[Can nivolumab be used safely in idiopathic pulmonary fibrosis?] / Le nivolumab peut-il être utilisé dans les fibroses pulmonaires idiopathiques ?

Anti-PD1 immunotherapies have become an essential treatment for bronchial cancer. According to published studies, PD1 and PD-L1 inhibitors have a better toxicity profile than chemotherapy. Nevertheless, some immune related toxicities can be potentially severe, such as induced interstitial lung disease (ILD). Currently, ILD patients are excluded from clinical trials using immunotherapy in lung cancer. IPF is the most frequent and severe form of ILD. Lung cancer represents a major complication of this disease and to date few data exist on the safety of immunotherapy in this context. We report 3 cases of IPF with lung cancer treated by nivolumab. All had a clinically mild to moderate IPF. The patients had received at least one line of chemotherapy before nivolumab and had progressive, metastatic lung cancer. Two patients experienced rapid cancer progression without immune toxicities. The third had a partial response but developed grade III immune colitis that led to discontinuation of the treatment. None developed lung toxicity or worsening of IPF on CT during follow-up, and death was always related to progression of the cancer. In our series of three patients with IPF, nivolumab was well tolerated with regard to their pulmonary condition. As inflammation and autoimmunity are probably marginal mechanisms in the pathogenesis of IPF, we do not believe that the presence of IPF should definitely disqualify potential candidates for treatment with nivolumab. Decisions should be taken, case-by-case, in selected patients without severe IPF and with no evidence of autoimmunity. In view of the epidemiology of lung cancer in IPF and the critical role of immunotherapy in the management of lung cancer, studies of prospective cohorts are urgently needed in this population.

Slow Gait Speed Is an Independent Predictor of Early Death in Older Cancer Outpatients: Results from a Prospective Cohort Study.

OBJECTIVE: To assess the predictive value of gait speed for early death in older outpatients with cancer. DESIGN: Prospective bicentric observational cohort study. SETTING: The Physical Frailty in Elder Cancer patients (PF-EC) study (France). PARTICIPANTS: One hundred and ninety outpatients with cancer during the first 6 months of follow up in the PF-EC study. MEASUREMENTS: The association between usual gait speed over 4 m alone (GS) or included in the short physical performance battery (SPPB) and overall survival within 6 months following a comprehensive geriatric assessment (CGA). A Cox proportional-hazard regression model was performed in non-survivors for clinical factors from the CGA, along with c reactive protein (CRP). Two models were created to assess GS alone and from inclusion in the SPPB. RESULTS: The mean age was 80.6 years, and 50.5% of the participants were men. Death occurred in 11% (n=22) of the participants within the 6 month follow up period. Of these participants, 98% had solid cancers, and 33% had a metastatic disease. A GS < 0.8 m/s (HR=5.6, 95%CI=1.6-19.7, p=0.007), a SPPB < 9 (HR=5.8, 95%CI=1.6-20.9, p=0.007) and a CRP of 50 mg/l or greater (p<0.0001) were significantly associated with early death in the two multivariate analyses. Cancer site and extension were not significantly associated with early death. CONCLUSION: Walking tests are associated with early death within the 6 month follow up period after a CGA independent of cancer site and cancer extension. GS alone < 0.8 m/s is at least as efficacious as the SPPB in predicting this outcome. GS alone could be used routinely as a marker of early death to adapt oncologic therapeutics. Further studies are needed to validate these preliminary data.

Role of physical activity and sport in oncology: scientific commission of the National Federation Sport and Cancer CAMI.

This overview reports published data about the interaction between physical activity and sport during and after cancer on one hand and improvement in psychological parameters, survival and biological mechanisms underlying this effect on the other hand. Practising physical activity and sport during cancer modifies parameters assessing fatigue and quality of life and reduces symptoms of depression. An association also exists between the practise of physical activity and sport and overall and cancer-specific survivals, especially after breast cancer, colon cancer and prostate cancer. These benefits seem to be mediated by a modification of circulating levels of estrogens, insulin, IGF-1 and by a decrease in insulin-resistance, by alterations in the secretion of adipokines, and by a reduction in chronic inflammation through decreased levels of cytokines. There exist some obstacles to the practise of physical activity. These obstacles are mainly related to a fear of pain induced by physical activity and to overweight. These programmes of physical activity and sport cannot be offered to all patients since there are several contra-indications, with some being present since the initial visit and others appearing during cancer management either due to disease progression or related to iatrogenic effects. Whereas benefits from physical activity and sport among cancer patients seem obvious, there are still several pending clinical and biological issues.

