Evaluation of quality of life and emotional distress in endometrial cancer patients: a 2-year prospective, longitudinal study.

OBJECTIVES: The aim of the study was to prospectively, and longitudinally assess Quality of Life (QoL) and emotional distress in a large series of endometrial cancer (EC) patients. METHODS: Global Health Status of the EORTC QLQ-C30 (GHS), the EORTC QLQ-CX24 (CX24), and the Hospital Anxiety and Depression Scale (HADS) questionnaires were administered at diagnosis, and after 3, 6, 12, and 24months since surgery. The Generalized Linear Model and the Between Subject test were used to analyze QoL changes over time, and the association between factors and patient QoL. RESULTS: GHS scores improved over time, although the statistical significance was not reached. Worse lymphedema scores were documented worsened over time with a trend to recover at the 12- and 24month evaluation (p-value=0.028). Scores for Menopausal Symptoms (MS) dramatically worsened over time reaching a 38.5 difference of mean±SE compared to baseline (p-value=0.011). Sexual Activity (SxA) scores improved until the 12-month evaluation (p-value=0.048), and showed a return to baseline levels at the last assessment (p-value=0.025). A significant improvement of anxiety scores was documented at the 3-month evaluation, and persisted over time. In multivariate analysis, unmarried status was associated with poor scores for sexual activity, while living with someone was associated with worse MS scores. CONCLUSIONS: Menopausal and lymphedema symptoms heavily affect QoL in EC patients. Since socio-demographic features play a major role in deteriorating SxA and MS, psycho-social intervention and patient education should be considered as an integral part of EC patient treatment.

Long-term prospective longitudinal evaluation of emotional distress and quality of life in cervical cancer patients who remained disease-free 2-years from diagnosis.

BACKGROUND: A long-term prospective assessment of QoL in cervical cancer patients is still lacking. Here, we provide the first 2-years prospective, longitudinal study evaluating emotional distress and QoL in early stage (ECC) and locally advanced (LACC) cervical cancer patients who remained disease-free 2-years from diagnosis. METHODS: The questionnaires: Hospital Anxiety and Depression Scale (HADS), Global Health Status items of EORTC QLQ-C30 (GHS), and EORTC QLQ-CX24 (CX24) have been administered by a dedicated team of psycho-oncologists, administered at baseline, and after 3, 6, 12 and 24 months from surgery The Generalized Linear Model for repeated measure was used to analyze modifications of QoL measures over time. RESULTS: In both groups, an early reduction of the percentage of patients with anxiety levels ≥11 was observed at the 3-month evaluation (ECC: 25.7% at baseline Vs 14.7% after 3 months, p value=0.001; LACC: 22.2% at baseline Vs 15.4% after 3 months, p value=0.001). Despite this favorable trend, after 2 years from diagnosis, 11.9% of ECC and 15.6% of LACC patients still showed an anxiety score ≥11. No significant changes over time were observed in term of Depression levels. Focusing on QoL issues, mean GHS and Sexual Activity scores showed an improvement over time in both groups compared to baseline (GHS: 5.7% difference for ECC, p value=0.001, and 11.0% in LACC, p value=0.001; SXA: 13.9% difference for ECC, p value=0.001; and 6.1% in LACC, p value=0.008). On the other hand, Body Image mean scores were significantly impaired by chemoradiation administration in LACC patients, without long-term recovery (7.5% difference, p value=0.001). Finally, in both groups, lymphedema (LY) and menopausal symptoms (MS) showed an early worsening which persisted 2-year after surgery (LY: 19.5% difference for ECC, p value=0.014, and 27.3% in LACC, p value=0.001; MS: 14.4% difference for ECC, p value=0.004, and 16.0% in LACC, p value=0.002). CONCLUSIONS: Despite a significant improvement over time, elevated anxiety levels are still detectable at 24 months after surgery in approximately 10% of cervical cancer patients. Much more attention should be focused on surgical/medical approaches able to minimize the negative impact of lymphedema and menopausal symptoms on QoL.

