Fatigue visual analogue scale score correlates with quality of life in cancer patients receiving epoetin alfa (Sandoz) for chemotherapy-induced anaemia: The CIROCO study.

PURPOSE: Available tools to measure fatigue and health-related quality of life (HRQoL) in cancer patients are often difficult to use in clinical practice. The fatigue visual analogue scale (VAS) provides a simple method to assess fatigue. This study evaluated the correlation between HRQoL and fatigue perceived by cancer patients undergoing chemotherapy. METHODS: This was a non-interventional prospective study of adult cancer patients in France presenting with chemotherapy-induced anaemia (CIA) treated with epoetin alfa (Sandoz). Data were collected using an electronic case report form at study inclusion (T0), after 2-3 chemotherapy cycles (T1) and after 4-6 cycles (T2). RESULTS: The study included 982 patients from September 2015 to October 2017. Overall, there was a negative correlation between fatigue VAS and HRQoL. The overall haemoglobin (Hb) change between T0 and T2 was +17.8 % (± 18.1 %). Fatigue assessed by both patients and physicians showed a clinically significant improvement during the study. Global HRQoL also increased. CONCLUSION: Treatment of CIA with epoetin alfa (Sandoz) improved Hb levels, fatigue, and HRQoL, with a correlation observed between fatigue VAS score and HRQoL. Fatigue VAS could act as a simple alternative to more complex methods to measure HRQoL; however, further analyses are required to confirm this association.

CHEOPS trial: a GINECO group randomized phase II assessing addition of a non-steroidal aromatase inhibitor to oral vinorelbine in pre-treated metastatic breast cancer patients.

BACKGROUND: The objective of the CHEOPS trial was to assess the benefit of adding aromatase inhibitor (AI) to metronomic chemotherapy, oral vinorelbine, 50 mg, three times a week for pre-treated, HR + /HER2- metastatic breast cancer patients. METHODS: In this multicentric phase II study, patients had to have progressed on AI and one or two lines of chemotherapy. They were randomized between oral vinorelbine (Arm A) and oral vinorelbine with non-steroidal AI (Arm B). RESULTS: 121 patients were included, 61 patients in Arm A and 60 patients in Arm B. The median age was 68 years. 109 patients had visceral metastases. They all had previously received an AI. The study had been prematurely stopped following the third death due to febrile neutropenia. Median PFS trend was found to be different with 2.3 months and 3.7 months in Arm A and Arm B, respectively (HR 0.73, 95%CI 0.50-1.06, p value = 0.0929). No statistical difference was shown in OS and better tumor response. 56 serious adverse events corresponding to 25 patients (21%) were reported (respectively, 12 (20%) versus 13 (22%) for arms A and B) (NS). CONCLUSION: The addition of AI to oral vinorelbine over oral vinorelbine alone in aromatase inhibitor-resistant metastatic breast cancer was associated with a non-significant improvement of PFS. Several unexpected serious adverse events were reported. Metronomic oral vinorelbine schedule, at 50 mg three times a week, requires close biological monitoring. The question of hormonal treatment and chemotherapy combination remains open.

Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience.

PURPOSE: To provide insights into the diagnosis and management of therapy-related myeloid neoplasms (t-MN) following PARP inhibitors (PARPi). EXPERIMENTAL DESIGN: In a French cancer center, we identified and described the profiles of 13 t-MN diagnosed among 37 patients with ovarian cancer referred to hematology consultation for cytopenia under PARPi. Next, we described these 13 t-MN post-PARPi among 37 t-MN post ovarian cancer according to PARPi exposure. Finally, we described 69 t-MN post-PARPi in a national cohort. RESULTS: From 2016 to 2021, cumulative incidence of t-MN was 3.5% (13/373) among patients with ovarian cancer treated with PARPi. At time of hematologic consultation, patients with t-MN had a longer PARPi exposure (9 vs. 3 months, P = 0.01), lower platelet count (74 vs. 173 G/L, P = 0.0005), and more cytopenias (2 vs. 1, P = 0.0005). Compared with t-MN not exposed to PARPi, patients with t-MN-PARPi had more BRCA1/2 germline mutation (61.5% vs. 0%, P = 0.03) but similar overall survival (OS). In the national cohort, most t-MN post-PARPi had a complex karyotype (61%) associated with a high rate of TP53 mutation (71%). Median OS was 9.6 months (interquartile range, 4-14.6). In multivariate analysis, a longer time between end of PARPi and t-MN (HR, 1.046; P = 0.02), olaparib compared with other PARPi (HR, 5.82; P = 0.003) and acute myeloid leukemia (HR, 2.485; P = 0.01) were associated with shorter OS. CONCLUSIONS: In a large series, we described a high incidence of t-MN post-PARPi associated with unfavorable cytogenetic and molecular abnormalities leading to poor OS. Early detection is crucial, particularly in cases of delayed cytopenia.

Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial.

BACKGROUND: In advanced oestrogen receptor-positive, HER2-negative breast cancer, acquired resistance to aromatase inhibitors frequently stems from ESR1-mutated subclones, which might be sensitive to fulvestrant. The PADA-1 trial aimed to show the efficacy of an early change in therapy on the basis of a rising ESR1 mutation in blood (bESR1mut), while assessing the global safety of combination fulvestrant and palbociclib. METHODS: We did a randomised, open-label, phase 3 trial in 83 hospitals in France. Women aged at least 18 years with oestrogen receptor-positive, HER2-negative advanced breast cancer and an Eastern Cooperative Oncology Group performance status of 0-2 were recruited and monitored for rising bESR1mut during first-line aromatase inhibitor (2·5 mg letrozole, 1 mg anastrozole, or 25 mg exemestane, orally once per day, taken continuously) and palbociclib (125 mg orally once per day on days 1-21 of a 28-day cycle) therapy. Patients with newly present or increased bESR1mut in circulating tumour DNA and no synchronous disease progression were randomly assigned (1:1) to continue with the same therapy or to switch to fulvestrant (500 mg intramuscularly on day 1 of each 28-day cycle and on day 15 of cycle 1) and palbociclib (dosing unchanged). The randomisation sequence was generated within an interactive web response system using a minimisation method (with an 80% random factor); patients were stratified according to visceral involvement (present or absent) and the time from inclusion to bESR1mut detection (<12 months or ≥12 months). The co-primary endpoints were investigator-assessed progression-free survival from random assignment, analysed in the intention-to-treat population (ie, all randomly assigned patients), and grade 3 or worse haematological adverse events in all patients. The trial is registered with Clinicaltrials.gov (NCT03079011), and is now complete. FINDINGS: From March 22, 2017, to Jan 31, 2019, 1017 patients were included, of whom 279 (27%) developed a rising bESR1mut and 172 (17%) were randomly assigned to treatment: 88 to switching to fulvestrant and palbociclib and 84 patients to continuing aromatase inhibitor and palbociclib. At database lock on July 31, 2021, randomly assigned patients had a median follow-up of 35·3 months (IQR 29·2-41·4) from inclusion and 26·0 months (13·8-34·3) from random assignment. Median progression-free survival from random assignment was 11·9 months (95% CI 9·1-13·6) in the fulvestrant and palbociclib group versus 5·7 months (3·9-7·5) in the aromatase inhibitor and palbociclib group (stratified HR 0·61, 0·43-0·86; p=0·0040). The most frequent grade 3 or worse haematological adverse events were neutropenia (715 [70·3%] of 1017 patients), lymphopenia (66 [6·5%]), and thrombocytopenia (20 [2·0%]). The most common grade 3 or worse adverse events in step 2 were neutropenia (35 [41·7%] of 84 patients in the aromatase inhibitor and palbociclib group vs 39 [44·3%] of 88 patients in the fulvestrant and palbociclib group) and lymphopenia (three [3·6%] vs four [4·5%]). 31 (3·1%) patients had grade 3 or worse serious adverse events related to treatment in the overall population. Three (1·7%) of 172 patients randomly assigned had one serious adverse event in step 2: one (1·2%) grade 4 neutropenia and one (1·2%) grade 3 fatigue among 84 patients in the aromatase inhibitor and palbociclib group, and one (1·1%) grade 4 neutropenia among 88 patients in the fulvestrant and palbociclib group. One death by pulmonary embolism in step 1 was declared as being treatment related. INTERPRETATION: PADA-1 is the first prospective randomised trial showing that the early therapeutic targeting of bESR1mut results in significant clinical benefit. Additionally, the original design explored in PADA-1 might help with tackling acquired resistance with new drugs in future trials. FUNDING: Pfizer.

