Supportive Care Organization in France: a national in-depth survey among patients and oncologists.

PURPOSE: Medical doctors' (MDs), but not patients', perception of supportive care in cancer (SCC) in France has been previously assessed in a national survey. This study evaluated MDs and patients' perceptions of the SCC organization and implementation in France. METHODS: The French SCC Association conducted two observational studies: study 1 (S1), containing a 30-point questionnaire sent to 2263 MDs, and study 2 (S2), containing a 40-point questionnaire sent to 2000 patients. RESULTS: Overall, 711 MDs completed S1 and 1562 patients completed S2. In S1, 81% of MDs reported relying on a SCC organization and 76% attended SCC multidisciplinary discussions. MDs considered palliative (98%), psychological (98%), and social care (98%) as the top 3 SCC areas of importance for patients. In contrast, patients' priorities were psychology (61%), nutrition (55%) and organization of intake consultations (55%). The concept of SCC was familiar to 34% of patients; according to MDs, this concept was introduced mainly by MDs (78%) and admission nurses (41%). Outpatients identified as professional resources for SCC information general practitioners (84%), nurses (58%), and pharmacists (52%). Patients reported supportive treatment being prescribed in 63% of cases, with 64% receiving information on the negative side-effects. Among MDs, 87% reported proposing palliative and 41% adjuvant SCC treatment. Furthermore, 72% of MDs recommended SCC treatment at the metastatic stage, and 36% immediately following diagnosis. DISCUSSION: Oncologists play a vital role in enhancing SCC efficacy. This can be increased by implementing a multidisciplinary integrated approach or by assuring the availability of patient information.

Recommandations francophones pour la pratique clinique concernant la prise en charge des cancers du sein de Saint-Paul-de-Vence 2022-2023.

With more than 60,000 new cases of breast cancer in mainland France in 2023 and 8% of all cancer deaths, breast cancer is the leading cancer in women in terms of incidence and mortality. While the number of new cases has almost doubled in 30 years, the percentage of patients at all stages alive at 5 years (87%) and 10 years (76%) testifies to the major progress made in terms of screening, characterisation and treatment. However, this progress, rapid as it is, needs to be evaluated and integrated into an overall strategy, taking into account the characteristics of the disease (stage and biology), as well as those of the patients being treated. These are the objectives of the St Paul-de-Vence recommendations for clinical practice. We report here the summary of the votes, discussions and conclusions of the Saint-Paul-de-Vence 2022-2023 RPCs.

Efficacy of trastuzumab in routine clinical practice and after progression for metastatic breast cancer patients: the observational Hermine study.

BACKGROUND: The Hermine study observed the use of trastuzumab for metastatic breast cancer (MBC) in routine practice, including patients who received trastuzumab treatment beyond progression (TBP). PATIENTS AND METHODS: The study observed 623 patients for > or = 2 years. Treatment was given according to oncologists' normal clinical practices. Endpoints included duration of treatment, efficacy, and cardiac safety. The TBP subanalysis compared overall survival (OS) in 177 patients who received first-line trastuzumab and either continued trastuzumab for > or = 30 days following progression or stopped at or before progression. RESULTS: The median treatment duration was 13.3 months. In the first-, second-, and third-line or beyond treatment groups, the median time to progression (TTP) were 10.3 months, 9.0 months, and 6.3 months, and the median OS times were 30.3 months, 27.1 months, and 23.2 months, respectively. Heart failure was observed in 2.6% of patients, although no cardiac-associated deaths occurred. In the TBP subanalysis, the median OS duration from treatment initiation and time of disease progression were longer in patients who continued receiving trastuzumab TBP (>27.8 months and 21.3 months, respectively) than in those who stopped (16.8 months and 4.6 months, respectively). However, the groups were not completely comparable, because patients who continued trastuzumab TBP had better prognoses at treatment initiation. The median TTP was longer in patients who continued trastuzumab TBP (10.2 months) than in those who stopped (7.1 months). CONCLUSION: The Hermine findings confirm that the pivotal trials of first-line trastuzumab treatment in MBC patients are applicable in clinical practice. The subanalysis suggests that trastuzumab TBP offers a survival benefit to MBC patients treated with first-line trastuzumab.

