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Supervised exercise dietary programs are recommended to relieve cancer-related fatigue and weight increase induced by adjuvant treatment of early breast cancer (EBC). As this recommendation lacks a high level of evidence, we designed a multicenter randomized trial to evaluate the impact of an Adapted Physical Activity Diet (APAD) education program on fatigue. We randomized 360 women with EBC who were receiving adjuvant chemotherapy and radiotherapy to APAD or usual care at eight French cancer institutions. Data were collected at baseline, end of chemotherapy, end of radiotherapy, and 6 months post-treatment. The primary endpoint was the general cancer-related fatigue score using the MFI-20 questionnaire. Fatigue correlated with the level of precariousness, but we found no significant difference between the two groups in terms of general fatigue ( p = 0.274). The APAD arm has a smaller proportion of patients with confirmed depression at the end of follow-up ( p = 0.052). A transient modification in physical activity levels and dietary intake was reported in the experimental arm. However, a mixed hospital- and home-based APAD education program is not enough to improve fatigue caused by adjuvant treatment of EBC. Cancer care centers should consider integrating more proactive diet-exercise supportive care in this population, focusing on precarious patients.

Background: Triple-negative breast cancer (TNBC) has a worse prognosis compared with other breast cancer subtypes, and biomarkers to identify patients at high risk of recurrence are needed. Here, we investigated the expression of human epidermal receptor (HER) family members in TNBC and evaluated their potential as biomarkers of recurrence., Methods: We developed Time Resolved-Förster Resonance Energy Transfer (TR-FRET) assays to quantify HER1, HER2 and HER3 in formalin-fixed paraffin-embedded (FFPE) tumour tissues. After assessing the performance and precision of our assays, we quantified HER protein expression in 51 TNBC specimens, and investigated the association of their expression with relapse-free survival., Results: The assays were quantitative, accurate, and robust. In TNBC specimens, HER1 levels ranged from ≈4000 to more than 2 million receptors per cell, whereas HER2 levels varied from ≈1000 to 60,000 receptors per cell. HER3 expression was very low (less than 5500 receptors per cell in all samples). Moderate HER2 expression was significantly associated with higher risk of recurrence (HR = 3.93; P = 0.003)., Conclusions: Our TR-FRET assays accurately quantify HER1, HER2 and HER3 in FFPE breast tumour specimens. Moderate HER2 expression may represent a novel prognostic marker in patients with TNBC.

Background: Patients with breast cancer undergoing chemotherapy and radiotherapy experience fatigue and other treatment side effects. Integrative therapies combining physical activity and dietary counseling are recommended; however to date no large randomized controlled trial has been conducted during adjuvant therapy. The Adapted Physical Activity and Diet (APAD) intervention was evaluated for its ability to decrease fatigue (primary outcome), anxiety, depression, body mass index (BMI), and fat mass, and enhance muscular and cognitive performances, and quality-of-life (QoL)., Methods: Women diagnosed with early breast cancer (N = 143, mean age = 52 ± 10 years) were randomized to APAD or usual care (UC). APAD included thrice-weekly moderate-intensity mixed aerobic and resistance exercise sessions and 9 dietetic consultations. Patient-reported outcomes (PROs) and anthropometric, muscular, and cognitive variables were measured at baseline, 18 weeks (end of chemotherapy), and 26 weeks (end of radiotherapy and intervention), and at 6- and 12-month post-intervention follow-ups. Multi-adjusted linear mixed-effects models were used to compare groups over time., Results: Significant beneficial effects of the APAD intervention were observed on all PROs (i.e., fatigue, QoL, anxiety, depression) at 18 and 26 weeks. The significant effect on fatigue and QoL persisted up to 12-month follow-up. Significant decreases in BMI, fat mass, and increased muscle endurance and cognitive flexibility were observed at 26 weeks, but did not persist afterward. Leisure physical activity was enhanced in the APAD group vs UC group at 18 and 26 weeks. No significant effect of the intervention was found on major macronutrients intake., Conclusions: A combined diet and exercise intervention during chemotherapy and radiotherapy in patients with early breast cancer led to positive changes in a range of psychological, physiological and behavioral outcomes at the end of intervention. A beneficial effect persisted on fatigue and QoL at long term, i.e., 1 year post-intervention. Diet-exercise supportive care should be integrated into the management of early breast cancer patients., Trial Registration: The APAD study was prospectively registered on ClinicalTrials.gov (NCT01495650; date of registration: December 20, 2011).

