Impact of geriatric assessment for the therapeutic decision-making of breast cancer: results of a French survey. AFSOS and SOFOG collaborative work.

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.

The New Combination Docetaxel, Prednisone and Curcumin in Patients with Castration-Resistant Prostate Cancer: A Pilot Phase II Study.

OBJECTIVES: 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). METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Management of anemia and iron deficiency in a cancer center in France.

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.

Treatment with Ruta graveolens 5CH and Rhus toxicodendron 9CH may reduce joint pain and stiffness linked to aromatase inhibitors in women with early breast cancer: results of a pilot observational study.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Is it important to adapt neoadjuvant chemotherapy to the visible clinical response? An open randomized phase II study comparing response-guided and standard treatments in HER2-negative operable breast cancer.

BACKGROUND: Neoadjuvant treatment provides a unique opportunity to evaluate individual tumor sensitivity. This study evaluated whether a response-guided strategy could improve clinical outcome compared with a standard treatment. METHODS: Overall, 264 previously untreated stage II-III operable breast cancer patients were randomized to receive either standard treatment (arm A, n = 131), consisting of fluorouracil, epirubicin, and cyclophosphamide (FEC100: 500, 100, and 500 mg/m(2), respectively, for 3 cycles) followed by docetaxel (100 mg/m(2) for 3 cycles), or adapted treatment (arm B, n = 133), beginning with 2 cycles of FEC100 and switching to docetaxel if tumor size decreased by <30% after 2 cycles or <50% after 4 cycles of FEC100 (ultrasound assessments according to World Health Organization criteria). Otherwise, FEC100 was given for six cycles before surgery. Intent-to-treat analysis was performed. RESULTS: Similar results were observed for clinical response (objective response was 54% vs 56%, p = .18), breast conservation surgery (BCS; 67% vs 68%, p = .97), and pathological complete response rate (Chevallier classification: 14% vs 11%, p = .68; Statloff classification: 16% vs 13%, p = .82) between arms A and B. Similar toxicities were observed, even with unbalanced numbers of FEC100 and docetaxel courses. CONCLUSION: Adapted and standard treatments had similar results in terms of tumor response, BCS rate, and tolerability. Further survival outcome data are expected.

Prognostic factors in operable breast cancer treated with neoadjuvant chemotherapy: towards a quantification of residual disease.

OBJECTIVE: 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. METHODS: 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%). RESULTS: 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. CONCLUSIONS: 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.

Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study.

BACKGROUND: Brain metastases occur in 30-50% of patients with metastatic HER2-positive breast cancer. In the case of diffuse brain metastases, treatment is based on whole brain radiotherapy (WBRT). Few systemic options are available. We aimed to investigate the combination of lapatinib plus capecitabine for the treatment of previously untreated brain metastases from HER2-positive breast cancer. METHODS: In this single-arm phase 2, open-label, multicentre study, eligible patients had HER2-positive metastatic breast cancer with brain metastases not previously treated with WBRT, capecitabine, or lapatinib. Tretament was given in 21 day cycles: patients received lapatinib (1250 mg, orally) every day and capecitabine (2000 mg/m(2), orally) from day 1 to day 14. The primary endpoint was the proportion of patients with an objective CNS response, defined as a 50% or greater volumetric reduction of CNS lesions in the absence of increased steroid use, progressive neurological symptoms, and progressive extra-CNS disease. All responses had to be confirmed 4 weeks after initial response. Efficacy analyses included all patients who received the study drugs and were assessable for efficacy criteria. This trial is registered with ClinicalTrials.gov, number NCT00967031. FINDINGS: Between April 15, 2009, to Aug 2, 2010, we enrolled 45 patients, 44 (98%) of whom were assessable for efficacy, with a median follow-up of 21·2 months (range 2·2-27·6). 29 patients had an objective CNS response (65·9%, 95% CI 50·1-79·5); all were partial responses. Of all 45 treated patients, 22 (49%) had grade 3 or grade 4 treatment-related adverse events, of which the most common were diarrhoea in nine (20%) patients and hand-foot syndrome in nine (20%) patients. 14 (31%) patients had at least one severe adverse event; treatment was discontinued because of toxicity in four patients. No toxic deaths occurred. INTERPRETATION: The combination of lapatinib and capecitabine is active as first-line treatment of brain metastases from HER2-positive breast cancer. A phase 3 trial is warranted. FUNDING: GlaxoSmithKline-France and UNICANCER.