Validation of the geriatric vulnerability score in older patients with ovarian cancer: an analysis from the GCIG-ENGOT-GINECO EWOC-1 study.

BACKGROUND: Older patients with ovarian cancer represent a heterogeneous population. The French National Group of Investigators for the Study of Ovarian and Breast Cancer developed the geriatric vulnerability score (GVS) to identify geriatric parameters predictive of poor outcomes. A prospective validation of the GVS was needed. METHODS: The EWOC-1 study (NCT02001272) was an international, open-label, phase 2, three-arm trial designed according to a two-step process. Patients aged 70 years or older with newly diagnosed stage III or IV ovarian cancer were identified and the GVS determined. Those with a GVS of 3 or greater were randomly assigned to the EWOC-1 trial, stratified by country and surgical outcome, to receive three different carboplatin with or without paclitaxel regimens; those not included in the EWOC-1 trial were followed up in the EWOC-1 registry. External validation of the GVS was a secondary endpoint of the trial. Three validation cohorts were identified: the total population (validation cohort 1 [V1], n=447), the registry-only population (validation cohort 2 [V2], n=327), and the carboplatin-paclitaxel-treated population (validation cohort 3 [V3], n=320). FINDINGS: From Dec 11, 2013, to Nov 16, 2018, 447 patients were included in 48 academic centres in six countries; 120 in the EWOC-1 trial and 327 in the EWOC-1 registry. Median follow-up was 19·7 (95% CI 8·5-29·7) months for the total cohort; missing values were low (<2%). According to the maximum likelihood analysis, the hazard ratio (HR) of death in V1 was 1·8 (95% CI 1·1-3·1, p=0·029) for those with a GVS of 1; 2·4 (1·4-4·0, p=0·0009) with a GVS of 2; 4·1 (2·5-7·0, p<0·0001) for a GVS of 3; 5·5 (3·3-9·3, p<0·0001) for a GVS of 4; and 9·1 (4·7-17·5, p<0·0001) for a GVS of 5 compared with a score of 0. Whatever the validation cohort, GVS of 3 or more significantly segregated two groups with different overall survival: V1 (median 13·2 [95% CI: 10·8-18·7] vs 40·8 [32·0-45·6] months; HR 2·8 [95% CI 2·2-3·7]; p<0·0001); V2 (11·9 [95% CI 8·8-18·1] vs 40·8 [32·0-45·6] months, HR 3·5 [2·5-4·9]; p<0·0001); and V3 (18·1 [95% CI 15·8-31·8] vs 43·0 [40·6-49·7] months, HR 2·6 [1·9 to 3·7]; p<0·0001). INTERPRETATION: The GVS has high prognostic performance for overall survival in patients with advanced ovarian cancer, independently of geographic and historic effect (V1), as well as treatment patterns (V3), validated in an international population. Even though the GVS is time consuming it will allow the stratification of populations for clinical research and might permit the orientation of the geriatric intervention to specific domains. FUNDING: French National Cancer Institute. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Efficacy and Safety of First-line Single-Agent Carboplatin vs Carboplatin Plus Paclitaxel for Vulnerable Older Adult Women With Ovarian Cancer: A GINECO/GCIG Randomized Clinical Trial.

