Upfront FOLFOXIRI plus bevacizumab with or without atezolizumab in the treatment of patients with metastatic colorectal cancer (AtezoTRIBE): a multicentre, open-label, randomised, controlled, phase 2 trial.

BACKGROUND: Immune checkpoint inhibitors have not shown clinical benefit to patients with metastatic colorectal cancer who had proficient mismatch repair (pMMR) or microsatellite stable (MSS) tumours in previous studies. Both an active combination chemotherapy (FOLFOXIRI; fluorouracil, leucovorin, oxaliplatin, and irinotecan) and bevacizumab seem able to increase the immunogenicity of pMMR or MSS tumours. We aimed to provide preliminary evidence of benefit from the addition of the anti-PD-L1 agent atezolizumab to first-line FOLFOXIRI plus bevacizumab in patients with metastatic colorectal cancer. METHODS: AtezoTRIBE was a multicentre, open-label, randomised, controlled, phase 2 study of patients (aged 18-70 years with an Eastern Cooperative Oncology Group [ECOG] performance status of 0-2 and aged 71-75 years with an ECOG performance status of 0) with histologically confirmed, unresectable, previously untreated metastatic colorectal cancer and adequate organ function, who were recruited from 22 oncology centres in Italy. Patients were stratified according to centre, ECOG performance status, primary tumour site, and previous adjuvant therapy. A randomisation system incorporating a minimisation algorithm randomly assigned (1:2) patients via a masked web-based allocation procedure to two groups: the control group received first-line FOLFOXIRI (intravenous 165 mg/m2 irinotecan, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin, and 3200 mg/m2 fluorouracil as a 48 h infusion) plus bevacizumab (5 mg/kg intravenously), and the atezolizumab group received the same regimen plus atezolizumab (840 mg intravenously). Combination treatments were administered up to eight 14-day cycles followed by maintenance with fluorouracil and leucovorin plus bevacizumab with or without atezolizumab, according to randomisation group, until disease progression, unacceptable adverse events, or consent withdrawal. The primary endpoint was progression-free survival, analysed by the intention-to-treat principle. Safety was assessed in patients who received at least one dose of the study treatment. The study recruitment is completed. The trial is registered with Clinicaltrials.gov, NCT03721653. FINDINGS: Between Nov 30, 2018, and Feb 26, 2020, 218 patients were randomly assigned and received treatment (73 in the control group and 145 in the atezolizumab group). At the data cutoff (Aug 1, 2021), median follow-up was 19·9 months (IQR 17·3-23·9). Median progression-free survival was 13·1 months (80% CI 12·5-13·8) in the atezolizumab group and 11·5 months (10·0-12·6) in the control group (hazard ratio [HR] 0·69 [80% CI 0·56-0·85]; p=0·012; adjusted HR 0·70 [80% CI 0·57-0·87]; log-rank test p=0·018). The most frequent all-cause grade 3-4 adverse events were neutropenia (59 [42%] of 142 patients in the atezolizumab group vs 26 [36%] of 72 patients in the control group), diarrhoea (21 [15%] vs nine [13%]), and febrile neutropenia (14 [10%] vs seven [10%]). Serious adverse events were reported in 39 (27%) patients in the atezolizumab group and in 19 (26%) patients in the control group. Two (1%) treatment-related deaths (due to acute myocardial infarction and bronchopulmonary haemorrhage) were reported in the atezolizumab group; none were reported in the control group. INTERPRETATION: The addition of atezolizumab to first-line FOLFOXIRI plus bevacizumab is safe and improved progression-free survival in patients with previously untreated metastatic colorectal cancer. FUNDING: GONO Foundation, ARCO Foundation, F Hoffmann-La Roche, and Roche.

Treatments after progression to first-line FOLFOXIRI and bevacizumab in metastatic colorectal cancer: a pooled analysis of TRIBE and TRIBE2 studies by GONO.