Muc1/Cd227 immunohistochemistry in routine practice is a useful biomarker in breast cancers.

Over-expression of MUC1/CD227 is observed in 90% of breast tumors. Classical morphologic description and semi-quantitative digital measurement of MUC1 were performed from immunohistochemical stained slides of 123 routine histological samples. Measures of MUC1 expression showed statistical differences between non tumoral (NT) breast tissue and Ductal Carcinoma In Situ (DCIS) or infiltrating carcinoma (IC), p < 0.0001. Loss of MUC1 was correlated with high Ki67 index (p = 0.001) and loss of hormonal receptors (p = 0.03), whereas no correlations were found with HER2 expression. High-grade DCIS or IC showed increasing loss of apical polarised and cytoplasmic expression of MUC1.

Circulating Tumor Cells and Bevacizumab Pharmacokinetics during Neoadjuvant Treatment Combining Chemotherapy and Bevacizumab for Early Breast Cancer: Ancillary Analysis of the AVASTEM 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), p = 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), p = 0.017, log-rank test). However, CTC status at baseline was not predictive of pCR (p = 0.74). CTC status after one cycle was not a significant prognostic factor (HR = 1.56; 95%CI (0.19-12.67); p = 0.68 for OS and HR = 2.76; 95%CI (0.60-12.61); p = 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.

Interventions to improve physical performances of older people with cancer before complex medico-surgical procedures: Protocol for an umbrella review of systematic reviews and meta-analyses.

BACKGROUND: Current demographics lead increasing older cancer patients to undergo complex medico-surgical procedures, with substantial risk of decompensations and deconditioning. The Prehabilitation & Rehabilitation in Oncology: Adaptation to Disease and Accompaniment of Patients' Trajectories (PROADAPT) project is currently being developed with the aim of improving care, through standardized care pathways guided by existing evidence and implementation programs. A working group will specifically focus on improvement of physical performances before such procedures. These interventions may have been developed in different contexts: before surgery in large, before carcinologic surgery or complex medical interventions (chemotherapy, radiotherapy), or in primary care for elderly patients to prevent sarcopenia and frailty. Post-surgical interventions are out of the scope of this review. The objective of this review is to summarize the level of evidence to support physical reconditioning interventions and identify areas where further work is required. METHODS: This umbrella review will include moderate to high quality systematic reviews, meta-analysis, and pre-existing umbrella or meta-reviews. Two reviewers will independently search the following databases: PubMed/MedLine, Cochrane Library, Embase, and CINAHL. Research strategy will use diverse keywords used to refer to the concepts of "prehabilitation," "preoperative exercise," or "preoperative rehabilitation," with prespecified inclusion and exclusion criteria and only systematic reviews selection. The distinct types of interventions presented using PRISMA guidelines and a narrative reporting of results. A focus will be made on outcomes such as physical performances, quality of life, autonomy in everyday activities, or number of hospital bed days. ETHICS AND DISSEMINATION: Ethical approval is not required for such an umbrella review. Our review will be submitted for publication in a peer-reviewed international journal using open access option if available. It will be complementary to reviews focused on hospital discharge of older people. PROSPERO REGISTRATION NUMBER: CRD42020100110.

Stem Cells Inhibition by Bevacizumab in Combination with Neoadjuvant Chemotherapy for Breast Cancer.

