To Treat or Not to Treat Metastatic Cancer Patients with Poor Performance Status: a Prospective Experience.

Administration of cytotoxic chemotherapy for patients with metastatic cancer and poor performance status is a daily clinical challenge. Guidelines only help to select a therapeutic regimen but do not offer a clear response whether or not the patients should be treated. We performed a prospective analysis in 139 metastatic patients with performance status > 1 according to the Eastern Cooperative Oncology Group scale. A decision was considered correct if patients treated with a medical anticancer treatment lived over 3 months or alternatively patients not treated had a survival under 3 months. The predominant tumor type was non-small cell lung cancer. Patients were chemotherapy naive in 87 cases (63 %). A new line of medical anticancer treatment was started in 107 cases (77 %). The median survival of the study population was 11 weeks (range, 1-53). 84 patients (60 %) died within 3 months while 55 patients (40 %) lived more than 3 months after decision. Treatment decisions were considered as appropriate in 81 cases (58 %). No patient was considered as undertreated. The analysis by pathology allowed to identify pathologies where decisions were correct in the majority of the cases (renal, urothelial and small cell lung cancers), pathologies where appropriate and inappropriate decisions were balanced (prostate, ovarian and breast cancers) and pathologies where decisions for treatment were excessive (non-small cell lung cancer and unknown primary). This prospective study was conducted as part of the evaluation of professional practices in our department. Administration of a medical anticancer treatment validated with patients with good performance status may be harmful for patients with poor performance status. The findings resulted in recommendations for daily practice in order to help physicians, especially for the "don't go" decisions. Until the identification of new prognostic factors for survival and/or the development of therapies making sensitive currently chemoresistant diseases, the initiation of a medical anticancer treatment outside standard situations should result from a consensual decision team or the inclusion in a clinical trial.

A phase II study of afatinib, an irreversible ErbB family blocker, added to letrozole in patients with estrogen receptor-positive hormone-refractory metastatic breast cancer progressing on letrozole.

UNLABELLED: Phase II, open-label study assessing the efficacy and safety of the ErbB family blocker afatinib combined with letrozole in estrogen receptor-positive metastatic breast cancer (MBC) patients who had progressed on letrozole monotherapy. Adult females (N = 28) received oral afatinib (50 [n = 7], 40 [n = 13] or 30 [n = 8] mg/day) plus letrozole 2.5 mg/day in 28-day cycles until disease progression. Primary endpoint was the progression-free rate at or after 16 weeks of afatinib. At 16 weeks, four patients remained on afatinib without progression; two of these were HER2 negative. Fifteen (54 %) patients had a best response of stable disease according to Response Evaluation Criteria in Solid Tumors. Median progression-free survival was 60, 107 and 79 days with 50, 40 and 30 mg/day afatinib, respectively. Diarrhea, asthenia, rash, mucosal inflammation and nausea were the most frequent adverse events. In this small, exploratory study, afatinib combined with letrozole was able to induce disease stabilization in 54 % of hormone-refractory MBC patients previously progressing on letrozole. CLINICAL TRIAL REGISTRATION: NCT00708214.

Prospective Clinical Utility Study of the Use of the 21-Gene Assay in Adjuvant Clinical Decision Making in Women With Estrogen Receptor-Positive Early Invasive Breast Cancer: Results From the SWITCH Study.