BACKGROUND: FOLFOXIRI/bevacizumab (bev) is a first-line regimen of proven activity and efficacy in metastatic colorectal cancer. The upfront exposure to three cytotoxics raises concerns about the efficacy of treatments after progression. METHODS: We performed a pooled analysis of treatments after progression to upfront FOLFOXIRI/bev in patients enrolled in two randomised Phase 3 studies (TRIBE and TRIBE2) that compared FOLFOXIRI/bev to doublets (FOLFOX or FOLFIRI)/bev. Response rate, progression-free survival (2nd PFS) and overall survival (2nd OS) during treatments after progression were assessed. The RECIST response in first line and the oxaliplatin and irinotecan-free interval (OIFI) were investigated as potential predictors of benefit from FOLFOXIRI ± bev reintroduction. RESULTS: Longer 2nd PFS was reported in patients receiving FOLFOXIRI ± bev reintroduction compared to doublets ± bev or other treatments (6.1 versus 4.4 and 3.9 months, respectively, P = 0.013), and seems limited to patients achieving a response during first line (6.9 versus 4.2 and 4.7 months, respectively, P = 0.005) and an OIFI ≥ 4 months (7.2 versus 6.5 and 4.6 months, respectively, P = 0.045). CONCLUSIONS: First-line FOLFOXIRI/bev does not impair the administration of effective second-line therapies. First-line response and longer OIFI seem associated with improved response and 2nd PFS from FOLFOXIRI ± bev reintroduction, without impacting 2nd OS.

Response shift in health-related quality of life measures in the presence of formative indicators.

BACKGROUND: Response shift (RS) has been defined as a change in the meaning of an individual's self-evaluation that needs to be accounted for when assessing longitudinal changes in health-related quality of life (HRQoL). RS detection through structural equation modeling is accomplished by adopting Oort's procedure based on a measurement model in which the observed variables are defined as reflective indicators of the HRQoL latent variable; that is, the latent variable causes the variation in the reflective indicators. This study aims to propose a procedure that assesses RS when formative indicators are used in measuring HRQoL; in this last case, the latent variable is considered to be a function of some formative indicators. A secondary aim is to compare the new procedure with Oort's procedure to highlight similarities and differences. METHODS: The data were retrieved from a consecutive series of 258 patients newly diagnosed with colorectal cancer and undergoing chemotherapy and/or surgery. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QOL-C30) was administered twice, once before and once six months after treatment. Structural equation modeling was used to evaluate RS and true change with the newly proposed method (in which fatigue and pain were defined as formative indicators) and with Oort's procedure (in which fatigue and pain were defined as reflective indicators). RESULTS: According to the new procedure, there was no measurement bias, and on average, patients' quality of life improved by 3.53 points (on a scale ranging from 0 to 100) at the 6-month follow-up. With Oort's procedure, the loading of the pain indicator was not invariant across the two time points, suggesting the presence of reprioritization, whereas the estimation of true change was very similar to the previous one: 3.87. CONCLUSIONS: RS and true change in HRQoL can be evaluated in the presence of formative indicators. Defining a measurement model by formative or reflective indicators can lead to different results.

Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial.

