[Show abstract][Hide abstract] ABSTRACT: Background
The combinations of methotrexate, vinblastine, Adriamycin, cisplatin (Pharmanell, Athens, Greece) (MVAC) or gemcitabine, cisplatin (GC) represent the standard treatment of advanced urothelial cancer (UC). Dose-dense (DD)-MVAC has achieved longer progression-free survival (PFS) than the conventional MVAC. However, the role of GC intensification has not been studied. We conducted a randomized, phase III study comparing a DD-GC regimen with DD-MVAC in advanced UC.Patients and methodsOne hundred and thirty patients were randomly assigned between DD-MVAC: 66 (M 30 mg/m(2), V 3 mg/m(2), A 30 mg/m(2), C 70 mg/m(2) q 2 weeks) and DD-GC 64 (G 2500 mg/m(2), C 70 mg/m(2) q 2 weeks). The median follow-up was 52.1 months (89 events).ResultsThe median overall survival (OS) and PFS were 19 and 8.5 months for DD-MVAC and 18 and 7.8 months for DD-GC (P = 0.98 and 0.36, respectively). Neutropenic infections were less frequent for DD-GC than for DD-MVAC (0% versus 8%). More patients on DD-GC received at least six cycles of treatment (85% versus 63%, P = 0.011) and the discontinuation rate was lower for DD-GC (3% versus 13%).Conclusions
Although DD-GC was not superior to DD-MVAC, it was better tolerated. DD-GC could be considered as a reasonable therapeutic option for further study in this patient population.Clinical Trial NumberACTRN12610000845033, www.anzctr.org.au.
[Show abstract][Hide abstract] ABSTRACT: Asymptomatic multiple myeloma (AMM) is characterized by a constant risk of progression to symptomatic myeloma. To evaluate previously recognized risk factors and to identify high-risk features we analyzed 96 patients with AMM and at least 18 months of follow-up. The progression rate at 1,2, and 3 years was 8%, 15% and 26%, respectively, and the projected 5-year progression rate was 38%. Extensive bone marrow (BM) infiltration, abnormal free light chain (FLC) ratio and serum monoclonal (M)-protein3 gr/dl were the most significant factors for progression, whereas the type of heavy (IgG vs IgA) or light chain or immunoparesis of the uninvolved immunoglobulins were not. Abnormal marrow signal of magnetic resonance imaging of the spine was associated with a significant risk of progression (median 15 months, P=0.001). Extensive BM infiltration 60% (hazard ratio, HR: 13.7, P<0.001) and FLC ratio100 (HR: 9, P=0.003) independently identified a 'very high-risk' group, which included 12.5% of patients with AMM and who progressed 18 months from initial diagnosis. Development of anemia and/or lytic bone lesions were the most common features of symptomatic progression. In conclusion, there is a subgroup of patients who have a substantial risk of progression to symptomatic disease that can be detected at diagnosis (either by extensive BM infiltration60% or FLC ratio100) and may be considered for immediate treatment.Leukemia advance online publication, 27 November 2012; doi:10.1038/leu.2012.309.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 11/2012; · 10.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSEThis study compared the efficacy and safety of patupilone with those of pegylated liposomal doxorubicin (PLD) in patients with platinum-refractory or -resistant epithelial ovarian, primary fallopian tube, or primary peritoneal cancer. PATIENTS AND METHODS
Patients with three or fewer prior regimens were eligible if they had received first-line taxane/platinum-based combination chemotherapy and were platinum refractory or resistant. Patients were randomly assigned to receive patupilone (10 mg/m(2) intravenously every 3 weeks) or PLD (50 mg/m(2) intravenously every 4 weeks).ResultsA total of 829 patients were randomly assigned (patupilone, n = 412; PLD, n = 417). There was no statistically significant difference in overall survival (OS), the primary end point, between the patupilone and PLD arms (P = .195; hazard ratio, 0.93; 95% CI, 0.79 to 1.09), with median OS rates of 13.2 and 12.7 months, respectively. Median progression-free survival was 3.7 months for both arms. The overall response rate (all partial responses) was higher in the patupilone arm than in the PLD arm (15.5% v 7.9%; odds ratio, 2.11; 95% CI, 1.36 to 3.29), although disease control rates were similar (59.5% v 56.3%, respectively). Frequently observed adverse events (AEs) of any grade included diarrhea (85.3%) and peripheral neuropathy (39.3%) in the patupilone arm and mucositis/stomatitis (43%) and hand-foot syndrome (41.8%) in the PLD arm. CONCLUSION
Patupilone did not demonstrate significant improvement in OS compared with the active control, PLD. No new or unexpected serious AEs were identified.