BACKGROUND: The 21-gene Oncotype DX Recurrence Score assay is a validated assay to help decide the appropriate treatment for estrogen receptor-positive (ER+), early-stage breast cancer (EBC) in the adjuvant setting. The choice of adjuvant treatments might vary considerably in different countries according to various treatment guidelines. This prospective multicenter study is the first to assess the impact of the Oncotype DX assay in the French clinical setting. METHODS: A total of 100 patients with ER+, human epidermal growth factor receptor 2-negative EBC, and node-negative (pN0) disease or micrometastases in up to 3 lymph nodes (pN1mi) were enrolled. Treatment recommendations, physicians' confidence before and after knowing the Recurrence Score value, and physicians' perception of the assay were recorded. RESULTS: Of the 100 patients, 95 were evaluable (83 pN0, 12 pN1mi). Treatment recommendations changed in 37% of patients, predominantly from chemoendocrine to endocrine treatment alone. The proportion of patients recommended chemotherapy decreased from 52% pretest to 25% post-test. Of patients originally recommended chemotherapy, 61% were recommended endocrine treatment alone after receiving the Recurrence Score result. For both pN0 and pN1mi patients, post-test recommendations appeared to follow the Recurrence Score result for low and high values. Physicians' confidence improved significantly. CONCLUSION: These are the first prospective data on the impact of the Oncotype DX assay on adjuvant treatment decisions in France. Using the assay was associated with a significant change in treatment decisions and an overall reduction in chemotherapy use. These data are consistent with those presented from European and non-European studies.

¹8F-FDG-PET/CT in staging, restaging, and treatment response assessment of male breast cancer.

PURPOSE: Male breast cancer (BC) is a rare disease, with patterns different from those found in women. Most tumors are detected at more advanced stages than in women. The aim of this study was to analyze the performance of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) in staging, restaging, and therapy response assessment. METHODS: We performed a systematic analysis in the database of Saint-Louis Hospital to identify male patients with BC referred for PET/CT. (18)F-FDG-PET/CT findings considered suspicious for malignancy were compared to biopsy results, further work-up and/or patient follow-up of at least 6 months. Performances of (18)F-FDG-PET/CT were compared to that of conventional imaging (CI) using the McNemar test. The impact of PET/CT on management was evaluated. RESULTS: During 6 consecutive years, among 12,692 (18)F-FDG-PET/CT oncology studies, 30 were performed in 15 men with BC: 7 examinations for initial staging, 11 for restaging, and 12 for response assessment. Tumors profile was ER+ and one had HER2 overexpression. PET/CT sensitivity, specificity, positive predictive value, negative predictive value and accuracy to detect distant metastases were 100%, 67%, 86%, 100% and 89%, respectively. PET/CT was more informative than CI in 40% of studies (p=0.03; 95% confidence interval: 3.26 - 40%). Findings from (18)F-FDG-PET/CT led to modification in the planned treatment in 13/30 cases (43%). CONCLUSION: Although all the tumors were ER+, primary lesions and metastases were diagnosed with high sensitivity. (18)F-FDG-PET/CT seems to be a powerful imaging method to perform staging, restaging and treatment response assessment in male patients with BC.

A retrospective pooled analysis of trabectedin safety in 1,132 patients with solid tumors treated in phase II clinical trials.

PURPOSE: To summarize the safety experience obtained from phase II clinical trials conducted with trabectedin as single-agent therapy in patients with advanced solid tumors. METHODS: This retrospective analysis includes 1,132 patients exposed to trabectedin in 19 phase II trials carried out between February 1999 and April 2008. Trabectedin was administered intravenously as 1 of 3 schedules: 24-hour infusion every 3 weeks (q3wk 24-h; n = 570/2,818 cycles), 3-hour infusion every 3 weeks (q3wk 3-h; n = 258/1,003 cycles), and 3-hour infusion for three consecutive weeks every 4 weeks (qwk 3-h; n = 304/1,198 cycles). RESULTS: The majority of patients (90%) had received previous chemotherapy. Patients were given a median of three treatment cycles of trabectedin (range, 1-59). Nausea, fatigue and vomiting were the most common trabectedin-related adverse events, reported in ≥20% of patients. Reversible myelosuppression (mainly neutropenia) and transient reversible transaminase increases were the most common laboratory abnormalities seen with trabectedin, with a very low incidence of relevant clinical consequences. Deaths associated with drug-related adverse events were infrequent, occurring in 19 (1.7%) patients. CONCLUSION: Single-agent trabectedin treatment was reasonably well tolerated. Trabectedin can be administered for prolonged periods to patients with sustained clinical benefit (induction of disease stability or shrinkage) without cumulative toxicities over time.

