Background: The development of oral anticancer drug has resulted in several challenges. Prescriptions require a specific monitoring of the patient during his treatment. The objective of this work, resulted from collaboration among health professionals, was to assess the feasibility of setting up a pharmaceutical consultation in department of medical oncology. In addition, we aimed to evaluate the impact of this consultation in reducing prescription errors, drug-drug interactions finding, the early detection of adverse events (AEs) and in the patients’ adherence to both their treatments and the present approach. Methods: Before the initiation of oral chemotherapy, the oncologist proposed to the patient at participating in a pharmaceutical consultation. Following the patients’ agreement, the pharmacist collected several datas (medical history, community pharmacy medical prescriptions, treating physician) and agreed to an appointment with him. This process allowed to obtain the Best Possible Medication History and establish with the patient the treatment plan. During consultation, the resident assessed the patients’ compliance (with Morisky Scale questionnaire) and informed about the preventive and corrective measures to be implemented in case of AEs. All this datas were related in a specific notebook. A telephone follow-up was proposed to the patient. At last, a report containing all the pharmaco-therapeutic analysis was sent to the oncologist. Results: The pharmaceutical consultations allowed follow-up of 17 patients. Of the 19 pharmaceutical interventions conducted during the consultations, 94% involved drug-drug interactions. All patients participated to the telephone follow-up. 49 telephones calls allowed the detection of 25 AEs, half of which were referred to other health professionals. For 2 patients, anticancer drug had to be stopped for a bad tolerance finding telephone follow-up. Compliance remained constant over time for all patients. An average score of 9.4/10 was noted by patients for global satisfaction with the activity. Conclusions: Those results have showed that pharmaceutical consultation could enhance quality management of patients treated by oral anticancer drugs. It highlighted the major interest of this new health professional’s collaboration. Legal entity responsible for the study: Isabelle Debrix Funding: Hospital Tenon (Paris 20ème) Disclosure: All authors have declared no conflicts of interest.

Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is a questionable prognostic factor for all breast cancer (BC) subtypes. We assessed the importance of other clinical and pathological parameters as prognostic factors after NAC. From 2005 to 2014, 236 non metastatic BC patients were consecutively treated in our institution with the same NAC combining sequentially anthracyclines-cyclophosphamide followed by taxanes (trastuzumab was added in HER2 positive population). All the data concerning patient population, initial tumor stage, pathological characteristics on biopsy, as also after surgery were collected. Pathological analysis was centralized. pCR was defined according to UICC criteria, disease free survival (DFS) was calculated since the day of first surgery. Analyses employed logistic regression and Cox proportional hazard models. Of 236 patients, 140 (59%) were ER positive, 44 (19%) were triple negative and 52 (22%) were Her2 positive. The overall pCR rate was 26.3%. We found that High Ki67, low PgR and low ER are associated with a pCR. In the group of ER positive population, a cut-off of Ki67 at 30% was associated in a multivariate analysis with the probability of pCR (> 30% versus 30% - odds ratio= 3.09, IC 95% = 1.13-8.91, p= 0.028) as well as ER 90% (>90% vs 90% - OR = 0.24, IC 95% = 0.07-0.68, p = 0.007). The association of these two factors gave a pCR with an odds ratio of 7.8 (p = 0.0015). Even if pCR was not achieved, we found a molecular down-staging particularly among the luminal B population (defined by IHC criteria) (58.1% change into luminal A). Among patients that did not achieve pCR, several parameters are associated with better survival after surgery. In multivariate analysis, the clinical stage and the decrease of the Ki67 (defined by (final Ki67-initial Ki67)/initial Ki67) are associated with a reduced risk of disease relapse (hazard ratio = 2.93, IC 95% = 1.19-7.24, p = 0.02). Our data suggest that particularly in HR positive population, pathological characteristics of residual tumor (ER, PgR, Ki67) might be very informative for clinical outcome of patient that did not achieve pCR after NAC.

