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1.
Gynecol Oncol ; 165(3): 453-458, 2022 06.
Article in English | MEDLINE | ID: mdl-35397918

ABSTRACT

OBJECTIVE: The aims of the present study were to assess the oncological outcomes of platinum-sensitive recurrent ovarian cancer patients undergoing secondary cytoreduction (SCS) after treatment with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) at diagnosis and to compare the performance of different selection models in these patients. METHODS: Retrospective, observational, single-center cohort study including patients with platinum-sensitive recurrent epithelial ovarian cancer with abdominal/inguinal/cardiophrenic disease between November 2012 and November 2020. Patients were selected as surgical candidates with PET/CT-scan and with diagnostic laparoscopy. RESULTS: 272 patients were included in the study. Of these, 165 (60.7%) patients were treated with PDS at diagnosis and 107 (39.3%) with IDS. SCS was performed in 178 (65.4%) cases, with complete gross resection achieved in 155/178 (87.1%). No progression-free survival (PFS) difference was demonstrated when patients treated with PDS were compared with those treated with NACT+IDS at first diagnosis (median 21 versus 21 months; p = 0.684); no post-recurrence survival (PRS) difference was evident between the two groups (median 81 versus 77 months, respectively; p = 0.574). Current selection models to candidate patients to SCS adequately performed in patients treated with IDS at diagnosis, as well as in the PDS group, with combination of PET/CT-scan and laparoscopy being an accurate tool in prediction of no gross residual disease at SCS in this pre-selected population. CONCLUSIONS: Patients with platinum-sensitive recurrent epithelial ovarian cancer treated with NACT/IDS as primary treatment have similar post-recurrence survival outcomes of those treated with PDS. Current models to select patients for SCS can be safely applied to IDS patients.


Subject(s)
Cytoreduction Surgical Procedures , Ovarian Neoplasms , Carcinoma, Ovarian Epithelial/drug therapy , Carcinoma, Ovarian Epithelial/surgery , Chemotherapy, Adjuvant , Cohort Studies , Female , Humans , Neoadjuvant Therapy , Neoplasm Recurrence, Local/drug therapy , Neoplasm Staging , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , Positron Emission Tomography Computed Tomography , Retrospective Studies
2.
Int J Gynecol Cancer ; 31(8): 1154-1158, 2021 08.
Article in English | MEDLINE | ID: mdl-33883231

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, cancer care had to be reorganized; national and international recommendations were published to manage anticancer treatments safely and to reduce the risk of SARS-CoV-2 infection for patients and health workers. OBJECTIVE: To evaluate whether the adoption of recommendations for the management of patients with gynaecologic cancer receiving treatment during the pandemic resulted in containment of infections and continuing oncologic care. METHODS: Based on the published recommendations, and according to the local Health Direction guidelines, we developed and drafted a security protocol to modify access of patients with gynaecologic cancer to the "Fondazione Policlinico Agostino Gemelli-IRCCS, Rome" between February 1 and April 30, 2020 and compared results with the corresponding 3 months of 2019. RESULTS: Between February and April 2019, we registered 3254 admissions, including 2253 patients receiving intravenous chemotherapies, 298 receiving oral therapies, and 703 having hospital visits. Between February and April 2020, we registered 3213 admissions, including 2221 patients receiving intravenous chemotherapies, 401 receiving oral therapies, and 591 having hospital visits. Oral treatments and general visits were different in the two time periods (p<0.001). Despite the elevated patient flow, only one patient (0.1%) tested positive for COVID-19 and there were no cases among healthcare staff. CONCLUSIONS: Based on the adopted security protocol we provided continuity of care for all patients and limited the spread of the COVID-19 infection.


Subject(s)
COVID-19/epidemiology , Genital Neoplasms, Female/therapy , Female , Humans , Pandemics , SARS-CoV-2/isolation & purification
3.
Int J Gynecol Cancer ; 31(6): 875-882, 2021 06.
Article in English | MEDLINE | ID: mdl-33931498