The yield of 18F-FDG PET/CT in patients with clinical stage IIA, IIB, or IIIA breast cancer: a prospective study.

UNLABELLED: The purpose of this study was to prospectively evaluate the role of (18)F-FDG PET/CT in patients with stage IIA, IIB, or IIIA breast cancer. METHODS: During 56 mo, 131 consecutive patients with large (>2 cm) breast cancer and clinical stage IIA, IIB, or IIIA (based on clinical examination, mammography, breast MRI, and ultrasonography) underwent (18)F-FDG PET/CT. The nuclear physician was unaware of the results of any other procedure (bone scan, chest radiography, liver ultrasound, or thoracoabdominal CT scan). RESULTS: Of the 131 examined patients, 36 had clinical stage IIA (34 T2N0 and 2 T1N1), 48 stage IIB (20 T3N0 and 28 T2N1), and 47 stage IIIA (29 T3N1, 9 T2N2, and 9 T3N2). (18)F-FDG PET/CT modified staging for 5.6% of stage IIA patients, for 14.6% of stage IIB patients, and for 27.6% of stage IIIA patients. However, within stage IIIA, the yield was specifically high among the 18 patients with N2 disease (56% stage modification). When considering stage IIB and primary operable IIIA (T3N1) together, the yield of (18)F-FDG PET/CT was 13% (10/77); extraaxillary regional lymph nodes were detected in 5 and distant metastases in 7 patients. In this series, (18)F-FDG PET/CT outperformed bone scanning, with only 1 misclassification versus 8 for bone scanning (P = 0.036). CONCLUSION: (18)F-FDG PET/CT provided useful information in 13% of patients with clinical T3N0, T2N1, or T3N1 disease. The yield was more modest in patients with stage IIA. The high yield in the case of N2 disease demonstrates that stage IIIA comprises 2 quite distinct groups of patients.

[Node negative breast cancer. Beyond international consensus: a pragmatic approach]. / Le cancer du sein sans envahissement ganglionnaire. Au-delà des consensus internationaux: une approche pragmatique.

Apart from therapeutic advances related to new treatments, our practices in the management of early breast cancer have been modified by to key organizational settings (1) mass screening, substantially altering the presentation and epidemiology of breast cancer and (2) the development of guidelines to ensure that any patient management is in agreement with the demonstrated impact in the adjuvant treatment. In daily practice, the impact of screening and guidelines recommendations has put us now in a paradoxical situation: while the majority of non-metastatic breast cancers treated in the hexagon are node negative, most of the results of clinical studies on chemotherapy and targeted therapies today arise from populations predominantly node positive. Therefore, it seemed legitimate to convene a working group around a reflection on the directions of adjuvant chemotherapy in a growing node negative population in order to better respond to the questions of the field oncologists, trying to address the discrepancies between different existing guidelines.

[Evaluating the benefits of mammographic breast cancer screening]. / A mammográfiás emlorákszurés nyereségének mérlegelése.

Mammographic breast cancer screening is one of the most popular cancer death preventive programs worldwide, as well as in Hungary. Breast cancer mortality and incidence started to decrease some years after international introduction of the screening program. The role played by mammography in the advantageous turn is not known. Potential points in evaluating the benefits of a screening program are reviewed. We focus on the average lifetime gain, which is 1 to 3 weeks in case of mammography, according to age groups.

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.

[Efficacy of weekly epoetin Beta in the treatment of chemotherapy-induced anemia in solid tumors]. / Efficacité de l'époétine bêta hebdomadaire dans l'anémie des tumeurs solides sous chimiothérapie.