[Impact of omission of axillary dissection on adjuvant therapy in patients with metastatic sentinel lymph nodes according to the ACOSOG Z0011 criteria]. / Impact de l'omission du curage axillaire sur les traitements adjuvants chez les patientes ayant un ganglion sentinelle métastatique et répondant aux critères d'inclusion de l'ACOSOG Z0011.

OBJECTIVES: The results of the ACOSOG Z0011 questioned the usefulness of axillary lymph node dissection (ALND) in case of metastatic sentinel lymph node (SLN). The aim of our study was to assess the impact of the omission of ALND according to the inclusion criteria of the ACOSOG Z0011 study if SLN are metastatic but also the consequences on prescription of the application of a new standard of care for adjuvant treatment. PATIENTS AND METHODS: This retrospective study included, between November 2007 and January 2012, patients with T1-T2N0 breast cancer and metastatic SLN meeting the criteria for omission of completion ALND according to the study of the ACOSOG Z0011. Patients were submitted anonymously and randomly in multidisciplinary meeting (MM) 3 times: with complete information including ALND (MM1), with information from SLN alone (MM2) and with complete information of ALND according to the current protocols in 2013 (MM3). During each presentation, we collected the decision of the different adjuvant treatments proposed: chemotherapy, hormonal therapy, radiotherapy (with radiation fields). Then, we compared therapeutic proposals of the 3 presentations. RESULTS: Fifty-eight patients were eligible for inclusion criteria of the ACOSOG Z0011. Treatments actually proposed during MM1 consisted of 94.8 % of chemotherapy, 77.6 % of breast and lymph nodes radiotherapy and 91.4 % of hormone therapy. During the MM2, there was no significant difference compared to the decision taken during MM1. In fact, during MM2, we decided chemotherapy, radiotherapy and hormonotherapy respectively in 89.7, 79.3 and 91.4 % of the cases. During the MM3, it was shown a significant decrease in the indications of chemotherapy (82.8 %, P=0.03) and lymph nodes irradiation (56.9 %, P=0.02) compared to the therapeutic proposals of the MM1. DISCUSSION AND CONCLUSION: The lack of information of ALND does not seem to significantly alter indications for adjuvant treatment. Otherwise, the evolution of our references causes a decrease in adjuvant therapy.

A phase III adjuvant randomised trial of 6 cycles of 5-fluorouracil-epirubicine-cyclophosphamide (FEC100) versus 4 FEC 100 followed by 4 Taxol (FEC-T) in node positive breast cancer patients (Trial B2000).

BACKGROUND: Standard adjuvant chemotherapy regimens for patients with node positive (N+) breast cancer consisted of anthracycline followed by taxane. The European Association for Research in Oncology embarked in 2000 on a phase III trial comparing 6 cycles of FEC100 versus 4 FEC100 followed by 4 Taxol. Primary end-point was disease free survival. Secondary end-points were overall survival, local recurrence free interval, metastases free interval and safety. PATIENTS AND METHODS: Between March 2000 and December 2002, 837 patients were randomised between 6FEC100 for 6 cycles (417patients) or FEC100 for 4 cycles then Taxol 175mg/m(2)/3 weeks for 4 cycles (4FEC100-4T) (420 patients). One thousand patients had been planned initially but the trial was closed earlier due to slow accrual. RESULTS: Hazard ratios (HRs) were 0.99 for disease-free survival (DFS) (95%CI: 0.77-1.26; p=0.91), and 0.85 for overall survival (OS) (95%CI: 0.62-1.15; p=0.29). Nine-year DFS were 62.9% versus 62.5% for 6FEC100 and 4FEC100-4T, respectively. Nine-year OS were 73.9% versus 77% for 6FEC100 and 4FEC100-4T, respectively. Toxicity analyses based on 803 evaluable patients showed that overall grade 3-4 toxicities were similar in both arms (63% versus 58% for 6FEC100 arm and 4FEC100-4T arm, respectively; p=0.16). CONCLUSION: In this trial replacing the last 2 FEC100 cycles of 6FEC100 regimen by 4 Taxol does not lead to a discernable DFS or OS advantage. The lack of a significant difference between the randomised treatment arms may however be due to a lack of power of this trial to detect small, yet clinically worthwhile, treatment benefits.