ABSTRACT

OBJECTIVE: To explore the clinical and biological prognostic factors for advanced ovarian cancer patients receiving first-line treatment with carboplatin, paclitaxel, and bevacizumab. METHODS: A multicenter, phase IV, single arm trial was performed. Patients with advanced (FIGO (International Federation of Gynecology and Obstetrics) stage IIIB-IV) or recurrent, previously untreated, ovarian cancer received carboplatin (AUC (area under the curve) 5), paclitaxel (175 mg/m2) plus bevacizumab (15 mg/kg) on day 1 for six 3-weekly cycles followed by bevacizumab single agent (15 mg/kg) until progression or unacceptable toxicity up to a maximum of 22 total cycles. Here we report the final analysis on the role of clinical prognostic factors. The study had 80% power with a two-tailed 0.01 α error to detect a 0.60 hazard ratio with a factor expressed in at least 20% of the population. Both progression-free and overall survival were used as endpoints. RESULTS: From October 2012 to November 2014, 398 eligible patients were treated. After a median follow-up of 32.3 months (IQR 24.1-40.4), median progression-free survival was 20.8 months (95% CI 19.1 to 22.0) and median overall survival was 41.1 months (95% CI 39.1 to 43.5). Clinical factors significantly predicting progression-free and overall survival were performance status, stage, and residual disease after primary surgery. Neither baseline blood pressure/antihypertensive treatment nor the development of hypertension during bevacizumab were prognostic. There were two deaths possibly related to treatment, but no unexpected safety signal was reported. CONCLUSIONS: Efficacy and safety of bevacizumab in combination with carboplatin and paclitaxel and as maintenance were comparable to previous data. Hypertension, either at baseline or developed during treatment, was not prognostic. Performance status, stage, and residual disease after primary surgery remain the most important clinical prognostic factors. TRIAL REGISTRATION NUMBER: EudraCT 2012-003043-29; NCT01706120.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/therapeutic use , Carboplatin/therapeutic use , Carcinoma, Ovarian Epithelial/drug therapy , Paclitaxel/therapeutic use , Aged , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Bevacizumab/pharmacology , Carboplatin/pharmacology , Carcinoma, Ovarian Epithelial/mortality , Female , Humans , Middle Aged , Paclitaxel/pharmacology , Prognosis , Progression-Free Survival
4.
Int J Gynecol Cancer ; 31(10): 1348-1355, 2021 10.
Article in English | MEDLINE | ID: mdl-34462317

ABSTRACT

INTRODUCTION: The use of routine antithrombotic prophylaxis is not recommended for advanced cancer patients receiving chemotherapy. The effect of bevacizumab-containing therapy on the risk of thromboembolic events remains controversial in ovarian cancer patients. We report on the incidence of thromboembolic events and the prevalence of antithrombotic therapy in patients enrolled in the single arm, phase IV, MITO-16A/MaNGO-OV2A trial. METHODS: In this trial, potential prognostic factors for patients with previously untreated ovarian cancer receiving a combination of platinum-based chemotherapy and bevacizumab were explored and the final analysis has already been reported. In this secondary analysis, the occurrence of thromboembolic events and the use of antithrombotic therapy were described according to the clinical characteristics of the patients. The prognostic role of thromboembolic events for progression-free and overall survival were also evaluated. RESULTS: From October 2012 to November 2014, 398 eligible patients were enrolled. 76 patients (19.1%) were receiving some type of anticoagulant or anti-aggregant treatment at baseline. Overall, 24 thromboembolic events were reported (cumulative incidence of 6.0%). The occurrence of thromboembolic events was not associated with baseline patient characteristics and was not modified by the use of antithrombotic prophylaxis (HR 0.60, 95% CI 0.18 to 2.0). Occurrence of thromboembolic events was not associated with progression-free survival (HR 1.34, 95% CI 0.83 to 2.15) or overall survival (HR 0.78, 95% CI 0.37 to 1.61). CONCLUSIONS: In our study, a 6.0% rate of thromboembolic events was reported during treatment with bevacizumab plus chemotherapy. Thromboembolic events were not associated with the clinical characteristics of the patients or with the use of antithrombotic prophylaxis, nor did they significantly affect the long-term prognosis. TRIAL REGISTRATION NUMBER: NCT01706120.