Ga-68 is a positron emitter, obtained from a Ge-68/Ga-68 generator, which can be used to label peptides of clinical interest. DOTATOC is a tracer of high affinity for the type 2 somatostatin receptors and is used for imaging of tumours which are expressing them, including endocrine tumours. We report on the case of a patient with a history of small bowel carcinoid tumour with hepatic metastases, treated by somatostatin analogues, in whom somatostatin receptor scintigraphy showed three liver foci and DOTATOC-(Ga-68) PET/CT highlighted much more liver lesions. Two recent studies emphasised on the superiority of DOTATOC- (Ga-68) PET over somatostatin receptor scintigraphy, and its complementarity with CT, especially for the diagnosis of bone metastases. DOTATOC-(Ga-68) PET/CT, which associates the specificity of somatostatin receptor scintigraphic detection with the spatial resolution of PET and the anatomical precision of CT, seems to be promised to a brilliant future, the more so as it offers many advantages to the patient: a shorter waiting time, one single image acquisition and a satisfying dosimetry. (C) 2008 Published by Elsevier Masson SAS.

La place de la chimiothérapie à haute dose, dans la prise en charge des cancers du sein, a fait l’objet d’un grand nombre d’essais randomisés depuis 15 ans. Les données actuellement disponibles ne permettent pas de proposer une intensification thérapeutique hors essai clinique, que ce soit en situation adjuvante ou métastatique. Des études plus récentes, en situation adjuvante, ont montré le profil de tolérance acceptable d’une chimiothérapie dose-densifiée sous couvert de facteurs de croissance hématopoïétiques. Le bénéfice observé, même modeste sur la survie sans rechute et la survie globale, consacre la densité de dose comme une des options thérapeutiques dans le traitement adjuvant des patientes à haut risque de rechute. Dans les cancers du sein inflammatoires, nous ne disposons pas de données comparatives et prospectives.

Breast cancer is often an estrogen-dependent disease. The primary goals of the treatment of breast carcinomas are multiple, depending on the situation in which the patients are treated. In adjuvant setting, the aims are to delete the time of relapse, to increase the overall survival, and to offer to the patients the best quality of life they may expect. Tamoxifen is the standard hormonal agent for premenopausal women with receptor-positive breast cancer. Recent data show an increasing role for aromatase inhibitors in postmenopausal women. In metastatic setting, the primary goals are improved quality of life and prolonged survival; effective therapies with minimal toxicity, such as endocrine therapy, are highly desirable and should be considered a primary option over chemotherapy for selected estrogen-receptor positive patients. Ovarian ablation has been worldwide used. Methods of irreversible ovarian ablation include surgical oophorectomy and ovarian irradiation. Potentially reversible castration can be medically accomplished using luteinizing hormone releasing hormone analogues (LHRH agonists). In the metastatic setting, ovarian ablation (induced by the use of LHRH agonists or by surgical ovarian ablation) and tamoxifen monotherapies produce comparable outcomes, and may be more effective when used together (combined estrogen blockade). In advanced breast cancer, the combination prolongs the progression-free survival and increases response rates and duration of response rate relative to the use of LHRH agonist alone. In the adjuvant setting, data suggest that ovarian ablation followed by tamoxifen produces similar results to those obtained with adjuvant chemotherapy in hormone-receptor positive breast cancer women. The value of combining these modalities remains unclear, but the addition of the LHRH analogue goserelin to standard treatment results in a significant benefit in terms of relapse-free and overall survival, especially for estrogen-receptor positive patients. Finally, considering the efficacy of the new aromatase inhibitors, the interest of combining these drugs with the LHRH analogues has yet to be defined, both for pre- and post-menopausal patients.