[Phyllodes tumors and breast sarcomas: a review]. / Tumeurs phyllodes et sarcomes du sein: mise au point.

Phyllodes tumors and sarcomas of the breast are non-epithelial tumors of the breast. Phyllodes tumors are benign tumors, tumors of intermediate malignancy or malignant tumors. The differential diagnosis with a very proliferant fibroadenoma may be difficult. Histological sub-type, type of surgery (definitive or not) and stromal proliferation determine the prognosis. There is a risk of local relapse and distant metastases, in particular to the lung. Surgery (often radical) is the standard treatment. Radiotherapy is recommended in case of high-grade tumor and after conservativetreatment. Breast sarcomas are even rarer. All histological types exist with a predominance of histiofibrocytome type tumors. Grade, involved margins and sometimes tumor necrosis are major prognostics factors. Among the various sub-types, angiosarcoma is characterized by a high risk of occurrence in irradiated fields and by a poor prognosis with a high risk of lung metastases. The treatment is mostly based on mastectomy without lymph node dissection given the exceptional flooding axillary. In some situations, a conservative treatment can be discussed, based on tumor size, grade and volume of the breast. Locoregional radiotherapy is often proposed for tumors over 5 cm and/or of high grade. Systemic chemotherapy is not a standard but should be discussed in the forms at high risk of relapse (like angiosarcoma).

A phase II study of Yondelis (trabectedin, ET-743) as a 24-h continuous intravenous infusion in pretreated advanced breast cancer.

Yondelis (trabectedin, ET-743) is a novel marine-derived anticancer compound found in the ascidian Ecteinascidia turbinata. It is currently under phase II/III development in breast cancer, hormone refractory prostate cancer, sarcomas and ovarian cancer. Activity in breast cancer experimental models has been reported, and preliminary evidence of activity in this setting during the phase I programme has also been observed. The present study assessed the activity and feasibility of trabectedin in women with advanced breast cancer previously treated with conventional therapies. Patients with advanced disease previously treated with at least one but not more than two regimens that included taxanes or anthracyclines as palliative therapy were eligible. Trabectedin 1.5 mg m(-2) was administered as a 24-h continuous infusion every 3 weeks. Patients were kept on therapy until disease progression, unacceptable toxicity or patient refusal. Twenty-seven patients were included between April 1999 and September 2000. Their median age was 54 years (range: 36-67) and 63% of them had two metastatic sites. Twenty-two patients were performance status 1. All patients had previously received anthracyclines, and 23 out of 27 patients had received taxanes. Of 21 patients with measurable disease, three confirmed partial responses, one unconfirmed partial response and two minor responses (49 and 32% tumour shrinkage) were observed; six patients had stable disease. Median survival was 10 months (95% confidence interval: 4.88-15.18). Transient and noncumulative transaminitis was observed in most of the patients. The pharmacokinetic profile of trabectedin in this patient's population is in line with the overall data available with this schedule. The policy of dose adjustments based on the intercycle peaks of bilirubin and alkaline phosphatase appears to have a positive impact in the therapeutic index of trabectedin. Trabectedin can induce response and tumour control in previously treated advanced breast cancer, with manageable toxicity, thus warranting further development as a single agent or in combination regimens.

Dealing with metastatic breast cancer in elderly women: results from a French study on a large cohort carried out by the 'Observatory on Elderly Patients'.

