taxane and Carcinoma

To quantify the impact of complete cytoreduction to no gross residual disease on overall survival among patients with advanced-stage ovarian cancer treated during the platinum-taxane era.. PubMed and Cochrane Library databases were searched for all articles on primary cytoreductive surgery for advanced-stage ovarian cancer published from 1/1996 to 7/2011. A total of 18 relevant studies (13,257 patients) were identified for analysis. Simple and multiple linear regression analyses, with weighted correlation calculations, were used to assess the effect on median survival time of clinical and treatment-related factors.. The mean weighted median overall survival time for all cohorts was 44.4 months (range, 27.6-66.9 months). Simple linear regression analysis revealed that residual disease, stage IV disease, and use of intraperitoneal chemotherapy were significantly associated with median survival time. After controlling for other factors on multiple linear regression analysis, each 10% increase in the proportion of patients undergoing complete cytoreduction to no gross residual disease was associated with a significant and independent 2.3-month increase (95%CI = 0.6-4.0, p = 0.011) in cohort median survival compared to a 1.8-month increase (95%CI = 0.6-3.0, p = 0.004) in cohort median survival for optimal cytoreduction (residual disease≤1cm). Each 10% increase in the proportion of patients receiving intraperitoneal chemotherapy was associated with a significant and independent 3.9-month increase (95%CI = 1.1-6.8, p=0.008) in median cohort survival time.. For advanced-stage ovarian cancer treated during the platinum-taxane era, the proportions of patients left with no gross residual disease and receiving intraperitoneal chemotherapy are independently significant factors associated with the most favorable cohort survival time.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma; Chemotherapy, Adjuvant; Female; Humans; Neoplasm Staging; Neoplasm, Residual; Ovarian Neoplasms; Platinum Compounds; Survival Analysis; Taxoids

Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, stem cell factor receptor (KIT), and colony-stimulating factor-1 receptor. This phase II, open-label, multicenter study evaluated sunitinib monotherapy in patients with metastatic breast cancer (MBC).. Sixty-four patients previously treated with an anthracycline and a taxane received sunitinib 50 mg/d in 6-week cycles (4 weeks on, then 2 weeks off treatment). The primary end point was objective response rate. Plasma samples were obtained for pharmacokinetic and biomarker analysis.. Seven patients achieved a partial response (median duration, 19 weeks), giving an overall response rate of 11%. Three additional patients (5%) maintained stable disease for >or= 6 months. Median time to progression and overall survival were 10 and 38 weeks, respectively. Notably, responses occurred in triple negative tumors and HER2-positive, trastuzumab-treated patients. Thirty-three patients (52%) required dose interruption during >or= 1 cycle, and 25 patients required dose reduction (39%). Thirty-six patients (56%) had dose modifications due to adverse events (AEs). Treatment was associated with increases in plasma VEGF and decreases in soluble VEGFRs and KIT. The most common AEs were fatigue, nausea, diarrhea, mucosal inflammation, and anorexia. Most AEs were mild to moderate (grade 1 to 2) in severity and were effectively managed with dose delays or reductions.. Sunitinib is active in patients with heavily pretreated MBC. Most AEs were of mild-to-moderate severity and manageable with supportive treatment and/or dose modification. Further studies in breast cancer are warranted.

Topics: Administration, Oral; Adult; Aged; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma; Drug Administration Schedule; Fatigue; Female; Gastrointestinal Diseases; Hematologic Diseases; Humans; Indoles; Middle Aged; Protein-Tyrosine Kinases; Pyrroles; Sunitinib; Survival Rate; Taxoids