Fertility preservation, contraception and menopause hormone therapy in women treated for rare ovarian tumours: guidelines from the French national network dedicated to rare gynaecological cancers.

INTRODUCTION: Rare ovarian tumours include complex borderline ovarian tumours, sex-cord tumours, germ cell tumours and rare epithelial tumours. Indications and modalities of fertility preservation (FP), infertility management, contraindications for hormonal contraception or menopause hormone therapy are frequent issues in clinical practice. A panel of experts from the French national network dedicated to rare gynaecological cancers, and experts in reproductive medicine and gynaecology have built guidelines on FP, contraception and menopause hormone therapy in women treated for ovarian rare tumours. MATERIAL AND METHODS: A panel of 35 experts from different specialties contributed to the preparation of the guidelines, following the DELPHI method (formal consensus method). Statements were drafted after a systematic literature review and then rated through two successive rounds. RESULTS: Thirty-five recommendations were identified, concerning indications for FP, contraindications for ovarian stimulation, contraceptive options and menopause hormone therapy for each tumour type. DISCUSSION: Overall, caution has been recommended in the case of potentially hormone-sensitive tumours such as sex-cord tumours, serous and endometrioid low-grade adenocarcinomas, as well as for high-risk serous borderline ovarian tumours. CONCLUSION: In the context of a scarce literature, a formal consensus method allowed the elaboration of guidelines, which will help clinicians in the management of these patients.

Impact of organised programs on colorectal cancer screening.

PURPOSE: Colorectal cancer (CRC) screening has been shown to decrease CRC mortality. Organised mass screening programs are being implemented in France. Its perception in the general population and by general practitioners is not well known. METHODS: Two nationwide observational telephone surveys were conducted in early 2005. First among a representative sample of subjects living in France and aged between 50 and 74 years that covered both geographical departments with and without implemented screening services. Second among General Practionners (Gps). Descriptive and multiple logistic regression was carried out. RESULTS: Twenty-five percent of the persons(N = 1509) reported having undergone at least one CRC screening, 18% of the 600 interviewed GPs reported recommending a screening test for CRC systematically to their patients aged 50-74 years. The odds ratio (OR) of having undergone a screening test using FOBT was 3.91 (95% CI: 2.49-6.16) for those living in organised departments (referent group living in departments without organised screening), almost twice as high as impact educational level (OR = 2.03; 95% CI: 1.19-3.47). CONCLUSION: CRC screening is improved in geographical departments where it is organised by health authorities. In France, an organised screening programs decrease inequalities for CRC screening.

[Fertility preservation, contraception and menopause hormone therapy in women treated for rare ovarian tumors: Guidelines from the French national network dedicated to rare gynaecological cancer]. / Préservation de la fertilité, contraception et traitement hormonal de la ménopause chez les femmes traitées pour tumeurs malignes rares de l'ovaire : recommandations du réseau national dédié aux cancers gynécologiques rares (TMRG/GINECO).

INTRODUCTION: Rare ovarian tumors include complex borderline ovarian tumors, sex-cord tumors, germ cell tumors, and rare epithelial tumors. Indications and modalities of fertility preservation, infertility management and contraindications for hormonal contraception or menopause hormone therapy are frequent issues in clinical practice. A panel of experts from the French national network dedicated to rare gynaecological cancers, and of experts in reproductive medicine and gynaecology have worked on guidelines about fertility preservation, contraception and menopause hormone therapy in women treated for ovarian rare tumors. METHODS: A panel of 39 experts from different specialties contributed to the preparation of the guidelines, following the DELPHI method (formal consensus method). Statements were drafted after a systematic literature review, and then rated through two successive rounds. RESULTS: Thirty-five recommendations were selected, and concerned indications for fertility preservation, contraindications for ovarian stimulation (in the context of fertility preservation or for infertility management), contraceptive options (especially hormonal ones), and menopause hormone therapy for each tumor type. Overall, prudence has been recommended in the case of potentially hormone-sensitive tumors such as sex cord tumors, serous and endometrioid low-grade adenocarcinomas, as well as for high-risk serous borderline ovarian tumors. DISCUSSION: In the context of a scarce literature, a formal consensus method allowed the elaboration of guidelines, which will help clinicians in the management of these patients.