BACKGROUND: Treatment of elderly patients with metastatic breast cancer (MBC) is not clearly defined and seems to vary according to the subjective appreciation of the physician. PATIENTS AND METHODS: After interviewing 107 French specialists qualified in oncology, data concerning 1009 MBC patients were collected: 500 patients were between 65 and 74 years and 509 were >75 years of age. Differences in diagnosis and treatment strategy were analyzed for both age groups to identify the physician's criteria of choice and the eventual use of the geriatric assessment among those criteria. RESULTS: At diagnosis, synchronous metastatic disease was more frequent in patients over 75 years old (52% versus 39%; P<0.001). Physicians indicated that treatment was based on age and on a subjective evaluation of the patient's general status. Sixty-eight per cent of younger patients and only 31% of older ones received chemotherapy (P<0.001). In the older group drug doses were lower than those usually recommended in three-quarters of cases. Only 10% of physicians considered that they under-treat patients using the FEC 50 regimen. Over 75 years of age, hormone therapy was offered to most patients, including 8% with hormone-independent tumors. Geriatric covariates were never considered. Geriatricians rarely, if ever, played a role in the therapeutic decision. CONCLUSIONS: Inclusion of elderly patients with MBC in prospective trials is warranted to define standards of care and reduce heterogeneity in the decision-making process.

[Chemotherapy in soft tissue sarcomas]. / La chimiothérapie des sarcomes des tissus mous.

Despite they represent an heterogeneous entity, the same protocols were applied to all subtypes of soft-tissue sarcomas until recently. Although doxorubicin and ifosfamide remain the cornerstone of therapy, their association yields enhanced response rates but has no obvious effect on survival. The benefit of adjuvant therapy is still matter of debate; however, it seems to improve relapse-free survival and might of particular interest for patients with high-grade tumours of the extremities. Yet, the major change occurring over the past few years is probably the development of subtype-specific regimens. Whether targeted therapies could provide additional benefit is a major concern but further studies are needed.

Efficacy and safety of single agent capecitabine in pretreated metastatic breast cancer patients from the French compassionate use program.

BACKGROUND: A retrospective source review identifying predictive factors and assessing safety and efficacy in pretreated metastatic breast cancer (MBC) patients treated with capecitabine in a French compassionate-use program. PATIENTS AND METHODS: 197 patients received capecitabine at an initial total dose 0.25-3.0 g/m2/day, twice daily for 14 consecutive days, every 3 weeks. RESULTS: Median patient age was 56 years (range, 31-88), 19% had performance status (PS) 3-4. Prior palliative and adjuvant treatment was reported in 96 and 61% of patients respectively. Best overall response rate (ORR) was 15% (95% confidence interval [CI], 11-21%) and 49% had benefit (CR, PR or SD). Median time to progression (TTP) and overall survival were 4.8 and 14.7 months, respectively. Median TTP in responders was 8.9 months (95%CI 6.1-11.7). Grade 3/4 neutropenia and grade 3 thrombocytopenia occurred in 8 and 3% of patients respectively. Hand-foot syndrome (grade 3/4 in 16% of patients), diarrhea, stomatitis and asthenia were prevalent. Multivariate analysis showed ORR was significantly influenced by PS > or = 2 (p = 0.004), time from metastases diagnosis to capecitabine treatment (p = 0.015) and presence of liver metastases at inclusion (p = 0.047). Abnormal liver function tests at baseline were associated with severe thrombocytopenia and anemia. Four treatment-related deaths occurred. CONCLUSION: Capecitabine is active in heavily pretreated MBC patients and has a favorable toxicity profile with the added advantage of being an oral drug administered in an outpatient setting.

Multimodal therapy with intravenous biweekly leucovorin, 5-fluorouracil and irinotecan combined with hepatic arterial infusion pirarubicin in non-resectable hepatic metastases from colorectal cancer (a European Association for Research in Oncology trial).

BACKGROUND: The purpose of this study was to evaluate the tolerance and efficacy of combining i.v. irinotecan, 5-fluorouracil (5-FU) and leucovorin (LV) with hepatic arterial infusion (HAI) of pirarubicin in non-resectable liver metastases from colorectal cancer. PATIENTS AND METHODS: Thirty-one patients were included in a phase II trial with i.v. irinotecan/5-FU/LV administered every 2 weeks, combined with HAI pirarubicin 60 mg/m(2) on day 1 every 4 weeks. In most cases HAI was administered via a percutaneous catheter. RESULTS: The main grade 3/4 toxicity was neutropenia, encountered in 78% of the patients. When all patients were considered in the analysis, tumour response rate was 15 out of 31 [48%; 95% confidence interval (CI) 32% to 65%]. Liver resection was made possible in 11 patients (35%; 95% CI 21% to 53%). There were no toxic death. Median overall survival was 20.5 months, and median progression-free survival was 9.1 months. In patients with completely resected metastases, median overall survival was not reached and median progression-free survival was 20.2 months. CONCLUSION: The multimodality approach used in the present study was well-tolerated and yielded dramatic responses. An aggressive approach combining i.v. and HAI chemotherapy deserves further investigation.

