taxane and Peritoneal-Neoplasms

Ovarian cancer is the most lethal gynecologic malignancy. It appears that the vast majority of what seem to be primary epithelial ovarian and primary peritoneal carcinomas is, in fact, secondary from the fimbria, the most distal part of the fallopian tube. Treatment of epithelial ovarian cancer is based on the combination of cytoreductive surgery and combination chemotherapy using taxane and platinum. Although clear cell type is categorized in indolent type, it is known to show relatively strong resistance to carboplatin and paclitaxel regimen and thus poor prognosis compared to serous adenocarcinoma, especially in advanced stages. Irinotecan plus cisplatin therapy may effective for the clear cell adenocarcinoma. The larger expectation for improved prognosis in ovarian carcinoma is related to the use of the new biological agents. One of the most investigated and promising molecular targeted drugs in ovarian cancer is bevacizumab, a monoclonal antibody directed against VEGF. PARP inhibitor is another one. A few recent studies demonstrated positive results of bevacizumab on progression-free survival in ovarian cancer patients, however, investigation of molecular targeting drugs in patients with ovarian cancer are still underway.

Topics: Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Combined Modality Therapy; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Humans; Molecular Targeted Therapy; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Peritoneal Neoplasms; Platinum; Prognosis; Taxoids

PURPOSE Ixabepilone (BMS-247550) is a microtubule-stabilizing epothilone B analog with activity in taxane-resistant metastatic breast cancer. The Gynecologic Oncology Group conducted a phase II evaluation of the efficacy and safety of ixabepilone in patients with recurrent or persistent platinum- and taxane-resistant primary ovarian or peritoneal carcinoma. PATIENTS AND METHODS Patients with measurable platinum- and taxane-resistant ovarian or peritoneal carcinoma, defined as progression during or within 6 months of one prior course of treatment with each agent, received intravenous ixabepilone 20 mg/m(2) administered over 1 hour on days 1, 8, and 15 of a 28-day cycle. Results Of 51 patients entered, 49 were eligible. The objective response rate was 14.3% (95% CI, 5.9% to 27.2%), with three complete and four partial responses. Twenty patients (40.8%) had stable disease, whereas sixteen (32.7%) had increasing disease. The median time to progression was 4.4 months (95% CI, 0.8 to 32.6+ months); median survival was 14.8 months (95% CI, 0.8 to 50.0) months. Patients received a median of two treatment cycles (range, 1 to 29 cycles), and 18.4% of patients received > or = six cycles. Adverse effects included peripheral grade 2 (28.5%) and grade 3 (6.1%) neuropathy, grades 3 to 4 neutropenia (20.4%), grade 3 fatigue (14.3%), grade 3 nausea/emesis (22%), grade 3 diarrhea (10%), and grade 3 mucositis (4%). CONCLUSION Ixabepilone 20 mg/m(2) over 1 hour on days 1, 8, and 15 of a 28-day cycle demonstrates antitumor activity and acceptable safety in patients with platinum- and taxane-resistant recurrent or persistent ovarian or primary peritoneal carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Bridged-Ring Compounds; Drug Resistance, Neoplasm; Epothilones; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Ovarian Neoplasms; Peritoneal Neoplasms; Taxoids; Tubulin Modulators

To compare progression-free survival (PFS), overall survival (OS) and toxicities of thalidomide versus tamoxifen and to evaluate serum vascular endothelial growth factor (VEGF) in biochemical-recurrent epithelial ovarian cancer, primary peritoneal cancer or fallopian tube carcinoma (EOC/PPC/FTC).. Biochemical recurrence was defined as a rising CA-125 exceeding twice the upper limit of normal without evidence of disease as defined by RECIST 1.0 criteria. Women with FIGO stages III and IV, histologically confirmed EOC/PPC/FTC who were free of disease following first-line chemotherapy were randomized to oral thalidomide 200mg daily with escalation to a maximum of 400 mg or tamoxifen 20mg orally twice daily for up to 1 year, progression or adverse effect prohibited further treatment. VEGF was quantified by ELISA in pre and post-treatment serum.. Of the 139 women randomized, 138 were eligible. Interim analysis showed that thalidomide did not reduce the recurrence rate relative to tamoxifen, and the trial was closed. Thalidomide versus tamoxifen was associated with a similar risk of progression (HR = 1.31, 95% confidence interval [CI] = 0.93-1.85), an increased risk of death (HR = 1.76, 95% CI = 1.16-2.68) and more grades 3 and 4 toxicities (55% versus 3%). The most common grades 3 and 4 toxicities were constitutional (12%), somnolence (12%), pulmonary (9%), venous thromboembolism (VTE) (6%) and peripheral neurologic (6%) for thalidomide, with VTE (1.4%) and gastrointestinal (1.4%) for tamoxifen. Serum VEGF was not associated with clinical characteristics, treatment, PFS or OS.. Thalidomide was not more effective than tamoxifen in delaying recurrence or death but was more toxic. VEGF was not prognostic in this cohort.