IMPORTANCE: Single-agent carboplatin is often proposed instead of a conventional carboplatin-paclitaxel doublet in vulnerable older patients with ovarian cancer. Such an approach could have a detrimental effect on outcomes for these patients. OBJECTIVE: To compare the feasibility, efficacy, and safety of single-agent carboplatin every 3 weeks, weekly carboplatin-paclitaxel, or conventional every-3-weeks carboplatin-paclitaxel in vulnerable older patients with ovarian cancer. DESIGN, SETTING, AND PARTICIPANTS: This international, open-label, 3-arm randomized clinical trial screened 447 women 70 years and older with newly diagnosed stage III/IV ovarian cancer by determining their Geriatric Vulnerability Score; 120 patients with a Geriatric Vulnerability Score of 3 or higher were stratified by country and surgical outcome. Enrollment took place at 48 academic centers in France, Italy, Finland, Denmark, Sweden, and Canada from December 11, 2013, to April 26, 2017. Final analysis database lock April 2019. Data analysis was performed from February 1 to December 31, 2019. INTERVENTIONS: Patients were randomized to receive 6 cycles of (1) carboplatin, area under the curve (AUC) 5 mg/mL·min, plus paclitaxel, 175 mg/m2, every 3 weeks; (2) single-agent carboplatin, AUC 5 mg/mL·min or AUC 6 mg/mL·min, every 3 weeks; or (3) weekly carboplatin, AUC 2 mg/mL·min, plus paclitaxel, 60 mg/m2, on days 1, 8, and 15 every 4 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was treatment feasibility, defined as the ability to complete 6 chemotherapy cycles without disease progression, premature toxic effects-related treatment discontinuation, or death. RESULTS: A total of 120 women were randomized. The mean and median age was 80 (interquartile range, 76-83; range, 70-94) years; 43 (36%) had a Geriatric Vulnerability Score of 4 and 13 (11%) had a Geriatric Vulnerability Score of 5; 40 (33%) had stage IV disease. During its third meeting, the independent data monitoring committee's recommendation led to the termination of the trial because single-agent carboplatin was associated with significantly worse survival. Six cycles were completed in 26 of 40 (65%), 19 of 40 (48%), and 24 of 40 (60%) patients in the every-3-weeks combination, single-agent carboplatin, and weekly combination groups, respectively. Treatment-related adverse events were less common with the standard every-3-weeks combination (17 of 40 [43%]) than single-agent carboplatin or weekly combination therapy (both 23 of 40 [58%]). Treatment-related deaths occurred in 4 patients (2 of 40 [5%] in each combination group). CONCLUSIONS AND RELEVANCE: This randomized clinical trial shows that compared with every-3-weeks or weekly carboplatin-paclitaxel regimens, single-agent carboplatin was less active with significantly worse survival outcomes in vulnerable older patients with ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02001272.

Feasibility of a prehabilitation programme dedicated to older patients with cancer before complex medical-surgical procedures: the PROADAPT pilot study protocol.

BACKGROUND: Ageing is associated with an increased prevalence of comorbidities and sarcopenia as well as a decline of functional reserve of multiple organ systems, which may lead, in the context of the disease-related and/or treatment-related stress, to functional deconditioning. The multicomponent 'Prehabilitation & Rehabilitation in Oncogeriatrics: Adaptation to Deconditioning risk and Accompaniment of Patients' Trajectories (PROADAPT)' intervention was developed multiprofessionally to implement prehabilitation in older patients with cancer. METHODS: The PROADAPT pilot study is an interventional, non-comparative, prospective, multicentre study. It will include 122 patients oriented to complex medical-surgical curative procedures (major surgery or radiation therapy with or without chemotherapy). After informed consent, patients will undergo a comprehensive geriatric assessment and will be offered a prehabilitation kit that includes an advice booklet with personalised objectives and respiratory rehabilitation devices. Patients will then be called weekly and monitored for physical and respiratory rehabilitation, preoperative renutrition, motivational counselling and iatrogenic prevention. Six outpatient visits will be planned: at inclusion, a few days before the procedure and at 1, 3, 6 and 12 months after the end of the procedure. The main outcome of the study is the feasibility of the intervention, defined as the ability to perform at least one of the components of the programme. Clinical data collected will include patient-specific and cancer-specific characteristics. ETHICS AND DISSEMINATION: The study protocol was approved by the Ile de France 8 ethics committee on 5 June 2018. The results of the primary and secondary objectives will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03659123. Pre-results of the trial.

Feasibility and efficacy of a supervised home-based physical exercise program for metastatic cancer patients receiving oral targeted therapy: study protocol for the phase II/III - UNICANCER SdS 01 QUALIOR trial.