BACKGROUND: The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab showed improved outcomes for patients with metastatic colorectal cancer, compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. However, the actual benefit of the upfront exposure to the three cytotoxic drugs compared with a preplanned sequential strategy of doublets was not clear, and neither was the feasibility or efficacy of therapies after disease progression. We aimed to compare a preplanned strategy of upfront FOLFOXIRI followed by the reintroduction of the same regimen after disease progression versus a sequence of mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) and FOLFIRI doublets, in combination with bevacizumab. METHODS: TRIBE2 was an open-label, phase 3, randomised study of patients aged 18-75 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 2, with unresectable, previously untreated metastatic colorectal cancer, recruited from 58 Italian oncology units. Patients were stratified according to centre, ECOG performance status, primary tumour location, and previous adjuvant chemotherapy. A randomisation system incorporating a minimisation algorithm was used to randomly assign patients (1:1) via a masked web-based allocation procedure to two different treatment strategies. In the control group, patients received first-line mFOLFOX6 (85 mg/m2 of intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab (5 mg/kg intravenously over 30 min) followed by FOLFIRI (180 mg/m2 of intravenous irinotecan over 120 min concurrently with 200 mg/m2 of leucovorin; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab after disease progression. In the experimental group, patients received FOLFOXIRI (165 mg/m2 of intravenous irinotecan over 60 min; 85 mg/m2 intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 3200 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab followed by the reintroduction of the same regimen after disease progression. Combination treatments were repeated every 14 days for up to eight cycles followed by fluorouracil and leucovorin (at the same dose administered at the last induction cycle) plus bevacizumab maintenance until disease progression, unacceptable adverse events, or consent withdrawal. Patients and investigators were not masked. The primary endpoint was progression-free survival 2, defined as the time from randomisation to disease progression on any treatment given after first disease progression, or death, analysed by intention to treat. Safety was assessed in patients who received at least one dose of their assigned treatment. Study recruitment is complete and follow-up is ongoing. This trial is registered with Clinicaltrials.gov, NCT02339116. FINDINGS: Between Feb 26, 2015, and May 15, 2017, 679 patients were randomly assigned and received treatment (340 in the control group and 339 in the experimental group). At data cut-off (July 30, 2019) median follow-up was 35·9 months (IQR 30·1-41·4). Median progression-free survival 2 was 19·2 months (95% CI 17·3-21·4) in the experimental group and 16·4 months (15·1-17·5) in the control group (hazard ratio [HR] 0·74, 95% CI 0·63-0·88; p=0·0005). During the first-line treatment, the most frequent of all-cause grade 3-4 events were diarrhoea (57 [17%] vs 18 [5%]), neutropenia (168 [50%] vs 71 [21%]), and arterial hypertension (25 [7%] vs 35 [10%]) in the experimental group compared with the control group. Serious adverse events occurred in 84 (25%) patients in the experimental group and in 56 (17%) patients in the control group. Eight treatment-related deaths were reported in the experimental group (two intestinal occlusions, two intestinal perforations, two sepsis, one myocardial infarction, and one bleeding) and four in the control group (two occlusions, one perforation, and one pulmonary embolism). After first disease progression, no substantial differences in the incidence of grade 3 or 4 adverse events were reported between the control and experimental groups, with the exception of neurotoxicity, which was only reported in the experimental group (six [5%] of 132 patients). Serious adverse events after disease progression occurred in 20 (15%) patients in the experimental group and 25 (12%) in the control group. Three treatment-related deaths after first disease progression were reported in the experimental group (two intestinal occlusions and one sepsis) and four in the control group (one intestinal occlusion, one intestinal perforation, one cerebrovascular event, and one sepsis). INTERPRETATION: Upfront FOLFOXIRI plus bevacizumab followed by the reintroduction of the same regimen after disease progression seems to be a preferable therapeutic strategy to sequential administration of chemotherapy doublets, in combination with bevacizumab, for patients with metastatic colorectal cancer selected according to the study criteria. FUNDING: The GONO Cooperative Group, the ARCO Foundation, and F Hoffmann-La Roche.

Upfront Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan Plus Bevacizumab With or Without Atezolizumab for Patients With Metastatic Colorectal Cancer: Updated and Overall Survival Results of the ATEZOTRIBE Study.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report 4-year results of the phase II randomized AtezoTRIBE study. Eligible patients with metastatic colorectal cancer (mCRC) received first-line fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/bevacizumab (control group, n = 73) or FOLFOXIRI/bevacizumab plus atezolizumab (experimental group, n = 145). We present overall survival (OS) and updated outcomes according to tumor immune-related biomarkers, both in the intention-to-treat (ITT) population and the cohort of patients with proficient mismatch repair (pMMR) tumors. Median follow-up was 45.2 months (IQR, 42.6-49.2). In the ITT population, median OS was 33.0 and 27.2 months for experimental and control groups, respectively (hazard ratio [HR], 0.78 [80% CI, 0.61 to 0.98]; P = .084). An interaction effect between Immunoscore Immune-Checkpoint (IC) and treatment arm was observed (Pint, .089), with higher benefit from atezolizumab in the Immunoscore IC-high group. In the pMMR cohort (N = 202), median OS was 30.8 and 29.2 months for experimental and control groups, respectively (HR, 0.80 [80% CI, 0.63 to 1.02]; P = .117). Interactions between treatment group and tumor mutational burden (TMB) and Immunoscore IC were reported (Pint, .043 and .092, respectively), with patients bearing TMB-high and Immunoscore IC-high tumors deriving higher benefit from the addition of atezolizumab. First-line FOLFOXIRI/bevacizumab plus atezolizumab improves OS in patients with mCRC. In the pMMR group, patients with Immunoscore IC-high and/or TMB-high tumors are identified as a subgroup of interest to further develop this treatment.