Importance: Hypnosis is now widespread in medical practice and is emerging as an alternative technique for pain management and anxiety. However, its effects on postoperative outcomes remain unclear., Objective: To evaluate the efficacy of a preoperative hypnosis session for reducing postoperative breast pain in patients who underwent minor breast cancer surgery., Design, Setting, and Participants: The HYPNOSEIN prospective randomized clinical trial was conducted from October 7, 2014, to April 5, 2016. In this multicenter study in France, 150 women scheduled for minor breast cancer surgery were randomized between control and hypnosis arms, and 148 (71 control and 77 hypnosis) were included in the intent-to-treat analysis., Intervention: On the day of surgery, eligible patients were randomly assigned (1:1) to the control arm or the hypnosis arm. Patients (but not the care teams) were blinded to the arm to which they were assigned. A 15-minute hypnosis session before general anesthesia in the operating room was performed in the hypnosis arm., Main Outcomes and Measures: The primary end point was breast pain reduction (by 2 on a visual analog scale), assessed immediately before discharge from the postanesthesia care unit (PACU). Secondary end points were nausea/vomiting, fatigue, comfort/well-being, anxiety, and PACU length of stay, assessed at different times until postoperative day 30., Results: The median patient age was 57 years (range, 33-79 years) in the control arm and 53 years (range, 20-84 years) in the hypnosis arm. Baseline characteristics were similar in the 2 arms. The median duration of the hypnosis session was 6 minutes (range, 2-15 minutes). The use of intraoperative opioids and hypnotics was lower in the hypnosis arm. The mean (SD) breast pain score (range, 0-10) was 1.75 (1.59) in the control arm vs 2.63 (1.62) in the hypnosis arm (P = .004). At PACU discharge and with longer follow-up, no statistically significant difference in breast pain was reported. Fatigue was significantly lower in the hypnosis arm on the evening of surgery (mean [SD] score, 3.81 [2.15] in the control arm vs 2.99 [2.56] in the hypnosis arm; P = .03). The median PACU length of stay was 60 minutes (range, 20-290 minutes) in the control arm vs 46 minutes (range, 5-100 minutes) in the hypnosis arm (P = .002). Exploratory analyses according to patient perception of whether she received hypnosis showed significantly lower fatigue scores in the perceived hypnosis subgroup on the evening of surgery (mean [SD], 4.13 [2.26] for no perceived hypnosis vs 2.97 [2.42] for perceived hypnosis; P = .01). Anxiety was also significantly lower on the evening of surgery in the perceived hypnosis subgroup (mean [SD], 0.75 [1.64] for perceived hypnosis vs 1.67 [2.29] for no perceived hypnosis; P = .03)., Conclusions and Relevance: The results of this study do not support a benefit of hypnosis on postoperative breast pain in women undergoing minor breast cancer surgery. However, other outcomes seem to be improved, which needs to be confirmed by further studies., Trial Registration: EudraCT Identifier: 2014-A00681-46 and ClinicalTrials.gov Identifier: NCT03253159.

Background: A minority of early breast cancer (EBC) patients treated with adjuvant or neoadjuvant chemotherapy have sufficient baseline vitamin D (vitD) level. This randomized phase III study assessed the safety and efficacy of a tailored, high-dose, oral vitD supplementation in restoring a normal 25-hydroxy vitD (25OHD) level in this population., Patients and Methods: Participants received a 6-month conventional (C) vitD and calcium supplementation or a 6-month high-dose oral vitD regimen tailored on the deficiency (T) and a conventional calcium supplementation. The primary end point was the 6-month percentage of 25OHD serum level normalization., Results: A total of 215 patients including 197 patients with vitD deficiency were recruited, and 195 patients were randomized (T, 100; C, 95). Compliance to the daily oral supplementation was 68.4% and 67% in the C and T arms, respectively. Discontinuous high-dose vitD compliance appeared higher in the T arm (77%). At 6 months, more patients presented with a normalized vitD level in the T arm (30% versus 12.6%; P = 0.003). Supplementation was well tolerated, and no significant difference in the treatment-related toxicity between the two arms was reported. Fifty-two patients without vitD normalization from the C arm switched to the T arm after 6 months. At 12 months, 44% of these patients achieved vitD normalization., Conclusion: A tailored high-dose oral vitD supplementation safely allows a higher percentage of the serum 25OHD level normalization compared with a conventional regimen in chemotherapy-treated EBC patients. As compliance to a daily oral supplementation remains poor in this setting, an adaptation of the treatment schedule is warranted., Clinical Trial Number: NCT01480869., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

