESULTS: Twenty-three patients (50%) showed p53 mutations at exons 5 to 9. Sixteen (34.8%) patients had a polymorphism at codon 72 in exon 4 (SNP codon 72): 10 were Pro/Pro homozygous and 6 Pro/Arg heterozygous. Four polymorphic patients had a second mutation at exons 5 to 9. An inverse correlation was evidenced between the SNP codon 72 and mutations at exons 5 to 9, with the latter more frequently found in wild-type (Arg/Arg) codon 72 (19/30 versus 4/16, 63.3% versus 25.0%; p=0.03) cases. A clear trend for a higher response rate and longer progression-free and overall survival was observed in wild-type p53 and Pro/Pro polymorphic patients as compared to patients with mutant p53. CONCLUSION: The addition of paclitaxel to carboplatin does not appear to overcome the negative predictive and prognostic significance of p53 gene mutations in serous ovarian cancer. Nevertheless, the comprehensive analysis of p53 genotype, including the SNP codon 72, warrants further investigation in order to envisage individual responsiveness to cancer therapy.

Adult↗

PubMedDate not supplied

Intratumoral microvessel density in advanced epithelial ovarian cancer and its use as a prognostic variable.

BACKGROUND: The aim of this retrospective study was to assess whether the intratumoral microvessel density (IMD) in primary tumour specimens had any impact on the clinical outcome of patients with advanced epithelial ovarian cancer treated in two Italian departments of gynaecological oncology. MATERIALS AND METHODS: The study was conducted on 101 patients who underwent initial surgery followed by platinum-based chemotherapy (37) or paclitaxel/platinum-based chemotherapy (64) for International Federation of Gynecology and Obstetrics (FIGO) stage III-IV epithelial ovarian cancer. The median follow-up of survivors from initial surgery was 65 months (range, 27 to 132 months). Paraffin-embedded sections of primary tumour specimens were analysed for IMD by immunohistochemistry using anti-CD34 antibodies. RESULTS: Progression-free survival and overall survival were significantly better in patients with IMD > or =40 microvessels/field compared with those with lower IMD (p = 0.0105 and p = 0.0065, respectively). Cox model showed that IMD was the strongest independent prognostic variable for both progression-free survival (p = 0.0267) and overall survival (p = 0.0189). CONCLUSION: An elevated IMD was associated with a significantly better progression-free survival and overall survival in patients with stage III-IV epithelial ovarian cancer who underwent initial surgery followed by chemotherapy, mainly consisting of a paclitaxel/platinum-based regimen.

Antineoplastic Combined Chemotherapy Protocols↗