Favorable phase I results justified this pilot phase II study to assess the efficacy of docetaxel/curcumin in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (CRPC).
...Thirty patients with progressing CRPC and a rising prostate-specific antigen (PSA) received docetaxel/prednisone in standard conditions for 6 cycles in combination with per os curcumin, 6,000 mg/day (day -4 to day +2 of docetaxel). The co-primary endpoint was the overall response rate determined by PSA and target assessments. An ancillary study assessed the seric values of chromogranin A (CgA) and neuron-specific enolase (NSE).
Twenty-six patients received the scheduled treatment, 2 progressed and 2 died before the end of treatment. A PSA response was observed in 59% of patients (14% of PSA normalization) and achieved within the first three cycles for 88% of responders. Partial response was reached for 40% of evaluable patients. The regimen was well tolerated, and no adverse event was attributed to curcumin. Twenty patients were 100% curcumin compliant. The PSA level and objective response rate were not correlated with the serum values of CgA and NSE.
This study produced additional data on curcumin as a treatment for cancer, with a high response rate, good tolerability and patient acceptability, justifying the interest to conduct a randomized trial.
The phase II AVASTEM trial explored the impact of chemotherapy-bevacizumab combination on breast cancer stem cells in the neoadjuvant setting. We aimed to identify biological features associated with ...preoperative chemotherapy efficacy and prognosis by analyses of circulating tumor cells (CTCs) and bevacizumab pharmacokinetics (PK). The main objective was to assess the prognostic (relapse-free survival and overall survival) and predictive (pathological complete response, pCR) values of CTCs (CellSearch technology) and bevacizumab PK (ELISA). Seventy-five patients were included. Out of them 50 received bevacizumab-chemotherapy and 25 received chemotherapy alone. CTC results were available for 60 patients and PK data for 29 patients in the experimental arm. The absence of CTC at inclusion was correlated to better outcome. Five-years overall survival (OS) was 91% for CTC-negative patients vs. 54% for CTC-positive cases (HR = 6.21; 95%CI (1.75-22.06),
= 0.001, log-rank test). Similar results were observed for RFS with 5 y-RFS of 78% vs. 44% (HR = 3.51; 95%CI (1.17-10.52),
= 0.017, log-rank test). However, CTC status at baseline was not predictive of pCR (
= 0.74). CTC status after one cycle was not a significant prognostic factor (HR = 1.56; 95%CI (0.19-12.67);
= 0.68 for OS and HR = 2.76; 95%CI (0.60-12.61);
= 0.17 for RFS, log-rank test). Bevacizumab serum levels could not predict pCR and survival. PK values were not associated with treatment-related toxicities. In conclusion, CTCs detection at baseline is a prognostic marker for breast cancer receiving a neoadjuvant chemotherapy-bevacizumab combination independently of tumor response.
Background
Cancer management in the elderly is often considered as suboptimal, highly variable, and rarely evidence-based. Data are needed to understand decision-making processes in this population.
...Materials and methods
A survey was performed in France to describe decision-making in gynaecologic patients over 70. It followed a three-step method: (1) 101 representative physicians questioned about treatment decision criteria; (2) simplified individual data were collected; (3) as well as detailed data patients receiving chemotherapy. This analysis refers to breast cancer subgroup of patients.
Results
Main decision criteria were performance status, comorbidities, and renal function. In adjuvant setting, the main concern was life expectancy, whereas it was quality of life in metastatic setting. Of the 631 patients entered in the simplified analysis, 41% had been evaluated by a geriatrician, 67% received chemotherapy. In the detailed analysis, patients older than 75 were more likely to receive a monochemotherapy and to be treated with weekly/divided dose. In adjuvant setting, respectively, 19, 55, and 26% of the patients were treated with regimen validated in the elderly, validated in a younger population, and not validated. A G-CSF was prescribed in 48% of the patients, as primary prophylaxis in 78 and in 41% of patients with a risk of febrile neutropenia < 10%.
Conclusion
Geriatric covariates become an increasing concern in the decision-making process. This survey also suggests an insufficient use of validated chemotherapy regimens. To date, age remains a risk factor for heterogeneity in oncologic practice justifying a persistent effort for elaborating and disclosing specific recommendations.