To improve treatment efficacy, we decided to simultaneously target HER1 and HER2 with trastuzumab and cetuximab. Following promising preclinical results, we conducted a phase 1-2 trial in advanced pancreatic cancer patients after first-line gemcitabine-based chemotherapy failure. In this single-arm, non-randomized, multicenter trial, patients received weekly cetuximab (400mg/m², then 250mg/m²). They were sequentially included in two trastuzumab dose levels: 3.0 or 4.0mg/kg, then 1.5 or 2.0mg/kg/weekly. Endpoints were the objective response rate, safety, progression-free (PFS) and overall survival (OS). During phase 1 (n=10 patients), toxicities were evenly distributed except for skin toxicities that frequently caused compliance issues. The higher dose level was defined as the trastuzumab recommended dose. During phase 2 (n=39 patients), toxicities were mainly cutaneous reactions and asthenia. No objective response was observed. Nine patients were stabilized but arrested treatment due to toxicity. Median PFS was 1.8 months (95%CI: 1.7-2.0 months) and median OS was 4.6 months (95%CI: 2.7-6.6 months). Both were positively correlated with skin toxicity severity (P=0.027 and P=0.001, respectively). Conventional phase 1 dose-escalation schedules are unsuitable for targeted therapies because most cutaneous toxicities are not considered dose-limiting toxicities. The compliance issues caused by skin toxicities were particularly detrimental because of the toxicity-response correlation.

Background: Poly(adenosine diphosphate-ribose) polymerase 1 (PARP-1) and the balance between BRCA1 and 53BP1 play a key role in the DNA repair and cell stress response. PARP inhibitors show promising clinical activity in metastatic triple negative (TN) or BRCA-mutated breast cancer. However, a comprehensive analysis of PARP-1 activity, BRCA1 promoter methylation and 53BP1 expression in tumours without known BRCA1 mutation has not yet been carried out., Methods: We investigated cytosolic PARP-1 activity, 53BP1 protein levels and BRCA1 promoter methylation in 155 surgical breast tumour samples from patients without familial breast cancer history or known BRCA1 mutations who were treated between January 2006 and November 2009 and evaluated their statistical association with classical predictive and prognostic factors., Results: The mitotic count score was the only parameter clearly associated with PARP-1 activity. BRCA1 promoter hypermethylation (15.4% of all cancers) was significantly associated with uPA and PAI-1 levels, tumour grade, mitotic count score, hormone receptor and HER2 negative status and TN profile (29% of TN tumours showed BRCA1 promoter hypermethylation compared to 5% of grade II-III hormone receptor-positive/HER2-negative and 2% of HER2-positive tumours). No statistical association was found between BRCA1 promoter hypermethylation and PARP-1 activity. High 53BP1 protein levels correlated with lymph node positivity, hormone receptor positivity, molecular grouping, unmethylated BRCA1 promoter and PARP-1 activity. In TN tumours, BRCA1 promoter methylation was only marginally associated with age, PARP-1 activity was not associated with any of the tested clinico-pathological factors and high 53BP1 protein levels were significantly associated with lymph node positivity. Only 3 of the 14 TN tumours with BRCA1 promoter hypermethylation presented high 53BP1 protein levels., Conclusions: Breast cancers that harbour simultaneously high 53BP1 protein level and BRCA1 promoter hypermethylation and are the putative target population of drugs targeting DNA repair appear to be restricted to a small subgroup of TN tumours.