Novel therapeutic strategies combining antihormonal and biological targeted therapies in breast cancer: focus on clinical trials and perspectives.

Several models have been proposed to explain the mechanisms of endocrine resistance including aberrant growth-signaling pathways, and have led to the rational design of studies combining hormonotherapy with signal transduction inhibitors (STI) in advanced breast cancer. This article reviews the current status of these clinical trials. Preliminary results from the randomized controlled trials are rather disappointing. The mTOR inhibitor temsirolimus and the farnesyl transferase inhibitor tipifarnib combined with letrozole did not show any benefit compared to letrozole alone. As neoadjuvant therapy, gefinitib did not enhance the response rate induced by anastrozole. Interesting results were obtained with exemestane combined to celecoxib but should be further explored with adequate cardiac monitoring. Trastuzumab combined with anastrozole was more effective than anastrozole in terms of response rate and progression-free survival but not survival. Several controlled trials as first- or second-line therapy have started recently and over the next few years we should learn whether this approach will provide significant gains in efficacy.

Pharmacogenetics of capecitabine in advanced breast cancer patients.

PURPOSE: Germinal gene polymorphisms can explain a part of the interpatient pharmacodynamic variability of anticancer drugs, particularly fluoropyrimidines. Genes for which polymorphisms may potentially influence pharmacodynamics of fluoropyrimidines, including capecitabine, are thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and dihydropyrimidine dehydrogenase (DPD). EXPERIMENTAL DESIGN: The aim of this prospective pilot study was to analyze the effect of TS, MTHFR, and DPD gene polymorphisms on toxicity and efficacy in advanced breast cancer patients receiving capecitabine as monotherapy. Germinal polymorphisms of TS (6 bp deletion in the 3' region and 28 bp repeats, including G>C mutation in the 5' region), MTHFR (677C>T and 1298A>C), and DPD (IVS14+1G>A) were determined in 105 consecutive patients. RESULTS: A trend toward a higher global toxicity grade 3 and 4 was observed in patients homozygous for the TS 3RG allele compared with patients heterozygous for the 3RG allele or patients not carrying the 3RG allele (50% versus 19% versus 13% respectively, P=0.064). The sole patient bearing the DPD IVS14+1G>A mutation (heterozygous) deceased from hematologic toxicity. The median response duration was 5.8 months (95% confidence interval, 4.3-7.2). Duration of response was significantly shortened in patients homozygous for the 3RG allele compared with others (P=0.037). CONCLUSIONS: The present data suggest that 3RG3RG breast cancer patients are not good candidates for capecitabine therapy. In addition, attention should be paid to DPD deficiency in breast cancer patients receiving capecitabine. These preliminary data require further confirmation on a larger number of patients.

Mise à jour 2016 des recommandations pour la pratique clinique de Nice/Saint-Paul-de-Vence dans le cancer de l'ovaire et du col de l'utérus à un stade avancé.

UPDATED 2016 RECOMMENDATIONS FOR THE CLINICAL PRACTICE OF NICE/SAINT-PAUL-DE-VENCE IN OVARIAN CANCER AND ADVANCED CERVICAL CANCER: Since the first edition of the 2012-2013 Clinical Practice Recommendations Nice-Saint-Paul for gynecological cancers, the management of ovarian cancer has become more complex with a better definition of histological subtypes of ovarian cancers, the update of the anatomo-clinical classifications, the evolution of the recommended quality criteria for surgery. In addition, the integration of new medical options, such as PARP inhibitors, requires us to review our management of ovarian cnacer patients (including early systematic oncogenetic research of homologous recombination pathway deficiency). Similarly, medical treatment has evolved in advanced cervical cancer with the new option of bévacizumab therapy. On behalf of the GINECO group, we have updated the guidelines for ovarian epithelial cancer (excepted rare tumors) and advanced cervical cancer in order to allow rapid dissemination of the latest advances to the medical community in order to adjust the daily practice.

Epirubicin increases long-term survival in adjuvant chemotherapy of patients with poor-prognosis, node-positive, early breast cancer: 10-year follow-up results of the French Adjuvant Study Group 05 randomized trial.