Journal of Clinical Oncology 09/2012; · 18.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The role of thalidomide, bortezomib and lenalidomide in multiple myeloma patients presenting with renal impairment was evaluated in 133 consecutive newly diagnosed patients who were treated with a novel agent-based regimen. A significant improvement of renal function (renalPR (renal partial response)) was observed in 77% of patients treated with bortezomib, in 55% with thalidomide and in 43% with lenalidomide (P=0.011). In multivariate analysis, bortezomib-based therapy was independently associated with a higher probability of renal response compared with thalidomide- or lenalidomide-based therapy. Other important variables included eGFR (estimated glomerular filtration rate) 30 ml/min, age 65 years and myeloma response. Patients treated with bortezomib achieved at least renalPR in a median of 1.34 months vs 2.7 months for thalidomide and >6 months for lenalidomide-treated patients (P=0.028). In multivariate analysis bortezomib-based therapy, higher doses of dexamethasone (160 mg during the first month of treatment), an eGFR 30 ml/min and age 65 years were independently associated with shorter time to renal response. In conclusion, bortezomib-based therapies may be more appropriate for the initial management of patients with myeloma-related renal failure; however, thalidomide and lenalidomide are also associated with significant probability of improvement of their renal function.Leukemia advance online publication, 27 July 2012; doi:10.1038/leu.2012.182.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 07/2012; · 10.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two pivotal, phase III, randomised, placebo-controlled, registration trials (MM-009 and MM-010) showed that lenalidomide plus dexamethasone was more effective than placebo plus dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma. This pooled, retrospective subanalysis of MM-009 and MM-010 analysed outcomes according to patient age. A total of 704 patients (390 aged <65 years, 232 aged 65-74 years, and 82 aged ≥75 years) received lenalidomide or placebo, both in combination with dexamethasone. The overall response rate (ORR) was significantly higher in patients treated with lenalidomide plus dexamethasone versus placebo plus dexamethasone in all age groups (P < 0.0001 for all). Median progression-free survival (PFS) and median time-to-progression (TTP) were similar, and both were significantly longer with lenalidomide plus dexamethasone in all age groups (P < 0.001 for all). Median overall survival (OS) favoured lenalidomide plus dexamethasone in all age groups, although the difference was not statistically significant. Adverse events of anaemia, febrile neutropenia, deep-vein thrombosis, neuropathy, and gastrointestinal disorders increased with age. Lenalidomide combined with dexamethasone improved the ORR and prolonged PFS, TTP, and OS compared with placebo plus dexamethasone, irrespective of age. This finding was consistent with the overall MM-009 and MM-010 populations.