Abstract PET is a crucial technique in molecular imaging, allowing in vivo assessment and localization of pathological processes, thanks to its ability to detect very small amounts of radioactive ...molecules. This is of particular interest in oncology where abnormal metabolism or synthesis in tumor cells but also various tumor characteristics can be studied using this nuclear medicine technique. FDG is currently the most widely used tracer, nowadays essential in the management of various malignancies, with large applications in diagnosis, initial assessment, therapy monitoring, and recurrence detection. The combination of anatomical information provided by PET/CT further increased its interest. Beyond its spread use in daily practice, future applications of PET will involve other tracers than FDG and develop research applications in humans as well as in small animals.
This trial evaluated the efficacy of maintenance erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, after first-line chemotherapy.
Eligible patients had high-risk ...International Federation of Gynecology and Obstetrics stage I or stage II to IV epithelial ovarian, primary peritoneal, or fallopian tube cancer and were not selected for EGFR expression. All patients underwent first-line platinum-based chemotherapy (CT) and showed no signs of progression at the end of CT. Patients were randomly assigned to maintenance erlotinib 150 mg orally daily for 2 years or to observation. EGFR immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and mutation analyses were performed in 318 patients.
Between October 2005 and February 2008, 835 patients were randomly assigned (median follow-up, 51 months). Twenty-six percent of the patients stopped erlotinib as a result of adverse effects (of these, 67% were due to rash). For erlotinib and observation, respectively, the median progression-free survival was 12.7 and 12.4 months (hazard ratio HR, 1.05; 95% CI, 0.90 to 1.23), and the median overall survival was 50.8 and 59.1 months (HR, 0.99; 95% CI, 0.81 to 1.20 months), respectively. No subgroup could be identified with improved effect of erlotinib, based on IHC or FISH for EGFR, or mutations in genes related to the EGFR pathway, or on rash during erlotinib therapy. However, patients with a positive FISH EGFR score had a worse overall survival (46.1 months) than those with a negative score (67.0 months; HR, 1.56; 95% CI, 1.01 to 2.40; P = .044). Global health/quality-of-life scores showed a significant difference during the first year (P = .0102) in favor of the observation arm.
Maintenance erlotinib after first-line treatment in ovarian cancer did not improve progression-free or overall survival.
Age is a risk factor for chemo-induced febrile neutropenia (FN). According to ASCO guidelines, granulocyte colony-stimulating factor (G-CSF) use should be considered for regimens leading to a 10- to ...20-percent risk of FN.
A survey was undertaken describing the prescription of G-CSF in routine practices by 101 French physicians for 791 patients ≥70 years, having breast or gynaecological cancers, and receiving chemotherapy.
G-CSF was prescribed in 51% of the cases. A primary prophylaxis was prescribed in 90%, 59% and 36% of patients receiving regimens presenting a FN-risk of ≥20%, 10-20% and <10%, respectively. Covariates associated with the use of G-CSF were adjuvant chemotherapy, 3- or 4-weekly regimens, and geriatric assessment. Validated risk factors of FN were rarely considered.
The prescription of G-CSF was multi-factorial. The estimation of FN risk was mainly based on physician's experience, explaining differences between guidelines and routine practice.
To determine the possible effect of two homeopathic medicines, Ruta graveolens 5CH and Rhus toxicodendron 9CH, in the prevention of aromatase inhibitor (AI) associated joint pain and/or stiffness in ...women with early, hormone-receptor positive, breast cancer.
This prospective, unrandomized observational study was carried out between April and October 2014. Women were recruited in two groups, according to which of the two study centres they attended: one receiving homeopathy in addition to standard treatment (group H) and a control group, receiving standard treatment (group C). All women were treated with an AI. In addition, women in group H also took Ruta graveolens 5CH and Rhus toxicodendron 9CH (5 granules, twice a day) up to 7 days before starting AI treatment. The homeopathic medicines were continued for 3 months. Demographic and clinical data were recorded using a self-assessment questionnaire at inclusion (T0) and 3 months (T3). Primary evaluation criteria were the evolution of scores for joint pain and stiffness, the impact of pain on sleep and analgesic consumption in the two groups after 3 months of treatment.