Currently, there is no gold standard for the treatment of patients with metastatic breast carcinoma who have experienced failure with anthracyclines and taxanes. A biologic rationale suggests that the mechanism of taxane resistance could be because of an excess of depolymerized tubulin that could enhance sensitivity to vinorelbine. The objective of the study was to assess the tolerance and efficiency of weekly vinorelbine in metastatic breast carcinoma after failure with taxanes.. Patients with measurable disease, a World Health Organization performance status of less than 3 and a life expectancy longer than 3 months were eligible. Persistent taxane-induced neuropathy higher than Grade 1 was an exclusion criterion. The initial planned dose was 30 mg/m(2)/week on an outpatient basis without granulocyte colony-stimulating factor (G-CSF). Neutrophil and platelet counts of 1.0 and 80 g/L, respectively, were required before each new injection; otherwise vinorelbine was delayed for 7 days with a dose reduction of 5 mg/m(2) at the second episode. The dose also was reduced if Grade 3 or 4 toxicity occurred. If the adverse event persisted or if the delay exceeded 14 days between 2 injections given at a dose of 20 mg/m(2), vinorelbine was definitively discontinued.. Between November 1997 and March 1999, 40 patients with a median age of 49 (range, 39-69) were enrolled. All of them had previously received anthracyclines and taxanes. Because of the delays in neutrophil recovery, the median dose intensity did not exceed 22.5 mg/m(2)/week (range, 11.25-30), and the initial planned dose of 30 mg/m(2)/week appeared unfeasible without G-CSF. The starting dose therefore was 25 mg/m(2)/week after the first 6 patients. Neutropenia led to fever in only three patients. Other severe toxicities were Grade 2-3 neuropathy (n = 5), Grade 2-3 ileus (n = 7), Grade 3 anemia (n = 4), and Grade 3 sepsis (n = 1). Objective responses were observed in 10 of 40 patients (25%), 7 of whom had visceral metastases and 4 who were refractory to taxanes (including 2 patients with liver involvement > 50%). The median time to failure was 6 months (range, 4-12) for responding patients. Disease stabilization was achieved in 9 patients (23%) for a median duration of 5 months (range, 4-6). The median survival duration for the whole population was 6 months (range, 2-18+).. Weekly vinorelbine is an active salvage therapy for metastatic breast carcinoma after failure with anthracyclines and taxanes, even in patients with taxane-refractory metastatic breast carcinoma. This confirms that vinorelbine and taxanes are not cross-resistant.

Topics: Adult; Aged; Anemia; Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma; Disease Progression; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Granulocyte Colony-Stimulating Factor; Humans; Infusions, Intravenous; Intestinal Obstruction; Middle Aged; Neoplasm Metastasis; Neutropenia; Palliative Care; Salvage Therapy; Sepsis; Survival Analysis; Taxoids; Treatment Outcome; Vinblastine; Vinorelbine

Even though tamoxifen has significantly improved the survival of estrogen receptor positive (ER+) mammary carcinoma (MC) patients, the development of drug resistance with consequent disease recurrence has limited its therapeutic efficacy. Trefoil factor-3 (TFF3) has been previously reported to mediate anti-estrogen resistance in ER+MC. Herein, the efficacy of a small molecule inhibitor of TFF3 (AMPC) in enhancing sensitivity and mitigating acquired resistance to tamoxifen in ER+MC cells was investigated. AMPC induced apoptosis of tamoxifen-sensitive and resistant ER+MC cells and significantly reduced cell survival in 2D and 3D culture in vitro. In addition, AMPC reduced cancer stem cell (CSC)-like behavior in ER+MC cells in a BCL2-dependent manner. Synergistic effects of AMPC and tamoxifen were demonstrated in ER+MC cells and AMPC was observed to improve tamoxifen efficacy in tamoxifen-sensitive cells and to re-sensitize cells to tamoxifen in tamoxifen-resistant ER+MC in vitro and in vivo. Additionally, tamoxifen-resistant ER+MC cells were concomitantly resistant to anthracycline, platinum and fluoropyrimidine drugs, but not to Taxanes. Taxane treatment of tamoxifen-sensitive and resistant ER+MC cells increased TFF3 expression indicating a combination vulnerability for tamoxifen-resistant ER+MC cells. Taxanes increased CSC-like behavior of tamoxifen-sensitive and resistant ER+MC cells which was reduced by AMPC treatment. Taxanes synergized with AMPC to promote apoptosis and reduce CSC-like behavior in vitro and in vivo. Hence, AMPC restored the sensitivity of tamoxifen and enhanced the efficacy of Taxanes in tamoxifen-resistant ER+MC. In conclusion, pharmacological inhibition of TFF3 may serve as an effective combinatorial therapeutic strategy for the treatment of tamoxifen-resistant ER+MC.