PURPOSE: The French Adjuvant Study Group 05 (FASG-05) showed that fluorouracil 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 100 mg/m2 (FEC 100) was superior to the same regimen with epirubicin 50 mg/m2 (FEC 50) in terms of disease-free survival (DFS) and overall survival (OS) in adjuvant treatment of early breast cancer. We report 10-year data on efficacy, and long-term side effects for FASG-05. PATIENTS AND METHODS: We randomly assigned 565 patients to treatment with FEC 50 or FEC 100 after surgery. Postmenopausal patients also received tamoxifen for 3 years, and almost all patients (96%) also received radiotherapy. RESULTS: Median follow-up was 110 months. The 10-year DFS was 45.3% (95% CI, 41.9% to 48.7%) with FEC 50 and 50.7% (95% CI, 47.3% to 54.1%) with FEC 100 (Wilcoxon P = .036; log-rank P = .08). The 10-year OS was 50.0% (95% CI, 46.7% to 53.3%) with FEC 50 and 54.8% (95% CI, 51.3% to 58.3%) with FEC 100 (Wilcoxon P = .038; log-rank P = .05). Delayed cardiac toxicity (before relapse) occurred in four patients (1.5%) in the FEC 50 arm and three patients (1.1%) in the FEC 100 arm. Cardiac toxicity after relapse occurred in six (4.3%) and five (4.1%) patients treated with FEC 50 and FEC 100, respectively. CONCLUSION: Treatment with adjuvant FEC 100 demonstrated superior DFS and OS versus FEC 50 at 10 years of follow-up. This survival advantage was not offset by long-term complications such as cardiac toxicity and second malignancy. Given the risk-benefit ratio, FEC 100 is a more optimal regimen for long-term survival in patients with poor prognosis.

[Perception of pT1a,b pN0 breast tumor prognosis by the French oncology community: Results of the EURISTIC national survey]. / Perception du pronostic des tumeurs mammaires pT1a,b pN0 par la communauté oncologique française : résultats de l'enquête nationale EURISTIC.

The prognosis of infracentimetric breast cancers (BC) is heterogeneous. The EURISTIC survey describes how French oncology specialists perceive the prognosis of pT1a,b pN0 BCs. A self-administered questionnaire has been sent to over 2000 French BC specialists. Six hundred and sixty-three physicians responded. Fifty-eight percent do not consider tumor size as a key prognostic criterion. They consider that the cutoff for poor prognosis is 22mm, 10mm and 7mm for hormone receptors (HRs)+, HER2+ and triple-negative (TN) tumors respectively. Eighty-three percent of respondents consider that a HR+ pT1a,b tumor has a good prognosis (21% and 8% for HER2+ and TN respectively). Factors perceived as most detrimental are: HER2 overexpression (29% of respondents); HR- (20%); high grade (20%); TN status (14%); high KI67 (5%); presence of lymphovascular invasion (3%); young age (2%) and high mitotic index (1%). For French specialists, immunohistochemical characteristics, in particular hormone and HER2 status, are strong prognostic factors in BCs below 1cm.

Breast cancer with synchronous metastases: trends in survival during a 14-year period.

PURPOSE: Although new drugs were approved during the 1990s for the treatment of metastatic breast cancer, it is not clear whether their use has changed the outcome of patients in daily practice. This study sought to determine whether survival has improved over time for breast cancer patients who had metastases at diagnosis. PATIENTS AND METHODS: A total of 724 patients have been treated in three French cancer centers for an initially metastatic breast cancer between 1987 and 2000; 343 were diagnosed between 1987 and 1993, and 381 were diagnosed between 1994 and 2000. Tumor characteristics, treatments, and outcomes of these patients were compared by chi(2) test, log-rank test, and Cox regression analysis. RESULTS: Characteristics were not different between the patients diagnosed from 1987 to 1993 and those diagnosed from 1994 to 2000. Ten percent of patients treated from 1987 to 1994 and 58% of patients treated from 1994 to 2000 have received either a taxane or a new aromatase inhibitor. The 3-year overall survival rates were 27% for patients treated from 1987 to 1993 and 44% for patients treated from 1994 to 2000 (P <.001). The treatment period (1994 to 2000 v 1987 to 1993) was a prognostic factor in multivariate analysis (relative risk, 0.6; P <.001). CONCLUSION: The survival of breast cancer patients presenting with metastases at diagnosis has improved over time. This study strongly suggests that this improvement is related to treatment.