Supportive Care Needs and the Impact of Loss of Functioning and Symptom Burden on the Quality of Life in Patients with Advanced Colorectal Cancer.

BACKGROUND/AIMS: Relationships between loss of functioning, symptom burden, supportive care needs, and quality of life (QoL) have been suggested in cancer populations. This cross-sectional study further investigates these relationships through mediation analyses. METHODS: A total of 276 advanced colorectal cancer (CRC) patients completed validated instruments to assess cancer-related functioning, symptoms, supportive care needs, and QoL. Pearson's correlations and multiple mediation models with bootstrapping method were performed. RESULTS: QoL had negative correlations with supportive care needs, positive correlations with functioning measures, and negative correlations with symptom scales. Supportive care needs had negative correlations with functioning measures and positive correlations with symptom scales. Mediation analyses showed significant indirect effects of CRC-related functioning and symptoms on QoL through supportive care needs. CONCLUSIONS: Significant links between CRC-related loss of functioning, symptom burden, QoL, and supportive care needs have been established. Longitudinal studies are planned to clarify cause-and-effects relationships and establish sequences of events.

Concurrent Chemoradiation in Anal Cancer Patients Delivered with Bone Marrow-Sparing IMRT: Final Results of a Prospective Phase II Trial.

We investigated the role of the selective avoidance of haematopoietically active pelvic bone marrow (BM), with a targeted intensity-modulated radiotherapy (IMRT) approach, to reduce acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent chemo-radiation. We designed a one-armed two-stage Simon's design study to test the hypothesis that BM-sparing IMRT would improve by 20% the rate of G0-G2 (vs. G3-G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05; ß = 0.20). A minimum of 21/39 (54%) with G0-G2 toxicity represented the threshold for the fulfilment of the criteria to define this approach as 'promising'. We employed 18FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. From December 2017 to October 2020, we enrolled 39 patients. Maximum observed acute HT comprised 20% rate of ≥G3 leukopenia and 11% rate of ≥G3 thrombocytopenia. Overall, 11 out of 39 treated patients (28%) experienced ≥G3 acute HT. Conversely, in 28 patients (72%) G0-G2 HT events were observed, above the threshold set. Hence, 18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in this clinical setting.

Tailoring chemotherapy supply according to patients' preferences: a quantitative method in colorectal cancer care.

Objectives: The aim of this study was to conduct a discrete choice experiment with patients affected by colorectal cancer to understand their preferences for different attributes of the chemotherapy supply. Our overall goal is to provide evidence on the relative importance of each attribute in order to tailor chemotherapy supply according to patients' priorities in the design or reorganization processes of cancer services.Methods: Focus groups were used to identify the attributes and levels for the discrete choice experiment. The attributes were: continuity of care, understanding, information, treatment choice, and time for therapy. Respondents were asked to choose between two mutually exclusive hypothetical alternatives of chemotherapy supply. Patients completed the discrete choice experiment along with the health-related quality of life and patients' satisfaction questions. Conditional and mixed logistic models were used to analyses the data.Results: Patients with colorectal cancer treated with chemotherapy (n = 76) completed the survey. The most important aspects of chemotherapy supply were: "Providing detailed and complete information" and "High ability in understanding" patients. Preferences were also influenced by the availability of a trusted doctor. Except for one attribute (waiting time for therapy), all other characteristics significantly influenced respondents' preferences.Conclusions: Results should support a policy of strengthening medical doctors' capabilities to communicate with patients, providing them complete information and involving them in the clinical decisions. Specifically, the findings should be used to improve the current provision of cancer care by identifying areas of preferred intervention from the perspectives of patients in order to tailor the service supply accordingly.

Health-related quality of life in patients with RAS wild-type metastatic colorectal cancer treated with panitumumab-based first-line treatment strategy: A pre-specified secondary analysis of the Valentino study.

