ABSTRACT
BACKGROUND: Tenosynovial giant cell tumour (TGCT) is a locally aggressive neoplasm for which few systemic treatment options exist. This study evaluated the efficacy and safety of vimseltinib, an oral, switch-control, CSF1R inhibitor, in patients with symptomatic TGCT not amenable to surgery. METHODS: MOTION is a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial done in 35 specialised hospitals in 13 countries. Eligible patients were adults (aged ≥18 years) with a histologically confirmed diagnosis of TGCT for which surgical resection could potentially worsen functional limitation or cause severe morbidity. Patients were randomly assigned (2:1) with interactive response technology to vimseltinib (30 mg orally twice weekly) or placebo, administrated in 28-day cycles for 24 weeks. Patients and site personnel were masked to treatment assignment until week 25, unless progressive disease was confirmed earlier. The primary endpoint was objective response rate by independent radiological review using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) at week 25 in the intention-to-treat population. Safety was assessed in all patients who received the study drug. The trial is registered with ClinicalTrials.gov, NCT05059262, and enrolment is complete. FINDINGS: Between Jan 21, 2022, and Feb 21, 2023, 123 patients were randomly assigned (83 to vimseltinib and 40 to placebo). 73 (59%) patients were female and 50 (41%) were male. Nine (11%) of 83 patients assigned to vimseltinib and five (13%) of 40 patients assigned to placebo discontinued treatment before week 25; one patient in the placebo group did not receive any study drug. Objective response rate per RECIST was 40% (33 of 83 patients) in the vimseltinib group vs 0% (none of 40) in the placebo group (difference 40% [95% CI 29-51]; p<0·0001). Most treatment-emergent adverse events (TEAEs) were grade 1 or 2; the only grade 3 or 4 TEAE that occurred in more than 5% of patients receiving vimseltinib was increased blood creatine phosphokinase (eight [10%] of 83). One patient in the vimseltinib group had a treatment-related serious TEAE of subcutaneous abscess. No evidence of cholestatic hepatotoxicity or drug-induced liver injury was noted. INTERPRETATION: Vimseltinib produced a significant objective response rate and clinically meaningful functional and symptomatic improvement in patients with TGCT, providing an effective treatment option for these patients. FUNDING: Deciphera Pharmaceuticals.
ABSTRACT
PURPOSE: To evaluate the addition of ofranergene obadenovec (ofra-vec, VB-111), a novel gene-based anticancer targeted therapy, to once a week paclitaxel in patients with recurrent platinum-resistant ovarian cancer (PROC). METHODS: This placebo-controlled, double-blind, phase III trial (ClinicalTrials.gov identifier: NCT03398655) randomly assigned patients with PROC 1:1 to receive intravenous ofra-vec every 8 weeks with once a week IV paclitaxel or placebo with paclitaxel until disease progression. The dual primary end points were overall survival (OS) and progression-free survival (PFS) as assessed by Blinded Independent Central Review. RESULTS: Between December 2017 and March 2022, 409 patients were randomly assigned. The median PFS was 5.29 months in the ofra-vec arm and 5.36 months in the control arm, hazard ratio (HR) 1.03 (CI, 0.83 to 1.29; P = .7823). The median OS with ofra-vec was 13.37 months versus 13.14 months, HR 0.97 (CI, 0.75 to 1.27; P = .8440). Objective response rates (ORRs) per RECIST 1.1 were similar in both arms: 28.9% with ofra-vec versus 29.6% with control. In both treatment arms, response to CA-125 was a substantial prognostic factor for both PFS and OS. In the ofra-vec arm, the HR in CA-125 responders compared with that in nonresponders for PFS was 0.2428 (CI, 0.1642 to 0.3588), and for OS, the HR was 0.3343 (CI, 0.2134 to 0.5238). Safety profile was characterized by common transient flu-like symptoms such as fever and chills. CONCLUSION: The addition of ofra-vec to paclitaxel did not improve PFS or OS. The PFS and ORR in the control arm exceeded the results that were anticipated on the basis of the AURELIA chemotherapy control arm. CA-125 response was a substantial prognostic biomarker for PFS and OS in patients with PROC treated with paclitaxel.