Topics: Breast Neoplasms; Carcinoma; Cell Line, Tumor; Drug Resistance, Neoplasm; Female; Humans; Neoplasm Recurrence, Local; Tamoxifen; Taxoids; Trefoil Factor-3

Topics: Animals; Antineoplastic Agents; Autophagy; Bridged-Ring Compounds; Carcinoma; Cell Line, Tumor; Cell Proliferation; Cisplatin; Drug Resistance, Neoplasm; Energy Metabolism; Female; Humans; Mice, Nude; Mitochondria; Mitophagy; Ovarian Neoplasms; Oxidation-Reduction; Signal Transduction; Taxoids

The overall survival (OS) of patients with ovarian cancer is poor while epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. The aim of the present study was to evaluate the clinico-pathologic characteristics, especially the prognostic factors, for patients with epithelial ovarian cancer (EOC) in Taiwan. Information about newly diagnosed patients with EOC from 2009 to 2012 was retrieved from the database of the Taiwan Cancer Registry. Data from 2009 to 2013 for the respective cases from the claims database of Taiwan's National Health Insurance and National Death Registry were then retrieved. Potential prognostic factors were analyzed. The mean age at diagnosis of the 2,498 patients was 52.8 years. Serous carcinoma and clear cell carcinoma were diagnosed in 43.3% and 22.8% of the total patients, respectively. For patients with early-stage disease, taxane-based adjuvant chemotherapy, stage I, and younger age at diagnosis led to better overall survival (p = 0.030, p = 0.002, p<0.001, respectively) in multivariable analysis. For advanced-stage patients, histology (endometrioid type), taxane-based adjuvant chemotherapy, stage, and age at diagnosis had a significant impact on OS (p<0.001, p = 0.020, p<0.001, p<0.001, respectively). In conclusion, taxane-based chemotherapy impacts the outcome of patients with EOC. Personalized medicine may be needed for different histological types of EOC because of their different outcomes.

Topics: Adenocarcinoma, Clear Cell; Adult; Aged; Antineoplastic Agents; Bridged-Ring Compounds; Carcinoma; Carcinoma, Ovarian Epithelial; Chemotherapy, Adjuvant; Female; Humans; Middle Aged; Multivariate Analysis; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Prognosis; Registries; Survival Rate; Taxoids; Young Adult

Metastatic breast cancer (MBC) rest an incurably disease associated with bad prognosis and a median overall survival of 23-31 months. There are several treatment options including chemotherapy and sometimes endocrine therapy. Currently, there is no standard treatment for patients with MBC who have already benefited from anthracyclines and taxanes therapy. Many drugs like capecitabine, eribulin, gemcitabine, vinorelbin and liposomal doxorubicin are conventionally used as monotherapy. One important complication from MBC is life threating visceral crisis that needs a fast-effective treatment.. We report here a case of an evolution of metastatic breast cancer with lymphangitic carcinomatosis after taxane based chemotherapy and endocrine therapy. This 37-year-old woman was referred to our hospital with complaints of dyspnea and dry cough. There was clinical concern for visceral crisis and a chemotherapy with eribulin was initiated. Pulmonary lymphangitic carcinomatosis disappeared and the patient achieved a good partial response.. We reported a case of rapid, positive treatment response using eribulin on metastatic breast cancer with visceral crisis and we could quoted others. Therefore, eribulin may be an appropriate chemotherapeutic option in instances requiring rapid symptom control.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma; Female; Furans; Humans; Ketones; Lung Neoplasms; Taxoids