OBJECTIVE: The aim of the study was to assess the efficacy and safety of epoetin beta once-weekly in anemic patients with solid tumors treated with chemotherapy. METHOD: Prospective, open-label, multicenter, single-arm study of epoetin beta 30 000 I.U. once-weekly in anemic patients with solid tumors receiving chemotherapy (n = 365). RESULTS: Epoetin beta increased mean haemoglobin (Hb) levels from 10.3 +/- 0.9 g/dL at baseline to 12.3+/-2.0 g/dL at week 12. The response rate was achieved in 61% (CI 95%: 55-68) of the patients. The mean Hb level increased was 1.8 g/dL (CI 95%: 1.5-2,0); in lung cancer patients (n = 102) Hb increase was 2.7 g/dL. Treatment with epoetin beta was well tolerated; only 1.4 % patients had thrombotic events. CONCLUSION: Epoetin beta (30 000 I.U. once weekly) increased Hb levels and was well-tolerated to correct anemia in patients with solid tumors treated with chemotherapy.

2007 Standards, Options, and Recommendations: use of erythropoiesis-stimulating agents (ESA: epoetin alfa, epoetin beta, and darbepoetin) for the management of anemia in children with cancer.

The Standards, Options, and Recommendations (SOR) project undertaken by the French National Federation of Cancer Centers (FNCLCC) to develop and disseminate clinical practice guidelines in oncology has now been taken over by the French National Cancer Institute. In 2007, the SOR updated the information related to the use of erythropoiesis-stimulating agents (ESA) in anemic children with cancer. Updates were based on a review of the most reliable scientific data available, followed by critical appraisal by a multidisciplinary group of experts and validation by independent experts. The literature review identified four randomized trials likely to provide reliable new information on the use of ESA in children. This review confirmed four points: treatment increases hemoglobin levels and decreases the need for blood transfusions; no quality-of-life and no survival benefit has been demonstrated; treatment does not seem associated with significantly more side effects; impact on thromboembolic events and patient quality of life remains unclear. The main result of the study was the elaboration of a new standard of care unavailable at the time of the 2003 version. Systematic administration of ESA is not recommended for the prevention or treatment of anemia in pediatric cancer patients. However, treatment decision must be made on a case-by-case basis and, when treatment is considered, the intravenous route must be preferred. The full French document is available at www.sor-cancer.fr.

18F-FDG PET/CT imaging for an early assessment of response to sunitinib in metastatic renal carcinoma: preliminary study.

PURPOSE: Sunitinib is a new standard for the treatment of metastatic renal-cell carcinoma (RCC). We evaluated the accuracy of 18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in assessing early response to this antiangiogenic drug, which cannot be obtained with conventional CT. PROCEDURES: Patients had an FDG-PET/CT at baseline and another one for follow-up at the end of the first cycle (at day 42). For each examination, all lesions were registered and the maximum standardized uptake value (SUV(max)) was measured. The metabolic response on PET at day 42 was assessed, using European Organization for Research and Treatment of Cancer criteria. Morphologic response on CT at day 84 (after two cycles), using Response Evaluation Criteria in Solid Tumors criteria, was used as the reference standard. The long-term outcome was assessed by the progression-free survival. RESULTS: Twelve (12) patients who completed at least two cycles of sunitinib were assessed. The SUV(max) for the lesions with the highest uptake ranged between 2.9 and 11.8 for the 12 patients (mean = 6.3). Early PET/CT findings, after one cycle of sunitinib, were consistent with later CT results in 9 patients of 11 assessable patients: 1 patient progressed on PET and CT, 7 patients had stable disease, and 1 had a partial response. The other 2 patients had a metabolic partial response on PET and stable disease on CT. However, 1 patient achieved a partial response later in follow-up, suggesting that metabolic early changes are an indication of sunitinib activity. CONCLUSION: FDG-PET/CT seems to be an interesting tool for the early evaluation of response to sunitinib in metastatic RCC. Larger studies are needed to confirm these preliminary results and establish a prognostic value for PET/CT.

[Lung cancers in the elderly]. / La prise en charge thérapeutique des cancers bronchiques chez le sujet âgé.