Exercise practice and appropriate nutrition have been advanced as non pharmacological supportive care to reduce side effects related to cancer and its treatment, but large sample-sized randomized controlled trials are needed to confirm such results. The Adapted Physical Activity and Diet counseling (APAD) study is a prospective randomized controlled trial designed to evaluate the effectiveness of a 26-week hospital- and home-based lifestyle intervention on cancer-related fatigue in women receiving breast cancer adjuvant treatment (chemotherapy and radiotherapy). The aim of this paper is to describe the APAD study protocol. Study recruitment goal is 264 adult breast cancer women with newly, histologically proven, incident and non metastatic breast cancer scheduled for 6 cycles of adjuvant chemotherapy followed by radiotherapy. Patients are randomized either in the experimental arm with tailored exercise training and diet counseling program or in the control arm without any lifestyle intervention (usual care). Outcome measures are collected at baseline, and at 15 weeks (i.e., mid-intervention), 26 weeks (i.e., immediately post-intervention), and at 12-month and 18-month of follow-up. Intervention effect is assessed on fatigue (emotional, cognitive, physical), quality-of-life, anxiety, depression, body weight and composition. In addition, levels of physical activity, dietary intakes and adjuvant therapy observance are measured and a cost-utility analysis will be performed. If improvements in fatigue, quality-of-life and a better weight control are observed, the APAD study could demonstrate the feasibility and the effectiveness of such exercise and nutrition supportive care with limited additional cost in patients receiving adjuvant breast cancer therapy., (© 2013 Elsevier Inc. All rights reserved.)

Objective: To determine the efficacy and toxicity of danusertib (formerly PHA-739358) administered i.v. over two different dosing schedules with equivalent dose intensity in patients with metastatic castration-resistant prostate cancer with progressive disease after docetaxel-based treatment., Patients and Methods: In this open-label, multicentre phase II trial 88 patients were randomly assigned (1:1 ratio) to receive either danusertib 330 mg/m(2) over 6 h i.v. on days 1, 8 and 15 (arm A, n = 43) or 500 mg/m(2) over 24 h i.v. on days 1 and 15 (arm B, n = 38), every 4 weeks. The primary endpoint chosen for this exploratory study was PSA response rate at 3 months., Results: Sixty patients (31/43 in arm A and 29/38 in arm B) were evaluable for the primary endpoint. Median progression-free survival was 12 weeks in both arms. PSA response occurred in one patient in each arm; best overall response was stable disease in eight (18.6%) and 13 (34.2%) patients in arms A and B, respectively. Eleven out of 81 (13.6%) treated patients had stable disease for ≥6 months. Danusertib was generally well tolerated; the most common grade 3 and 4 drug-related adverse event was neutropenia which occurred in 37.2% (arm A) and 15.8% (arm B) of the patients., Conclusion: Danusertib monotherapy shows minimal efficacy in patients with castration-resistant prostate cancer. Further studies are required to establish specific biomarkers predictive for either response or prolonged disease stabilization., (© 2012 The Authors BJU International © 2012 BJU International.)

Patients with locally advanced breast cancer treated with neoadjuvant chemotherapy are at risk of cancer treatment-induced bone loss and consequently of increased skeletal morbidity. In addition, this situation could be worsened by the fact that only a minority of patients with breast cancer have sufficient vitamin D. A comprehensive evaluation of bone homeostasis is critical in this context. We retrospectively evaluated the serum levels of calcium, vitamin D, TRAIL, RANK ligand (RANKL), Osteoprotegerin (OPG), Bone TRAP, CrossLaps and DKK1 in 77 patients (median age: 50 years; range 25-74), with locally advanced breast cancer treated in our institute with anthracyclines-taxane neoadjuvant chemotherapy (7 cycles of 21 days/each) between March 2007 and August 2008. Serum samples were collected before the first (baseline) and the last treatment cycle. Variations and correlations between biomarker levels were evaluated. At baseline, 79.5 % of patients had vitamin D insufficiency (<30 ng/ml), increasing to 97.4 % at the end of the neoadjuvant chemotherapy (p < 0.0001). Calcium and RANKL serum concentrations were also significantly decreased, while OPG was significantly increased, resulting in lower RANKL/OPG ratio. Calcium and vitamin D, RANKL and vitamin D and RANKL and OPG levels were significantly correlated (Spearman's coefficient r = 0.2721, p = 0.0006; r = 0.1916, p = 0.002; and r = -0.179, p = 0.03, respectively). Nearly all included patients suffered from vitamin D insufficiency by the end of the neoadjuvant chemotherapy with changes in the calcium/RANKL/OPG axis that are evocative of deregulation of a functional regulatory mechanism. Further studies are needed to determine how drugs modulate this regulatory mechanism to preserve bone homeostasis in patients with breast cancer.