Phase II study of pemetrexed in breast cancer patients pretreated with anthracyclines.

BACKGROUND: To assess antitumor activity and toxicity of pemetrexed in metastatic breast cancer (MBC) patients previously treated with anthracyclines. PATIENTS AND METHODS: Seventy-seven MBC patients from 12 European institutions were entered into the study. Seventy-two patients were considered evaluable for response and toxicity. Forty-two patients were classified as anthracycline-failure (relapse >30 days after completion of a prior anthracycline regimen) and 30 as anthracycline-refractory (progression within 30 days after anthracycline therapy). Pemetrexed 600 mg/m(2) was administered intravenously every 3 weeks until progressive disease or unacceptable toxicity. RESULTS: There were three complete and 12 partial responders [response rate 21% (95% confidence interval 12%)]. Response rates in the anthracycline-failure and anthracycline-refractory groups were 24% and 17%, respectively. A subset of 31 patients pretreated with anthracyclines and taxanes had a response rate of 26%. Median duration of response and median survival were 5.5 and 10.7 months, respectively (13 months in the failure group and 5.7 months for refractory). Grade 3/4 toxicities included neutropenia and thrombocytopenia in 56% and 19% of patients, respectively. Nine patients (12%) experienced neutropenic fever. Grade 3/4 non-hematological toxicities included skin rash (10%), nausea (12%), fatigue (10%) and stomatitis (5%). CONCLUSION: Our trial demonstrates pemetrexed to be active in breast cancer, with manageable toxicity. Activity of pemetrexed did not appear to be adversely affected by prior taxane, 5-fluorouracil or endocrine treatments.

Prognostic factors in primary breast sarcomas: a series of patients with long-term follow-up.

PURPOSE: To describe the pathologic characteristics and prognostic factors of primary breast sarcomas (PBSs). PATIENTS AND METHODS: We reviewed the clinical records and pathologic slides of 83 women with PBS treated in our institution between 1954 and 1991, with a median follow-up of 7.8 years. The majority of patients had undergone surgical treatment. RESULTS: The main histologic type was malignant fibrohistiocytoma (n = 57). For the whole population, the 10-year overall survival (OS) and disease-free survival (DFS) rates were 62% and 50%, respectively. For Fédération Nationale des Centres de Lutte Contre le Cancer grade 1, 2, and 3 tumors, the 10-year OS and DFS rates were 82% and 61%, 62% and 51%, and 36% and 25%, respectively (P =.00007 and.004, respectively). For tumors measuring less than 5 cm, 5 to 10 cm, and more than 10 cm, the 10-year OS and DFS rates were 76% and 66%, 68% and 55%, and 28% and 15%, respectively (P =.002 and.009, respectively). In the multivariate analysis, the tumor size and histologic grade were correlated with the 10-year DFS rate (P =.04 and.01, respectively), but only the histologic grade was correlated with OS (P =.01). Angiosarcoma was the only histologic type significantly associated with a poorer outcome in the multivariate analysis. CONCLUSION: PBSs have the same clinical history and prognostic factors as sarcomas arising at other sites. Therefore, it is legitimate to use a similar treatment strategy for PBS as for other sarcomas.

Phase II study of oxaliplatin and fluorouracil in taxane- and anthracycline-pretreated breast cancer patients.