Subject(s)
Ovarian Neoplasms , Paclitaxel , Humans , Female , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Neoplasm Recurrence, Local/drug therapy , Carcinoma, Ovarian Epithelial/drug therapy , Progression-Free Survival , Angiogenesis Inhibitors/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report the final prespecified analysis for overall survival (OS), along with updated progression-free survival (PFS) and objective response rate (ORR), and safety from the open-label, randomized, phase III Study 309/KEYNOTE-775. In total, 827 patients with advanced, recurrent, or metastatic endometrial cancer (EC) were randomly assigned to receive lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously once every 3 weeks (n = 411) or chemotherapy of the treating physician's choice (doxorubicin 60 mg/m2 intravenously once every 3 weeks or paclitaxel 80 mg/m2 intravenously once weekly [3 weeks on; 1 week off] [n = 416]). Efficacy was reported for patients with mismatch repair proficient (pMMR) tumors and all-comers, and by subgroups (histology, prior therapy, MMR status). Updated safety was also reported.Lenvatinib plus pembrolizumab showed benefits in OS (pMMR HR, 0.70; 95% CI, 0.58 to 0.83; all-comer HR, 0.65; 95% CI, 0.55 to 0.77), PFS (pMMR HR, 0.60; 95% CI, 0.50 to 0.72; all-comer HR, 0.56; 95% CI, 0.48 to 0.66), and ORR (pMMR patients, 32.4% v 15.1%; all-comers, 33.8% v 14.7%) versus chemotherapy. OS, PFS, and ORR favored lenvatinib plus pembrolizumab in all subgroups of interest. No new safety signals were observed. Lenvatinib plus pembrolizumab continued to show improved efficacy versus chemotherapy and manageable safety in patients with previously treated advanced EC.
Subject(s)
Antibodies, Monoclonal, Humanized , Endometrial Neoplasms , Female , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Endometrial Neoplasms/drug therapy , Phenylurea Compounds/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
El objetivo de este estudio es la elaboración de un cuestionario de evaluación del miedo a la recurrencia del cáncer en español. Método: se presenta un estudio piloto de diseño correlacional trasversal elaborado en dos fases: 1) creación del cuestionario del miedo a la recurrencia del cáncer (CMRC) y de la Escala General del Miedo a la Recurrencia del Cáncer (EGMRC); 2) evaluación de sus propiedades psicométricas. Resultados: para la elaboración de los cuestionarios se utilizó el acuerdo entre expertos medido por la V de Aiken. El CMRC queda finalmente configurado con 8 ítems que se responden con una escala tipo Likert de 0-4 y un Alfa de Cronbach de 0,85. La EGMRC de una sola pregunta que se responde con una escala de 0-100 correlaciona hasta un 0,84 con el CMRC. Se utilizó una muestra de 50 mujeres supervivientes de cáncer ginecológico seleccionadas en el Hospital Universitario Clínico San Carlos de Madrid. Ambas escalas correlacionan con el nivel de ansiedad de las pacientes y la función emocional de calidad de vida. No se hallan correlaciones con los niveles de depresión. Conclusiones: El CMRC y la EGMRC son dos instrumentos que pueden ser válidos para la evaluación del miedo a la recurrencia del cáncer en pacientes supervivientes de cáncer ginecológico (AU)
The objective of this study is the elaboration of a questionnaire for the evaluation of the fear of recurrence of cancer in Spanish. Method: A pilot study with a cross-sectional correlational design is presented, elaborated in two phases: 1) creation of the Fear Cancer recurrence Questionnaire (CMRC) and the General Scale of Fear of Cancer Recurrence (EGMRC); 2) evaluation of their psychometric properties. Results: for the elaboration of the questionnaires, the agreement between experts was used, measured by Aikens V. The CMRC questionnaire is finally configured with 8 items that are answered with a Likert-type scale of 0-4 and a Cronbachs Alpha of 0.851. The EGMRC consists of a single question that is answered with a scale of 0-100 correlates up to 0.84 with the CMRC. A sample of 50 female survivors of gynecological cancer selected from the Hospital Universitario Clínico San Carlos in Madrid was used. Both scales correlate with the level of anxiety of the patients and the emotional function of quality of life. No correlations with levels of depression were found. Conclusions: The CMRC and the EGMRC are two instruments that may be valid for the evaluation of FCR in Spanish for survivors of gynecological cancer (AU)
Subject(s)
Humans , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Genital Neoplasms, Female/psychology , Neoplasm Recurrence, Local/psychology , Surveys and Questionnaires , Fear/psychology , Reproducibility of Results , Pilot Projects , Psychometrics , SpainABSTRACT