BACKGROUND: Currently, oral targeted therapies are known to be effective and are frequently used to treat metastatic cancer patients, but fatigue is a frequently reported early side effect of these treatments. This fatigue may impact the patient's treatment adherence and result in a negative impact on quality of life. Physical exercise significantly improved the general well-being and quality of life of advanced cancer patients. However, there is no specific physical activity program adapted for patients with advanced disease. METHODS: QUALIOR is a two-part, randomized, open-label, and multicenter with two arms phase II/III trial. Patients (phase II: n = 120; phase III: n = 312) with metastatic cancer (breast cancer, kidney cancer, lung cancer, and other cancers [including but not limited to colon cancer, melanoma, sarcoma, or hepatocarcinoma]) treated with a first- or second-line oral targeted therapy without chemotherapy will be included. Patients will be randomized (2:1) to a 3-month supervised home-based standardized physical activity program or to a recommended adapted physical activity (via a booklet). The primary objective of the phase II is to evaluate the feasibility of the supervised program. The primary objective of the phase III is the evaluation of the benefit of the supervised home-based program compare to the recommended program in terms of fatigue and quality of life at 3 months. The secondary objectives aim to evaluate the impact of the supervised program on fatigue over time, pain, physical capacities, psychosocial and cognitive functions, general quality of life, frequency of dose reduction and patients' adherence to the targeted therapy, overall survival, and progression-free survival. This study will also evaluate the medico-economic impact of supervised program compared to the recommended adapted physical activity program. DISCUSSION: The aim of this study is to evaluate home-based physical exercise program for metastatic cancer patients treated with oral targeted therapies to help patients to cope with fatigue and improve quality of life. TRIAL REGISTRATION: This trial was registered in ClinicalTrials.gov since May 2017 ( NCT03169075 ).

Interventions to improve physical performances of older people with cancer before complex medico-surgical procedures: Protocol for an umbrella review of systematic reviews and meta-analyses.

BACKGROUND: Current demographics lead increasing older cancer patients to undergo complex medico-surgical procedures, with substantial risk of decompensations and deconditioning. The Prehabilitation & Rehabilitation in Oncology: Adaptation to Disease and Accompaniment of Patients' Trajectories (PROADAPT) project is currently being developed with the aim of improving care, through standardized care pathways guided by existing evidence and implementation programs. A working group will specifically focus on improvement of physical performances before such procedures. These interventions may have been developed in different contexts: before surgery in large, before carcinologic surgery or complex medical interventions (chemotherapy, radiotherapy), or in primary care for elderly patients to prevent sarcopenia and frailty. Post-surgical interventions are out of the scope of this review. The objective of this review is to summarize the level of evidence to support physical reconditioning interventions and identify areas where further work is required. METHODS: This umbrella review will include moderate to high quality systematic reviews, meta-analysis, and pre-existing umbrella or meta-reviews. Two reviewers will independently search the following databases: PubMed/MedLine, Cochrane Library, Embase, and CINAHL. Research strategy will use diverse keywords used to refer to the concepts of "prehabilitation," "preoperative exercise," or "preoperative rehabilitation," with prespecified inclusion and exclusion criteria and only systematic reviews selection. The distinct types of interventions presented using PRISMA guidelines and a narrative reporting of results. A focus will be made on outcomes such as physical performances, quality of life, autonomy in everyday activities, or number of hospital bed days. ETHICS AND DISSEMINATION: Ethical approval is not required for such an umbrella review. Our review will be submitted for publication in a peer-reviewed international journal using open access option if available. It will be complementary to reviews focused on hospital discharge of older people. PROSPERO REGISTRATION NUMBER: CRD42020100110.

Does a homeopathic medicine reduce hot flushes induced by adjuvant endocrine therapy in localized breast cancer patients? A multicenter randomized placebo-controlled phase III trial.

