Aims: Breast cancer liver metastases (BCLM) usually indicate the presence of disseminated cancer with a very poor prognosis. However, systemic treatments now allow control of tumour progression in ...certain cases. We evaluated, in a group of highly selected patients with stabilization or complete response to systemic therapy, a particular management protocol for medically controlled BCLM: «adjuvant» liver surgery. Methods: Fifty-two patients underwent surgery between May 1988 and September 1997. Results of this strategy are reported, together with analysis of prognostic factors for survival and recurrence in the remaining liver (RRL). Results: The mean number of cycles of chemotherapy, before surgery, was seven (3–24). Resection was considered to be curative in 86% of cases. The median follow-up was 23 months (1–72 months). The survival after surgery, was 86% at 12 months, 79% at 24 months and 49% at 36 months. The 36-month survival rate differed according to the time to onset of BCLM: 45% before versus 82% after 48 months (P=0.023). The RRL rate at 36 months differed according to the lymph node status of the initial breast cancer: 41% for N0–N1 versus 83% for N1b–N2 (P=0.021). Conclusions: Adjuvant liver surgery allowed discontinuation of chemotherapy in 46% of cases and, in this highly selected patient group, allowed good quality prolonged survival. It could be included in multicentre treatment protocols for controlled BCLM, one arm with prolonged chemotherapy, one with adjuvant liver surgery.
Butyric acid, a short chain fatty acid (SCFA), is a natural component of the animal metabolism. Physiological concentrations induce multiple and reversible biological effects. They concern regulatory ...mechanisms of gene expression conducing to promote markers of cell differentiation, apoptosis and cell growth control. The described hyperacetylation of histones and the induction of several immune or non-immune cell-activating mediators are consistent with the pleiotropic stimulatory effect of the agent. Butyric acid is considered as a biological response modifier (BRM) and is an interesting tool for biological studies. The history of butyric acid as a putative medication in human health is spanning since 60 years and is confusing in part because of conflicting data between exciting experimental results and clinical trials. In light of minimal impact of systemic therapy and the short half-life of the saline molecule used, it is evident that continuous infusions of butyrate are required to improve the efficacy of the treatment. Butyric acid has been viewed with skepticism because of less convenient for long-term chronic therapy. New experimental data from several studies conduced within the past decade with butyric derivatives, delivery systems, and long-acting prodrugs, have demonstrated the practical value of the therapeutic concept. To support issues regarding clinical development, it was of interest to evaluate the recent information, showing butyric acid currently considered as therapeutic purposes in the treatment of colorectal cancer and hemoglobinopathies.
Neoadjuvant chemotherapy is able to reduce the size of the majority of breast tumours and down-stage axillary-node status. The aim of this study was to assess the prognostic value of persistent node ...involvement after neoadjuvant chemotherapy. A total of 488 patients with T2-T3, N0-N1 breast cancer treated by neoadjuvant chemotherapy followed by tumour excision and axillary lymph-node dissection between 1981 and 1992 were selected from the Institut Curie database. Median follow-up was 7 years. Overall objective response rate before local treatment was 52% and breast tumour size was reduced in 83% of patients. No pathologic nodal involvement was observed in 46. 5% of patients. Patients with > or = eight positive nodes had a very poor median disease-free survival of only 20 months. Their 10-year disease-free survival rate was 7%, while the 10-year disease-free survival rate for patients with no node involvement was 64%. Median survival for patients with > or = eight nodes positive was 48 months and the 10-year survival rate was 26% (P < 0.0001). On multivariate analysis, outcome was strongly correlated with pathological nodal status, tumour grade, hormonal receptor status and clinical response of the tumour. In conclusion, patients with extensive nodal involvement after neoadjuvant chemotherapy have a very poor outcome. Second-line treatment should be considered in this population.
To determine whether the prognosis of invasive cancers of the uterine cervix is related to the type of human papillomavirus (HPV) associated with the tumor.
Two hundred ninety-seven patients with ...invasive cervical cancer were prospectively registered from 1986 to 1994. HPV typing was performed on DNA extracted from frozen tumor specimens by means of Southern blot hybridization (SBH) and polymerase chain reaction (PCR) techniques. The median follow-up was 38 months.
HPV sequences were detected in 246 patients (83%): 150 patients had HPV16, 31 patients had HPV18, and 14 patients had one of the intermediate-oncogenic-risk HPV types (HPV31, 33, 35, 52, 58). In 51 patients, HPV type remained undetermined, and in 51 patients, no viral sequences were found. No significant associations were observed between virologic data and tumor stage or node status. The 5-year disease-free survival (DFS) rate was 100% for patients with intermediate-risk HPV-associated tumors, 58% for patients with HPV16-positive tumors, and 38% for patients with HPV18-positive tumors (P = .02). In multivariate analysis, patients with HPV18-associated tumors had a relative risk (RR) of death 2.4 times greater (95% confidence interval CI, 1.29-4.59) than that for patients with HPV16, and 4.4 times greater (95% CI, 3.48-5.32) than that for patients with a tumor associated with a viral type different from HPV16/18.