BACKGROUND: Quality of life (QoL) patient-reported outcomes (PROs) data from pivotal first-line trials in metastatic colorectal cancer (mCRC) are poor. The Valentino study showed that de-escalation to single-agent panitumumab after 4-month induction with panitumumab-FOLFOX is inferior to panitumumab-5-FU/LV in patients with RAS wild-type mCRC, although slightly reducing toxicity. We report QoL, a secondary end-point. METHODS: PROs were assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30), EORTC QLQ-CR29, EuroQol EQ-5D questionnaires, at baseline and every 8 weeks until disease progression. First two evaluations correspond to induction treatment (identical in both arms), while subsequent to maintenance. To describe QoL changes over time, mean changes from baseline at each time point were calculated in overall population. To compare maintenance between two arms, mean changes and proportion of improved/stable/worse patients versus baseline were compared for each item. RESULTS: In arm A/B, 91.5%/92.0% of enrolled patients completed questionnaires at baseline. No significant differences in the two arms were reported in compliance, baseline scores and mean changes versus baseline for the three questionnaires during maintenance (24/32/40 weeks). Overall, mean changes versus baseline showed an early deterioration during induction with partial recovering during maintenance for global QoL, functional scales and several symptoms/items of QLQ-C30 (fatigue, nausea/vomiting, appetite loss, diarrhoea) and QLQ-CR29 (body image, dry mouth, hair loss, taste, faecal incontinence, sore skin), and EQ-5D Visual Analogue Scale (VAS) score. CONCLUSION: In patients with RAS wild-type mCRC, induction with oxaliplatin-containing chemotherapy plus anti-EGFRs induces a transient significant QoL deterioration. After induction phase, treatment deintensification determines an overall recovery of health-related QoL, besides the expected prevention of oxaliplatin-related neurotoxicity.

Efficacy and skin toxicity management with cetuximab in metastatic colorectal cancer: outcomes from an oncologic/dermatologic cooperation.

PURPOSE: The aim of this study was to investigate the efficacy of the combination of irinotecan/cetuximab and to plan related skin toxicity management with an oncologic/dermatologic team. PATIENTS AND METHODS: Thirty-four patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer received cetuximab 400 mg/m2 as an initial dose and 250 mg/m2 weekly thereafter. In addition, patients received irinotecan 180 mg/m2 every 2 weeks. RESULTS: Thirty-two patients were evaluated for response rate (RR) and skin toxicity to establish the best management. In our study, the responses observed with cetuximab treatment were complete response in 1 patient (3%), partial response in 11 patients (34%), disease stabilization in 6 patients (19%), and progressive disease in 14 patients (44%). Of 34 patients evaluable for cutaneous toxicity, 10 patients (29%) presented with grade 1 eruption, 13 (38%) with grade 2 eruption, and 4 (12%) with grade 3 eruption. Allergic reactions such as flushing and urticaria (grade 2) were seen in 2 patients (6%). CONCLUSION: Cutaneous reactions consisted of follicular rash, xerosis, painful fissures in palms and soles, alterations in hair growth, and mucositis. In the majority of patients (80%-90%), the worst recorded skin effects were mild (grade 1) to moderate (grade 2). The incidence of severe cases (grade 3) was approximately 15%. All dermatologic effects were reversible and generally without sequelae within 4 weeks after treatment discontinuation. We observed significant correlations between degree of cutaneous toxicity and increased RR. Correct identification and treatment by oncologic/dermatologic cooperation of EGFR cutaneous side effects help to improve quality of life.

Pituitary lesions in breast cancer patients: A report of three cases.

Pituitary metastases occur in 6-8% of breast cancer cases, but are seldom diagnosed and rarely reported. Therefore, it can be challenging to establish a clinical differential diagnosis, and at present, a definitive criteria is not available. The present study discusses the pituitary lesions identified in three patients with breast cancer, and describes their management within the collaborative framework of the Breast Unit at the Città della Salute Hospital, which also included assessment by endocrinologists. The patients were evaluated for anterior and posterior pituitary function, the appearance of the pituitary upon magnetic resonance imaging (MRI), and the oncology status and treatment. In addition, successive analysis of prolactin levels and the MRI was performed. The patients, aged 75, 83 and 76 years old, differed in their clinical presentation and successive evolution. One patient demonstrated an abrupt onset of diabetes insipidus, the second exhibited overt hypopituitarism and the final patient had a pituitary mass discovered by chance. Cases one and three exhibited systemic spread of the breast cancer, with bone and/or parenchymal metastasis, but not brain metastasis. Case two presented with a secondary pituitary tumour alone. In case three, a secondary nature to the pituitary lesion was unlikely, since there was no lesion evolution evident following MRI and as stable prolactin levels were observed over the course of the study period. By contrast, case one presented with a rapid increase of sellar lesions on MRI, together with a progressive rise in prolactin levels. Taking into account the frailty of breast cancer patients who are monitored for disease progression, management in a collaborative framework, such as at the Breast Unit, makes it possible to establish a diagnosis of sellar lesions, which is adequate for the comprehensive management of the patient with successive pituitary MRIs and prolactin evaluations, and avoids unnecessary invasive neurosurgery.