Le cancer du sein est dans la plupart des cas un cancer hormonodépendant. Les traitements que l'on peut proposer sont multiples et dépendent du stade de la maladie traitée. En situation adjuvante, ces traitements ont pour but d'augmenter la survie sans récidive et la survie globale, tout en préservant la qualité de vie des patientes. Le tamoxifène constitue l'hormonothérapie de référence chez les patientes non ménopausées présentant une tumeur avec récepteurs hormonaux positifs (RH+). Les inhibiteurs de l'aromatase ont démontré leur efficacité chez les patientes ménopausées. En situation métastatique, l'objectif des traitements étant l'amélioration de la survie avec le maintien d'une qualité de vie adéquate, il faut privilégier les traitements les plus efficaces et les moins toxiques comme l'hormonothérapie qui, chez les patientes RH+, peut parfois être préférée à la chimiothérapie. La suppression ovarienne est utilisée depuis longtemps. Elle peut être irréversible lorsque la méthode utilisée est l'irradiation ou la castration chirurgicale, réversible avec les analogues de la LHRH (Luteinizing Hormone Releasing Hormone). En situation métastatique, la suppression ovarienne (médicamenteuse avec les analogues, ou chirurgicale) et le tamoxifène sont des traitements efficaces en monothérapie, et surtout en association. L'association des analogues au tamoxifène permet d'augmenter le taux de réponse objective, d'allonger la survie sans progression et la durée de la réponse comparativement à la castration seule. En situation adjuvante, l'association analogues et tamoxifène donne des résultats comparables à ceux obtenus avec la chimiothérapie chez les patientes RH+. Les modalités de tels traitements en association ou non à la chimiothérapie restent mal définies. L'efficacité supérieure des antiaromatases sur le tamoxifène rend intéressante la combinaison de ces molécules aux analogues de la LHRH, mais la place de ces traitements n'est pas encore définie.

The first studies on intensive chemotherapy for metastatic breast cancer conducted in the 80s were disappointing. Despite good response rates, the duration of remission was short and long-term survivals exceptional. Nevertheless, these phase I and II trials helped to develop a better understanding of the potential indications of this new therapeutic approach and apprehend its technical aspects. Over the last 5 years, considerable progress has been made in grafting techniques and hematopoietic support greatly improving the safety of the method. Notwithstanding the financial considerations involved, it must be noted that the efficacy autologous stem cell support, in terms of recurrence-free overall survival, has not yet been demonstrated although the (controversial) results of two randomized controlled trials have recently been published. In France, the PEGASE programs for the study of autologous stem cell support in breast cancer have been developed in an attempt to elucidate the question.

Background. Advanced pancreatic adenocarcinoma is a rapidly fatal disease for which an active chemotherapy regimen is sought. Here we report the outcome of a phase II trial to assess the toxicity and efficacy of a combination of 5-fluorouracil (5-FU), leucovorin and cisplatin (CDDP).Methods. A regimen combining leucovorin (200 mg/m(2)/d x 5d), 5-FU (375 mg/m(2)/d x 5d in a 2-hour infusion) and CDDP (15 mg/m(2)/d x 5d) was given to 52 patients with histologically-proven, previously untreated, locally advanced (n = 13) and/or metastatic (n = 39) pancreatic adenocarcinoma.Results. Of 48 patients evaluable for response, 10 achieved partial responses, for an overall response rate of 21% (95% CI 9.5%-32.5%), and a palliative effect was observed in 52%. The median survival was 9.5 months (18 months for locally-advanced and 5 months for metastatic disease) with a 1-year survival of 34.6% and a median progression-free survival of 4.5 months. Chemotherapy was well tolerated with grades 3 or 4 nausea/vomiting in 12%, diarrhea in 6%, anaemia in 17%, neutropenia in 12%, and thrombocytopenia in 10%. Eleven patients (21%) had Grade 2 peripheral neuropathy.Conclusion. The combination of leucovorin, 5-FU and CDDP seems to be an effective palliative treatment, with moderate toxic effects,, in advanced pancreatic adenocarcinoma.

Autologous bone marrow transplantation for the treatment of gynecologic tumors in adults remains an uncommon therapeutic approach. The feasibility of such high-dose therapies is clearly proved, especially with the advent of hematopoietic growth factors and the rescue by the peripheral stem cells to reduce the duration of the chemotherapy-induced myeloid aplasia. The question is to exactly define the place of high-dose therapy in the land of solid tumors. In the treatment of poor prognosis breast cancer, high-dose therapy with autologous bone marrow transplantation or with peripheral stem cells support is able to convert some patients with partial response into complete responders. However, the consequences on overall survival and disease-free survival are not convincing. For metastatic breast cancer and for poor-prognosis tumors (inflammatory breast cancer, axillary metastatic nodes > or = 8), the interest of high-dose therapy has to be determined by randomized studies. These studies are ongoing in USA and in France. For the treatment of poor-prognosis ovarian cancer, the situation is more difficult to appraise. Randomized studies have to be done to precisely define the interest of high-dose therapy in terms of response and disease-free survival for the treatment of ovarian carcinomas.