The prognosis for invasive cancers of the uterine cervix is dependent on the oncogenic potential of the associated HPV type. HPV typing may provide a prognostic indicator for individual patients and is of potential use in defining specific therapies against HPV-harboring tumor cells.
Purpose: To determine the maximum tolerated dose (MTD), the dose-limiting toxicity (DLT) and the recommended dose of docetaxel in combination with doxorubicin, and to evaluate the activity in ...patients with advanced breast cancer. Patients and methods: Forty-two women with untreated metastatic breast cancer (79% with visceral metastases; 52% with prior adjuvant anthracycline therapy) were treated with doxorubicin (40–60 mg/m2) i.v. bolus followed one hour later by docetaxel (50–85 mg/m2) one-hour i.v. infusion every three weeks, without G-CSF support. Results: The MTD occurred at the dose level combining 85 mg/m2 of docetaxel and 50 mg/m2 of doxorubicin, with the DLT being neutropenic sepsis. Neutropenia and /or its complications were manageable and no grade 3–4 or severe non-hematological toxicities were observed. Fluid retention was frequent but never severe. With a median cumulative dose of doxorubicin of 392 mg/m2 (240–559 mg/m2) and a median follow-up time of 29 months (9$−41), no congestive heart failure was observed. High activity was observed at all dose levels, particularly the last four, with a response rate of 81% (95% confidence interval (95% CI): 62.5–92.5). Median time to progression was 46 weeks (6$-62). Two-year survival was 66%, and median survival has not yet been reached. Conclusions: Docetaxel-doxorubicin is feasible, safe and highly active. The incidence of febrile neutropenia without G-CSF requires careful monitoring but is acceptable in this setting. There does not appear to be an increase in the cardiac toxicity of doxorubicin. The recommended dose is either docetaxel 75 mg/m2 and doxorubicin 50 mg/m2 or docetaxel 60 mg/m2 and doxorubicin 60 mg/m2, administered every three weeks.
Introduction Les fibres prébiotiques modifient la flore intestinale, celle-ci jouant un rôle physiologique sur l’organisme. Elle pourrait notamment réduire le lipopolysaccharide (LPS) circulant ...responsable d’une endotoxinémie impliquée dans les altérations métaboliques et inflammatoires, et liée à la production de cytokines en cas d’obésité. Objectif : mesurer l’effet d’une combinaison de fibres (nouvelle préparation de XOS prébiotique, associée à de l’inuline) sur les cytokines de la réponse inflammatoire et le LPS circulant. Matériels et Méthodes Quarante jeunes adultes sains, de poids normal, consommant 13 à 18 g de fibres quotidiennement ont été randomisés en 2 groupes, après une stabilisation alimentaire, en double aveugle, et ont reçu un mélange de 1 g de xylooligosaccharides (XOS) +3 g d’inuline, administrés en 2 prises pendant 4 semaines. Les IgA secrétoires et le LPS circulant ont été mesurés in vivo , les autres cytokines Th1 et Th2 ont été mesurées ex-vivo après incubation du sang circulant avec une dose non toxique de LPS. Les paramètres cliniques et les apports nutritionnels étaient identiques en base et sont restés inchangés durant l’étude. TNFα et IL10 étaient également identiques en base. Résultats Comparativement au placebo, les IgA secrétoires ont augmenté de 70 % mais de façon non significative (p = 0,155). Concernant la voie Th1, IL1β est inférieure de 20 % (p = 0,045) par rapport au placebo, TNFα a diminué de 50 % entre le début et 4 semaines (p = 0,014) ; IL8, IL12 et INFγ n’ont pas changé significativement malgré une valeur inférieure de 220 % pour IL12. Concernant la voie Th2, IL13 est supérieur de 55 % par rapport au placebo (p = 0,010), IL10 a augmenté de 50 % entre le début et 4 semaines (p = 0,064), IL4 n’a pas varié. Le LPS circulant est significativement plus bas que pour le placebo (-30 %) à 4 semaines (p = 0,026). Conclusion Ce mélange de fibres prébiotiques (XOS-inuline) diminue la réponse inflammatoire en inhibant la production de cytokines traduisant une réduction de la voie Th1 et une stimulation de la voie Th2. Il entraîne une diminution du LPS circulant : il s’agit de la première étude le montrant chez l’homme.