Gemcitabine and vinorelbine as second-line treatment in patients with metastatic breast cancer: a phase II study.

BACKGROUND: To evaluate the feasibility and activity of gemcitabine and vinorelbine as a second/third-line approach in patients with advanced breast cancer. METHODS: Entered into the study were 51 consecutive patients. All had been previously treated with anthracyclines. Of these 51 patients, 36 had experienced failure or relapse after one chemotherapy line for advanced disease, and 15 after two chemotherapy lines. The dominant sites of involvement were brain in 4 patients (7.8%), liver in 22 (43.2%), lung in 10 (19.6%), bone in 10 (19.6), and soft-tissue in 5 (9.8%). Treatment consisted of vinorelbine 25 mg/m(2) and gemcitabine 1000 mg/m(2) administered on days 1 and 8 every 21 days. RESULTS: The scheme was well tolerated. Grade 3/4 neutropenia was observed in 11% of patients. Grade 3 nausea and vomiting occurred in 6%, and grade 2 neurotoxicity in 6%. No patients experienced grade 3/4 alopecia. The median relative dose intensity was 94.6% (49.7-100%) and 90.0% (23.1-100%) for vinorelbine and gemcitabine, respectively. Two patients (3.9%) were not evaluable for disease response, 4 (7.8%) attained a clinical complete response, 13 (25.5%) a partial response (for an overall response rate of 33.3%, 95% coefficient interval 20.0-46.0%), 23 (45.2%) showed stable disease, and 9 (17.6%) progressed. The median time to progression of responding patients was 10.8 months, and the median overall survival of the entire population was 17.8 months. CONCLUSIONS: Vinorelbine and gemcitabine is a manageable scheme with moderate activity in pretreated patients with advanced breast cancer.

The effects of Reiki therapy on pain and anxiety in patients attending a day oncology and infusion services unit.

Reiki is a system of natural healing techniques administered by laying of hands and transferring energy from the Reiki practitioner to the recipient. We investigated the role of Reiki in the management of anxiety, pain and global wellness in cancer patients. Building on the results of a pilot project conducted between 2003 and 2005 by a volunteer association at our hospital, a wider, 3-year study was conducted at the same center. The volunteer Reiki practitioners received 2 years of theory and practical training. The study population was 118 patients (67 women and 51 men; mean age, 55 years) with cancer at any stage and receiving any kind of chemotherapy. Before each session, the nurses collected the patient's personal data and clinical history. Pain and anxiety were evaluated according to a numeric rating scale by the Reiki practitioners. Each session lasted about 30 min; pain and anxiety scores were recorded using a Visual Analog Scale (VAS), together with a description of the physical feelings the patients perceived during the session. All 118 patients received at least 1 Reiki treatment (total number, 238). In the subgroup of 22 patients who underwent the full cycle of 4 treatments, the mean VAS anxiety score decreased from 6.77 to 2.28 (P <.000001) and the mean VAS pain score from 4.4 to 2.32 (P = .091). Overall, the sessions were felt helpful in improving well-being, relaxation, pain relief, sleep quality and reducing anxiety. Offering Reiki therapy in hospitals could respond to patients' physical and emotional needs.

Hemolytic uremic syndrome induced by infusion of oxaliplatin: a case report.

INTRODUCTION: Oxaliplatin is a third-generation platinum compound with proven antitumor activity in the treatment of colorectal cancer. The occurrence of life-threating hemolitic uremic syndrome has been observed after oxaliplatin therapy. The kind of tumor and treatment modalities seem to influence the onset of hemolitic uremic syndrome. METHODS: The clinical course of the case is reviewed and compared with reports of other similar cases in the literature. RESULTS: We describe the development of hemolitic uremic syndrome as a result of prolonged oxaliplatin treatment of a colon cancer patient. CONCLUSIONS: Although this rare event requires the concurrence of other unknown factors, it should be considered in a decision-making setting.