Subject(s)
Carcinoma, Ovarian Epithelial/drug therapy , Fibrinolytic Agents/therapeutic use , Ovarian Neoplasms/drug therapy , Thromboembolism/prevention & control , Aged , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Combined Chemotherapy Protocols , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Female , Humans , Middle Aged
6.
Int J Gynecol Cancer ; 27(6): 1141-1148, 2017 07.
Article in English | MEDLINE | ID: mdl-28574933

ABSTRACT

BACKGROUND: Trabectedin (T) plus pegylated liposomal doxorubicin (PLD) is approved for treatment of platinum-sensitive recurrent ovarian cancer (ROC). Despite the recommendations and guidelines, variations in managing T/PLD administration in routine clinical practice cannot be excluded. We aimed at setting up an Italian survey collecting data about management of T/PLD administration in ROC patients. METHODS: We carried out the development of a questionnaire-based survey on routine clinical practice in the management of ROC patients administered T/PLD. The survey registered the physicians' approach to modification/discontinuation of treatment, type of modifications, reasons why, and so on. The survey was transmitted to medical oncologists and gynecologic oncologists practicing in national centers/institutions. RESULTS: Fifty-eight Italian centers/institutions returned the compiled questionnaire; participants practiced at community cancer centers or hospitals (56.9%), academic institutions (36.2%), and other settings (private clinics, etc) (6.9%). There was no statistically significant difference in the distribution of practice setting according to geographic areas. Most responders were medical oncologists (84.5%) and were members (82.8%) of at least 1 scientific society or cooperative group. Almost 31.5% of responders reported interruption of the whole treatment, mostly because of toxicity (41.2%), followed by patients' choice (29.4%), or achievement of clinical benefit (23.5%). Dose reduction was referred by 47.4% of responders. Reduction of dose for both drugs was referred by 88.5% of responders, and the extent of dose reduction ranged between 10% and 30%. CONCLUSIONS: This survey highlights the gaps in transposing evidence-based or consensus guidelines in the real-world management of T/PLD administration; these findings could be useful in order to focus the attention on specific knowledge and/or experience gaps and plan pertinent educational programs.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Oncologists/statistics & numerical data , Ovarian Neoplasms/drug therapy , Practice Patterns, Physicians'/statistics & numerical data , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Dioxoles/administration & dosage , Dioxoles/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Doxorubicin/analogs & derivatives , Female , Humans , Italy/epidemiology , Neoplasm Recurrence, Local/epidemiology , Ovarian Neoplasms/epidemiology , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Surveys and Questionnaires , Tetrahydroisoquinolines/administration & dosage , Tetrahydroisoquinolines/adverse effects , Trabectedin
7.
BMC Cancer ; 14: 947, 2014 Dec 13.
Article in English | MEDLINE | ID: mdl-25495785

ABSTRACT

BACKGROUND: The aim of this multicenter, retrospective study was to evaluate the efficacy and safety of metronomic oral cyclophosphamide (MOC) in heavily treated, relapsed ovarian cancer (ROC) patients. METHODS: oral cyclophosphamide (Endoxan®, Baxter, Italy) was administered at the dose of 50 mg daily, continuously. Treatment-related toxicity and response to treatment were assessed by the NCI-CTC criteria, and RECIST criteria, respectively. Progression-free (PFS), and overall survival (OS) were also assessed. RESULTS: 54 patients were analyzed: 20 patients (37.0%) were considered primarily platinum refractory/resistant, while 34 patients (63.0%) were defined as platinum sensitive; 79.6% of patients had received ≥2 previous lines before starting MOC. The objective response rate (ORR) was 20.4%. Eleven patients (20.4%) experienced stable disease and 8 of them had a response duration ≥6 months. A total of 32 patients (59.2.%) progressed during treatment. Median PFS was 4 months, and the 12-month PFS rate was 19.6%; median OS was 13 months, and the 12-month OS rate was 51.5% . Patients responding to MOC showed a more favorable PFS (median = 17 months) compared to patients with stabilization (median = 6 months) or progression of disease (median = 3 months) (p value = 0.0001). Median OS of responding patients was 30 months compared to 11 months in cases achieving stabilization, or progression of disease (median = 8 months) (p value = 0.0001). Only 1 patient experienced grade 3 anemia. Non-hematological grade 3 toxicity was registered in 2 patients. CONCLUSIONS: MOC could provide a valid alternative in terms of risk/benefit ratio in the palliative treatment of heavily treated ROC patients.