Randomized parallel study of doxorubicin plus paclitaxel and doxorubicin plus cyclophosphamide as neoadjuvant treatment of patients with breast cancer.

PURPOSE: This randomized, noncomparative, parallel-group study was designed to evaluate the pathologic complete response (pCR) rate of combined doxorubicin plus paclitaxel (AP) and doxorubicin plus cyclophosphamide (AC) as neoadjuvant chemotherapy in patients with previously untreated breast cancer who were unsuitable for conservative surgery. PATIENTS AND METHODS: A total of 200 patients with T2-3, N0-1, M0 disease were randomly assigned in a 2:1 ratio to receive preoperative chemotherapy with either doxorubicin 60 mg/m(2) plus paclitaxel 200 mg/m(2) as a 3-hour infusion (AP) or doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2) (AC) every 3 weeks for 4 courses followed by surgery. RESULTS: A pCR (eradication of invasive carcinoma in tumor and in axillary lymph nodes) was found in 16% and 10% of patients in the AP and AC arms, respectively, by study center pathologists, and in 8% and 6% of patients, respectively, by independent pathologists. Patients with pCRs tended to have unifocal disease, tumors with negative hormonal receptor status, and less differentiation (Scarff, Bloom, and Richardson scale grade 3). Breast-conserving surgery was performed in 58% and 45% of patients in the AP and AC arms, respectively. An objective clinical response was achieved in 89% of patients in the AP arm and 70% in the AC arm. At a median follow-up of 31 months, disease-free survival (DFS) was higher in patients who reached pCR versus those without pCR (91% v 70%). CONCLUSION: The encouraging pathologic and clinical responses of patients with breast cancer after neoadjuvant chemotherapy with doxorubicin plus paclitaxel warrant additional investigation of paclitaxel in the neoadjuvant setting of breast cancer management.

Disease-free survival advantage of weekly epirubicin plus tamoxifen versus tamoxifen alone as adjuvant treatment of operable, node-positive, elderly breast cancer patients: 6-year follow-up results of the French adjuvant study group 08 trial.

PURPOSE: To assess whether an epirubicin (EPI) -based chemotherapy plus hormonal regimen improves disease-free (DFS) in women older than 65 years, with node-positive, operable breast cancer (BC), relative to tamoxifen (TAM) alone. PATIENTS AND METHODS: A total of 338 patients were randomly assigned after surgery to receive TAM 30 mg/d for 3 years (TAM, n = 164), or EPI 30 mg on days 1, 8, and 15 every 28 days for six cycles plus TAM 30 mg/d for 3 years (EPI-TAM, n = 174). In both arms, patients received radiotherapy, delivered after chemotherapy (CT) in the EPI-TAM group. RESULTS: The 6-year DFS rates were 69.3% with TAM and 72.6% with EPI-TAM (P = .14). The multivariate analysis shows a relative risk of relapse of 1.93 (95% CI, 1.70 to 2.17) with TAM compared with EPI-TAM (P = .005). The 6-year OS, related to disease progression, was 79.1% and 79.8%, respectively (P = .41). Compliance with CT was good: 96.9% of patients received six cycles. The acute toxicity per patient was mild: grade 2 neutropenia in 5.9%, grade 2 anemia in 2.0%, grade 3 nausea or vomiting in 4.6%, and grade 3 alopecia in 7.2%. Five cases (in five patients) of decreased left ventricular ejection fraction occurred after CT: three after adjuvant CT, and two after anthracycline-based CT for relapse. One patient died as a result of dysrhythmia related to carcinomatous lymphangitis. No secondary leukemia occurred. CONCLUSION: This study conducted in node-positive elderly patients demonstrates a significant contribution of a weekly EPI regimen in terms of DFS. Moreover, this regimen is safe for hematologic, nonhematologic, and cardiac toxicities.