PURPOSE: Phase II study evaluating efficacy and safety of combined oxaliplatin/fluorouracil (5-FU) in taxane-pretreated advanced and metastatic breast cancer (ABC) patients. PATIENTS AND METHODS: Sixty-four taxane- and anthracycline-pretreated (within 6 months of study entry) women were treated with oxaliplatin 130 mg/m(2) (2-hour intravenous [IV] infusion), day 1, and 5-FU 1,000 mg/m(2)/d (continuous IV infusion) days 1 to 4, every 3 weeks. RESULTS: Median patient age was 51 years (range, 34 to 71 years), with a median of two involved organs (range, one to six organs), and metastases in the liver (70%), bone (47%), and lung (34%). Patients had a median of two prior chemotherapy regimens (range, one to six regimens), and 78% had previous hormonal therapy, with clinical taxane and anthracycline resistance in 53% and 34%, respectively. A total of 367 cycles were administered, with a median of six cycles/patient (range, one to 15 cycles). Sixty patients were assessable for response (World Health Organization criteria): 17 partial response, 26 stable disease, and 17 disease progression, giving an overall response rate of 27% (95% confidence interval, 16.3% to 39.1%), and 26% and 36% in taxane- and anthracycline-resistant populations, respectively, all responders having metastatic liver disease. Median time to progression was 4.8 months, and median overall survival was 11.9 months. Four treatment-related serious adverse events occurred, seven patients withdrew because of treatment-related toxicity. Hematotoxicity was prevalent but rarely severe, with grade 3-4 neutropenia, leukopenia, and thrombocytopenia in 34%, 19%, and 16% of patients, respectively, and a single episode of febrile neutropenia. One third of patients developed grade 2-3 peripheral neuropathy (oxaliplatin-specific scale), with grade 3 in only 8%. CONCLUSION: This oxaliplatin/5-FU combination is effective with an excellent safety profile in anthracycline/taxane-pretreated ABC patients, showing encouraging activity in patients with anthracycline/taxane-resistance or visceral disease.

Weekly vinorelbine is an effective palliative regimen after failure with anthracyclines and taxanes in metastatic breast carcinoma.

BACKGROUND: Currently, there is no gold standard for the treatment of patients with metastatic breast carcinoma who have experienced failure with anthracyclines and taxanes. A biologic rationale suggests that the mechanism of taxane resistance could be because of an excess of depolymerized tubulin that could enhance sensitivity to vinorelbine. The objective of the study was to assess the tolerance and efficiency of weekly vinorelbine in metastatic breast carcinoma after failure with taxanes. METHODS: Patients with measurable disease, a World Health Organization performance status of less than 3 and a life expectancy longer than 3 months were eligible. Persistent taxane-induced neuropathy higher than Grade 1 was an exclusion criterion. The initial planned dose was 30 mg/m(2)/week on an outpatient basis without granulocyte colony-stimulating factor (G-CSF). Neutrophil and platelet counts of 1.0 and 80 g/L, respectively, were required before each new injection; otherwise vinorelbine was delayed for 7 days with a dose reduction of 5 mg/m(2) at the second episode. The dose also was reduced if Grade 3 or 4 toxicity occurred. If the adverse event persisted or if the delay exceeded 14 days between 2 injections given at a dose of 20 mg/m(2), vinorelbine was definitively discontinued. RESULTS: Between November 1997 and March 1999, 40 patients with a median age of 49 (range, 39-69) were enrolled. All of them had previously received anthracyclines and taxanes. Because of the delays in neutrophil recovery, the median dose intensity did not exceed 22.5 mg/m(2)/week (range, 11.25-30), and the initial planned dose of 30 mg/m(2)/week appeared unfeasible without G-CSF. The starting dose therefore was 25 mg/m(2)/week after the first 6 patients. Neutropenia led to fever in only three patients. Other severe toxicities were Grade 2-3 neuropathy (n = 5), Grade 2-3 ileus (n = 7), Grade 3 anemia (n = 4), and Grade 3 sepsis (n = 1). Objective responses were observed in 10 of 40 patients (25%), 7 of whom had visceral metastases and 4 who were refractory to taxanes (including 2 patients with liver involvement > 50%). The median time to failure was 6 months (range, 4-12) for responding patients. Disease stabilization was achieved in 9 patients (23%) for a median duration of 5 months (range, 4-6). The median survival duration for the whole population was 6 months (range, 2-18+). CONCLUSIONS: Weekly vinorelbine is an active salvage therapy for metastatic breast carcinoma after failure with anthracyclines and taxanes, even in patients with taxane-refractory metastatic breast carcinoma. This confirms that vinorelbine and taxanes are not cross-resistant.