BACKGROUND: Standard therapy for advanced endometrial cancer after failure of platinum-based chemotherapy remains unclear. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced endometrial cancer who had previously received at least one platinum-based chemotherapy regimen to receive either lenvatinib (20 mg, administered orally once daily) plus pembrolizumab (200 mg, administered intravenously every 3 weeks) or chemotherapy of the treating physician's choice (doxorubicin at 60 mg per square meter of body-surface area, administered intravenously every 3 weeks, or paclitaxel at 80 mg per square meter, administered intravenously weekly [with a cycle of 3 weeks on and 1 week off]). The two primary end points were progression-free survival as assessed on blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1, and overall survival. The end points were evaluated in patients with mismatch repair-proficient (pMMR) disease and in all patients. Safety was also assessed. RESULTS: A total of 827 patients (697 with pMMR disease and 130 with mismatch repair-deficient disease) were randomly assigned to receive lenvatinib plus pembrolizumab (411 patients) or chemotherapy (416 patients). The median progression-free survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 6.6 vs. 3.8 months; hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.50 to 0.72; P<0.001; overall: 7.2 vs. 3.8 months; hazard ratio, 0.56; 95% CI, 0.47 to 0.66; P<0.001). The median overall survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 17.4 vs. 12.0 months; hazard ratio for death, 0.68; 95% CI, 0.56 to 0.84; P<0.001; overall: 18.3 vs. 11.4 months; hazard ratio, 0.62; 95% CI, 0.51 to 0.75; P<0.001). Adverse events of grade 3 or higher occurred in 88.9% of the patients who received lenvatinib plus pembrolizumab and in 72.7% of those who received chemotherapy. CONCLUSIONS: Lenvatinib plus pembrolizumab led to significantly longer progression-free survival and overall survival than chemotherapy among patients with advanced endometrial cancer. (Funded by Eisai and Merck Sharp and Dohme [a subsidiary of Merck]; Study 309-KEYNOTE-775 ClinicalTrials.gov number, NCT03517449.).
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Endometrial Neoplasms/drug therapy , Phenylurea Compounds/administration & dosage , Quinolines/administration & dosage , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Endometrial Neoplasms/mortality , Female , Humans , Middle Aged , Phenylurea Compounds/adverse effects , Quinolines/adverse effects , Survival AnalysisABSTRACT
BACKGROUND: The combination of lenvatinib plus pembrolizumab has shown efficacy in treatment of advanced endometrial carcinoma (that is not microsatellite instability-high or mismatch repair deficient) following prior systemic therapy in any setting in the open-label, single-arm, phase Ib/II Study 111/KEYNOTE-146. With the exception of hypothyroidism, the safety profile of the combination was comparable to that of each monotherapy. Given the medical complexity and fragility of patients with endometrial carcinoma, further characterization of adverse reactions (ARs) associated with treatment will help health care professionals to optimize treatment with lenvatinib plus pembrolizumab combination therapy. PATIENTS AND METHODS: In Study 111/KEYNOTE-146, patients received lenvatinib at a starting dose of 20 mg orally once daily and pembrolizumab 200 mg intravenously every 3 weeks. Selected ARs (hypertension, fatigue, nausea/vomiting, diarrhea, decreased appetite/weight loss, hypothyroidism, palmar-plantar erythrodysesthesia syndrome, musculoskeletal pain, stomatitis, and proteinuria) were chosen for detailed post hoc analyses. RESULTS: Median times to first onset of the selected ARs in this analysis all occurred within the first 10 weeks of treatment. Of the selected ARs, grade ≥3 severity of fatigue, hypertension, and nausea occurred in ≥5% of patients. Overall incidence of hypothyroidism was 51%, primarily of grade 2 severity (46%). Most of the ARs assessed were managed with a combination of study drug dose modifications and concomitant medications. CONCLUSION: No new safety signals were identified and the toxicity profile in this study was manageable with supportive medications, dose interruptions, and/or lenvatinib dose reductions. This analysis provides AR management guidance for patients with endometrial cancer receiving lenvatinib plus pembrolizumab combination therapy. IMPLICATIONS FOR PRACTICE: Lenvatinib plus pembrolizumab has shown efficacy in the treatment of patients with advanced endometrial