Topics: Administration, Oral; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; CA-125 Antigen; Disease-Free Survival; Endpoint Determination; Fallopian Tube Neoplasms; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Ovarian Neoplasms; Peritoneal Neoplasms; Tamoxifen; Taxoids; Thalidomide; Vascular Endothelial Growth Factor A

To determine the efficacy, toxicity, and quality of life of capecitabine (Xeloda), an oral 5-fluorouracil derivative, in patients with chemorefractory recurrent mullerian cancers.. Patients with chemorefractory persistent or recurrent ovarian, fallopian tube, or peritoneal cancer with measurable disease were enrolled. Capecitabine was administered beginning at 2000 mg/m2/day orally in two divided doses with meals on a 21-day cycle: 14 days of capecitabine followed by a 7-day rest period. One dose escalation or reduction was allowed. Response was assessed after cycle 2 and cycle 4 and every third cycle thereafter. Standard evaluation included two-dimensional measurement of evaluable disease. Standard criteria for response were used. Therapy was discontinued if progression occurred after at least two cycles of therapy. Quality of life and symptoms were assessed.. Forty-one patients were enrolled. Ninety-two percent of patients had >2 previous chemotherapy regimens. All patients had platinum- and taxane-resistant disease. Thirty-six patients were evaluable for response. Three patients had a partial response, with a median response duration of five cycles. Twenty-two patients had stable disease for 3 to 11 cycles (median, 6 cycles). Eleven had progressive disease. The only grade 4 toxicity was abdominal pain (n = 2). The most common grade 3 toxicities were fatigue (n = 19), hand-foot syndrome (n = 11), abdominal pain (n = 7), and diarrhea (n = 4). One patient had a grade 3 hematologic toxicity (anemia).. Capecitabine at the dosages used in this study is well tolerated and has minimal hematologic toxicity.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Bridged-Ring Compounds; Capecitabine; Deoxycytidine; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Platinum Compounds; Taxoids

DX-8951f is a water-soluble camptothecin derivative with greater in vivo and in vitro activity than topotecan or irinotecan. The objectives of this phase II study were to determine the antitumor activity, safety and pharmacokinetic profile of DX-8951f administered intravenously for five consecutive days, every 3 weeks in patients with advanced ovarian, tubal and peritoneal cancer resistant to platinum, taxane and topotecan.. Enrolled in the study at The University of Texas M. D. Anderson Cancer Center were 16 patients with measurable cancer resistant to platinum, taxane and topotecan. All 16 patients were assessable for safety and 15 for efficacy analyses. Treatment consisted of a daily infusion of DX-8951f at 0.3 mg/m(2) per day (except for one minimally pretreated patient who started at 0.5 mg/m(2) per day) over 30 min for five consecutive days every 3 weeks. The pharmacokinetic and excretory profiles of DX-8951, the anhydrous form of DX-8951f, were also characterized.. Disease was stable in 7 of 16 patients (44%) (4 minor response and 3 stable disease). The median time to tumor progression was 43 days (95% CI 37-92 days). The median overall survival was 117 days (95% CI 90-279 days). The main toxic effect was neutropenia and leukopenia with 50% of patients experiencing grade 3 or 4 neutropenia and leukopenia. One episode of neutropenic fever was observed. Grade 3 or more anemia and thrombocytopenia were seen in 25% and 13% of patients, respectively. Grade 3 nonhematologic side effects included nausea (25% of patients) and fatigue (19%). Other side effects were not more than grade 2, and included gastrointestinal dysfunction, stomatitis, dermatitis, alopecia, liver dysfunction and drug fever. DX-8951 displayed linear pharmacokinetic characteristics at the doses administered. The average plasma clearance, total volume of distribution, and terminal elimination half-life were 2.1 l/h per m(2), 20 l/m(2) and 9.5 h, respectively.. DX-8951f administered parenterally as a single agent daily at a dose of either 0.5 or 0.3 mg/m(2) per day for 5 days is feasible in patients with advanced ovarian, tubal and peritoneal cancer resistant to platinum, taxane and topotecan. Although no responses were observed, a significant number of patients had stable disease with a decrease in CA-125 levels. In this heavily pretreated population, DX-8951f has clinically relevant hematologic and gastrointestinal toxicities in about 25% of patients. DX-8951 appeared to have linear pharmacokinetic characteristics on the basis of multiple administrations.