The first studies on intensive chemotherapy for metastatic breast cancer conducted in the 80s were disappointing, Despite good response rates, the duration of remission was short and long-term survivals exceptional, Nevertheless, these phase I and II trials helped to develop a better understanding of the potential indications of this new therapeutic approach and apprehend its technical aspects, Over the last 5 years, considerable progress has been made in grafting techniques and hematopoietic support greatly improving the safety of the method, Notwithstanding the financial considerations involved, it must be noted that the efficacy autologous stem cell support, in terms of recurrence-free overall survival, has not yet been demonstrated although the (controversial) results of two randomized controlled trials have recently been published. In Prance, the PEGASE programs for the study of autologous stem cell support in breast cancer have been developed in an attempt to elucidate the question.

Autologous bone marrow transplantation for the treatment of gynecologic tumors in adults remains an uncommon therapeutic approach, The feasibility of such high-dose therapies is clearly proved, especially with the advent of hematopoietic growth factors and the rescue by the peripheral stem cells to reduce the duration of the chemotherapy-induced myeloid aplasia. The question is to exactly define the place of high-dose therapy in the land of solid tumors, In the treatment of poor prognosis breast cancer, high-dose therapy with autologous bone marrow transplantation or with peripheral stem cells support is able to convert some patients with partial response into complete responders. However, the consequences on overall survival and disease-free survival are not convincing, For metastatic breast cancer and for poor-prognosis tumors (inflammatory breast cancer, axillary metastatic nodes greater than or equal to 8), the interest of high-dose therapy has to be determined by randomized studies. These studies are ongoing in USA and in France. For the treatment of poor-prognosis ovarian cancer, the situation is more difficult to appraise, Randomized studies have to be done to precisely define the interest of high-dose therapy in terms of response and disease-free survival for the treatment of ovarian carcinomas.

Autologous bone marrow transplantation for the treatment of solid tumors in adults remains an uncommon therapeutic approach. The feasibility of such high-dose therapies is clearly proved, especially with the advent of hematopoietic growth factors and the rescue by the peripheral stem cells to reduce the duration of the chemotherapy-induced myeloid aplasia. The question is to exactly define the place of high-dose therapy in the land of solid tumors. For the treatment of primary chemoresistant gonadal germ-cell tumors, the possibility to cure the patients and the interest of high-dose therapy with autologous bone marrow transplantation are clearly demonstrated. As consolidation for the treatment of poor prognosis tumors, the place of high-dose therapies remains moot. For the treatment of chemoresistant extragonadal germ-cell tumors, especially for primary mediastinal tumors, the level of resistance to cisplatin-based chemotherapy regimens is generally too high to be overcome by intensive therapies given as single course or as tandem courses. However in association with debulking surgery, this therapeutic approach has to be considered for some patients. In the treatment of poor prognosis breast cancer, high-dose therapy with autologous bone marrow transplantation or with peripheral stem cells support is able to convert some patients with partial response into complete responders. However, the consequences on overall survival and on disease-free survival are not evident. For metastatic breast cancer and for poor-prognosis tumors (inflammatory breast cancer, axillary metastatic nodes > or = 8), the interest of high-dose therapy has to be determined by randomized studies. These studies are ongoing in USA and in Europe. For the treatment of poor-prognosis ovarian cancer, the situation is more difficult to appraise. Once again, randomized studies have to be done to precisely define the place of high-dose therapy. In the land of small-cell lung carcinomas, high-dose therapy is actually forsaken by most of authors, even for limited diseases. The results of previous studies are disappointing. Moreover, occult medullary micrometastases involvement is frequent, once again even in limited diseases. However new therapeutic associations, as the ICE regimen (IFM, Carboplatin, VP-16) delivered as single or tandem therapy, have to be studied, especially as early consolidation therapy for the treatment of limited small-cell lung carcinomas.