carcinoma (that is, not microsatellite instability-high or mismatch repair deficient) following at least one prior systemic therapy in any setting. Patients may experience toxicity associated with this combination, including adverse reactions of hypertension, fatigue, nausea/vomiting, diarrhea, decreased appetite/weight loss, hypothyroidism, palmar-plantar erythrodysesthesia syndrome, musculoskeletal pain, stomatitis, and proteinuria. These adverse reactions may be managed with a combination of concomitant supportive care medications and judicious lenvatinib dose modifications. This article provides context and guidance for the recognition and management of adverse reactions in patients receiving lenvatinib plus pembrolizumab.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Endometrial Neoplasms , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Endometrial Neoplasms/drug therapy , Female , Humans , Phenylurea Compounds/therapeutic use , QuinolinesABSTRACT
PURPOSE: Patients with advanced endometrial carcinoma have limited treatment options. We report final primary efficacy analysis results for a patient cohort with advanced endometrial carcinoma receiving lenvatinib plus pembrolizumab in an ongoing phase Ib/II study of selected solid tumors. METHODS: Patients took lenvatinib 20 mg once daily orally plus pembrolizumab 200 mg intravenously once every 3 weeks, in 3-week cycles. The primary end point was objective response rate (ORR) at 24 weeks (ORRWk24); secondary efficacy end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Tumor assessments were evaluated by investigators per immune-related RECIST. RESULTS: At data cutoff, 108 patients with previously treated endometrial carcinoma were enrolled, with a median follow-up of 18.7 months. The ORRWk24 was 38.0% (95% CI, 28.8% to 47.8%). Among subgroups, the ORRWk24 (95% CI) was 63.6% (30.8% to 89.1%) in patients with microsatellite instability (MSI)-high tumors (n = 11) and 36.2% (26.5% to 46.7%) in patients with microsatellite-stable tumors (n = 94). For previously treated patients, regardless of tumor MSI status, the median DOR was 21.2 months (95% CI, 7.6 months to not estimable), median PFS was 7.4 months (95% CI, 5.3 to 8.7 months), and median OS was 16.7 months (15.0 months to not estimable). Grade 3 or 4 treatment-related adverse events occurred in 83/124 (66.9%) patients. CONCLUSION: Lenvatinib plus pembrolizumab showed promising antitumor activity in patients with advanced endometrial carcinoma who have experienced disease progression after prior systemic therapy, regardless of tumor MSI status. The combination therapy had a manageable toxicity profile.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Endometrial Neoplasms/drug therapy , Phenylurea Compounds/therapeutic use , Quinolines/therapeutic use , Aged , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Disease Progression , Endometrial Neoplasms/genetics , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Female , Humans , Microsatellite Instability , Middle Aged , Phenylurea Compounds/adverse effects , Progression-Free Survival , Quinolines/adverse effects , Time FactorsABSTRACT
Sarcomas comprise 1% of adult tumors and are very heterogeneous. Long-lasting and cumulative treatment side-effects detract from the (progression-free) survival benefit of treatment. Therefore, it is important to assess treatment effectiveness in terms of patient-reported outcomes (PROs), including health-related quality of life (HRQoL) as well. However, questionnaires capturing the unique issues of sarcoma patients are currently lacking. Given the heterogeneity of the disease, the development of such an instrument may be challenging. The study aims to (1) develop an exhaustive list of all HRQoL issues relevant to sarcoma patients and determine content validity; (2) determine a strategy for HRQoL measurement in sarcoma patients. We will conduct an international, multicenter, mixed-methods study (registered at clinicaltrials.gov: NCT04071704) among bone or soft tissue sarcoma patients ≥18 years, using EORTC Quality of Life Group questionnaire development guidelines. First, an exhaustive list of HRQoL issues will be generated, derived from literature and patient (n = 154) and healthcare professional (HCP) interviews (n = 30). Subsequently, another group of sarcoma patients (n = 475) and HCPs (n = 30) will be asked to rate and prioritize the issues. Responses will be analyzed by priority, prevalence and range of responses for each item. The outcome will be a framework for tailored HRQoL measurement in sarcoma patients, taking into account sociodemographic and clinical variables.