Forty patients (mean age 64.9±8.1 years) were recruited, 20 in each group. Two-thirds of the patients had joint pain before starting AI treatment. There was a significant difference in the evolution of mean composite pain score between T0 and T3 in the two groups (-1.3 in group H vs. +3.4 in group C; p=0.0001). The individual components of the pain score (frequency, intensity and number of sites of pain) also decreased significantly in group H. Nine patients in group C (45%) vs. 1 (5%) in group H increased their analgesic consumption between T0 and T3 (p=0.0076). After 3 months of treatment, joint pain had a worse impact on sleep in patients in group C (35% vs. 0% of patients; p=0.0083). The differences observed in the evolution of morning and daytime stiffness between the two groups were smaller (p=0.053 and p=0.33, respectively), with the exception of time necessary for the disappearance of morning stiffness which was greater in group C (37.7±23.0 vs. 17.9±20.1 min; p=0.0173).
These preliminary results suggest that treatment with Ruta graveolens 5CH and Rhus toxicodendron 9CH may decrease joint pain/stiffness in breast cancer patients treated with AIs. A larger-scale randomized study is required to confirm these results.
Neoadjuvant chemotherapy (NACT) allows for a more frequent use of breast-conservative surgery; it is also an in vivo model of individual tumor sensitivity which permits to determine new prognostic ...factors to personalize the therapeutic approach.
Between 2000 and 2012, 318 patients with primary invasive breast cancer were treated with a median of 6 cycles of NACT; they received either an anthracycline-based FEC 100 protocol (31.1%), or anthracyclines + taxanes (53.5%), with trastuzumab if indicated (15.4%).
After a median follow-up of 44.2 months, the pathological complete response rate according to the classification of Chevallier et al. Am J Clin Oncol 1993;16:223-228 was 19.3%, and overall (OS) and disease-free survival (DFS) at 10 years were 60.2 and 69.6%, respectively. Univariate analyses demonstrated that the Residual Disease in Breast and Nodes (RDBN) index was the most significant prognostic factor for OS (p = 0.0082) and DFS (p = 0.0022), and multivariate analyses mainly revealed that the residual tumor size, residual involved node number and post-chemotherapy Scarff-Bloom-Richardson (SBR) grading were the most significant prognostic factors.
In a cohort of patients who were all homogeneously treated with some of the most common drugs for breast cancer, we demonstrate that NACT may provide additional prognostic factors and confirm the RDBN index. As this index allows for the prediction of survival with different breast cancer subtypes, we suggest that it should be calculated routinely to help clinicians to select patients who need adjuvant treatments.
Purpose
Anemia affects most patients treated for cancer by chemotherapy. It is a known major contributor to fatigue and loss of quality of life and is likely to have a negative effect on prognosis ...and mortality from cancer. The main purpose of this study was to characterize the management of anemia and iron deficiency in a French oncology day-care center.
Methods
A retrospective study was conducted between May and November 2012 in the oncology day unit of the Jean Godinot Cancer Center (France). The 133 patients included were all over the age of 18 and being treated by chemotherapy and had mild, moderate, or severe anemia.
Results
Over half (58 %) the patients were shown to be receiving no specific treatment for anemia. Iron balance was assessed in 71 patients and iron deficiency diagnosed in 37. Stepwise logistic regression showed that patients with severe to moderate anemia were nearly four times more likely to have an iron balance assessment than those with mild anemia (OR, 3.78; 95 % CI, 1.84–7.76;
P
= 0.0003). Classical logistic regression shows that older patients (≥70) are three times less likely to have an iron balance assessment than patients <70 years (OR, 0.32; 95 % CI, 0.12–0.86;
P
= 0.06).
Conclusion
An ideal medical setting for the management of anemia and iron deficiency, and the associated quality-of-life concerns, has yet to be defined for patients with cancer. Screening and treatment of mild to moderate anemia are inadequate, despite the advent of erythropoiesis-stimulating agents. Large scale, multicenter studies are required to define a clear medical framework for the management of anemia and iron deficiency.
Gastropleural fistula frequently occurs as a complication of peptic ulcer, surgery, or as a consequence of trauma or malignant disease. Here, we report the case of a 59- year old woman with a history ...of metastatic ovarian cancer, who was hospitalized with a suspected diagnosis of pneumonia. During hospitalization, a left pneumothorax was found requiring a thoracic drain. After drainage, chest X-ray showed a massive pleural effusion and thoracic Computed Tomography (CT) scan demonstrated a gastropleural fistula. Because of the patient's clinical condition, surgery was not possible and the patient was treated with supportive care. This case report illustrates a rare complication of an oncological disease which could be treated, in optimal clinical conditions, with a surgical approach.
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