Topics: Adult; Aged; Antineoplastic Agents, Phytogenic; Bridged-Ring Compounds; Camptothecin; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Fallopian Tube Neoplasms; Female; Humans; Infusions, Intravenous; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Peritoneal Neoplasms; Taxoids; Topotecan

Preclinical and clinical data have demonstrated the importance of schedule in optimizing the cytotoxic potential of topotecan, one of the most active agents in ovarian cancer. The availability of oral topotecan permits the exploration of the clinical utility of prolonged treatment programs employing this drug.. Patients with platinum/taxane resistant ovarian and primary peritoneal cancers were treated with oral topotecan at an initial fixed dose of 1.5 mg/day for 5 days, followed by a 2-day break, with treatment continued on this schedule until disease progression or unacceptable toxicities.. Seven patients (median age 61) were entered into this phase 2 trial before further enrollment was discontinued due to the development of excessive side effects (grade 3: fatigue (n = 3); emesis (n = 1), thrombocytopenia with bleeding (n = 1). Two additional patients noted grade 2 fatigue. Four patients experienced reductions in hemoglobin concentrations >4.0 g/dl from baseline during treatment, with two patients requiring red cell transfusions and two receiving recombinant erythropoietin. Three patients developed grade 3 neutropenia, while there were no episodes of > or =grade 2 diarrhea. Three patients exhibited biological evidence of an anti-neoplastic effect of therapy (>50% declines in serum CA-125 levels).. Despite the strong theoretical appeal (as well as limited biological evidence of activity in platinum/taxane-refractory disease) associated with prolonging exposure of cycling ovarian cancer cells to topotecan, the specific oral regimen employed in this trial was associated with excessive bone marrow suppression, especially treatment-induced anemia, resulting in an unacceptable incidence of severe fatigue.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carboplatin; Cisplatin; Drug Administration Schedule; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Fallopian Tube Neoplasms; Female; Humans; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Taxoids; Topotecan

Topics: Antineoplastic Agents, Phytogenic; Bridged-Ring Compounds; Camptothecin; Drug Administration Schedule; Drug Resistance, Multiple; Fallopian Tube Neoplasms; Female; Humans; Infusions, Intravenous; Ovarian Neoplasms; Peritoneal Neoplasms; Platinum Compounds; Taxoids; Topotecan

Low-grade serous carcinoma of the ovary/peritoneum (LGSC) is relatively chemoresistant in the adjuvant, neoadjuvant, and recurrent settings. We sought to expand our prior work and evaluate response rates of women with LGSC to neoadjuvant chemotherapy (NACT) compared to women with high-grade serous carcinoma of the ovary/peritoneum (HGSC).. Thirty-six patients with LGSC who received NACT were matched to patients with HGSC. A single radiologist re-reviewed pre- and post-NACT imaging for response using RECIST 1.1. Pre- and post-NACT CA-125 values were compared using paired t-tests. Kaplan-Meier estimates of progression free survival (PFS) and overall survival (OS) were performed.. All patients received neoadjuvant platinum-based regimens. LGSC patients received a median of 5 cycles (range 3-9), HGSC patients received a median of 4 cycles (range 3-9). Interval cytoreductive surgery was performed in 29/36 (81%) of LGSC and 32/36 (89%) HGSC patients. Complete cytoreduction was reported and achieved in 11/29 (38%) of LGSC patients and 24/32 (75%) of HGSC patients (p = 0.002). Median pre- and post-treatment CA-125 levels for LGSC patients were 295.5 U/mL and 144 U/mL (52% decrease) (p < 0.001). The median pre- and post-treatment CA-125 levels for HGSC patients were 767.5 and 35.6 (96% decrease) (p < 0.001). For LGSC patients, 4/36 (11%) had partial response (PR), 30/36 (83%) had stable disease (SD), and 2/36 (6%) had progressive disease (PD). In HGSC patients, 27/36 (75%) had PR, and 9/36 (25%) SD. Median PFS for LGSC patients was 18.5 months and median OS was 47.4 months.. This study provides further evidence of relative chemoresistance of LGSC in patients treated with NACT.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; CA-125 Antigen; Cystadenocarcinoma, Serous; Drug Resistance, Neoplasm; Female; Humans; Ki-67 Antigen; Membrane Proteins; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Ovarian Neoplasms; Peritoneal Neoplasms; Progression-Free Survival; Response Evaluation Criteria in Solid Tumors; Taxoids; Young Adult