International journal of hematology 07/2012; 96(2):254-62. · 1.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction: Natural Killer (NK) cells represent important effectors against hematological and non-hematological malignances. They are highly efficient in killing ex-vivo-derived tumor cells and are effective against tumor cells with stem cell properties, the ultimate target of both conventional and innovative therapies. Clinical evidences however, show that, in vivo, tumors could avoid NK-mediated attack. Indeed it has been shown that NK cell cytolytic activity can be down-regulated by soluble mediators released by tumor cells and/or by immune cell types recruited at the tumor site. The observation that NK cells are often scarce within tumors, despite high local levels of chemokines prompted us to analyze whether tumor cells could avoid NK-mediated immunosurveillance by modulation of NK cell chemokine receptor repertoire. This study has been focused on immunomodulatory role of Neuroblastoma (NB), a poorly differentiated extracranial neuroectodermal tumor that accounts for 15% of all childhood cancer deaths. Material and Methods: NK cells were purified from peripheral blood mononuclear cells of healthy donors by Human NK Cell Isolation kits. NB cell lines utilized: SH-SY-5Y, HTLA-230, SK-NF-1, IMR32, GI-LI-N and SK-N-SH. For cytofluorimetric analysis cells were stained with PE-conjugated mAbs or with unconjugated mAbs followed by conjugated goat anti-mouse second reagent and analyzed by a cytometer. Neuroblastoma-conditioned supernatants were analyzed for the presence of 50 soluble factors using Multiplex Human Cytokine assays. Chemotaxis of neuroblastoma conditioned-NK cells was evaluated by standard assays. Results and Discussion: Freshly purified human NK cells were cultured under trans-well conditions in the presence of NB cell lines. After co-cultures, NK cells were analyzed for the expression of a panel of chemokine receptors known to regulate their migratory capacity. This analysis showed that NB-conditioning up regulates on NK cells CXCR3 and CXCR4 expression. On the contrary NB-conditioned NK cells were characterized by a significative decrease in CX 3 CR1 expression as compared to unconditioned NK cells. Thanks to the analysis of the soluble factors released by the different NB cell lines utilized and by the use of mAb-mediated blocking of specific soluble factors we identified the mediator responsible for the described effect. Interestingly the described immunomodulatory feature was shared only by some of the several NB cell lines utilized.: CD200 is an immunosuppressive molecule which over-expressed in some hematologic malignancies such as B-cell chronic lymphocytic leukemia (B-CLL) and multiple myeloma. It has been also shown to be an independent prognostic factor for patients with acute myeloid leukemia (AML). In this current study, simultaneous CD200 expression and foxp3+ regulatory T cells level were investigated in Iranian patients with AML. Material and Methods: CD200 and its receptor (CD200R) expression levels were examined on bone marrow and peripheral blood leukemic cells obtained from 43 AML patients by Flow cytometry. This technique was also used to determine the frequency of foxp3+ regulatory T cells in these patients. ELISA method was performed to investigate TGF-b and IL-10 production level in serum of patients. Results: Correlation analysis demonstrated simultaneously increasing of foxp3+ regulatory T cells and CD200 expression in AML patients (p = 0.003; r = 0.73). Our clinically poor prognosis patients have shown both higher expression of CD200 and frequency of foxp3+ regulatory T cells (p = 0.01 and p = 0.03, respectively). Moreover, the serum concentration of TGF-b (but not IL-10) was significantly correlated with the expression of CD200 on leukemic cells (p = 0.02). Conclusions: These data signify the CD200 roles in repression and suppression of anti tumor immune system response by stimulation of regulatory mechanisms in AML patients and can suggest that CD200 may have prognostic value in this malignancy.
[Show abstract][Hide abstract] ABSTRACT: The management of multiple myeloma has undergone profound changes over the recent past as a result of advances in our understanding of the disease biology as well as improvements in treatment and supportive care strategies. Notably, recent years have seen a surge in studies incorporating the novel agents thalidomide, bortezomib, and lenalidomide into treatment for different disease stages and across different patient groups. This article presents an update to a previous review of European treatment practices and is based on discussions during an expert meeting that was convened to review novel agent data published or presented at medical meetings until the end of 2011 and to assess their impact on treatment strategies.
The Oncologist 05/2012; 17(5):592-606. · 4.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Activin-A is a transforming growth factor -β superfamily member, which seems to be implicated in the biology of osteolytic disease in multiple myeloma. Design and methods Circulating activin-A was evaluated in 98 newly diagnosed myeloma patients (85 with symptomatic disease), in 40 patients with relapsed myeloma before and after four cycles of lenalidomide and dexamethasone (RD), in 27 healthy controls and in 10 monoclonal gammopathy of undetermined significance patients. Results Patients with newly diagnosed symptomatic myeloma had increased circulating activin-A compared with controls (P < 0.001), while patients with relapsed disease had elevated activin-A even compared with symptomatic patients at diagnosis (P < 0.001). High activin-A correlated with advanced International Staging System stage (P = 0.002), increased bone resorption (P < 0.001) and extensive bone disease (P = 0.03). Low levels of activin-A (<442 pg/ml) were associated with superior median overall survival: not reached versus 59 months (P = 0.04), while activin-A inversely correlated with survival as a continuous variable (P < 0.001). RD did not alter circulating activin-A after four cycles of treatment, even in responders. Conclusions High circulating activin-A correlates with advanced features of myeloma, supporting the rationale for the use of activin-A antagonists, such as sotatercept in myeloma. The inability of RD to reduce activin-A reveals RD as a good candidate for combination therapies with activin-A antagonists in myeloma.
