Effects of home-based exercise training on vo2 in breast cancer patients under adjuvant or neoadjuvant chemotherapy (sapa).

International audienceBreast cancer chemotherapy is associated with a decline in measured cardiorespiratory fitness and increased fatigue. Physical activity has emerged as a feasible intervention to limit these side effects. Quantitative evaluation is necessary to propose a better-adapted physical activity and to evaluate efficacy. We undertook a prospective study to assess the effects of a home-based adapted physical activity (APA) program on aerobic capacity, strength, and fatigue in women treated with adjuvant or neoadjuvant chemotherapy for breast cancer versus usual care. This was an open two-arm, randomized controlled trial. Study included outpatient groups in the Department of Physiology and Medical Oncology, at Limoges University Hospital, France. Forty-four patients treated with adjuvant or neoadjuvant chemotherapy for breast cancer. Patients were randomly assigned to a control group or an APA group. Intervention consisted of a 3-week, home-based, supervised, combined APA program (endurance and resistance training) during 27 weeks. The primary endpoint was cardiopulmonary function assessed by maximal peak oxygen consumption (VO2peak). Secondary endpoints included a 6-minute walking test (6MWT), and assessment of muscular strength, fatigue, quality of life, physical activity level, and anxiety/depression. At 27 weeks, VO2peak increased by 1.83 ± 0.68 ml.min-1.kg-1 in the APA group (P =0.009) and decreased by 1.31 ± 0.65 ml.min-1.kg-1 in the control group (P = 0.046). The difference between the two groups was not significant (2.26 ± 1.53 ml.min-1.kg-1, P = 0.140) in intention-to-treat analysis, but it was significant in per protocol analysis (3.49 ± 1.64 ml.min-1.kg-1, P = 0.049). At 27 and 54 weeks, no significant differences were observed between the two groups for the cardiopulmonary exercise test, 6MWT, quadriceps strength, or quality of life. In breast cancer patients, a home-based supervised program during chemotherapy and radiotherapy treatment may be safe, feasible and increase VO2peak. In this study, heavy evaluation tests explain patient's non-adherence and do not permit to obtain statistically significant results between APA and control groups. aerobic home-based adapted physical activity is beneficial on aerobic capacity

4521TUBIANA

Abstract. The purpose of this work was to determine the response rate and toxicity of a combination of Carmustine and The prognosis for primary brain tumors is very poor. Surgery and radiotherapy are currently the standard therapies to treat anaplastic astrocytoma (grade III) and glioblastoma multiforme (grade IV). No effective treatment is available, in spite of very active fundamental research on these tumors. Although major advances have been made in therapeutic methods such as surgery, radiotherapy, chemotherapy and various combinations, the overall prognosis for glioblastomas remains unfavorable (1,2) and the median survival time ranges from 6 to 12 months. Few patients are still alive 2 years after diagnosis. The initial therapeutic approach consists of surgical resection. It is rarely curative due to infiltration of tumor cells into the surrounding brain parenchyma and migration inside the brain. Resection represents a prognostic factor since there is a good correlation between patient survival and complete resection (3). However, resection is frequently impossible because of the volume or location of the tumor at a vital brain site. Post-operative radiotherapy produces only a minor prolongation in survival with median survival, increasing from 4.5 -6 months in the case of surgery alone to 9-10 months for a combination of surgery and post-operative radiotherapy (4). Chemotherapy has a limited impact on the survival, despite meta analyses of randomized cases which suggested a survival benefit of 5% to 10% at two years by adjuvant chemotherapy for high grade astrocytoma (5,6). Median survival increased from 9.4 to 12 months. The most commonly used chemotherapy consisted of nitrosoureas such as Carmustine (7). The timing of chemotherapy and radiotherapy is the subject of much debate. It is believed that the blood-brain barrier is more permeable to the penetration of cytotoxic drugs before radiotherapy rather than after, and that tumors are intrinsically less resistant prior to radiotherapy. However, some patients have chemoresistant tumors and therefore require early radiotherapy. We report the results of a pre-irradiation chemotherapy protocol, described first by Grossman et al. (8), used in 37 adults with a glioblastoma for whom complete resection was impossible. Planning of the protocol was based on Grossman's published results. Chemotherapy relied on a combination of 2 effective drugs: BCNU and Cisplatin. BCNU administered as single-drug therapy for postradiotherapy recurrent or progressive glioblastomas yielded a 29% response rate in glioblastomas and 64% in anaplastic astrocytomas, while the corresponding rates achieved with Cisplatin were, respectively, 73% and 83% (9). 1249 Correspondence to: N