Preclinical works have suggested cytotoxic chemotherapies may increase the number of cancer stem cells (CSC) whereas angiogenesis inhibition may decrease CSC proliferation. We developed a proof of concept clinical trial to explore bevacizumab activity on breast CSC. Breast cancer patients requiring preoperative chemotherapy were included in this open-label, randomized, prospective, multicenter phase II trial. All received FEC-docetaxel combination, and patients randomized in the experimental arm received concomitant bevacizumab. The primary endpoint was to describe ALDH1 (Aldehyde dehydrogenase 1) positive tumor cells rate before treatment and after the fourth cycle. Secondary objectives included safety, pathological complete response (pCR) rate, disease-free survival (DFS), relapse-free survival (RFS), and overall survival (OS). Seventy-five patients were included. ALDH1+ cells rate increase was below the predefined 5% threshold in both arms for the 32 patients with two time points available. Grade 3 or 4 adverse events rates were similar in both arms. A non-significant increase in pCR was observed in the bevacizumab arm (42.6% vs. 18.2%, p = 0.06), but survival was not improved (OS: p = 0.89; DFS: p = 0.45; and RFS: p = 0.68). The increase of ALDH1+ tumor cells rate after bevacizumab-based chemotherapy was less than 5%. However, as similar results were observed with chemotherapy alone, bevacizumab impact on breast CSC cells cannot be confirmed.

Mammalian target of rapamycin inhibitors in combination with letrozole in breast cancer.

Breast cancer is the most common malignancy and the second most common cause of cancer-related death in women. Endocrine therapy has been used for more than a century to treat advanced-stage breast cancer. The results obtained with the third-generation aromatase inhibitor letrozole demonstrated an actual improvement in patient outcome compared with tamoxifen. This benefit translates into disease-free survival improvement for adjuvant treatment and overall survival in patients with metastatic disease. The present clinical situation of hormonal therapy is stable; however, recently, new anticancer agents (temsirolimus and everolimus) that inhibit mammalian target of rapamycin protein kinase have been developed and seem to be very promising because of their synergistic activity with letrozole. The phase II study of a combination of temsirolimus or everolimus with letrozole demonstrated a better progression-free survival in the combination arm than in the letrozole alone arm. Consequently, the results of ongoing phase III studies are eagerly awaited.

Sequential addition of an anthracycline-based regimen to docetaxel as neoadjuvant chemotherapy in patients with operable breast cancer.

BACKGROUND: The objective of this phase II study was to attempt to maximize response and survival in patients with bulky, operable breast cancer by combining sequential neoadjuvant docetaxel to a semi-intensive anthracycline-based regimen. PATIENTS AND METHODS: Eligible patients (N = 53) were included to receive 4 cycles of docetaxel, followed by a maximum of 4 cycles of TNCF (THP [theprubican]-doxorubicin/vinorelbine/cyclophosphamide/5-fluorouracil) every 21 days before definitive surgery and radiation therapy. RESULTS: After a median number of 4 cycles of docetaxel and 2 cycles of TNCF, the overall clinical response rate was 81.1%, including a 13.2% complete remission rate and only 2 incidences of progressive disease. Breast conservation was achieved in 87% of patients. According to Chevallier classification, a pathologic complete response in breast and axilla was confirmed in 6 patients (11.3%) and in 9 patients (17%) using the Sataloff's classification. The important myelosuppression observed in this trial was expected but limited by the prophylactic use of growth factors. After a median follow-up of 40.4 months, only 5 recurrences were documented, with a median time to first recurrence of 12.8 months. CONCLUSION: Despite disappointing results of this trial for pathologic complete response rate, possibly because of the order of drug administration, clinical response, breast conservation, and survival were optimized.

IL-17E synergizes with EGF and confers in vitro resistance to EGFR-targeted therapies in TNBC cells.