Background: Biweekly schedule of capecitabine combined with irinotecan (XELIRI), consecutively with irinotecan and oxaliplatin (XELIRINOX), was evaluated in patients with metastatic cancer from any solid tumors., Patients and Methods: In this two-step phase I trial, seventeen and eleven patients were enrolled in the XELIRI and XELIRINOX stages, respectively., Results: In XELIRI, a total of 136 chemotherapy cycles were administered with a median number of 8 cycles per patient (2-16). Main dose-limiting toxicities (DLT) were grade 3-4 neutropenia, with one toxicity-related death. Maximum tolerated dose (MTD) for capecitabine combined with 180 mg/m(2) of irinotecan was 3,500 mg/m(2)/day. In XELIRINOX, capecitabine starting dose was 2,500 mg/m(2)/day. Fifty-eight chemotherapy cycles were administered with a median of 4 cycles per patient (1-16). DLT included 3 grade 4 neutropenia, associated with 1 grade 3 diarrhea, and 1 grade 4 pneumopathy leading to patient death. MTD for capecitabine with 180 mg/m(2) of irinotecan and 85 mg/m(2) of oxaliplatin was 3,000 mg/m(2)/day. The recommended doses for capecitabine were 3,000 and 2,500 mg/m(2)/day D1-D7 in combination with 180 mg/m(2) of irinotecan in XELIRI, plus 85 mg/m(2) of oxaliplatin in XELIRINOX (D1 = D14), respectively., Conclusion: XELIRI and XELIRINOX regimens are feasible and warrant further investigation in combination with targeted therapy in metastatic colorectal cancer patients.

Background: Triplet chemotherapy has demonstrated manageable toxicities and a favorable response rate. The addition of cetuximab to chemotherapy can increase treatment efficacy. We evaluated the efficacy and safety of cetuximab plus 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), the ERBIRINOX regimen, as first-line treatment in patients with unresectable metastatic colorectal cancer (mCRC)., Patients and Methods: In a phase II study, treatment consisted of weekly cetuximab plus biweekly. Treatment was continued for a maximum of 12 cycles and tumor response was evaluated every four cycles. The primary efficacy criterion was the complete response (CR) rate., Results: From April 2006 to April 2008, 42 patients were enrolled. The median age was 60 years (range, 32-76 years). The median duration of treatment was 5.2 months (range, 0.7-8.5 months), and a median of nine cycles was given per patient (range, 1-12 cycles). Five patients (11.9%) showed a CR, with a median duration of 23.1 months (95% confidence interval [CI], 10.8-39.7 months). The objective response rate was 80.9% (95% CI, 65.9%-91.4%). The median overall and progression-free survival times were 24.7 months (95% CI, 22.6 months to not reached) and 9.5 months (95% CI, 7.6-10.4 months), respectively. The most frequent grade 3-4 adverse events were diarrhea (52%), neutropenia (38%), and asthenia (32%)., Conclusion: The ERBIRINOX regimen appears to be effective and feasible in first-line treatment of mCRC patients. These promising results led us to initiate a multicenter, randomized, phase II trial ([Research Partnership for Digestive Oncology] PRODIGE 14) in patients with potentially resectable mCRC.