Inflammatory breast cancer (IBC) is a rare and aggressive disease treated with multimodality therapy: preoperative systemic therapy (PST) followed by modified radical mastectomy (MRM), chest wall and regional nodal radiotherapy, and adjuvant biologic therapy and/or endocrine therapy when appropriate. In non-IBC, the degree of pathologic response to PST has been shown to correlate with time to recurrence (TTR) and overall survival (OS). We sought to determine if pathologic response correlates with oncologic outcomes of IBC patients.. Following review of IBC patients' records (1997-2014), we identified 258 stage III IBC patients; 181 received PST followed by MRM and radiotherapy and were subsequently analyzed. Pathologic complete response (pCR) to PST, hormone receptor and human epidermal growth factor receptor 2 (HER2) status, grade, and histology were evaluated as predictors of TTR and OS by Cox model.. Overall, 95/181 (52%) patients experienced recurrence; 93/95 (98%) were distant metastases (median TTR 3.2 years). Seventy-three patients (40%) died (median OS 6.9 years). pCR was associated with improved TTR (hazard ratio [HR] 0.20, 95% confidence interval [CI] 0.09-0.46, p < 0.01, univariate; HR 0.17, 95% CI 0.07-0.41, p < 0.0001, multivariate) and improved OS (HR 0.26, 95% CI 0.11-0.65, p < 0.01, univariate). In patients with pCR, grade III (HR 1.91, 95% CI 1.16-3.13, p = 0.01), and triple-negative phenotype (HR 3.54, 95% CI 1.79-6.98, p = 0.0003) were associated with shorter TTR, while residual ductal carcinoma in situ was not (HR 0.85, 95% CI 0.53-1.35, p = 0.48, multivariate).. In stage III IBC, pCR was associated with prognosis, further influenced by grade, hormone receptor, and HER2 status. Investigating mechanisms that contribute to better response to PST could help improve oncologic outcomes in IBC.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma; Chemotherapy, Adjuvant; Cyclophosphamide; Hormones; Humans; Inflammatory Breast Neoplasms; Mastectomy, Modified Radical; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Staging; Neoplasm, Residual; Proportional Hazards Models; Radiotherapy, Adjuvant; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; Survival Rate; Taxoids; Time Factors

Topics: Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma; Female; Hematuria; Humans; Middle Aged; Mitosis; Taxoids; Urinary Bladder; Urothelium

In this study, we report an active targeting liposomal formulation directed by a novel peptide (T7) that specifically binds to the transferrin receptor (TfR) overexpressed on ovarian carcinoma cells. The objectives of this study were to evaluate the in vitro and in vivo tumor drug targeting delivery of T7-anchored liposomes on A2780 cells. T7 conjugated to the distal end of DSPE-PEG2000-maleimide was incorporated into the liposomes via a post-insertion method, the liposome could keep stability in 50% FBS for more than 24 h. The uptake efficiency of T7-LP was 3.7 times higher than that of LP on A2780 cells. The anti-proliferative activity of T7-LP-PTX against A2780 cells was much stronger compared to that of LP-PTX and free PTX, respectively. The homing specificity and anticancer efficacy of T7-LP-PTX were also evaluated on the tumor spheroids, which revealed that T7-LP-PTX was more efficaciously internalized into tumor cells than LP. Compared to LP, T7-LP-PTX showed the highest accumulation capability into tumor spheroids, and the greatest tumor growth inhibitory effect in vitro. In the in vivo study, the T7-LP-PTX showed the best inhibition effect of the tumor growth for the A2780-bearing mice and tumor accumulation. In brief, the T7-LP may be an efficient targeting drug delivery system for ovarian carcinoma.

Topics: Animals; Antineoplastic Agents; Bridged-Ring Compounds; Carcinoma; Cell Line, Tumor; Drug Delivery Systems; Female; Humans; Liposomes; Mice; Mice, Inbred BALB C; Microscopy, Confocal; Ovarian Neoplasms; Platinum Compounds; Receptors, Transferrin; Taxoids; Xenograft Model Antitumor Assays