Estrogen receptor-, progesterone receptor- and HER2-negative breast cancers, also known as triple-negative breast cancers (TNBCs), have poor prognoses and are refractory to current therapeutic agents, including epidermal growth factor receptor (EGFR) inhibitors. Resistance to anti-EGFR therapeutic agents is often associated with sustained kinase phosphorylation, which promotes EGFR activation and translocation to the nucleus and prevents these agents from acting on their targets. The mechanisms underlying this resistance have not been fully elucidated. In addition, the IL-17E receptor is overexpressed in TNBC tumors and is associated with a poor prognosis. We have previously reported that IL-17E promotes TNBC resistance to anti-mitotic therapies. Here, we investigated whether IL-17E promotes TNBC resistance to anti-EGFR therapeutic agents by exploring the link between the IL-17E/IL-17E receptor axis and EGF signaling. We found that IL-17E, similarly to EGF, activates the EGFR in TNBC cells that are resistant to EGFR inhibitors. It also activates the PYK-2, Src and STAT3 kinases, which are essential for EGFR activation and nuclear translocation. IL-17E binds its specific receptor, IL-17RA/IL17RB, on these TNBC cells and synergizes with the EGF signaling pathway, thereby inducing Src-dependent EGFR transactivation and pSTAT3 and pEGFR translocation to the nucleus. Collectively, our data indicate that the IL-17E/IL-17E receptor axis may underlie TNBC resistance to EGFR inhibitors and suggest that inhibiting IL-17E or its receptor in combination with EGFR inhibitor administration may improve TNBC management.

High-dose chemotherapy with haematopoietic stem cell transplantation for metastatic breast cancer patients: final results of the French multicentric randomised CMA/PEGASE 04 protocol.

The aim of our study was to evaluate the impact on time to progression (TTP) and overall survival (OS) of high-dose chemotherapy (HD-CT) over conventional CT in metastatic breast cancer patients. Between 09/92 and 12/96, 61 patients with chemosensitive metastatic breast cancer were randomised between HD-CT using the CMA regimen (Mitoxantrone, Cyclophosphamide, Melphalan) applied as consolidation (32 patients) or maintenance CT (29 patients). At randomisation, 13 patients were in complete response, 47 in partial response and one had stable disease. The median TTPs from randomisation were 6 and 12 months in the standard and intensive groups, respectively (P < 0.0056), with a relapse rate of 86.2% vs. 62.5% at 2 years, and 100% vs. 81.3% at 5 years. The median OS times were 19.3 and 44.1 months, with an OS rate of 13.8% vs. 36.8% at 5 years (P < 0.0294). The CMA regimen could prolong the TTP of patients with chemosensitive metastatic breast cancer. Further studies are needed to determine if this translates into an effect on OS.

PIK3CA Pathway Mutations Predictive of Poor Response Following Standard Radiochemotherapy ± Cetuximab in Cervical Cancer Patients.

PURPOSE: EGFR is frequently overexpressed in cervical cancer, suggesting EGFR blockade as a promising treatment approach. Cetuximab, an anti EGFR antibody, used conjointly with radiochemotherapy, was feasible in first-line treatment of cervix carcinoma limited to the pelvis. EXPERIMENTAL DESIGN: This randomized phase II trial enrolled 78 FIGO stage IB2-IIIB cervical cancer patients to either cisplatin-based radiochemotherapy alone (arm B, n = 38) or conjointly with a 6-week course of weekly cetuximab (arm A, n = 40). Brachytherapy was given to the pelvic mass. Primary endpoint was disease-free survival (DFS) at 2 years. EGFR expression and targeted sequencing were performed in 54 of 78 patients. RESULTS: Cetuximab over a 6-week period did not improve DFS at 24 months. At 31 months median follow-up, DFS was not significantly different (P = 0.18). Complete response at 4 to 6 months was strongly predictive for excellent DFS (log-rank test; P < 0.001). PIK3CA, KRAS, and STK11 mutations were observed in 22%, 4%, and 2% of patients, respectively. No tumor with a PI3K pathway mutation showed complete response (0/8 in arm A and 0/6 in arm B), whereas 14 of 52 (27%) tumors without mutations did (P = 0.021). PI3K pathway-mutated tumors showed a trend toward poorer DFS (P = 0.06) following cetuximab (8/22) as compared with those following standard treatment only (6/18). CONCLUSIONS: Similar to patients with head and neck cancer, patients with cervical cancer showed no gain in DFS at 2 years following a combined treatment of cetuximab with radiochemotherapy. Although treatment tolerance and compliance were satisfactory, it remains to be demonstrated whether maintenance therapy with cetuximab could be beneficial in selected patient groups.