PURPOSE: Endocrine therapy (ET) used to reduce the risk of recurrence in hormone receptor-expressing disease (75% of breast cancers) is associated with worsening of climacteric symptoms with a negative impact on quality of life (QoL). Homeopathy might allow a better management of hot flushes (HF). METHODS: In this multicenter randomized double-blind placebo-controlled phase III study ( ClinicalTrials.gov NCT01246427), we enrolled ≥ 18 years old women with histologically proven non metastatic localized breast cancer, with Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) ≤ 1, treated for at least 1 month with adjuvant ET, and complaining about moderate to severe HF. Patients should not be scheduled for chemotherapy or radiotherapy, and had no associated pathology known to induce HF. After a 2- to 4-week placebo administration, we randomly assigned (1:1) patients with HFS ≥ 10 using an interactive web-based centralized platform to BRN-01 homeopathic medicine complex (Actheane®) in arm A or Placebo (Arm P). Randomization was stratified by adjuvant ET (taxoxifen/aromatase inhibitor) and recruiting site. HF scores (HFS) were calculated as the mean of HF frequencies before randomization, at 4, and at 8 weeks post-randomization (pre-, 4w,- and 8w-) weighted by a 4-level intensity scale. Primary endpoint was assessed at 4-week post-randomization, as the variation between pre- and 4w-HFS. Secondary endpoints included HFS variation between pre- and 8w-HFS, compliance and tolerance assessed 8 weeks after randomization, and QoL and satisfaction assessed at 4- and 8-week post-randomization. RESULTS: Two hundred ninety-nine patients were included, and 138 (46.2%) randomized (A, 65; P, 73). Median 4w-HFS absolute variation (A, - 2.9; P, - 2.5 points, p = 0.756) and relative decrease (A, - 17%; P, - 15%, p = 0.629) were not statistically different. However, 4w-HFS decreased for 46 (75%) in A vs 48 (68%) patients in P arm. 4w-QoL was stable or improved for respectively 43 (72%) vs 51 (74%) patients (p = 0.470). CONCLUSIONS: The efficacy endpoint was not reached, and BRN-01 administration was not demonstrated as an efficient treatment to alleviate HF symptoms due to adjuvant ET in breast cancer patients. However, the study drug administration led to decreased HFS with a positive impact on QoL. Without any recommended treatment to treat or alleviate the HF-related disabling symptoms, Actheane® could be a promising option, providing an interesting support for better adherence to ET, thereby reducing the risk of recurrence with a good tolerance profile.

Cancer-associated thrombosis in patients with implanted ports: a prospective multicenter French cohort study (ONCOCIP).

The need to accurately identify cancer outpatients at high risk of thrombotic complications is still unmet. In a prospective, multicenter cohort study (ONCOlogie et Chambres ImPlantables [ONCOCIP]), consecutive adult patients with a solid tumor and implanted port underwent 12-month follow-up. Our primary objective was to identify risk factors for (1) catheter-related thrombosis, defined as ipsilateral symptomatic upper-limb deep-vein thrombosis with or without pulmonary embolism, and (2) venous thromboembolism other than catheter-related, defined as any symptomatic superficial- or deep-vein thrombosis (other than catheter-related) or pulmonary embolism, and incidental pulmonary embolism. All events were objectively confirmed and centrally adjudicated. Rate assessments integrated competing risk of death. Overall, 3032 patients were included (median age: 63 years; women: 58%). The most frequent cancer locations were breast (33.7%), lung (18.5%), and colorectal (15.6%), cancer being metastatic in 43.2% of patients. Most patients (97.1%) received chemotherapy. By 12 months, 48 (1.6%) patients had been lost to follow-up and 656 (24.6%) had died; 3.8% (n = 111) of patients had experienced catheter-related thrombosis, and 9.6% (n = 276) venous thromboembolism other than catheter-related. By multivariate analysis, use of cephalic vein for catheter insertion predicted catheter-related thrombosis, whereas ongoing antiplatelet therapy was protective; risk factors for venous thromboembolism other than catheter-related were advanced age, previous venous thromboembolism, cancer site, and low hemoglobin level or increased leukocyte count before chemotherapy. In conclusion, this large prospective cohort study showed a high rate of venous thromboembolism in patients with a solid tumor and implanted port. Risk factors for catheter-related thrombosis differed from those for venous thromboembolism not catheter-related. This trial was registered at www.clinicaltrials.gov as #NCT02025894.

Treatment patterns and survival in an exhaustive French cohort of pazopanib-eligible patients with metastatic soft tissue sarcoma (STS).