Subject(s)
Antineoplastic Agents, Alkylating/administration & dosage , Cyclophosphamide/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Administration, Metronomic , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Alkylating/adverse effects , Cyclophosphamide/adverse effects , Female , Humans , Middle Aged , Ovarian Neoplasms/pathology , Retrospective Studies , Salvage Therapy/methods , Survival Analysis , Treatment Outcome
8.
J Vasc Access ; 24(3): 507-510, 2023 May.
Article in English | MEDLINE | ID: mdl-34399639

ABSTRACT

Physical exercise is often encouraged in cancer patients, mainly for the purpose of rehabilitation and for its psychological benefit. Some authors also suggest that exercise-specially in patient with peripherally inserted central venous access devices-may contribute to reduce the risk of catheter-related thrombosis. Still, the impact of physical exercise on the risk of device-related complications is not yet defined.We report a case of secondary migration of the tip of an arm port, caused by high-intensity exercise in a woman undergoing chemotherapy because of ovarian cancer. Tip migration was suspected because of malfunction (persistent withdrawal occlusion) and diagnosis established after ultrasound examination and chest x-ray.Even if exercise may yield benefit in the cancer patient on chemotherapy, the risk of mechanical complication of the venous access device-such as tip migration-should be considered in the case of high-intensity exercise.


Subject(s)
Catheterization, Central Venous , Catheterization, Peripheral , Central Venous Catheters , Neoplasms , Thrombosis , Female , Humans , Catheterization, Central Venous/adverse effects , Neoplasms/drug therapy , Ultrasonography , Catheterization, Peripheral/adverse effects
9.
J Gynecol Oncol ; 31(1): e6, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31788996

ABSTRACT

OBJECTIVE: Bevacizumab maintenance following platinum-based chemotherapy is an effective treatment for epithelial ovarian cancer (EOC), both in primary and recurrent disease. Our aim was to identify criteria to select elderly patients who can safely benefit from bevacizumab addition. METHODS: This is a case-control study on patients with primary or recurrent EOC who received platinum-based chemotherapy plus bevacizumab, between January 2015 and December 2016. Patient characteristics, treatment details and adverse events were reviewed and analyzed in 2 settings: younger (<65 years, group 1) and elderly (≥65 years, group 2). A binary logistic model was applied to correlate clinical variables and severe (grade ≥3) toxicity risk. RESULTS: Overall, 283 patients with EOC were included, with 72 (25.4%) older patients compared with 211 (74.6%) younger women. Bevacizumab had been administered to 234 patients (82.7%) as first-line treatment and in 49 (17.3%) with recurrent disease. At diagnosis, elderly patients presented with at least one comorbidity and were taking at least 1 medication in 84.7% and 80.6% of the cases respectively, compared with correspondingly 47.4% and 37.4% in group 1 (p<0.001). Nonetheless, the occurrence of serious (grade ≥3) adverse events did not increase among the older group. Creatinine serum levels >1.1 g/dL, estimated glomerular filtration rate (eGFR) ≤60 mL/min, ≥3 comorbidities were independently associated with a higher severe toxicity. CONCLUSIONS: Elderly patients with EOC can safely be treated with bevacizumab; factors other than age, as higher creatinine serum levels, eGFR and number of comorbidities should be considered to better estimate bevacizumab-related toxicity risk.


Subject(s)
Angiogenesis Inhibitors/adverse effects , Bevacizumab/adverse effects , Carcinoma, Ovarian Epithelial/drug therapy , Maintenance Chemotherapy/adverse effects , Ovarian Neoplasms/drug therapy , Age Factors , Aged , Angiogenesis Inhibitors/administration & dosage , Bevacizumab/administration & dosage , Carcinoma, Ovarian Epithelial/mortality , Case-Control Studies , Databases, Factual , Female , Humans , Maintenance Chemotherapy/methods , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/mortality , Progression-Free Survival , Retrospective Studies
10.
Cancer Chemother Pharmacol ; 83(3): 431-438, 2019 03.
Article in English | MEDLINE | ID: mdl-30506402