Autologous bone marrow transplantation for the treatment of solid tumors in adults remains an uncommon therapeutic approach. The feasibility of such hight-dose therapies is clearly proved, especially with the advent of hematopoietic growth factors and the rescue by the peripheral stem cells to reduce the duration of the chemotherapy-induced myeloid aplasia. The question is to exactly define the place of high-dose therapy in the land of solid tumors. For the treatment of primary chemoresistant gonadal germ-cell tumors, the possibility to cure the patients and the interest of high-dose therapy with autologous bone marrow transplantation are clearly demonstrated. As consolidation for the treatment of poor prognosis tumors, the place of high-dose therapies remains moot. For the treatment of chemoresistant extragonadal germ-cell tumors, especially for primary mediastinal tumors, the level of resistance to cisplatin-based chemotherapy regimens is generally too high to be overcome by intensive therapies given as single course or as tandem courses. However in association with debulking surgery, this therapeutic approach has to be considered for some patients. In the treatment of poor prognosis breast cancer, high-dose therapy with autologous bone marrow transplantation or with peripheral stem cells support is able to converte some patients with partial response into complete responders. However, the consequences on overall survival and on disease-free survival are not evident. For metastatic breast cancer and for poor-prognosis tumors (inflammatory breast cancer, axillary metastatic nodes greater-than-or-equal-to 8), the interest of high-dose therapy has to be determined by randomized studies. These studies are ongoing in USA and in Europe. For the treatment of poor-prognosis ovarian cancer, the situation is more difficult to appraise. Once again, randomized studies have to be done to precisely define the place of high-dose therapy. In the land of small-cell lung carcinomas, high-dose therapy is actually forsaken by most of authors, even for limited diseases. The results of previous studies are disappointing. Moreover, occult medullary micrometastases involvement is frequent, once again even in limited diseases. However new therapeutic associations, as the ICE regimen (IFM, Carboplatin, VP-16) delivered as single or tandem therapy, have to be studied, especially as early consolidation therapy for the treatment of limited small-cell lung carcinomas.

L'intensification thérapeutique avec autotransplantation médullaire dans le traitement des tumeurs solides de l'adulte reste une thérapeutique d'exception. La faisabilité d'une telle approche thérapeutique est clairement démontrée, notamment depuis l'arrivée des facteurs de croissance hématopoïétique et les possibilités de recourir à un support transfusionnel par réinjection des cellules-souches dites périphériques. Pour le traitement des dysgerminomes gonadiques réfractaires à la chimiothérapie, le rôle de l'intensification thérapeutique est pour nous bien démontré. En tant que thérapeutique de consolidation chez les patients atteints d'une tumeur ayant des critères initiaux de mauvais pronostic, la place de cette thérapeutique reste à démontrer. Pour le traitement des dysgerminomes extragonadiques réfractaires à la chimiothérapie, et notamment des dysgerminomes thoraciques primitifs, le niveau de résistance est tel que ces thérapeutiques même répétées sont hélas souvent insuffisantes pour contourner la chimiorésistance. Ce type de traitement ne doit, selon nous, être réalisé que si, dans une optique uniquement curative, un acte chirurgical peut être envisagé au décours de la phase de chimiothérapie intensive. Pour le traitement des tumeurs mammaires métastatiques, les chimiothérapies délivrées à hautes doses sont capables de convertir les réponses partielles en réponses complètes, mais hélas sans impact sur la survie sans rechute. Dans les formes métastatiques et dans les formes dites à haut-risques de rechute (atteinte ganglionnaire axillaire ≥ 8, forme inflammatoire), l'intérêt de l'intensification thérapeutique avec réinjection des cellules-souches dites périphériques doit être démontré dans des études comparatives. Dans le traitement des tumeurs ovariennes de stade avancé, la situation est encore plus difficile. La faisabilité est réelle, mais là encore, seules des études comparatives permettront de définir la place de telles thérapeutiques. Enfin, dans le domaine des tumeurs bronchiques à petites cellules, l'histoire de l'intensification thérapeutique avec autotransplantation médullaire est décevante et la plupart des équipes ont abandonné cette voie de recherche clinique. Le fréquent envahissement médullaire a en partie contribué à ce désintérêt. Cependant, de nouveaux conditionnements thérapeutiques, tels que le schéma ICE (IFM-CBDCA-VP-16), méritent d'être étudiés dans les formes localisées au thorax avec un support hématologique par cellules-souches périphériques.