Lung cancer is the leading cause of cancer-related death worldwide. The world population is getting increasingly older. The incidence of lung cancer is therefore growing among elderly patients. However, in spite of the universal recognition of the importance of clinical research to guide therapeutic decisions, elderly lung cancer patients are largely under-represented in cancer treatment trials. Age alone must not be a limiting factor in the choice of treatment. Indications for surgery should not vary with age. Fit elderly patients benefit from concurrent chemoradiotherapy. For metastatic patients, single-agent monotherapy with a third-generation agent (vinorelbine, gemcitabine or docetaxel) is the recommended option. Platinum-based chemotherapy may represent a valid option for fit elderly patients with adequate function. The role of the new biologic target-based agents is to be found. There is an absolute need of clinical trials specifically dedicated to elderly patients with lung cancer.

[Decision making process in oncology: rationale and delineation of a composite index of relative antitumoral efficacy (In-RATE)]. / Critères de choix thérapeutique en oncologie : définition et intérêt d'un nouvel index d'efficacité relative des agents antitumoraux (In-RATE).

Over the last decade, the development of new therapeutic options has made more patients benefit from antitumoral strategies including several lines of chemotherapy, the aim of which is a long-term control of the disease progression. In such a context of "chronic" management, the choice of tumor response as a single parameter appears restrictive to assess those new therapeutic options. For that reason, we have recently proposed a composite index of relative efficacy including response rate as well as parameters related to tumour stabilization and duration of the response. The objective of this index, published as the In-RATE is to allow the comparison of two treatments a and b as follows: In-RATE a/b = (response rate a/response rate b) x (time to progression a/time to progression b) x (progression rate b/progression rate a). Values significantly higher or less than 1 suggest the superiority, in terms of efficacy, of treatments a or b, respectively. When retrospectively applied to randomised studies, the In-RATE showed that some results and conclusions based on the response rate as a unique endpoint might be reconsidered, and that a significant difference between protocols could be detected in published reports having concluded to statistical equivalence. This paper reviews the rationale and principle of this work, and discusses the potential clinical applications of the In-RATE.

[Standards & options: recommendations for the use of erythropoiesis-stimulating agents (ESA) in anaemic cancer patients undergoing radiotherapy (2007 update)]. / Standards, Options : recommandations 2007 indication des agents stimulant l'érythropièse (ASE) dans la prise en charge de l'anémie induite par la radiothérapie (mise à jour).

INTRODUCTION: Beginning 1998, a working group of specialists convened by the guidelines department (Standards, Option and Recommendations: SOR) of the National French Federation of Comprehensive Cancer Centres (FNCLCC) published then regularly updated Recommendations relative to the use of ESA(epoetin alfa, epoetin bêta, darbepoetin) in anaemic patients with cancer. This article presents the updated Recommendations set up in 2007. METHODS: This updating process is based on the methodology developed and used in the "Standards, Options: Recommendations" programme. The methodological approach combines systematic review with the judgement of a multidisciplinary group of experts. On the basis of analysis of literature, the conclusions and their level of evidence are established. Then, the conclusions accompanied by experts' judgement lead to the Recommendations. A Recommendation is a proposal of one or several clinical attitudes intended to improve cancer patient care. Before publication, the RPC-SOR are re-examined by independent reviewers selected according to the same principles as the group of expert writers. RESULTS: New data, relative to the "use of ESA in anaemic cancer patients undergoing radiotherapy", didn't lead to update the latest Recommendations validated in 2003. However, new data relative to the "use of ESA in anaemic prophylaxis among adult patients with cancer" and to the "use of iron with ESA in cancer patients" were sufficient to generate either major or minor modifications to the initial Recommendations. CONCLUSIONS: Thus, it appears relevant to re-examine these Recommendations according to a systematic monitoring process which should be renewed in two years.