To investigate residual disease status after primary cytoreductive surgery(PCS)in patients with advanced ovarian, Fallopian tube, or peritoneal carcinoma and long-term progression-free survival(PFS).. The study included patients with stage III C/IVepithelial ovarian, fallopian tube, or peritoneal carcinoma who had undergone surgery and carbo- platin/taxane chemotherapy, and had a PFSduration of ≥48 months.. The study group consisted of 11 patients with stage III C disease, which accounted for 23%(8/35)of stage III C patients aged ≤59 years and 11%(3/27)of stage III C patients aged ≥60 years. No stage IV patients had a long-term PFS(0/11). Of 8 patients aged ≤59 years, 2 had residual disease of 0.1-1 cm(optimal debulking), 5 had residual disease of >1 cm after PCS, and 1 who had received neoadjuvant chemotherapy(NAC)had optimal debulking during interval cytoreductive surgery. Of 3 patients aged ≥60 years, 2 had no macroscopic residual disease, and 1 had residual disease of >1 cm after PCS.. In patients with stage III C ovarian, fallopian tube, or peritoneal carcinoma, a subgroup of those aged ≤59 years had long-term PFSdespite suboptimal PCS. In this age group, carboplatin/taxane chemotherapy may improve the prognosis, irrespective of residual disease status after PCS. In contrast, complete cytoreduction during PCSappears to be necessary in patients aged ≥60 years who achieve long-term PFS.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carboplatin; Disease Progression; Disease-Free Survival; Fallopian Tube Neoplasms; Female; Humans; Middle Aged; Neoplasm Staging; Neoplasm, Residual; Ovarian Neoplasms; Peritoneal Neoplasms; Retrospective Studies; Taxoids

Platinum-resistant and refractory cancers of the ovary, fallopian tube, and peritoneum have a poor prognosis, yet in some cases, they can respond to multiple lines of chemotherapy. Uncertainty remains over optimal drug choice and when therapeutic focus should be switched from active therapy to supportive care.. A retrospective case note review was performed on 274 women treated for platinum-resistant/refractory ovarian, fallopian tube, or peritoneal carcinoma at the Christie Hospital between 2004 and 2008. Baseline data at onset of platinum resistance and outcomes from subsequent lines of therapy were recorded.. A total of 689 lines of therapy were administered with a median overall survival from initiation of first-line therapy for platinum-resistant disease of 61 weeks. Twenty-eight percent of women commenced cytotoxic therapy in the last 3 months of life. Treatment efficacy declined rapidly with successive lines of therapy particularly if disease progression occurred during first-line therapy. Factors independently associated with worse overall survival at recognition of platinum resistance were performance status, presence of stage IV disease, elevated cancer antigen 125, and platinum-refractory disease.. A significant proportion of women who were treated received therapy within the last few months of life with little clinical benefit. Disease progression on 2 consecutive lines of therapy should be used as a guide to discontinue cytotoxic treatment. A subset of patients with poor prognosis at the onset of platinum resistance, who may have little gain from anticancer treatment, can be identified.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; CA-125 Antigen; Carcinoma; Carcinoma, Ovarian Epithelial; Cisplatin; Cytotoxins; Deoxycytidine; Disease-Free Survival; Doxorubicin; Drug Resistance, Neoplasm; Etoposide; Fallopian Tube Neoplasms; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Paclitaxel; Peritoneal Neoplasms; Platinum; Polyethylene Glycols; Prognosis; Proportional Hazards Models; Retrospective Studies; Survival Analysis; Taxoids; Treatment Outcome