Annals of Oncology 04/2012; 23(10):2681-6. · 7.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Peripheral neuropathy (PN) is one of the most important complications of multiple myeloma (MM) treatment. PN can be caused by MM itself, either by the effects of the monoclonal protein or in the form of radiculopathy from direct compression, and particularly by certain therapies, including bortezomib, thalidomide, vinca alkaloids and cisplatin. Clinical evaluation has shown that up to 20% of MM patients have PN at diagnosis and as many as 75% may experience treatment-emergent PN during therapy. The incidence, symptoms, reversibility, predisposing factors and etiology of treatment-emergent PN vary among MM therapies, with PN incidence also affected by the dose, schedule and combinations of potentially neurotoxic agents. Effective management of treatment-emergent PN is critical to minimize the incidence and severity of this complication, while maintaining therapeutic efficacy. Herein, the state of knowledge regarding treatment-emergent PN in MM patients and current management practices are outlined, and recommendations regarding optimal strategies for PN management during MM treatment are provided. These strategies include early and regular monitoring with neurological evaluation, with dose modification and treatment discontinuation as indicated. Areas requiring further research include the development of MM-specific, patient-focused assessment tools, pharmacogenomic analysis of patient DNA, and trials to assess the efficacy of pharmacological interventions.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 12/2011; 26(4):595-608. · 10.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neutropenia is a hematologic adverse event characterized by an absolute neutrophil count (ANC) lower than 1500 cells/mL. This reduction may be due to decreased neutrophil production, accelerated use, a shift in compartments of neutrophils, or a combination of these factors. Neutropenia is often associated with infections, which are major causes of morbidity and mortality in patients with cancer. In patients with multiple myeloma, the novel agents thalidomide, lenalidomide, and bortezomib have improved outcome, but chemotherapy-related neutropenia should be carefully considered. Chemotherapy-related high-risk factors for severe neutropenia include regimens with an expected neutropenia rate of > 50%, such as the 3-drug combinations including lenalidomide plus alkylating agents or doxorubicin, whereas low-risk regimens include combinations of the novel agents with dexamethasone alone. Patient characteristics, disease stage, type of current and previous treatment, and ANC < 1000 cells/mL at baseline are additional factors that define the risk of severe neutropenia. Granulocyte-colony stimulating factor (G-CSF) should be used to manage chemotherapy-related neutropenia so that patients may stay on treatment for a longer time and benefit from it. Primary G-CSF prophylaxis should be used when high-risk regimens are administered or when low/intermediate-risk regimens are used and additional risk factors are present. Reactive G-CSF treatment is indicated when patients undergoing low-risk chemotherapy experience grade 3/4 neutropenia. If ANC restores to > 1000 cells/mL, therapy can be resumed with no dose modifications. In case of persistence of severe neutropenia, treatment should be delayed until ANC reaches > 1000 cells/mL, and dose reductions are necessary.
[Show abstract][Hide abstract] ABSTRACT: In recent years the use of intravenously
administered bisphosphonate drugs is
widespread, with excellent therapeutic benefits
for cancer patients suffering from multiple
six months or annually for control and
prevention, had fewer caries lesions, better oral
hygiene and improved periodontal condition,
compared to thosewho rarely visited the dentist
due to pain.
myeloma, breast, prostate and lung cancer.