[Clinical Practice guidelines for the use of erythropoiesis-stimulating agents (ESA: epoetin alfa, epoetin bêta, darbepoetin) in anaemic patients with cancer: 2007 update (summary report)]. / Standards, Options: recommandations 2007. Indication des agents stimulant l'érythropoïèse (ASE: époétine alpha, époétine bêta et darbépoétine) dans la prise en charge de l'anémie en cancérologie (mise à jour), rapport abrégé.

UNLABELLED: Beginning 1998, a working group of specialists convened by the guidelines department (Standards, Options and Recommendations: SOR) of the National French Federation of Comprehensive Cancer Centres (FNCLCC) published then regularly updated Recommendations relative to the use of ESA in anaemic patients with cancer. This article presents a short version of the Recommendations updated in 2007. METHODS: This updating process is based on the methodology developed and used in the "Standards, Options: Recommendations" programme. The methodological approach combines systematic review with the judgement of a multidisciplinary group of experts. A Recommendation is a proposal of one or several clinical attitudes intended to improve cancer patient care. There are two levels of gradation for the Recommendations: Standards and Options. Their setting takes into account the organisational context of care, the particular situation of the patient and the expression of his preferences. Before publication, the RPC-SOR are re-examined by independent reviewers selected according to the same principles as the group of expert writers. RESULTS: New data are sufficiently important to update the latest Recommendations validated in 2003. Thus, five clinical questions were updated. The resulting modifications were either major (new Options or new Standards) or minor (increased level of evidence). It should be noted that for the clinical question--use of ESA in radiotherapy--new data are not sufficient to generate modifications in the initial Recommendations which remain valid. CONCLUSIONS: Because of the important new data published on the subject between 2003 and 2007, it appears relevant to re-examine these Recommendations according to a systematic monitoring process which should be renewed in 2 years.

Effect of (18)F-FDG PET/CT imaging in patients with clinical Stage II and III breast cancer.

PURPOSE: To investigate the potential effect of using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the initial assessment of patients with clinical Stage II or III breast cancer. METHODS AND MATERIALS: During 14 consecutive months, 39 patients (40 tumors) who presented with Stage II or III breast cancer on the basis of a routine extension assessment were prospectively included in this study. PET/CT was performed in addition to the initial assessment. RESULTS: In 3 cases, PET/CT showed extra-axillary lymph node involvement that had not been demonstrated with conventional techniques. Two of these patients had hypermetabolic lymph nodes in the subpectoral and infraclavicular regions, and the third had a hypermetabolic internal mammary node. PET/CT showed distant uptake in 4 women. Of these 4 women, 1 had pleural involvement and 3 had bone metastasis. Overall, of the 39 women, the PET/CT results modified the initial stage in 7 (18%). The modified staging altered the treatment plan for 5 patients (13%). It led to radiotherapy in 4 patients (bone metastasis, pleural lesion, subpectoral lymph nodes, and internal mammary nodes) and excision of, and radiotherapy to, the infraclavicular lymph nodes in 1 patient. CONCLUSIONS: PET/CT can provide information on extra-axillary lymph node involvement and can uncover occult distant metastases in a significant percentage of patients. Therefore, initial PET/CT could enable better treatment planning for patients with Stage II and III breast cancer.

Rationale and delineation of a composite index of relative antitumoural efficacy (In-RATE).

Over the last decades, the development of new drugs has allowed cancer patients to experience several lines of chemotherapy, the objective of which is a long term stabilization of the tumour. The objectives of this work was to delineate a composite index of relative antitumoural efficacy (In-RATE) of a regimen over another, including response rate (RR), median time to progression (TTP) and progression rate (PR). When considering two treatments a and b, the In-RATE was defined as RRa/RRb x TTPa/TTPb x PRb/PRa. Values significantly superior or inferior to 1 reveal an advantage for treatment a or b, respectively. The applicability of the In-RATE to published randomized trials in four frequent tumour types (colorectal, non-small cell lung, advanced ovarian and metastatic breast cancers) was suggested to more precisely distinguish the effects of different drugs, and sometimes to detect a significant difference when the published data did not conclude to statistical difference.