Objectives: The aim of this study was to evaluate the efficacy and safety profile of 4 dose-dense cycles of docetaxel followed by 3 cycles of FEC100 neoadjuvant chemotherapy in patients with operable advanced breast cancer., Methods: Women were treated by 4 cycles of 100 mg/m² docetaxel every 2 weeks, followed by 3 cycles of FEC100 given every 3 weeks. The primary end point was pathologic complete response., Results: Forty-five patients were treated. Ninety-three percent of the patients completed the planned 7 chemotherapy courses. The median relative dose intensity for docetaxel, 5-fluorouracil, epirubicin, and cyclophosphamide were 0.98, 0.97, 0.96, and 0.97, respectively. There were no therapy-related deaths. Two patients stopped chemotherapy because of cutaneous toxicity. During the docetaxel sequence, the most common grade 3-4 toxicities were (% pts): neutropenia (13.3), grade 3: cutaneous (24.4), myalgia and arthralgia (6.7). No clinical cardiac toxicity was observed. The pathologic complete response rate was 21.4% and 26.2% using Sataloff and Chevallier classifications, respectively. The conservative surgery rate was 62.2%. The median follow-up was 38.5 months. Two and 3-year disease-free survival rates were 79% and 64%, respectively. Two- and 3-year overall survival rate were 93% and 88%, respectively., Conclusions: This trial confirms the feasibility and efficacy of this dose dense docetaxel neoadjuvant regimen.

Prognostic factors are used to help clinical decision-making in selecting the appropriate treatment for individual patients. The purpose of this retrospective study was to identify one or more factors associated with overall survival (OS) and disease-free survival (DFS), in 710 patients with operable breast cancer, subjected to neoadjuvant chemotherapy followed by surgery, radiotherapy and adjuvant treatments. At a median follow-up of 7.6 years, univariate analysis showed that pathological complete response (pCR) was significantly related to survival (p < 0.003), as well as accepted prognostic factors, as SBR and MSBR grades, hormonal receptors or node involvement at surgery, who remained significant in our study (p < 0.001). The revised Nottingham prognostic index (NPI) and related indices (BGI, MNPI and MBGI) were also significantly associated to survival (p < 0.003). In multivariate analysis, node involvement and MSBR grade remained prognostic factors for OS and DFS (p < 0.0003 and p < 0.02, respectively). The MNPI and pCR were significantly related with OS (p = 0.04) and pts with hormonal receptor-positive tumours had a better DFS than others (p = 0.004). Among all clinical and pathological parameters, axillary dissection after neoadjuvant chemotherapy is still important to determine node involvement, a major prognostic factor. Moreover, MSBR grade seemed to be more accurate and predictive of long-term outcome than the standard SBR grade. It is concluded that, outside any other 'biological' factor, residual disease in breast and nodes must be strongly considered after an induction chemotherapy so as to choose adjuvant treatment for the individual patient.

Background: As a single agent, 100 mg/m(2) of docetaxel every 3 weeks remains the standard schedule in the first-line treatment for metastatic disease. At this dose level, the major limiting toxicity is neutropenia. The current study was conducted to assess the feasibility of reducing time intervals between cycles while delivering standard doses of docetaxel with granulocyte-colony-stimulating factor (G-CSF; lenograstim)., Methods: In the first part of the study, 24 patients were randomized to receive 1 of 4 schedules: 100 mg/m(2) of docetaxel every 21 days without lenograstim; 100 mg/m(2) of docetaxel every 18 days with lenograstim; 100 mg/m(2) of docetaxel every 14 days with lenograstim; or 100 mg/m(2) of docetaxel every 10 days with lenograstim. In the second part of the study, 15 additional patients were included to confirm the feasibility of the recommended interval between cycles., Results: Of the 39 patients treated, 14 patients (36%) withdrew from therapy because of Grade 3 (according to standard World Health Organization criteria) nonhematologic limiting toxicities. Only 3 patients were treated in the 10-day interval arm and were withdrawn because of toxicity--1 patient had Grade 3 asthenia after the second cycle and 2 patients had Grade 3 dermatitis after 4 cycles. Of the 24 patients treated in the 14-day intervals, Grade 3 limiting toxicities occurred in 8 patients (33%), including dermatitis in 3 patients; diarrhea, myalgia/arthralgia, or asthenia in 4 patients; and ungual toxicity in 1 patient., Conclusions: Introduction of G-CSF (lenograstim) as primary prophylaxis allowed the administration of docetaxel every 14 days with manageable toxicities. Further studies are now required to assess the impact in terms of response rates and survival in patients with cancer., (Copyright 2004 American Cancer Society.)