Quality of life and emotional distress in early stage and locally advanced cervical cancer patients: a prospective, longitudinal study.

OBJECTIVES: This prospective, longitudinal study investigates QoL issues and emotional distress in early stage cervical cancer (ECC) patients undergoing radical surgery (RS) and in locally advanced cervical cancer (LACC) patients triaged to chemoradiation (CT/RT) followed by RS. METHODS: The Global Health Status scale of EORTC QLQ-C30 (GHS), the EORTC QLQ-CX24 (CX24) and the Hospital Anxiety and Depression Scale (HADS) questionnaire were administered at baseline, and after 3, 6, and 12 months from surgery. For LACC patients QoL assessment was also performed after CT/RT. Statistical analysis was performed by the ANOVA for repeated measures and the Between Subject test. RESULTS: In ECC and LACC patients, the GHS scores improved over time (5.5% difference in mean scores compared to baseline in ECC, and 7.0% difference in mean score compared to baseline in LACC patients). An early worsening of lymphedema scores was documented in ECC cases (14.6% difference in mean values compared to baseline, p value=0.001), and in LACC patients (difference up to 28.3% of mean values, value=0.0001). Menopausal symptoms persistently worsened over time reaching >15% difference of mean values compared to baseline in both groups. Sexual activity scores markedly improved both in ECC and LACC patients (difference of mean score values compared to baseline was 16.5% in ECC, and 6.7% in LACC patients). Both ECC and LACC patients experienced an improvement of anxiety scores. CONCLUSIONS: Lymphedema and menopausal symptoms were the most disabling treatment-related sequelae; the amount of QoL issues and their multifaceted aspects require the cooperation of multidisciplinary teams.

Phase II study of the combination carboplatin plus celecoxib in heavily pre-treated recurrent ovarian cancer patients.

BACKGROUND: Cyclooxygenase-2 overexpression is associated with poor outcome and resistance to platinum-based chemotherapy in ovarian cancer. We evaluated the antitumor activity and safety of the combination carboplatin plus the COX-2 inhibitor celecoxib in recurrent heavily-treated OC patients. METHODS: Patients were administered oral celecoxib (400 mg/day) in combination with intravenous carboplatin (AUC5, q28). A Simon's two-stage design was employed. RESULTS: 45 patients were enrolled: 23 (51.1%) presented platinum-resistance, and 27 (60%) had received at least 3 prior regimens for recurrence. The response rate was 28.9% with 3 complete and 10 partial responses (median duration of response = 6 months). Only one (0.4%) G4 non-febrile neutropenia was observed; G3 neutropenia, anemia, or thrombocytopenia, were observed in 2.5%, 1.7%, and 1.7% of the cycles, respectively. G3-4 vomiting was reported in only 1.7%, and 0.4% of the cycles were associated with G3 dyspepsia or diarrhea or constipation. Only one patient experienced G3 hypertension associated to G2 hypersensitivity reaction. No differences in baseline versus post-treatment Quality of Life scores were observed. Median progression free survival and overall survival were 5 and 13 months, respectively. CONCLUSIONS: Celecoxib combined with carboplatin showed promising activity and it is well tolerated in heavily-treated recurrent ovarian cancer patients. TRIAL REGISTRATION NUMBER: NCT01124435 (ClinicalTrials.gov Identifier) and 935/03 (study ID numbers).

Novel VEGF-independent strategies targeting tumor vasculature: clinical aspects.