However, osteonecrosis of the jaws as a side
effect of these drugs, which was recently
observed, motivated oncologists and dentists
internationally to conduct clinical research
studies for the prevention, diagnosis and
treatment of this lesion. Results of these surveys
highlight the importance ofmaintaining good oral
health. The absence of epidemiological studies
concerning the oral condition of oncology
patients and the consequent lack of information
of dental problems and the needs of oncology
patients receiving intravenous bisphosphonates,
was the starting point for the design of this
epidemiological research. The purposes of the
present studywere: a) to record and evaluate the
oral health status of oncology patients, receiving
intravenous bisphosphonates, b) to record the
cases of those developing osteonecrosis of the
jaw, c) to investigate a possible association
between oral health status and occurrence of
osteonecrosis of the jaw, d) to investigate the
possible association of demographic, social and
behavioral factors in the emergence and
development of osteonecrosis of the jaw. Α nonV
interventional clinical trial was conducted, to
record the level of oral health of oncology
patients receiving intravenous bisphosphonates,
by taking three epidemiological indicators and
completing a questionnaire. The survey took
place in the Oncology Clinic of the University
General Hospital "ALEXANDRA" and involved 104
oncology patients, of which 10 had developed
osteonecrosis, regardless of gender, age,
ethnicity, socioeconomic or educational level,
type and stage of cancer. All of the patientswere
receiving intravenous zoledronic acid (Zometa) in
intravenous infusion, once a month. The main
results of the study were: Prevalence and
severity of dental caries in patients with
bisphosphonate related osteonecrosis of the jaw
(BRONJ) were similar to those that have not
developed the lesion. Patients with BRONJ, had a
similar level of oral hygiene and their periodontal
condition was better compared to the level of
oral hygiene and the frequency and severity of
periodontal diseases in patientswho did not have
osteonecrosis. Dental caries and periodontal
diseases did not seem to be releasing factors of
BRONJ development. Themost serious oral health
problems of the patients examined, with or
without BRONJ, were caries and periodontal
diseases. Regarding dental caries, the index values
showed similar levels and variation to that of the
general greek population. Age is associated with
the development of dental caries: the younger
patients showed reduced disease severity
compared to older patients. Education level was
also associated with dental caries, oral hygiene
and periodontal status of the patients: the higher
the educational level, the better the oral health.
The frequency and the reasoning of visiting the
dentist had a direct relationship to dental caries,
periodontal status and the level of oral hygiene.
Patients who visited the dentist regularly every
[Show abstract][Hide abstract] ABSTRACT: Ovarian carcinomas have been classified into types I and II according to the hypothesised mode of carcinogenesis and molecular characteristics. The prognostic significance of this classification has not been studied.
Five hundred and sixty-eight patients with histologically confirmed, ovarian, fallopian tube or peritoneal carcinomas, international federation of gynecology and obstetrics (FIGO) stages IIC-IV, treated with paclitaxel/platinum following cytoreductive surgery, were included in this analysis. Type I included low-grade serous, mucinous, endometrioid and clear-cell and type II high-grade serous, unspecified adenocarcinomas and undifferentiated carcinomas.
Median overall survival (OS) was 49 months for type I versus 45 for type II (p=0.576). In contrast to type II, there was considerable prognostic heterogeneity among the subtypes included in type I. Cox regression analysis showed that cell-type classification: low-grade serous, mucinous, endometrioid, clear-cell, type II (high-grade serous, unspecified adenocarcinomas, undifferentiated carcinoma) was an independent predictor of survival (respective median OS 121 versus 15 versus 64 versus 29 versus 45 months, p=0.003). On the contrary, histopathological subtype or tumour type (I versus II) did not offer additional prognostic information.
The proposed model of ovarian tumourigenesis does not reflect tumour behaviour in advanced disease. Tumour-cell type is the most relevant histopathological prognostic factor in advanced ovarian cancer treated with platinum/paclitaxel.