Limited information is available regarding the usefulness of third-line chemotherapy for recurrent ovarian, fallopian tube, and primary peritoneal cancer treated with platinum-taxane regimens as first-line therapy.. We retrospectively reviewed the medical records of women with ovarian, fallopian tube, and primary peritoneal cancer who were treated at the National Cancer Center Hospital between 1999 and 2005 to investigate the relations of clinicopathological factors to important clinical endpoints such as the response rate (RR), time to progression (TTP) and overall survival (OS) after third-line chemotherapy.. A total of 172 patients received first-line platinum/taxane regimens during the study period, among whom 111 had disease progression after first-line chemotherapy. Eighty-one of these 111 patients received second-line chemotherapy, and 73 had disease progression. Fifty-four of the 73 patients with disease progression received third-line chemotherapy. The RR to third-line chemotherapy was 40.7% (95% CI, 27.6-53.8%). The median TTP was 4.4 months (range 0-19.5 months), and the median OS was 10.4 months (range 1.5-44.3 months). Performance status (PS) and primary drug-free interval (DFI) were independent predictive factors for the RR to third-line chemotherapy (P = 0.04 and P = 0.009). PS and primary DFI were also independent predictive factors for TTP and OS on multivariate analysis (P = 0.006, P = 0.005 and P = 0.01, P = 0.004, respectively).. PS and primary DFI are useful predictors of the response to third-line chemotherapy in women with recurrent ovarian, fallopian tube, and primary peritoneal cancer. In this setting, however, both of these variables are subject to several well-established potential biases and limitations; further prospective studies are thus needed.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; CA-125 Antigen; Disease Progression; Fallopian Tube Neoplasms; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasms, Second Primary; Ovarian Neoplasms; Peritoneal Neoplasms; Platinum Compounds; Retrospective Studies; Survival Analysis; Taxoids

The objective of this study was to evaluate the role of an in vitro drug resistance assay to platinum and taxane in the management of advanced epithelial ovarian, fallopian and primary peritoneal cancer. All patients with FIGO Stage IIIc and IV who received postoperative chemotherapy with platinum and taxane for more than 4 courses after the initial cytoreductive surgery between 1995 and 2008 were evaluated. Patients who received neoadjuvant chemotherapy were not included. An in vitro drug resistance assay (EDR Assay, Oncotech, Tustin, CA) was used to determine drug resistance for each patient's tumor tissue. Level of drug resistance was described as extreme (EDR), intermediate (IDR), or low (LDR). Response to chemotherapy and survival were correlated to the EDR Assay. Of the 335 patients who underwent primary cytoreductive surgery, 173 cases met the criteria for statistical evaluation. The 58 patients (33.5%) whose tumors had LDR to both platinum and taxane had statistically improved progression-free survival and overall survival (OS) compared with the 115 patients (66.5%) who demonstrated IDR or EDR to platinum and/or taxane (5-year OS rates, 41.1% vs. 30.9%, p = 0.014). The 5-year OS rates for the 28 (16.2%) cases that had optimal cytoreduction with LDR to both platinum and taxane was significantly improved over the 62 (35.8%) cases that were suboptimally cytoreduced with IDR or EDR to platinum and/or taxane (54.1% vs. 20.4%, respectively, p < 0.001). In conclusion, LDR to both platinum and taxane chemotherapy, as determined by an in vitro drug resistance assay, independently predicts improved survival in patients with advanced epithelial ovarian, fallopian and peritoneal cancer, especially in those patients who undergo optimal primary cytoreduction.

Topics: Adenocarcinoma, Clear Cell; Antineoplastic Combined Chemotherapy Protocols; Biological Assay; Bridged-Ring Compounds; Cystadenocarcinoma, Serous; Drug Resistance, Neoplasm; Endometrial Neoplasms; Fallopian Tube Neoplasms; Female; Humans; In Vitro Techniques; Lymphatic Metastasis; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Peritoneal Neoplasms; Prognosis; Retrospective Studies; Survival Rate; Taxoids

The objective of the study was to compare chemotherapy response and survival of patients with advanced primary peritoneal carcinoma (PPC) vs those with epithelial ovarian carcinoma (EOC).. From 1998 to 2004, 43 PPC patients were identified and matched to 129 patients with International Federation of Gynecology and Obstetrics stage IIIC-IV EOC by criteria abstracted from medical records. Primary endpoints were chemotherapy response, platinum resistance, progression-free survival (PFS), and overall survival (OS).. All patients received primary platinum-taxane chemotherapy. There was no significant difference in achieving a clinical complete response. PPC patients were more likely to be platinum resistant at 6 months and had significantly impaired PFS and OS. After multivariate analysis, PPC was independently associated with a worse prognosis for both survival endpoints.. PPC was associated with a similar initial response but a higher rate of platinum resistance and shorter PFS and OS. Consideration of these results may be useful for patient counseling, trial stratification, and molecular comparisons.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bridged-Ring Compounds; Case-Control Studies; Combined Modality Therapy; Databases, Factual; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Peritoneal Neoplasms; Prospective Studies; Survival Analysis; Taxoids; United States