In the last decades, the active research in the field of tumor angiogenesis has led to the development of a class of agents providing an effective inhibition of neo-vessel formation through the blockade of VEGF related pathways. More recently, the identification of other factors involved in tumor angiogenesis, such as platelet-derived growth factor, fibroblast growth factor and Angiopoietins has emphasized the need to develop agents targeting multiple pro-angiogenic pathways. Although contrasting data are currently available regarding the clinical efficacy of multikinase inhibitors, Sunitinib, Sorafenib and Pazopanib have displayed encouraging results, and have fuelled further evaluations. Moreover, definitive data are also eagerly awaited regarding the clinical role of angiopoietins inhibitors. On the other hand, the existence of morphological, functional and architectural differences between normal and tumor vasculature has provided solid basis for the development of a novel class of compounds, known as Vascular Disrupting Agents (VDAs) able to selectively disrupt existing tumor vessels. After initial concerns related to the potential development of severe cardiovascular toxicities, further clinical investigations have shown a safe toxicity profile for these agents. Moreover, despite the discouraging data on dolostatin-10 and ASA404, several VDAs, including CAP4, Ombrabulin and Pinabulin have already shown promising activity in phase I-II clinical trials warranting more advanced evaluations. In this review we aimed at summarizing the most relevant VEGF-independent strategies targeting tumor vasculature, focusing on the clinical development of novel antiangiogenic agents including multikinase and angiopoietins inhibitors as well as VDAs.

Solitary pancreatic lymph node metastasis from carcinoma of the breast: case report.

BACKGROUND: We report the first case of isolated pancreatic lymph node recurrence in a locally advanced breast cancer patient. CASE: A 41-year old woman underwent radical mastectomy according to Madden and removal of axillary lymph nodes for multicentric infiltrating ductal carcinoma pathologically staged as pT2N2M0. After six years from primary diagnosis, and four years from the diagnosis of lung recurrence, she developed an isolated metastatic lesion to pancreatic lymph node. After surgical excision of metastasis, hormone therapy with Exemestane was begun. At 16 months of follow-up, the patient appears free of disease. CONCLUSION: Because metastatization to visceral organ carries a very unfavorable prognosis, we think that the clinical significance of the elevation of CA 15.3 serum levels in the early detection of recurrence and in monitoring metastatic disease during follow-up, should be not underestimated.

Pharmacotherapy of cervical cancer.

IMPORTANCE OF THE FIELD: Cervical cancer (CC) remains an important health problem. It is the second most frequent malignancy in women worldwide, with one-third of patients dying from pharmacoresistant disease. AREAS COVERED IN THIS REVIEW: We reviewed pharmacotherapy approaches in the medical and multidisciplinary management of CC and conducted a systematic search of Pubmed for clinical trials, reviews and meta-analysis published in the last 20 years. Abstracts of the American Society of Clinical Oncology, European Society of Gynecological Oncology and International Gynecologic Cancer Society were also searched, together with the US National Institutes of Health clinical trial database. WHAT THE READER WILL GAIN: The state-of-the art of cytotoxic and biologically targeted therapies in early, locally advanced and metastatic/recurrent CC is discussed. TAKE HOME MESSAGE: Until recently, the role of pharmacotherapy in CC was restricted to palliation of advanced/metastatic or recurrent disease. During the past two decades, this reluctant attitude towards chemotherapy has been modified after a series of randomized trials demonstrated its beneficial contribution as an adjunct to radiotherapy or surgery in early and locally advanced CC. Moreover, new combinations of cytotoxics, together with novel molecular target agents, open new perspectives in the treatment of primary and recurrent CC.

Pegylated liposomal doxorubicin in the management of ovarian cancer.

Among the pharmaceutical options available for treatment of ovarian cancer, much attention has been progressively focused on pegylated liposomal doxorubicin (PLD), whose unique formulation, which entraps conventional doxorubicin in a bilayer lipidic sphere surrounded by a polyethylene glycol layer, prolongs the persistence of the drug in the circulation and potentiates intratumor drug accumulation. These properties enable this drug to sustain its very favorable toxicity profile and to be used safely in combination with other drugs. PLD has been already approved for treatment of advanced ovarian cancer patients failing first-line platinum-based treatment. Moreover, phase III trials have been already completed, and results are eagerly awaited, which hopefully will expand the range of PLD clinical application in this neoplasia both in front-line treatment, and in the salvage setting in combination with other drugs. Moreover, attempts are continuing to enable this drug to be combined with novel cytotoxic drugs and target-based agents. This review aims at summarizing the available evidence and the new perspectives for the clinical role of PLD in the management of patients with epithelial ovarian cancer.