ABSTRACT

PURPOSE: The role of dose-dense schedules in the neo-adjuvant treatment (NACT) of locally advanced cervical cancer (LACC) has been reported. This phase II study investigated activity of dose-dense paclitaxel/platinum before radical surgery (RS) in LACC patients. METHODS: The primary end-point was the rate of optimal pathological response (OPR: pathological complete/microscopic response). NACT (paclitaxel: 80 mg/m2) and carboplatin (AUC 2) were administered for 6 weeks. Overall response rate (ORR) to NACT was assessed by the RECIST criteria. Patients amenable to surgery were triaged to RS. The null hypothesis was that the OPR rate would improve from 30.0 to 45.0% (α error: 0.05, ß error: 0.2). The regimen would be considered active if > 25 OPRs were found. RESULTS: 36 patients were enrolled; 19 patients were stage IIB (52.8%) and 16 (44.4%) patients had pelvic lymph-node involvement at imaging. All patients completed neo-adjuvant chemotherapy; ORR was of 75.0%. RS was performed in 29 (93.5%) patients. Since the OPR was 16.1%, we evaluated the real chances to achieve the number of OPR required by the Simon design and decided to close the study. Grade 3/4 hematological toxicity occurred in 5 patients; surgical morbidity occurred in 14 patients. The 2-year PFS rate was 69.0%. CONCLUSION: Dose-dense neo-adjuvant paclitaxel/carboplatin is feasible and safe in LACC patients; however, failure to achieve the primary end-point has to be recognized. Given the heterogeneity of the available studies, robust data from an adequately sized prospective study focused on more homogeneous series are required.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carboplatin/administration & dosage , Hysterectomy/methods , Paclitaxel/administration & dosage , Uterine Cervical Neoplasms/therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/adverse effects , Cervix Uteri/drug effects , Cervix Uteri/pathology , Dose-Response Relationship, Drug , Feasibility Studies , Female , Humans , Lymph Node Excision , Middle Aged , Neoadjuvant Therapy/adverse effects , Neoadjuvant Therapy/methods , Paclitaxel/adverse effects , Prospective Studies , Response Evaluation Criteria in Solid Tumors
11.
Minerva Med ; 110(4): 367-384, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31124637

ABSTRACT

Ovarian cancer is the fifth leading cause of cancer death among women and the most lethal gynecologic malignancy. Most women with advanced epithelial ovarian cancer will experience many episodes of recurrent disease with progressively shorter disease-free intervals. For women whose disease continues to respond to platinum-based drugs, the disease can often be controlled for 5 years or more. Enormous progress has been made in the management of this disease, and new targeted treatments such as antiangiogenic drugs, poly(adenosine diphosphate-ribose) polymerase inhibitors, and immune checkpoint inhibitors offer potential for improved survival. A variety of combination strategies are being evaluated to leverage these agents. The objective of this review is to summarize results from clinical trials that tested cytotoxic drugs and target strategies for the treatment of ovarian cancer with particular attention to Phase III and ongoing trials.


Subject(s)
Ovarian Neoplasms/therapy , Carcinoma, Ovarian Epithelial/pathology , Carcinoma, Ovarian Epithelial/therapy , Female , Humans , Neoplasm Staging , Ovarian Neoplasms/pathology
12.
Gynecol Oncol ; 111(1): 144-50, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18692225

ABSTRACT

OBJECTIVE: The aim of the study was to analyze the Quality of life (QoL) scores in a single institution series of locally advanced cervical cancer patients (LACC) administered preoperative chemoradiation, compared to early stage disease (ECC) patients undergoing radical surgery. METHODS: The following criteria were required in order to enroll patients: age between 18 and 65years at initial diagnosis, at least 12 months from the end of treatment, no evidence of recurrence/second malignancy. The SF-36 questionnaire on general health, and the HADS questionnaire on mental distress were utilized. RESULTS: 93 subjects were available for the analysis. At time of analysis, median follow-up was 30 months (range 12-120). LACC patients showed QoL scores comparable to ECC patients with the exception of physical functioning (mean+/-SD=69.0+/-13.1 versus mean+/- SD=85.4+/-16.2, p value=0.0007). In the group of LACC patients, the presence of co-morbidities was significantly associated with the impairment of almost all subscales of QoL. A low education level and the status of unemployment were documented to negatively impact on the vast majority of SF-36 subscale scores. In the multivariate analysis, the presence of co-morbidities, low educational level, age> 50 years, and unemployment maintained their independent negative association with poor QoL scores. The percentage of cases with high levels HADS-anxiety was higher in LACC than ECC patients (27.6% versus 8.6%, p value=0.034). CONCLUSIONS: LACC patients administered preoperative chemoradiation showed QoL scores comparable to EEC patients, and a higher proportion of anxiety disorders; low educational level and unemployment status were mainly associated with poor QoL scores.