Microtubules play an important role in many cellular processes, including mitotic spindle formation and cell division. Taxane-based anticancer treatments lead to the stabilization of microtubules, thus preventing the uncontrolled proliferation of tumor cells. One of the striking physical features of taxane-treated cells is the localization of their microtubules, which can be observed via fluorescent microscopy as an intense fluorescent band and are referred to as a microtubule bundle. With the recent advances in capturing and analyzing tumor cells circulating in a patient's blood system, there is increasing interest in using these cells to examine a patient's response to treatment. This includes taxanes that are used routinely in clinics to treat prostate, breast, lung, and other cancers. Here, we have used a computational model of microtubule mechanics to investigate self-arrangement patterns of stabilized microtubules, which allowed for the identification of specific combinations of three physical parameters: microtubule stiffness, intracellular viscosity, and cell shape, that can prevent the formation of microtubule bundles in cells with stabilized microtubules, such as taxane-treated cells. We also developed a method to quantify bundling in the whole microtubule aster structure and a way to compare the simulated results to fluorescent images from experimental data. Moreover, we investigated microtubule rearrangement in both suspended and attached cells and showed that the observed final microtubule patterns depend on the experimental protocol. The results from our computational studies can explain the heterogeneous bundling phenomena observed via fluorescent immunostaining from a mechanical point of view without relying on heterogeneous cellular responses to the microtubule-stabilizing drug.

Topics: Antineoplastic Agents; Bridged-Ring Compounds; Carcinoma; Cell Adhesion; Cell Line, Tumor; Cell Shape; Computer Simulation; Cytoplasm; Elasticity; Female; Humans; Microscopy, Fluorescence; Microtubules; Models, Biological; Neoplastic Cells, Circulating; Ovarian Neoplasms; Taxoids; Viscosity

The aim of this retrospective study was to assess the efficacy and safety of the relatively old lowcost CMFVP regimen (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisolone) as compared to newer and more costly chemotherapeutic agents.. An analysis of the medical records of female patients with metastatic breast cancers treated with a CMFVP combination at the Shaare Zedek Medical Center (SZMC) was performed. 32 patients with measurable metastatic disease were included in the analysis. The median age was 59.9 years (range 36-102 years). 20 of the patients had previously been treated with both anthracyclines and taxanes.. Therapy was generally well tolerated and toxicity manageable. Median time to disease progression was 20.97 weeks (range 2-103 weeks). 6 patients (19%) demonstrated a partial response, and 7 patients (22%) had stable disease lasting 3 or more months for an overall clinical benefit of 41%. 4 of the 20 patients previously treated with both anthracyclines and taxanes had a partial response, and 4 patients had stable disease lasting 3 or more months for a clinical benefit of 40%.. On the basis of this small retrospective survey, we conclude that CMFVP combination chemotherapy is both effective and safe in patients with metastatic breast cancer previously treated with both taxanes and anthracyclines.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma; Cyclophosphamide; Female; Fluorouracil; Humans; Male; Methotrexate; Middle Aged; Prednisone; Taxoids; Treatment Outcome; Vincristine

An effective salvage chemotherapy for advanced and recurrent non-squamous carcinoma of the uterine cervix has not yet been established. The aim of the present study was to analyze the safety and efficacy of a combination chemotherapy for this disease using taxane, anthracycline, and platinum.. This was a retrospective analysis of advanced and recurrent non-squamous cervical cancers treated at the Osaka University Hospital and the Osaka Medical Center for Cancer and Cardiovascular Diseases during a 10 year study period from 2000 to 2009. Single agent chemotherapies and combination chemotherapies for advanced and recurrent cervical cancer cases of non-squamous histology which were reported in the English literature were also reviewed.. Salvage chemotherapy, using taxane, anthracycline and platinum, was performed for 5 advanced and 14 recurrent cases. Prior to the salvage chemotherapy, 15 (79%) of the 19 patients had already received either radiation or chemotherapy. A complete or partial tumor response was achieved in 8 (42%) of the 19 cases. The response rate for recurrent disease in a previously irradiated field was 40%. The median progression-free survival (PFS) and overall survival (OS) were 8 months (1-108) and 13 months (5-108), respectively. Grade 4 and febrile grade 3 neutropenia was observed in 6 cases (32%), but there was no case in which salvage chemotherapy had to be cancelled due to toxicity. According to previous reports, the cumulative response rate of combination chemotherapy (35%) was significantly higher than that of single agent chemotherapy (17%) (p<0.001). OS tended to be longer in the combination chemotherapy cases (8.7 months to 18 months) than that of single agent chemotherapy cases (7.3+ months to 9.1+ months).. Combination chemotherapy of taxane, anthracycline, and platinum was found to have a survival benefit for advanced and recurrent cervical cancer patients of non-squamous carcinoma histology, with a tolerable toxicity.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carboplatin; Carcinoma; Cisplatin; Female; Fever; Follow-Up Studies; Humans; Medical Records; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Retrospective Studies; Salvage Therapy; Survival Analysis; Taxoids; Uterine Cervical Neoplasms; Young Adult