Carcinoma of unknown primary (CUP) is characterized by dismal patient survival. The outcome of patients with two favourable risk CUP subsets was studied. Eighty patients diagnosed with either midline lymph node metastases (n=33) or peritoneal carcinomatosis (n=47) were analysed retrospectively. The majority had poorly differentiated adenocarcinoma or undifferentiated carcinoma, treated with platinum-taxane based chemotherapy from 1996 till 2002. Females with peritoneal carcinomatosis also underwent surgical debulking. Objective tumour regression was present in 44% of patients (nodal group 30% versus peritoneal group 53%, p=0.066). Complete responses were seen more often in peritoneal carcinomatosis patients (nodal group 9%, peritoneal group 36%, p=0.008). At a median follow up of 60 months, median progression-free and overall survival were 5 and 10 months respectively in the nodal group, 7 and 15 months in the peritoneal group. Five-year survival was 7% (nodal group 0% vs. peritoneal group 10%, p=0.05). Complete responders fared better than non-CR patients. Fewer than four metastatic sites, elevated CA 125, and normal CA 19-9 levels were favourable prognostic factors for survival. Modern combination chemotherapy has satisfactory activity, with a minority of CUP patients enjoying long-term responses. Research efforts towards complete remission consolidation and molecular profiling are imperative.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Bridged-Ring Compounds; Carcinoma; Female; Follow-Up Studies; Greece; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasms, Unknown Primary; Peritoneal Neoplasms; Prognosis; Proportional Hazards Models; Survival Analysis; Taxoids; Treatment Outcome

Dynamic contrast enhanced MRI (DCE-MRI) is being used increasingly in clinical trials to demonstrate that vascular disruptive and antiangiogenic agents target tumour microcirculation. Significant reductions in DCE-MRI kinetic parameters are seen within 4-24 and 48 h of treatment with vascular disruptive and antiangiogenic agents, respectively. It is important to know whether cytotoxic agents also cause significant acute reductions in these parameters, for reliable interpretation of results. This study investigated changes in transfer constant (K(trans)) and the initial area under the gadolinium curve (IAUGC) following the first dose of chemotherapy in patients with mostly gynaecological tumours. A reproducibility analysis on 20 patients (using two scans performed on consecutive days) was used to determine the significance of DCE-MRI parameter changes 24 h after chemotherapy in 18 patients. In 11 patients who received platinum alone or with a taxane, there were no significant changes in K(trans) or IAUGC in either group or individual patient analyses. When the remaining seven patients (treated with a variety of agents including platinum and taxanes) were included (n=18), there were also no significant changes in K(trans). Therefore, if combination therapy does show changes in DCE-MRI parameters then the effects can be attributed to antivascular therapy rather than chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Contrast Media; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Microcirculation; Middle Aged; Neovascularization, Pathologic; Organoplatinum Compounds; Ovarian Neoplasms; Pelvic Neoplasms; Peritoneal Neoplasms; Taxoids

There are very limited data in the oncology literature regarding the survival of women with both platinum and taxane-refractory ovarian cancer.. To examine this issue, we retrospectively reviewed the survival of patients treated on one (or more) of four previously reported nonrandomized single-agent phase 2 trials (topotecan, liposomal doxorubicin, gemcitabine, docetaxel), involving women with well-characterized platinum/taxane-resistant ovarian, fallopian tube, and primary peritoneal cancers. Following their most recent treatment with both classes of agents, patients must have either not responded to therapy or experienced a treatment-free interval of <3 months before documented disease progression.. The median survival of the 111 patients (median age 61) included in this analysis was 6 months (range 1-37 months). Whereas 36 patients (32%) survived for <4 months, 30 patients (27%) lived for > or =12 months following documentation of resistance to both platinum and taxane therapy.. With currently available antineoplastic drug therapy of platinum/taxane-resistant ovarian cancer, overall survival is relatively short, but a substantial minority of patients can be anticipated to live for periods in excess of 1 year. It remains uncertain whether such unexpectedly prolonged survival results from a biological response to chemotherapy or simply reflects the natural history of disease in a subset of patients with this malignancy.

Topics: Adult; Aged; Aged, 80 and over; Bridged-Ring Compounds; Clinical Trials, Phase II as Topic; Deoxycytidine; Docetaxel; Doxorubicin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Fallopian Tube Neoplasms; Female; Gemcitabine; Humans; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Peritoneal Neoplasms; Retrospective Studies; Survival Rate; Taxoids; Topotecan