Single-agent estramustine phosphate (EMP) is active in advanced breast cancer after failure with anthracyclines and taxanes.

PURPOSE: Estramustine phosphate (EMP) is an oral cytotoxic agent that depolymerizes tubuline, a mechanism of action that has been revisited during the last decade. Because of its lack of haematological toxicity and favourable tolerance profile, EMP is a good candidate for palliative chemotherapy. The aim of the study was to assess its tolerance and efficacy in advanced breast cancer after failure with usual regimens. PATIENTS AND METHODS: Patients with a life expectancy of at least 12 weeks and bi-dimensionally measurable disease having received at least 1 line of chemotherapy (including taxanes and/or anthracyclines) for advanced breast cancer (ABC) were eligible. EMP was given daily at a dose of 10 mg/kg until disease progression, unacceptable toxicity or patient refusal to continue chemotherapy. RESULTS: Forty patients were included between June 1998 and December 1999. Patients had previously received one to eight chemotherapy regimens (median is two) for ABC. Twenty-two patients (55%) had visceral involvement and eighteen patients (45%) had osseous, chest wall or soft tissue metastases. Adverse events leading to early interruption of EMP were grade 2 allergy (n = 1), grade 2-3 nausea (n = 6), deep-vein thrombosis (n = 1), grade 3 sepsis (n = 1). One patient died at twenty-four weeks from pulmonary embolism, and another at fourteen weeks from unknown cause. Seven objective responses were observed (17.5%; 95% confidence interval (CI): 6%-30%). Median time to failure was 24 weeks (14-52+) in responding patients. All objective responses but one were observed in patients with visceral metastases. In 10 other patients (25%), disease remained stable with a median time to failure of 27 weeks (16-50); 6 of these experienced a decrease of consumption of analgesics or an improvement of performance status. CONCLUSION: EMP is an active drug in ABC after failure with taxanes and anthracyclines, whose tolerance profile appears favourable.

A before-after study using OncoDoc, a guideline-based decision support-system on breast cancer management: impact upon physician prescribing behaviour.

Guideline-based decision support systems have been developed to influence the prescribing behaviour of clinicians, but they have not yet shown to increase physician compliance with best practices in routine. OncoDoc is a non-automated system that allows flexibility in guideline interpretation to obtain best patient-specific recommendations at the point of care. OncoDoc is applied to breast cancer management. We have experimented the system at the Institut Gustave Roussy with a before-after study in which treatment decisions for breast cancer patients were measured before and after using the system in order to evaluate its impact upon physicians' prescribing behaviour. After 4 months, 127 decisions were recorded. Physicians compliance with OncoDoc was significantly improved (p < 10(-4) ) to reach 85.03% after using the system. Comparison of initial and final decisions showed that physicians modified their prescription in 31% of the cases. Clinical trial accrual rate increased of 50%, though not statistically significant because estimated on small figures.

Chemotherapy of nonoperable colorectal liver metastases.

Biomodulated 5-fluorouracil-based therapy is the mainstay of treatment for advanced colorectal cancer. Patients with advanced disease do better with chemotherapy than they do without, but the overall survival in these patients is still poor. Combination of infusional and bolus 5-fluorouracil/folinic acid (leucovorin) regimens with newer agents, such as CPT-11 and oxaliplatin, in the fist-line treatment of patients with advanced colorectal cancer, has yielded increased response rates and progression-free survivals. In the case of CPT-11 this has also led to an increase in overall survival. Improved therapy combinations and the delivery of the therapy directly to the liver by hepatic arterial infusion, either alone or in combination with intravenous delivery, all herald an improvement in the clinical outcome of patients with nonoperable liver metastases. These patients should be offered the best chemotherapy option available coupled, where appropriate, with liver resection.

Gastric metastases from breast cancer: a retrospective series of 12 patients.

Although well described in the literature, gastric metastases are often misdiagnosed in patients with breast cancer. The accuracy of diagnosis is critical because systemic therapy is beneficial, affording symptom palliation and an opportunity to avoid an unnecessary gastrectomy.