Full oral chemotherapy (CT) is an active and convenient therapeutic option for patients with advanced breast cancer (ABC). In this retrospective analysis, we reviewed the characteristics and the outcome of patients treated by oral vinorelbine either as a single-agent or in combination with capecitabine as first- or second-line CT in the metastatic setting.. We analysed 216 patients with ABC who started treatment with a full oral CT at 13 centers and seven countries between 2006 and 2008. To be eligible, patients must have received either as a first-(56%) or second-line (44%) therapy oral vinorelbine as a single-agent (54%) or in combination with capecitabine (46%).. Main patients' characteristics in the full population (n=216): median age (range): 61 (32-87) years; categories of age: <50 years: 18%, 50-65 years: 44%, ≥ 65 years: 38%; hormone receptor-positive: 63%; ≥ 2 metastatic sites: 58%; visceral metastases: 49%; prior CT: 86%; prior CT for ABC: 44%; prior anthracycline treatment: 69%; prior taxane treatment: 43%, prior anthracycline plus taxane: 38%; prior endocrine therapy: 63%. Median number of cycles: 6 (range=1-54); 48% of patients received more than 6 cycles. G3/4 toxicities: neutropenia 8%, anaemia 2%, thrombocytopenia 1%, febrile neutropenia/neutropenic infection 2%, nausea 6%, vomiting 4%, diarrhea 6%, fatigue 6%, hand-foot syndrome 14% (combination with capecitabine), neuropathy 1%, alopecia (grade 2) 1%.. disease control was achieved in 77% of patients [95% confidence interval=71-83%], 74% as single-agent, 81% in combination, 82% in first-line, 71% in second-line. Median progression-free survival was 9.7 months [95% confidence interval=8.2-12.6 months] in first-line and 6.6 months [95% confidence interval=5.5-8.5 months] in second-line therapy. Caregivers described these oral regimens as convenient (81%), well-tolerated (84%) and with a good compliance by patients (76%).. These data from everyday practice confirm, as shown in different clinical trials, that oral vinorelbine is an active and well-tolerated CT for ABC, either as a first- or second-line in patients pre-treated with anthracyclines or taxanes. The convenience of its oral administration in association with its good tolerance profile, allows for continuation of treatment until disease progression without a pre-planned maximum of cycles.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Carcinoma; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Hematologic Diseases; Humans; Middle Aged; Patient Compliance; Retrospective Studies; Severity of Illness Index; Taxoids; Vinblastine; Vinorelbine

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

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

Significance of Technetium 99m ((99m)Tc)-MIBI scintigraphy in the prediction of response to anthracylines and taxanes (both are substrates for P-glycoprotein [P-gp]) as well as relation between (99m)Tc-MIBI uptake and P-gp or MDR1 mRNA expression in tumors were studied in patients with breast carcinoma.. Forty-six female patients with locally advanced (n = 15) or metastatic (n = 31) breast carcinoma were recruited in this study. Before chemotherapy (epirubicin and cyclophosphamide [n = 20] or decetaxel [n = 26]), (99m)Tc-MIBI scintigraphy was performed to obtain the T/N (tumor to normal tissue) ratios of (99m)Tc-MIBI uptake at 10 minutes (T/N[e]) and at 180 minutes (T/N[d]) after the (99m)Tc-MIBI injection. Expression of MDR1 mRNA and P-gp in tumors (n = 32) were determined by a quantitative real-time polymerase chain reaction and immunohistochemistry, respectively.. Clinical significance of T/N(e) and T/N(d) ratios in the prediction of chemotherapeutic response was evaluated using the arbitrary cutoff values of 3.0 for T/N(e) ratios and 2.0 for T/N(d) ratios. Positive predictive value, negative predictive value, and diagnostic accuracy of T/N(d) ratios (81.0%, 96.0%, and 89.1%, respectively) were higher, although statistically not significant, than those of T/N(e) ratios (73.3%, 77.4%, and 76.1%, respectively), and these values were not affected by type of chemotherapy. MDR1 mRNA levels were not significantly different between the lesions with high (> or = 2.0) and low (< 2.0) T/N(d) ratios, but P-gp expression was significantly (P < 0.01) higher in the lesions with low T/N(d) ratios than in those with high T/N(d) ratios.. T/N(d) ratios determined by (99m)Tc-MIBI scintigraphy are useful in the prediction of response to chemotherapy with epirubicin and cyclophosphamide or docetaxel as well as in the in vivo evaluation of P-gp expression status in tumors in patients with locally advanced or recurrent breast carcinoma.