Subject(s)
Uterine Cervical Neoplasms/psychology , Uterine Cervical Neoplasms/therapy , Adult , Aged , Anxiety/etiology , Combined Modality Therapy , Depression/etiology , Female , Humans , Middle Aged , Neoplasm Staging , Preoperative Care , Quality of Life , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/surgery
13.
Eur J Surg Oncol ; 43(12): 2270-2276, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28988767

ABSTRACT

INTRODUCTION: To identify a subset of cervical cancer (CC) patients administered chemoradiation (CT/RT) plus radical surgery (RS), who can be spared lymphadenectomy, and complications. PATIENTS AND METHODS: 430 Stage IB2-IIB patients without LN involvement at imaging were accrued (March 1996-December 2015) at Gynecologic Oncology Unit of the Catholic University of Rome/Campobasso. CT/RT consisted of pelvic irradiation plus cisplatin based chemotherapy. Objective response was evaluated according to RECIST criteria; radical hysterectomy and pelvic ± aortic lymphadenectomy was attempted in patients achieving response or stable disease. Surgical morbidity was classified according to the Chassagne grading system. RESULTS: 421 cases underwent RS; metastatic pelvic and aortic LNs were documented in 10.7%, and 8.8% of cases, respectively. In patients without residual tumor in the cervix, there was only 1 case (0.53%) with positive pelvic LNs, and 1 case (2.3%) with metastatic aortic LNs. Analysis of patients according to pre- and post-CT/RT imaging was able to select cases without any metastatic LNs: in patients with negative pelvic LNs at pre- and post-CT/RT imaging, none of cases without residual disease in the cervix had metastatic pelvic or aortic LNs. Of 149 early complications, 76 (51.0%) were lymphovascular. The most frequent late complications were lymphovascular (N = 25/61, 41.0%). CONCLUSION: Lymphadenectomy could be avoided in stage IB2-IIB CC patients undergoing preoperative CT/RT, when a careful evaluation of pre- and post-CT/RT imaging and histological assessment of no residual disease in the cervix is made. This approach may avoid lymphadenectomy in 40% of patients with a favourable impact on lymphovascular morbidity.


Subject(s)
Chemoradiotherapy , Lymph Node Excision , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Cisplatin/therapeutic use , Combined Modality Therapy , Female , Humans , Hysterectomy , Middle Aged , Neoplasm Staging , Retrospective Studies , Treatment Outcome
14.
Chem Biol ; 9(1): 93-101, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11841942

ABSTRACT

SB-T-1213 and IDN5109 are semisynthetic, orally available taxanes that are up to 400-fold more active than paclitaxel against drug-resistant cells. IDN5109 is in clinical trials. We investigated the primary target for SB-T-1213 and IDN5109 and whether the compounds interact with microtubules differently than paclitaxel. Unlike paclitaxel, at 1-10 microM both novel taxanes initiate microtubule polymerization in vitro with no lag. They enhance polymerization equally or more potently than paclitaxel. SB-T-1213 induces unusual microtubules with attached extra protofilaments or open sheets, and IDN5109 induces large protofilamentous sheets. Both inhibit HeLa cell proliferation, block mitosis at the metaphase/anaphase transition, bundle microtubules at high drug concentrations, and induce abnormal metaphase spindles and apoptosis. They target microtubules but alter their polymerization and structure differently than paclitaxel. These differences may play a role in their enhanced cytotoxicity and efficacy.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Bridged-Ring Compounds/pharmacology , Microtubules/drug effects , Mitosis/drug effects , Paclitaxel/analogs & derivatives , Paclitaxel/pharmacology , Taxoids , Tubulin/drug effects , Apoptosis/drug effects , Dose-Response Relationship, Drug , HeLa Cells , Humans , Microscopy, Electron , Microtubules/metabolism , Microtubules/ultrastructure , Tubulin/metabolism
15.
Curr Med Chem Anticancer Agents ; 3(2): 133-8, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12678907

ABSTRACT

Taxanes represent the most important class of antitumor agents introduced in cancer therapy in the last decade. The first member of the family was paclitaxel, firstly isolated from Taxus Brevifolia and found active as antitumor agent at the end of 60's. In the mid of 90's, a semi-synthetic taxane derived from 10-deacetylbaccatin III was introduced and thereafter named as docetaxel. Taxanes act by inhibiting microtubule dynamics, thereby inducing the arrest in M phase and the consequent activation of the apoptotic program. Since target of taxanes is not directly the genome, they are effective alone or in combination with DNA-damaging drugs in tumors not responding to conventional chemotherapeutics, such as advanced breast and non small cell lung cancer. In this review we will cover the aspects of clinical applications of the currently used taxanes as well as the clinical problems related to their use. Taking into consideration such problems, new taxanes have been developed in order to extend the spectrum of taxane-sensitive tumors and several of them are currently undergoing clinical trials. Among these agents, a newly developed taxane (BAY 59-8862) appears particularly interesting for the fact that it shows excellent oral bioavailability and activity in tumors with inherent resistance to paclitaxel.