BACKGROUND: The French EMS study prospectively collected exhaustive data from STS patients diagnosed in the Rhone-Alpes region from 2005 to 07. METHODS: The database included diagnosis/histology, surgery, radiotherapy, systemic treatments and treatment response. Treatment patterns and outcomes of patients with metastatic disease, excluding adipocytic sarcoma and GIST were analyzed. RESULTS: Of 888 total patients, 145 were included based on having metastatic disease and appropriate subtypes. All patients received treatment with systemic therapy being most common (74%, n = 107), followed by radiotherapy (30%, n = 44) and surgery (23%, n = 33). Doxorubicin, alone or in combination, was the most common first line systemic therapy (65%, n = 46). Drugs without license in sarcoma were used in 38-83% of treatments depending on treatment line. 24% of frontline patients demonstrated an objective response, decreasing to 11% objective responses in second line but no responses were documented beyond second line, with median PFS declining with each additional line. Median PFS also declined in patients receiving surgery compared to those receiving no surgery (8-15 m vs 5 m). Median OS from metastatic diagnosis for patients receiving systemic therapy was double that of patients without systemic treatment (24 m vs 12 m, p = 0.007). CONCLUSIONS: Outcomes in this population were poor and declined with successive treatment. However, results suggest that further anticancer therapies in recurrent sarcoma might be beneficial.

Geriatric factors analyses from FFCD 2001-02 phase III study of first-line chemotherapy for elderly metastatic colorectal cancer patients.

AIM: Several predictors of metastatic colorectal cancer (mCRC) outcomes have been described. Specific geriatric characteristics could be of interest to determine prognosis. METHOD: Elderly patients (75+) with previously untreated mCRC were randomly assigned to receive infusional 5-fluorouracil-based chemotherapy, either alone (FU) or in combination with irinotecan (IRI). Geriatric evaluations were included as an optional procedure. The predictive value of geriatric parameters was determined for the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). RESULTS: From June 2003 to May 2010, the FFCD 2001-02 randomised trial enrolled 282 patients. A baseline geriatric evaluation was done in 123 patients; 62 allocated to the FU arm and 61 to the IRI arm. The baseline Charlson index was ≤1 in 75%, Mini-Mental State Examination was ≤27/30 in 31%, Geriatric Depression Scale was >2 in 10% and Instrumental Activities of Daily Living (IADL) was impaired in 34% of the patients. Multivariate analyses revealed that no geriatric parameter was predictive for ORR or PFS. Normal IADL was independently associated with better OS. The benefit of doublet chemotherapy on PFS differed in subgroups of patients ≤80 years, with unresected primary tumour, leucocytes >11,000 mm3 and carcinoembryonic antigen >2N. There was a trend towards better OS in patients with normal IADL. CONCLUSION: The autonomy score was an independent predictor for OS. A trend toward a better efficacy of doublet chemotherapy in some subgroups of patients was reported and should be further explored.

Geriatric factors predict chemotherapy feasibility: ancillary results of FFCD 2001-02 phase III study in first-line chemotherapy for metastatic colorectal cancer in elderly patients.

PURPOSE: Elderly patients form a heterogeneous population. Evaluation of geriatric factors may help evaluate a patient's health status to better adapt treatment. PATIENTS AND METHODS: Elderly patients with previously untreated metastatic colorectal cancer (mCRC) were randomly assigned to receive fluorouracil (FU) -based chemotherapy either alone or in combination with irinotecan (IRI) in the Fédération Francophone de Cancérologie Digestive (FFCD) 2001-02 study. Sites participating in the geriatric substudy completed geriatric screening tools to perform prognostic factor analyses for treatment safety during the first 4 months after treatment initiation. RESULTS: The geriatric score was calculated in 123 patients (44%). Median age was 80 years (range, 75 to 91 years). The Charlson comorbidity index was ≤ 1 in 75%, Mini-Mental State Examination (MMSE) score was ≤ 27/30 in 31%, and Instrumental Activities of Daily Living (IADL) showed impairment in 34% of the patients. Seventy-one patients (58%) had grade 3 to 4 toxicity, 41 (33%) had a dose-intensity reduction of more than 33%, and 54 (44%) had at least one unexpected hospitalization during the first 4 months after starting treatment. In multivariate analysis, significant predictive factors for grade 3-4 toxicity were IRI arm (odds ratio [OR], 5.03), MMSE ≤ 27/30 (OR, 3.84), and impaired IADL (OR, 4.67); for dose-intensity reduction of > 33%, the significant predictive factors were alkaline phosphates > 2 × upper limit of normal (OR, 4.16) and IRI arm (OR, 6.85); and for unexpected hospitalization, significant predictive factors were MMSE ≤ 27/30 (OR, 4.56) and Geriatric Depression Scale ≤ 2 (OR, 5.52). CONCLUSION: Geriatric factors (MMSE and IADL) are predictive of severe toxicity or unexpected hospitalization (MMSE) in a randomized prospective phase III study in mCRC. These results suggest that cognitive function and autonomy impairment should be taken into account when choosing a regimen for chemotherapy.