Topics: Adult; Aged; Antibiotics, Antineoplastic; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma; Female; Genes, MDR; Humans; Middle Aged; Polymerase Chain Reaction; Predictive Value of Tests; Radionuclide Imaging; Radiopharmaceuticals; RNA, Messenger; Taxoids; Technetium Tc 99m Sestamibi; Treatment Outcome

Cancer of unknown primary site represents approximately 3% to 5% of all new cancer diagnoses. Adenocarcinomas account for 60% of all unknown primary cancers and poorly differentiated carcinomas or adenocarcinomas, for 30%. Historically, the prognosis for most patients with unknown primary tumors has been poor, with survival often less than 6 months from diagnosis. Recent advances in diagnostic techniques, including immunocytochemical and molecular genetic methods, have increased the probability of identifying a likely underlying tumor type. Based on clinical and pathologic features, approximately 40% of patients can be categorized within subsets for which specific treatment has been defined. Empiric therapy is an option for the remaining 60% of patients. In these patients, favorable prognostic factors for treatment response include tumor location in lymph nodes, fewer sites of metastases, younger age, and poorly differentiated carcinoma histology. Although experience remains limited, the incorporation of a taxane into empiric regimens appears to improve response rates and survival. A recent study of paclitaxel (Taxol), carboplatin (Paraplatin), and etoposide in 55 patients with cancer of unknown primary site reported an overall response rate of 47% and a median overall survival of 13.4 months. Investigations continue to explore new diagnostic techniques and novel therapeutic approaches.

Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carboplatin; Carcinoma; Etoposide; Evaluation Studies as Topic; Female; Humans; Male; Neoplasms, Unknown Primary; Paclitaxel; Prognosis; Survival Rate; Taxoids

Taxanes such as paclitaxel (Taxol) and docetaxel (Taxotere) are promising agents for use against ovarian cancer and other malignancies. Recently, SB-T-1011, a semisynthetic taxane, has been prepared from 14-hydroxy-10-deacetylbaccatin III. SB-T-1011 shows similar or greater in vitro cytostatic activity than paclitaxel, depending on the tumor cell line. The administration of taxanes is problematic due to their low solubility in most pharmaceutically acceptable solvents; formulations used clinically contain Cremophor/ethanol (diluent 12) or polysorbate 80/ethanol, excipients which may cause serious adverse effects. To eliminate these vehicles, we have prepared paclitaxel liposome formulations. The objective of the present work was to evaluate the antitumor activity of paclitaxel and two semisynthetic analogs in Cremophor-based and liposomal formulations. Antitumor activity was evaluated against A121a, a taxane-sensitive human ovarian tumor, growing as subcutaneous xenografts in athymic nude mice. Free and liposomal formulations of each taxane showed similar antitumor effect. The antitumor activity of paclitaxel and SB-T-1011 was similar, and docetaxel was more potent than either paclitaxel or SB-T-1011. Overall, taxane liposomes were better tolerated and more easily administered iv than taxane formulated in Cremophor/ethanol.

Topics: Animals; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma; Carcinoma, Non-Small-Cell Lung; Colonic Neoplasms; Docetaxel; Drug Carriers; Female; Humans; Liposomes; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Transplantation; Ovarian Neoplasms; Paclitaxel; Taxoids