European journal of cancer (Oxford, England: 1990) 10/2011; 48(10):1476-83. · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Multiple myeloma, a plasma cell neoplasm, is the second most common hematologic malignancy after non-Hodgkins lymphoma and is responsible for 2% of cancer deaths. Melphalan and prednisone (MP) has been the standard treatment in elderly patients for many decades. The VISTA study evaluated the effect of this combination with or without the first-in-class proteasome inhibitor bortezomib in newly diagnosed myeloma patients who were not candidates for autologous stem cell transplantation. Altogether 682 patients were enrolled and prospectively randomized in this trial. All patients received nine 6-week cycles of oral melphalan (9 mg/m(2)) and prednisone (60 mg/m(2)) on days 1-4, either alone or with bortezomib administered intravenously (1.3 mg/m(2) on days 1, 4, 8, 11, 22, 25, 29 and 32 during the first four cycles and on days 1, 8, 22, 29 during remaining course of therapy). Median time to progression (the primary end point of the trial) was 24 months in the bortezomib-containing group compared with 16.6 months in the control group (p < 0.001). Response was evaluated in 337 patients receiving bortezomib compared with 331 patients in the control group who received MP alone; the percentages of partial response or better was 71 vs 35% (p < 0.001), with complete response seen in 30 vs 4%, respectively (p < 0.001). Median response duration in both groups was 19.9 versus 13.1 months, respectively. Median overall survival has not been reached in VMP group compared with 43 months in the MP group (p < 0.001), and this benefit is maintained after long term follow-up and subsequent antimyeloma therapies. Hematological adverse events (AEs) were similar in both groups, although patients in the bortezomib group experienced more frequent peripheral sensory neuropathy (including 13% grade 3, with less than 1% grade 4). Overall, the occurrence of grade 3 AEs was higher in patients receiving bortezomib (53 vs 44%, p = 0.02), but the risk of grade 4 AEs was identical (28 vs 27%). These results confirm the superiority of MP plus bortezomib combination over MP therapy in treatment-naive patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation.
[Show abstract][Hide abstract] ABSTRACT: Dietary fat, both in terms of quantity and quality, has been implicated to cancer development, either positively or negatively. The aim of this work was to evaluate whether olive oil or monounsaturated fat intake was associated with the development of cancer. A systematic search of relevant studies, published in English, between 1990 and March 1, 2011, was performed through a computer-assisted literature tool (i.e., Pubmed). In total 38 studies were initially allocated; of them 19 case-control studies were finally studied (13800 cancer patients and 23340 controls were included). Random effects meta-analysis was applied in order to evaluate the research hypothesis. It was found that compared with the lowest, the highest category of olive oil consumption was associated with lower odds of having any type of cancer (log odds ratio = -0.41, 95%CI -0.53, -0.29, Cohran's Q = 47.52, p = 0.0002, I-sq = 62%); the latter was irrespective of the country of origin (Mediterranean or non-Mediterranean). Moreover, olive oil consumption was associated with lower odds of developing breast cancer (logOR = -0,45 95%CI -0.78 to -0.12), and a cancer of the digestive system (logOR = -0,36 95%CI -0.50 to -0.21), compared with the lowest intake. The strength and consistency of the findings states a hypothesis about the protective role of olive oil intake on cancer risk. However, it is still unclear whether olive oil's monounsaturated fatty acid content or its antioxidant components are responsible for its beneficial effects.
Lipids in Health and Disease 07/2011; 10:127. · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T0). The median age at diagnosis was 58 years, and time from diagnosis to T0 was 3.3 years. Following T0, 213 (74%) patients had a treatment recorded with one or more regimens (median=1; range 0–8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T0 in 94 patients (44%) including partial response in 69 (32%). The median overall survival and event-free survival from T0 were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs.Keywords: multiple myeloma; relapse; natural history; survival
[Show abstract][Hide abstract] ABSTRACT: Early-stage epithelial ovarian cancer represents a prognostically heterogenous group. We studied prognostic factors in patients treated with adjuvant paclitaxel/carboplatin chemotherapy.
Data was extracted from 147 patients with FIGO stage IA/IB, grade 2/3 or stage IC/IIA (any grade) who underwent primary surgery followed by paclitaxel/carboplatin chemotherapy.
Median follow-up was 88 months. Ten-year relapse-free (RFS) and disease-specific survival (DSS) were: 81% (95% confidence interval [CI]: 73-89) and 81% (95% CI: 73-89). On multivariate analysis, non serous histology was associated with reduced risk for RFS (0.294, 95% CI: 0.112-0.577, p=0.001) and DSS (0.194, 95% CI: 0.075-0.504, p=0.001), while high-risk category (stage IC/IIA and grade 2/3) with increased risk for RFS (3.989, 95% CI: 1.189-13.389, p=0.009) and DSS (3.989, 95% CI: 1.064-16.386, p=0.038). The combination of histology and grade identified 3 groups with distinctly different 10-year RFS and DSS rates (p<0.001): grade 1 (100% and 100%), non-serous grade 2/3 (83% and 86%) and serous grade 2/3 (60% and 60%).