The aim of this study was to assess a potential advantage in survival by neoadjuvant as compared to adjuvant chemotherapy. 414 premenopausal patients with T2-T3 N0-N1 M0 breast cancer were randomised ...to receive either four cycles of neoadjuvant chemotherapy (cyclophosphamide, doxorubicin, 5-fluorouracil), followed by local-regional treatment (group I) or four cycles of adjuvant chemotherapy after primary irradiation +/- surgery (group II). Surgery was limited to those patients with a persisting mass after irradiation, and aimed to be as conservative as possible. 390 patients were evaluable. With a median follow-up of 54 months, we observed a statistically significant difference (P = 0.039) in survival in favour of the neoadjuvant chemotherapy group. A similar trend was seen when the time to metastatic recurrence was evaluated (P = 0.09). At this stage, no difference in disease-free interval or local recurrence between these two groups could be observed. The mean total dose of chemotherapy administered was similar in both groups. On average, group I had more intensive chemotherapy regimes (doxorubicin P = 0.02) but fewer treatment courses (P = 0.008) as compared to the treated patients in group II. Haematological tolerance was reduced when chemotherapy succeeded to exclusive irradiation. Breast conservation was identical for both groups at the end of primary treatment (82 and 77% for groups I and II, respectively). Of the 191 evaluable patients in the neoadjuvant treatment arm, 65% had an objective response (> 50% regression) following four cycles of chemotherapy. The objective response rate to primary irradiation (55 Gy) was 85%. Improved survival figures in the neoadjuvant treatment arm could be the result of the early initiation of chemotherapy, but we cannot exclude that this difference might be attributable to a slightly more aggressive treatment. So far, the trend in favour of decreased metastases was not statistically significant. The local control appeared similar in both subgroups.
We describe the risk factors and microbiological findings of an outbreak of
Clostridium difficile (CD)-related diarrhoea in the Medical Oncology Department of the Curie Institute. Screening for CD in ...stools was performed on 59 patients with diarrhoea and 146 patients without diarrhoea. Toxin secretion, serotyping (enzyme-linked immunosorbant assay) and genotyping (AP-polymerase chain reaction) were performed on 39 CD strains from 32 patients. The risk factors for toxigenic CD-positive diarrhoea were also investigated. Twenty-seven (46%) patients with diarrhoea and 12 (8%) patients without diarrhoea were CD-positive (
P<0.001). Patients with diarrhoea were older (
P=0.03). Chemotherapy was a risk factor for toxigenic CD-related diarrhoea (
P=0.02) and antibiotic treatment was a risk factor only in those patients who were also receiving chemotherapy. Serotyping and genotyping showed that several strains were involved in this outbreak, with only two instances of patient-to-patient transmission, involving four and two patients.
To assess the outcome and the prognosis of adults with a neoplasm related to the Ewing's sarcoma family of tumors.
The outcomes of 182 consecutive patients older than 15 years with Ewing's sarcoma or ...related neoplasms managed from 1982 to 1992 were reviewed, without any selection according to primary tumor site or disease extension.
Of 182 patients, 53 had evidence of metastases at presentation (29%). Tumor size was greater than 10 cm in 70 patients (41%). With a median follow-up duration of 66 months, the 5-year overall survival (OS) rate was 41%. In patients with localized disease, 5-year OS rate was 54% and 5-year progression-free survival (PFS) rate, 43%. Late relapses after 5 years accounted for 9% of relapses. Metastasis at presentation (P = .00001), pelvic primary lesion (P = .0025), and tumor size greater than 10 cm (P = .004) were independent prognostic factors for survival. Five-year OS was 67% in patients with nonpelvic tumors < or = 10 cm, 52% in those with pelvic tumors less than 10 cm or extrapelvic tumors > or = 10 cm, 16% in those with pelvic tumors greater than 10 cm, and 9% in those with metastasis (P = .00001).
Based on our experience and a review of the literature, we concluded that the natural history and the prognosis of the Ewing's family of tumors in adults are not different from that found in children. A greater tumor bulk in adults may explain the less favorable prognosis previously reported by others. Outcome could be adequately monitored by a simple prognostic index.
This randomized, multicenter, phase III study compared doxorubicin and docetaxel (AT) with doxorubicin and cyclophosphamide (AC) as first-line chemotherapy (CT) in metastatic breast cancer (MBC).
...Patients (n = 429) were randomly assigned to receive doxorubicin 50 mg/m(2) plus docetaxel 75 mg/m(2) (n = 214) or doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2) (n = 215) on day 1, every 3 weeks for up to eight cycles.
Time to progression (TTP; primary end point) and time to treatment failure (TTF) were significantly longer with AT than AC (median TTP, 37.3 v 31.9 weeks; log-rank P =.014; median TTF, 25.6 v 23.7 weeks; log-rank P =.048). The overall response rate (ORR) was significantly greater for patients taking AT (59%, with 10% complete response CR, 49% partial response PR) than for those taking AC (47%, with 7% CR, 39% PR) (P =.009). The ORR was also higher with AT in patients with visceral involvement (58% v 41%; liver, 62% v 42%; lung, 58% v 35%), three or more organs involved (59% v 40%), or prior adjuvant CT (53% v 41%). Overall survival (OS) was comparable in both arms. Grade 3/4 neutropenia was frequent in both groups, although febrile neutropenia and infections were more frequent for patients taking AT (respectively, 33% v 10%, P <.001; 8% v 2%, P =.01). Severe nonhematologic toxicity was infrequent in both groups, including grade 3/4 cardiac events (AT, 3%; AC, 4%).
AT significantly improves TTP and ORR compared with AC in patients with MBC, but there is no difference in OS. AT represents a valid option for the treatment of MBC.
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