A phase III trial of exemestane plus bevacizumab maintenance therapy in patients with metastatic breast cancer after first-line taxane and bevacizumab: a GINECO group study

International audienceBACKGROUND: Maintenance strategies beyond response or tumor stabilization with first-line chemotherapy in metastatic breast cancer (MBC) have not been extensively studied. Endocrine therapy combined with continued bevacizumab may be a helpful option for estrogen receptor (ER)-positive MBC. PATIENTS AND METHODS: In this prospective, open-label, phase III study, patients with histologically confirmed ER-positive, HER2-negative MBC and non-progressive disease after 16-24 weeks of taxane plus bevacizumab (T + BEV) were randomized to continuation of T + BEV or maintenance bevacizumab plus exemestane (E + BEV). The primary end point was progression-free survival (PFS) from randomization. To have 80% power to detect an improvement in the 6-month PFS rate (PFS6m) from 50% to 65%, 186 assessable patients were needed for a total of 141 PFS events. An interim analysis was planned after 40% of the required events. RESULTS: The interim analysis with 98 patients showed that the probability of reaching a statistically significant improvement in PFS by the end of the study was only 7%. This led the Independent Data and Monitoring Committee to recommend termination of patient enrollment. After a median of 21-month follow-up of all randomized patients (117 in total), PFS6m from randomization was 67.2% [95% confidence interval (CI) 53.6-77.7] with T + BEV and 55.2% (95% CI 41.5-66.9) with E + BEV [hazard ratio (HR): 1.0, 95% CI 0.7-1.5, P = 0.998]. Median PFS from BEV initiation was 12.5 and 12.3 months in the T + BEV and E + BEV arms, respectively. In the T + BEV arm, taxane was prematurely stopped for the majority of patients (94.9%), mainly due to toxicity (49.2%). Updated data after 35 months' median follow-up showed death rates of 44% and 55% in T + BEV and E + BEV arms, respectively. CONCLUSION: In this trial, maintenance therapy with E + BEV in ER-positive, HER2-negative MBC patients with no evidence of progression after first-line T + BEV did not achieve longer PFS compared with continuation of T + BEV. CLINICALTRIALSGOV: NCT0130367

Prognostic factor analysis for elderly patients treated for metastatic colorectal cancer in the randomized phase II trial PRODIGE 20

International audienc

Bevacizumab+chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial-PRODIGE 20 study results

IF 11.855International audienceBackground :Metastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy (CT) is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific end points in this population.Patients and methods :Patients aged 75 years and over were randomly assigned to bevacizumab + CT (BEV) versus CT. LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator’s choice. The composite co-primary end point, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consider as inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria.Results :About 102 patients were randomized (51 BEV and 51 CT), median age was 80 years (range 75–91). Primary end point was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT, respectively. Median progression-free survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival was 21.7 months in BEV and 19.8 months in CT. The 36-month overall survival rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non-hematologic toxicities (80.4% in BEV, 63.3% in CT).Conclusion :Bevacizumab combined with CT was safe and efficient. Both arms met the primary safety and efficacy criteria

Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001–02)

International audienceBACKGROUND:Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients.PATIENTS AND METHODS:Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR).RESULTS:From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%).CONCLUSION:In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2.CLINICALTRIALSGOV:NCT00303771