Serous histology is an adverse prognostic factor in early-stage ovarian cancer treated with adjuvant paclitaxel/carboplatin. Risk stratification according to histology and grade is a useful discriminator of prognosis and can be used in the design of future studies.
[Show abstract][Hide abstract] ABSTRACT: This analysis assessed the effect of lenalidomide on progression-free survival (PFS). Patients with relapsed or refractory multiple myeloma (RRMM) who received lenalidomide plus dexamethasone in the MM-009 and MM-010 trials were pooled and those who had not progressed and were still receiving lenalidomide at 12 months were included. The median follow-up of surviving patients was 48 months. Of 353 patients who received lenalidomide plus dexamethasone, 116 (33%) had not progressed. Overall, 52 patients (45%) had no dose reductions, 25 (22%) had dose reductions ≥12 months and 39 (34%) had dose reductions before 12 months. Patients who had dose reductions ≥12 months had a significantly longer median PFS than those who had reductions before 12 months (P=0.007) or no dose reductions (P=0.039) (not reached vs 28.0 vs 36.8 months, respectively). In a multivariate Cox regression model, dose reduction ≥12 months was an independent predictor of improved PFS (hazard ratio, 0.47; 95% confidence interval, 0.23-0.98) after adjusting for patient characteristics. The data suggest that to achieve maximum PFS benefit, patients with RRMM should be treated for ≥12 months with full-dose lenalidomide plus dexamethasone. Thereafter, patients may benefit from lower-dose continued therapy; prospective studies are needed to confirm these findings.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 07/2011; 25(10):1620-6. · 10.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The International Staging System (ISS) is the most widely used staging system for patients with multiple myeloma (MM). However, serum β2-microglobulin increases in renal impairment (RI) and there have been concerns that ISS-3 stage may include 'up-staged' MM patients in whom elevated β2-microglobulin reflects the degree of renal dysfunction rather than tumor load.
In order to assess the impact of RI on the prognostic value of ISS, we analyzed 1516 patients with symptomatic MM and the degree of RI was classified according to the Kidney Disease Outcomes Quality Initiative-Chronic Kidney Disease (CKD) criteria.
Forty-eight percent patients had stages 3-5 CKD while 29% of patients had ISS-1, 38% had ISS-2 and 33% ISS-3. The frequency and severity of RI were more common in ISS-3 patients. RI was associated with inferior survival in univariate but not in multivariate analysis. When analyzed separately, ISS-1 and ISS-2 patients with RI had inferior survival in univariate but not in multivariate analysis. In ISS-3 MM patients, RI had no prognostic impact either in univariate or multivariate analysis. Results were similar, when we analyzed only patients with Bence-Jones >200 mg/day.
ISS remains unaffected by the degree of RI, even in patients with ISS-3, which includes most patients with renal dysfunction.
Annals of Oncology 06/2011; 23(3):722-9. · 7.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The introduction of the Immunomodulatory drugs (IMiDs) and proteasome inhibitors, used either as a single-agent or combined with classic anti-myeloma therapies, has improved the outcome for patients with relapsed myeloma. However, there is currently no generally accepted standard treatment for relapsed/refractory myeloma patients, partly because of the absence of trials comparing the efficacy of the novel agents in relapsed/refractory myeloma. Choice of a new treatment regimen depends on both patient and disease-specific characteristics. A lenalidomide-based regimen is the first choice in patients with neuropathy, while bortezomib has the highest efficacy in patients with renal insufficiency and is not associated with increased risk of thromboembolism. A second autologous stem cell transplantation (auto-SCT) can be applied in patients with a progression-free period of ≥ 18-24 months after the first auto-SCT. In high-risk relapse such as occurring early after auto-SCT consolidation with allogeneic SCT can be considered. In this review we provide an overview of the various salvage regimens and give recommendations for treatment of patients with relapsed/refractory myeloma in different clinical settings.
Cancer Treatment Reviews 06/2011; 37(4):266-83. · 6.02 Impact Factor