Randomized trial comparing six versus three cycles of epirubicin-based adjuvant chemotherapy in premenopausal, node-positive breast cancer patients: 10-year follow-up results of the French Adjuvant Study Group 01 trial.

PURPOSE: To evaluate the duration and dose intensity of epirubicin-based regimens in premenopausal patients with lymph node-positive breast cancer. PATIENTS AND METHODS: Between 1986 and 1990, 621 patients with operable breast cancer were randomly assigned to receive fluorouracil (Roche SA, Basel, Switzerland) 500 mg/m2, epirubicin (Pharmacia SA, Milan, Italy) 50 mg/m2, and cyclophosphamide (Asta Medica AG, Frankfurt, Germany) 500 mg/m2 every 21 days (FEC 50) for six cycles (6 FEC 50); FEC 50 for three cycles (3 FEC 50); or the same regimen with epirubicin 75 mg/m2 (FEC 75) for three cycles (3 FEC 75). All patients in the three arms received chest wall irradiation at the end of the third cycle. RESULTS: After a 131-month median follow-up, the 10-year disease-free survival (DFS) was 53.4%, 42.5%, and 43.6% (P =.05) in the three arms, respectively. Pairwise comparisons demonstrate that 6 FEC 50 was superior both to 3 FEC 50 (P =.02) and to 3 FEC 75 (P =.05). The 10-year overall survival (OS) for the 6 FEC 50 arm was 64.3%, for the 3 FEC 50 arm it was 56.6%, and for the 3 FEC 75 arm, it was 59.7% (P =.25), respectively. Pairwise comparisons demonstrate that 6 FEC 50 was more effective than 3 FEC 50 (P =.10). Cox regression analysis demonstrates that OS was significantly better in the 6 FEC 50 than in the 3 FEC 50 arm (P =.046). No severe infections (grade 3 to 4), acute cardiac toxicity, or deaths from toxicity have been observed. Only five patients developed delayed cardiac dysfunctions, and three patients developed acute myeloblastic leukemia. CONCLUSION: After a long-term follow-up in an adjuvant setting, the benefit of six cycles of FEC 50 compared with three cycles, whatever the dose, is highly significant in terms of DFS. As regards OS, the group receiving six cycles of FEC 50 has significantly better results than the group receiving three cycles of FEC 50.

The global breast cancer burden: variations in epidemiology and survival.

Breast cancer is the most common type of cancer and the most common cause of cancer-related mortality among women worldwide. However, the burden is not evenly distributed, and, according to the best available data, there are large variations in the incidence, mortality, and survival between different countries and regions and within specific regions. Many complex factors underlie these variations, including population structure (eg, age, race, and ethnicity), lifestyle, environment, socioeconomic status, risk factor prevalence, mammography use, disease stage at diagnosis, and access to high-quality care. We review recent breast cancer incidence and mortality statistics and explore why these vary so greatly across the world. Further research is needed to fully understand the reasons for variations in breast cancer outcomes. This will aid the development of tailored strategies to improve outcomes in general as well as the standard of care for underserved populations and reduce the burden of breast cancer worldwide.

The raltitrexed-vinorelbine combination: a phase I pharmacokinetic and pharmacodynamic trial in advanced breast cancer.