Aims: Computed tomography (CT) is the reference technique for evaluating response to chemotherapy. The potential helpfulness of tumour markers is debated., Materials and Methods: From March 1997 to January 1999, 91 consecutive patients receiving chemotherapy for metastatic colorectal carcinoma underwent whole-body spiral CT, estimates of anti-carcinoembryonic antigen (CEA) and CA19-9 every 8 weeks., Results: CEA and CA19-9 levels were above normal in 78 (85.7%) and 61 (67.5%) patients, respectively. Tumour response evaluation according to the RECIST criteria was obtained at 8-week evaluation in 83 (91%) patients. The positive predictive values (PPV) for response of a decrease of the marker levels were 53.8 for CEA and 41.7 for CA19-9 using a 30% decrease threshold, and 60/52.2, respectively, using a 50% decrease threshold. Meaningful PPV values (> 90%) for progression of an increase of the marker levels were only obtained using the 200% increase threshold for CEA alone or a combination of CEA and CA 19-9. A 100% CEA increase between baseline and the 8-week evaluation was correlated to overall survival (P = 0.0023). The need for a radiological confirmation of tumour progression could be avoided by the systematic dosage of tumour markers at baseline and after 8 weeks of treatment only in a sub-population of 13% of the patients with a 200% increase of CEA or CA 19-9 at 8 weeks., Conclusions: CEA, CA 19-9, or both should be used with caution for tumour response evaluation to chemotherapy in addition to CT in metastatic colorectal carcinoma.

Evaluation of tumour size modifications in response to treatment is a critical issue in the management of advanced malignancies. In 1981, the World Health Organization (WHO) established guidelines for tumour response assessment. These WHO1981 criteria were recently simplified in a revised version, named RECIST (Response Evaluation Criteria in Solid Tumours), which uses unidimensional instead of bidimensional measurements, a reduced number of measured lesions, withdrawal of the progression criteria based on isolated increase of a single lesion, and different shrinkage threshold for definitions of tumour response and progression. In order to validate these new guidelines, we have compared results obtained with both classifications in a prospective series of 91 patients receiving chemotherapy for metastatic colorectal cancer. Data from iterative tomographic measurements were fully recorded and reviewed by an expert panel. The overall response and progression rates according to the WHO1981 criteria were 19% and 58%, respectively. Using RECIST criteria, 16 patients were reclassified in a more favourable subgroup, the overall response rate being 28% and the progression rate 45% (non-weighted kappa concordance test 0.72). When isolated increase of a single measurable lesion is not taken into account for progression with the WHO1981 criteria, only 7 patients were reclassified and the kappa test was satisfying, i.e. > or =0.75, for the whole population as well as for each of the responding and progressive subgroups. Since it provides concordant results with a simplified method, the use of RECIST criteria is recommended for evaluation of treatment efficacy in clinical trials and routine practice.

It is a randomised cross-over multicenter study comparing the efficacy and the tolerance of granisetron (Gra) 1 mg and ondansetron (Ond) 8 mg, oral, given during two consecutive cycles to 188 naive patients scheduled to receive a moderately emetogenic chemotherapy. The antiemetic treatment is given one day per course, 1 hour before chemotherapy and the second administration from 8 to 12 hours after the beginning, during each of the two cycles; alternatively according to the randomisation. Five criteria are assessed; nausea (ordinal and visual analogic scales), emeric episodes (vomiting orland retching), complete response (minor or no nausea, no emetic episode and no rescue treatment), patient preference and tolerance. The intent to treat analysis showed no significant difference at cycle 1 between Gra and Ond; at cycle 2, there is no significant difference in the number of emetic episodes; for the prevention of nausea, the ordinal scale shows a significant difference (p = 0.028 in favour of Gra at day 1 (D1) but not from D2 to D5. Gra induced more complete response than Ond at D1 (p = 0.028), but not from D2 to D5. The cross-over study did not show any period or order effect, whereas a treatment effect on Ond was significant in favour of Gra (p = 0.01). There is no significant patients preference in favour of Gra or Ond. In conclusion, Gra was more efficient in preventing nausea and obtaining complete response on the first day of treatment, significantly at the second cycle. Both Gra and Ond had a good antiemetic activity for moderately emetogenic chemotherapy with complete response rates always over 50% on day 1; delayed emesis remain less weli controlled.