Subject(s)
Antineoplastic Agents/therapeutic use , Bridged-Ring Compounds/therapeutic use , Drug Resistance, Neoplasm , Neoplasms/drug therapy , Taxoids , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Bridged-Ring Compounds/chemical synthesis , Bridged-Ring Compounds/chemistry , Clinical Trials as Topic , Humans
16.
Cancer Chemother Pharmacol ; 49(3): 256-60, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11935219

ABSTRACT

PURPOSE: The present study was conducted to explore whether neoadjuvant chemotherapy with a combination of epirubicin, paclitaxel and cisplatin could improve the operability and pathological response rate in locally advanced cervical cancer patients. METHODS: Between April 1996 and July 2000, 42 patients with carcinoma of the uterine cervix, FIGO stage Ib(2)-IVa, were treated with two or three 21-day cycles of an epirubicin 100 mg/m(2), paclitaxel 175 mg/m(2), cisplatin 100 mg/m(2) regimen. RESULTS: All patients were eligible for evaluation of toxicity and response. A total of 92 courses of therapy were administered. Three patients had a 20% reduction from the starting dose due to haematological toxicity. Grade 3-4 leukopenia was observed in 15% of cycles, requiring G-CSF support in half of them. Major non-haematological toxicity consisted of grade 3 alopecia (100%), and grade 3 nausea and vomiting (40%). A total of 33 clinical responses (78.5%, 95% CI 63.8-93.2) were recorded, 8 complete responses (CR) and 25 partial responses (PR). Of the 42 patients, 32 (76.2%) underwent radical surgery. At pathological examination 8 complete or microscopic pathological responses, 17 PRs, and 9 patients with stable disease were observed. The median follow-up time was 17 months for the 42 patients enrolled (range 3-62 months). Among the patients submitted to radical surgery, five recurrences were observed, with a median disease-free survival of 47 months. Median overall survival had not been reached at the time of this report. These results appear to be in the range reported for other neoadjuvant cisplatin-based regimens not including paclitaxel. CONCLUSIONS: Neoadjuvant chemotherapy with the epirubicin, paclitaxel and cisplatin combination followed by radical surgery proved to be a safe and effective approach to advanced cervical cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Uterine Cervical Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Disease Progression , Disease-Free Survival , Epirubicin/administration & dosage , Female , Humans , Middle Aged , Neoplasm Staging , Paclitaxel/administration & dosage , Treatment Outcome , Uterine Cervical Neoplasms/pathology
17.
Life Sci ; 70(12): 1447-59, 2002 Feb 08.
Article in English | MEDLINE | ID: mdl-11883719

ABSTRACT

In this study we investigated whether the flavonoid silybin and its bioavailable derivative IdB 1016 (silipide) could enhance the antitumour activity of cisplatin (CDDP), the most commonly used drug in the treatment of gynaecological malignancies. Silybin alone up to 10 (M was unable to produce a relevant in vitro growth inhibition of A2780 cells, whereas CDDP was effective, giving an IC50 value of 0.5+/-0.14 microM. When silybin was combined with CDDP, a dose-dependent and statistically significant (p<0.05) increase of the CDDP activity was noticed, yielding IC50 values of 0.35+/-0.07 and 0.263+/-0.004 microM at silybin concentrations of 1 and 10 microM, respectively. The same trend was observed for in vivo experiments. IdB 1016 alone (1350 mg/kg) did not significantly affect tumour growth, whereas CDDP at the Maximum Tolerated Dose (12 mg/kg) produced a tumour weight inhibition (TWI%) of 80% and a log10 cell kill (LCK) of 0.7. Administration of both drugs resulted in a potentiation of the antitumour activity and TWI% and LCK increased to 90% and 1, respectively. Interestingly, mice receiving the combination recovered earlier in terms of body weight loss as compared to CDDP-treated mice. CDDP at 6 mg/kg yielded TWI of 44% and LCK of 0. The concomitant administration of IdB 1016 (1800 mg/kg) enhanced CDDP anti-tumour activity, with 68% TWI and 0.6 LCK. Finally, an antiangiogenic effect of IdB 1016 in an in vivo experimental model was demonstrated. Median haemoglobin value for the Matrigel from the vehicle-treated controls was 2.43 versus a value of 0.321 for the IdB 1016-treated animals.