Neoadjuvant FEC 100 for operable breast cancer: eight-year experience at Centre Jean Perrin.

This study investigated the efficacy and tolerability of FEC 100 (epirubicin 100 mg/m2 with 5-fluorouracil 500 mg/m2 and cyclophosphamide 500 mg/m2) every 21 days as neoadjuvant chemotherapy in women with stage I-III primary operable breast cancer. Forty patients were treated with 6 cycles of FEC 100, followed by surgery and radiation therapy. In addition, most patients also received an adjuvant treatment for residual disease (11 chemotherapies and 31 tamoxifen). After 6 cycles of FEC 100, the overall clinical response rate of 75% (CI 95%, 61.6-88.4) was achieved, 22.5% of which were complete responses. Breast conservation was achieved in 70% of patients. A pathologic complete response was confirmed in 6 patients (15%; CI 95%, 3.9-26.1) using Chevallier's classification and in 10 patients (25%; CI 95%, 11.6-38.4) using Sataloff's classification. After a median follow-up of 29.5 months, 3 metastatic relapses were observed. The principal toxicity of FEC 100 was myelosuppression; 51.3% of patients developed grade 3/4 neutropenia. Neoadjuvant FEC 100 was both effective and well tolerated in patients with early-stage operable breast cancer.

A multicenter phase II study of cisplatin and docetaxel (Taxotere) in the first-line treatment of advanced ovarian cancer: a GINECO study.

PURPOSE: A multicenter phase II study to evaluate the antitumor effect and safety of docetaxel in combination with cisplatin as first-line chemotherapy for advanced ovarian cancer. METHODS: Enrolled in the study were 45 patients who were to receive six courses of docetaxel 75 mg/m(2) plus cisplatin 75 mg/m(2) every 21 days with hydration and steroid prophylaxis after initial debulking surgery. Imaging techniques and radiography were used to assess clinical tumor response, and second-look surgery was required for patients with complete clinical responses and for those without clinically measurable disease. RESULTS: The overall clinical response rate in 29 patients with clinically measurable disease was 58% (41% complete response). A complete pathologic response was seen in 9 of 34 patients who underwent second-look laparotomy, while microscopic disease was found in 10 patients. The median time to progression was 14.4 months (95% CI 8.4-20.4 months), with a median overall survival of 43 months (95% CI 21.1-65.0 months). Patients received a median number of six cycles at a dose intensity of 98%. Grade 3-4 neutropenia was seen in 80% of patients, but was manageable. No patients withdrew because of fluid retention. CONCLUSIONS: The combination of docetaxel with cisplatin confers high clinical and pathologically verified tumor response rates and is well tolerated in the first-line management of advanced ovarian cancer.

Assessment of circadian rhythms by actimetry in healthy subjects and patients with advanced colorectal cancer.

Circadian rhythms can be altered in severe illness such as cancer; the rest-activity circadian cycle has been used as a reference for the administration of chemotherapy at specific times in order to improve tolerability and efficacy. We assessed the feasibility of the method in our center in a sample of patients with metastatic colorectal cancer selected for chronomodulated chemotherapy. Activity of the circadian rhythms were measured non-invasively in 10 patients with metastatic colorectal cancer by wrist actimetry, and compared to healthy subjects. Patients and healthy subjects were requested to wear an actigraph, a wristwatch that records the number of accelerations per minute, for 3 days. Healthy subjects exhibited high activity levels during daytime, followed by low activity levels during the night. In patients, the contrast between daytime activity and nocturnal sleep was noticeably less marked, and a wide inter-patient variability was observed. All the patients wore the actigraph with a total compliance. Actimetry may provide a simple and innovative tool to study the circadian system and may be considered as an objective and accurate method to evaluate the individual health status ("conditions of life") in cancer patients, independently of all ("quality of life" questionnaires.