PURPOSE: Combinations of vinorelbine (VRB) and drugs targeting thymidylate synthase (TS) such as 5-fluorouracil (5-FU) have proven clinical efficacy in the management of advanced breast cancer. Raltitrexed (RTX) is a recent TS inhibitor which shows advantages over 5-FU in terms of a lower incidence of toxicity along with a simpler administration schedule. We conducted a phase I trial of the VRB-RTX combination in 12 patients with advanced breast cancer. MATERIALS AND METHODS: Most of the patients were refractory to taxane-anthracycline combination therapy. Their median age was 51 years (range 33-70 years). RTX was given on day 1 and VRB on days 1 and 5 on a 3-week cycle. Three dose levels were initially planned with VRB and RTX increasing from 22.5 to 25 mg/m(2) and from 2.5 to 3 mg/m(2), respectively. RESULTS: From a total of 50 cycles (mean 4 cycles per patient, range 1-11), the maximal tolerated dose (MTD) was reached at VRB 25 mg/m(2) and RTX 3 mg/m(2) with grade 3-4 neutropenia as the dose-limiting toxicity (7/16 cycles and 3/5 patients at the MTD). Nine pretreated patients were evaluable for treatment efficacy and three of these showed an objective response (one complete response, two partial responses; mean duration 26 weeks, range 17-38 weeks). Pharmacokinetic follow-up was done for both drugs (RTX by LC-MS-MS and VRB by HPLC-UV detection). There was no interaction between RTX and VRB pharmacokinetics since the VRB AUC was not significantly modified between day 1 and day 5. There was no relationship between RTX AUC and hematological toxicity. In contrast, there was a highly significant relationship between the mean VRB AUC (days 1-5) and the absolute neutrophil count decrease (Emax model, Hill constant=4.38+/-2.59, EC(50)=508+/-53.2 micro g.h/l, r=0.75, P=0.0013). A similar relationship was noted for the platelet decrease but at the limit of statistical significance. CONCLUSIONS: The VRB-RTX combination appears to be a valuable treatment option in second-line treatment of advanced breast cancer. It is deliverable on an outpatient basis, shows an acceptable toxicity profile potentially manageable by VRB pharmacokinetic follow-up, and has promising antitumor activity in taxane-anthracycline-refractory patients. The recommended dose for further studies is VRB 22.5 mg/m(2) and RTX 3 mg/m(2).

Palliative 5-fluorouracil-based chemotherapy for advanced colorectal cancer in the elderly: results of a 10-year experience.

The aim of this study was to evaluate the objective tumor response rates and toxicities in elderly patients (older than 70 years) with advanced colorectal cancer treated with 5-fluorouracil (5-FU) as a first-line palliative chemotherapy regimen. Eighty-six consecutive patients were enrolled onto a retrospective study between January 1990 and February 1998. Patients were divided into two groups; group 1 consisted of patients who were 70 to 74 years old, and group 2 consisted of patients who were age 75 years and older. Four types of 5-FU-based chemotherapy were administered. First-line chemotherapy was continued until disease progression, unacceptable toxicity, or patient refusal. Primary tumor sites were the colon (n = 44), rectum (n = 29), and colorectal (n = 13). There was no difference in response (complete/partial) rates according to age groups (group 1: 21%, group 2: 26%). Median overall survival was 17 months for group 1 and 14 months for group 2, with 1-year survival at 63% and 55%, respectively (not statistically significant). Median time to progression was 6 months for both age groups. Chemotherapy in both groups increased performance status, and weight in 26% and 31%, respectively. No toxic death was reported. There was no difference in overall or severe toxicity between the two age groups, and all adverse events were manageable. Toxicity (grade III/IV) occurred in 25% of patients. Based on these findings, palliative first-line chemotherapy for colorectal cancer can be performed in selected elderly patients without increasing either morbidity or mortality, while obtaining response rates and side effects comparable to those in younger patients.

[Neoadjuvant endocrine therapy for breast cancer: an overview]. / Hormonothérapie néoadjuvante dans le cancer du sein : revue de la littérature.

The clinical benefits of endocrine therapy for patients with hormonosensitive breast cancer remains perfectly established. For instance, tamoxifen, the gold standard of the adjuvant treatment, has largely contributed of the effectiveness of such a therapy. The recent development of new endocrine agents (the third-generation aromatase inhibitors, selective estrogen receptors modulators), provides to physicians the opportunity of a more effective and tolerable therapeutic approach, in the metastatic disease setting or likely in adjuvant setting for breast cancer patients. Preoperative therapy has been widely used for the treatment of initially inoperable locally advanced breast cancers with the main objective of breast-conserving surgery. The benefits of neoadjuvant chemotherapy has widely been demonstrated; however, the success of neoadjuvant endocrine therapy is much recent. The clinical and pharmacological data of the main published studies using neoadjuvant hormonotherapy are presented herein this review. Therefore, clinical and histologic assessments of response brings essential informations about the breast cancer hormonal sensitivity, but may also be predictor of the future (adjuvant or metastatic) treatment responsiveness.