Could ovarian choriocarcinoma be detected by maternal serum screening for Down syndrome?

The incidence of ovarian malignancies during gestation ranges from 1 in 8000 to 1 in 20,000 deliveries. Ovarian malignancies that produce human chorionic gonadotropin (hCG) are limited to germ cell tumors, of which dysgerminoma is the most frequent (45%) malignant type encountered in pregnant patients, the others being ovarian choriocarcinoma and mixed germ cell tumors (Boulay and Podczaski, 1998). In women of childbearing age, it is hard to distinguish between metastatic choriocarcinoma on a complete mole and primary ovarian choriocarcinoma. Treatment is based on adnexectomy followed by chemotherapy. Given the extreme rarity of these tumors, the long-term prognosis is difficult to establish. Had the diagnosis for our patient been made during pregnancy, the therapeutic approach would have been discussed in terms of gestational age. In the last trimester, we could have suggested cesarean section followed by adnexectomy, and then chemotherapy. In the second-trimester, chemotherapy could have been discussed, although the fetal toxicity of cisplatin chemotherapy is not firmly defined (Ferrandina et al., 2005). This treatment is an alternative to termination of pregnancy. We retrospectively studied maternal serum biochemistry so as to assess the possibility of a diagnosis of ovarian choriocarcinoma at the time of maternal serum screening for Down syndrome.

Protocol for the treatment of malignant inoperable bowel obstruction: a prospective study of 80 cases at Grenoble University Hospital Center.

A prospective protocol for treatment of malignant inoperable bowel obstruction was implemented at Grenoble University Hospital Center for 4 years. All 80 episodes of obstruction resulted from peritoneal carcinomatosis and none could expect another treatment cure. The protocol comprised three successive stages. Stage I included treatment for 5 days with a corticosteroid, antiemetic, anticholinergic, and analgesic. Stage II provided a somatostatin analogue if vomiting persisted. After 3 days, Stage III provided a venting gastrostomy. Obstruction relief with symptom control was obtained by medical treatment in 29 cases and symptom control occurred alone in an additional 32 cases. Ten patients were relieved by venting gastrostomy. Symptom control without permanent nasogastric tube (NGT) placement occurred in 72 episodes (90%). Eight patients with refractory vomiting were obliged to continue the NGT until death. Fifty-eight obstruction episodes (73%) were controlled in 10 days or less. Median time before gastrostomy was 17 days. Median survival was 31 days. This series suggests that a staged protocol for the treatment of inoperable malignant bowel obstruction is highly effective in relieving symptoms. A subgroup experiences relief of obstruction using this approach.

The effectiveness of trastuzumab (Herceptin) combined with chemotherapy for gastric carcinoma with overexpression of the c-erbB-2 protein.

The c-erbB-2 protein is overexpressed in 7% of gastric cancer cases, suggesting that anti-c-erbB-2 antibody therapy (trastuzumab; Herceptin) could be used. We report here a 28-year-old woman with metastatic gastric cancer overexpressing c-erbB-2 (3 + strong membrane staining on immunohistochemistry) who was treated with trastuzumab in combination with chemotherapy. A complete response was obtained with a combination of trastuzumab and oxaliplatin and was maintained with trastuzumab alone for 18 months. The patient relapsed and chemotherapy (capecitabine, docetaxel) was combined with the anti-c-erbB-2 antibody. The patient survived for 4 years with metastatic disease controlled for 2 years by immunochemotherapy. We conclude that the combination of trastuzumab and chemotherapy is efficient in the treatment of metastatic gastric carcinoma with overexpression of the c-erbB-2 protein.