ABSTRACT
PURPOSE: This study estimated time without symptoms or toxicity (TWiST) with niraparib compared with routine surveillance (RS) in the maintenance treatment of patients with recurrent ovarian cancer. PATIENTS AND METHODS: Mean progression-free survival (PFS) was estimated for niraparib and RS by fitting parametric survival distributions to Kaplan-Meier data for 553 patients with recurrent ovarian cancer who were enrolled in the phase III ENGOT-OV16/NOVA trial. Patients were categorized according to the presence or absence of a germline BRCA mutation-gBRCAmut and non-gBRCAmut cohorts. Mean time with toxicity was estimated based on the area under the Kaplan-Meier curve for symptomatic grade 2 or greater fatigue, nausea, and vomiting adverse events (AEs). Time with toxicity was the number of days a patient experienced an AE post-random assignment and before disease progression. TWiST was estimated as the difference between mean PFS and time with toxicity. Uncertainty was explored using alternative PFS estimates and considering all symptomatic grade 2 or greater AEs. RESULTS: In the gBRCAmut and non-gBRCAmut cohorts, niraparib treatment resulted in a mean PFS benefit of 3.23 years and 1.44 years, respectively, and a mean time with toxicity of 0.28 years and 0.10 years, respectively, compared with RS. Hence, niraparib treatment resulted in a mean TWiST benefit of 2.95 years and 1.34 years, respectively, compared with RS, which is equivalent to more than four-fold and two-fold increases in mean TWiST between niraparib and RS in the gBRCAmut and non-gBRCAmut cohorts, respectively. This TWiST benefit was consistent across all sensitivity analyses, including modeling PFS over 5-, 10-, and 15-year time horizons. CONCLUSION: Patients who were treated with niraparib compared with RS experienced increased mean TWiST. Thus, patients who were treated with niraparib in the ENGOT-OV16/NOVA trial experienced more time without symptoms or symptomatic toxicities compared with control.
Subject(s)
Indazoles/administration & dosage , Neoplasm Recurrence, Local , Ovarian Neoplasms/drug therapy , Piperidines/administration & dosage , Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Disease Progression , Drug Administration Schedule , Female , Germ-Line Mutation , Humans , Indazoles/adverse effects , Maintenance Chemotherapy , Ovarian Neoplasms/genetics , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Piperidines/adverse effects , Poly(ADP-ribose) Polymerase Inhibitors/adverse effects , Progression-Free Survival , Randomized Controlled Trials as Topic , Risk Assessment , Risk Factors , Time FactorsABSTRACT
Background Sorafenib is a potent targeted-therapy that blockades angiogenesis and has demonstrated activity against some sarcoma subtypes. Preclinical studies suggested that treatment with sorafenib plus cytotoxic agents could result in additive efficacy. Methods Patients with advanced soft tissue sarcoma, with or without anthracycline pretreatment were included. Patients received oral sorafenib 400 mg twice daily starting on Day +2, ifosfamide 2.0 g/m2 iv infusion lasting 4 h on days 1, 2 and 3 with concurrent mesna 400 mg/m2 every three weeks until disease progression or unacceptable toxicity or up to a maximum of 6 cycles of ifosfamide (sorafenib could be continued until progressive disease or unacceptable toxicity). Primary objective was progression-free rate (PFR) at 3 and 6 months; secondary objectives were overall response rate (ORR), Progression-free survival (PFS), Overall survival (OS) and safety. This article reports the phase II part of a phase I/II clinical trial. Results Thirty-five patients were enrolled. PFR at 3 and 6 months was 66% (95% CI 48-81) and 37% (95% CI 22-55). Six patients (17%) achieved partial response and 17 (49%) stable disease. Median PFS was 4.8 months (CI 95% 1.94-6.36) and overall survival 16.2 months (95% CI 8.75-NA). Conclusion Treatment with sorafenib plus ifosfamide achieved a significant clinical benefit with an acceptable safety profile in patients with advanced soft tissue sarcoma resistant to anthracyclines, which warrants a more detailed study in randomized clinical trials.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ifosfamide/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Sarcoma/drug therapy , Soft Tissue Neoplasms/drug therapy , Sorafenib/therapeutic use , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Disease-Free Survival , Female , Humans , Ifosfamide/adverse effects , Intention to Treat Analysis , Male , Middle Aged , Neoplasm Staging , Patient Compliance , Protein Kinase Inhibitors/adverse effects , Sarcoma/pathology , Soft Tissue Neoplasms/pathology , Sorafenib/adverse effects , Spain , Treatment Outcome , Young AdultABSTRACT
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Subject(s)
Humans , Carcinoma, Medullary/diagnosis , Thyroid Neoplasms/drug therapy , /therapeutic use , Treatment OutcomeSubject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Medullary/drug therapy , Indoles/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrroles/therapeutic use , Thyroid Neoplasms/drug therapy , Aged , Carcinoma, Medullary/radiotherapy , Carcinoma, Medullary/secondary , Carcinoma, Medullary/surgery , Combined Modality Therapy , Hand-Foot Syndrome/etiology , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Male , Middle Aged , Neck Dissection , Neoplasms, Second Primary/drug therapy , Neoplasms, Second Primary/surgery , Sunitinib , Thrombocytopenia/chemically induced , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/surgery , ThyroidectomyABSTRACT
OBJECTIVES: Gemcitabine has well-recognized activity in the treatment of ovarian cancer. Fixed-dose rate (FDR) delivery has been proposed as a more rationale way to administer gemcitabine, to avoid saturation of the enzyme that catalyzes its intracellular transformation into the active metabolites, difluorodeoxycitidine biphosphate, and triphosphate. Our aim was to assess clinical activity of gemcitabine delivered by FDR infusion in patients with platinum resistant ovarian cancer. MATERIALS AND METHODS: Patients with platinum-resistant ovarian cancer received gemcitabine 1000 mg/m(2) over 120 minutes on days 1 and 8 of each cycle. Cycles were repeated every 3 weeks, and up to 6 cycles were delivered. RESULTS: Forty-eight patients were included in the study. Among 41 patients evaluable for response, 9 clinical responses (1 complete response and 8 partial responses) were observed, achieving a global response rate of 22%. Grade 3 to 4 hematological toxicity consisted of anemia (15% of patients), neutropenia (24%), and thrombopenia (10%). One patient died due to septic shock. The main grade 3 to 4 nonhematological toxicity was asthenia (7 patients, 17%). CONCLUSION: Activity of gemcitabine administered by FDR infusion in patients with platinum-resistant ovarian cancer seems similar to that achieved using 30-minute infusions, with higher toxicity.
Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Deoxycytidine/analogs & derivatives , Drug Resistance, Neoplasm , Organoplatinum Compounds/adverse effects , Ovarian Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , Adenocarcinoma, Clear Cell/drug therapy , Adenocarcinoma, Clear Cell/secondary , Adenocarcinoma, Mucinous/drug therapy , Adenocarcinoma, Mucinous/secondary , Adult , Aged , Aged, 80 and over , Carcinoma, Endometrioid/drug therapy , Carcinoma, Endometrioid/secondary , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/secondary , Deoxycytidine/administration & dosage , Female , Humans , Infusions, Intravenous , Middle Aged , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/pathology , Prognosis , Ribonucleotide Reductases/antagonists & inhibitors , Survival Rate , GemcitabineABSTRACT
Cardiac metastases are more frequent than primaryheart neoplasias. Nearly any malignant tumourmay metastasize to the heart, but the most commonare carcinomas rather than sarcomas. We report thecase of a patient who presented with heart metastasis6 years after resection of an uterine leiomyosarcoma.The patient died thirty months after surgicalresection without evidence of cardiac recurrence.Although cardiac metastases from uterine leiomyosarcomaare exceptional, they should be suspectedin the presence of suggestive symptoms, since theycan be associated with long survival after surgicaltreatment
No disponible
Subject(s)
Female , Middle Aged , Humans , Leiomyosarcoma/pathology , Heart Neoplasms/pathology , Neoplasm Metastasis/pathology , Heart Neoplasms/secondaryABSTRACT
INTRODUCTION: CNS metastases mean a great challenge. It has been suggested that the brain metastases incidence could be high in metastasic breast cancer patients receiving trastuzumab based-therapies. MATERIAL AND METHODS: We performed a descriptive analysis of our experience in this setting. 86 patients met the criteria (From Oct/99 to Oct/03). RESULTS: CNS progression occurred in 17 patients (19.5%). Mean age of CNS progression disease patients was 45.4 years while mean age for all the patients was 50.5 years. Response rate for the entire group of patients was: OR 39.7%; CB (OR + SD) 69%. Response rate to trastuzumab based-therapy was OR 82.4% and CB 88.2 at the time of CNS progression. Median time from the start of trastuzumab therapy up to the CNS progression was 10 months. OS was 23.4 weeks. CONCLUSIONS: The incidence of CNS involvement is high in young metastasic breast cancer women responding to trastuzumab-based therapies. This may lead to prophylactic cranial irradiation strategies or to the early detection in asymptomatic patients to improve surgery or radiosurgery results in these patients.
Subject(s)
Adenocarcinoma/secondary , Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Brain Neoplasms/secondary , Breast Neoplasms/drug therapy , Carcinoma/secondary , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Adenocarcinoma/radiotherapy , Adenocarcinoma/surgery , Adult , Antibodies, Monoclonal, Humanized , Brain Neoplasms/drug therapy , Brain Neoplasms/epidemiology , Brain Neoplasms/radiotherapy , Brain Neoplasms/surgery , Breast Neoplasms/chemistry , Breast Neoplasms/pathology , Carcinoma/chemistry , Carcinoma/drug therapy , Carcinoma/epidemiology , Cranial Irradiation , Disease Progression , ErbB Receptors/analysis , ErbB Receptors/antagonists & inhibitors , Female , Humans , Incidence , Middle Aged , Neoplasm Proteins/analysis , Neoplasm Proteins/antagonists & inhibitors , Receptor, ErbB-4 , Retrospective Studies , Survival Analysis , Trastuzumab , Treatment OutcomeABSTRACT
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Introduction. CNS metastases mean a great challenge.It has been suggested that the brain metastasesincidence could be high in metastasic breastcancer patients receiving trastuzumab based-therapies.Material and methods. We performed a descriptiveanalysis of our experience in this setting. 86 patientsmet the criteria (From Oct/99 to Oct/03).Results. CNS progression occurred in 17 patients(19.5%). Mean age of CNS progression disease patientswas 45.4 years while mean age for all the patientswas 50.5 years. Response rate for the entiregroup of patients was: OR 39.7%; CB (OR + SD)69%. Response rate to trastuzumab based-therapywas OR 82.4% and CB 88.2 at the time of CNS progression.Median time from the start of trastuzumabtherapy up to the CNS progression was 10 months.OS was 23.4 weeks.Conclusions. The incidence of CNS involvement ishigh in young metastasic breast cancer women respondingto trastuzumab-based therapies. This maylead to prophylactic cranial irradiation strategies orto the early detection in asymptomatic patients toimprove surgery or radiosurgery results in these patients