Subject(s)
Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cisplatin/pharmacology , Cisplatin/therapeutic use , Neoplasms, Experimental/drug therapy , Ovarian Neoplasms/pathology , Phosphatidylcholines/pharmacology , Phosphatidylcholines/therapeutic use , Silymarin/pharmacology , Silymarin/therapeutic use , Animals , Apoptosis/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Drug Synergism , Female , Mice , Mice, Nude , Neoplasms, Experimental/blood supply , Neoplasms, Experimental/pathology , Neovascularization, Pathologic/drug therapy , Ovarian Neoplasms/drug therapy , Tumor Cells, Cultured/drug effects
18.
Obstet Gynecol ; 121(2 Pt 2 Suppl 1): 443-7, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23344403

ABSTRACT

BACKGROUND: Postpartum hematomas are a potentially serious obstetric complication for which management options are not standardized. We report successful treatment of a large postpartum hematoma using arterial embolization as primary approach. CASE: A 29-year-old woman at term gestation underwent vacuum-assisted vaginal delivery. Two hours later, marked rectal pain developed. Examination revealed a large left vaginal hematoma and no obvious bleeding sites. Computed tomography demonstrated a 10-cm supralevator hematoma and extrauterine arterial bleeding. Angiography revealed contrast extravasation from a branch of the left internal pudendal artery. Selective embolization of this branch stopped the bleeding. The patient was discharged on the third postpartum day. Eight weeks after delivery, there was no evidence of the hematoma. CONCLUSION: Arterial embolization can be used as a first-line treatment for large postpartum hematomas.


Subject(s)
Embolization, Therapeutic , Hematoma/therapy , Puerperal Disorders/therapy , Vaginal Diseases/therapy , Adult , Female , Hematoma/diagnostic imaging , Humans , Radiography , Vacuum Extraction, Obstetrical , Vaginal Diseases/diagnostic imaging
20.
Ann Surg Oncol ; 14(3): 1129-35, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17206484

ABSTRACT

BACKGROUND: A retrospective study was planned in 127 locally advanced cervical cancer (LACC) to investigate: (1) the rate and pattern of metastatic lymph node involvement in patients administered preoperative chemoradiation (CT/RT) versus neoadjuvant chemotherapy (NACT), and (2) the profile of clinico-pathological parameters predictive of metastatic lymph node involvement in these two clinical settings. Finally, we investigated whether the pathologically assessed status of lower pelvic nodes (LPN) was able to predict the pathologically assessed status of upper pelvic nodes (UPN) and parametrium in cases administered CT/RT. METHODS: Patients were selected including LACC patients who were administered concomitant CT/RT (n = 87) or NACT (n = 40), before radical surgery. RESULTS: Metastatic pelvic lymph node involvement was significantly lower in cases administered CT/RT (11.5%) compared to cases administered NACT (30.0%) (P value = 0.009). In the CT/RT group, only MRI-assessed pelvic node status (both at staging and post-treatment evaluation) was associated with pathologic pelvic node status. In patients administered CT/RT, the status of LPN appeared associated with the status of UPN. CONCLUSIONS: (1) Preoperative CT/RT treatment is associated with a lower rate of pelvic node disease in LACC patients compared to NACT; (2) there is no association between the preoperative extent of residual cervical disease after CT/RT and pathologically assessed pelvic node status; (3) the pathological status of LPN is predictive of the pathological status of UPN and parametrium.


Subject(s)
Carcinoma, Squamous Cell/secondary , Carcinoma, Squamous Cell/therapy , Lymph Nodes/pathology , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/therapy , Adult , Aged , Brachytherapy , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Combined Modality Therapy , Female , Humans , Lymph Node Excision , Lymph Nodes/surgery , Lymphatic Metastasis , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Preoperative Care , Prognosis , Retrospective Studies , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/radiotherapy
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