Design: To provide timely and evidence-based recommendations for the diagnostic workup and treatment of patients with MBC, an international expert panel reviewed and discussed the evidence available from clinical trials regarding diagnostic, therapeutic and supportive measures with emphasis on their impact on the quality of life and overall survival of patients with MBC.

Results: Evidence-based recommendations for the diagnostic workup, endocrine therapy, chemotherapy, use of targeted therapies and bisphosphonates, surgical treatment and supportive care measures in the management of patients with MBC were formulated.

Conclusions: The present consensus manuscript updates evidence-based recommendations for state-of-the-art treatment of MBC depending on disease-associated and biological variables.

Patients and methods: A total of 52 women with advanced or recurrent endometrial cancer and carcinosarcoma were treated with four cycles of carboplatin area under the curve (AUC) 5 and doxorubicin (50 mg/m²) for four cycles before or after four cycles of carboplatin AUC5 and paclitaxel (175 mg/m²) with each cycle administered at 21-day intervals.

Results: Thirty-seven patients (71.2%) completed all planned treatment. Excluding six patients who did not complete treatment for non-drug-related causes, 80.4% completed all planned treatment. Three hundred and seventy-one treatment cycles were administered and 303 (81.7%) occurred on time. Common Toxicity Criteria grade 3/4 haematological toxic effects, particularly neutropenia and thrombocytopenia, were the predominant cause of treatment delays and dose reductions. A low incidence of grade 3 neurotoxicity and no cardiac toxicity were observed. The overall response rates for patients with evaluable disease were 82.1% and 66.7% for endometrial and carcinosarcoma, respectively. At a median follow-up of 21 months, the median progression-free survival for the endometrial adenocarcinoma and carcinosarcoma cohorts were 15.3 and 12.0 months, respectively.

Conclusion: This regimen is generally well tolerated with encouraging efficacy.

Patients and methods: Patients previously treated with less than two or two previous chemotherapy lines were randomized to receive trabectedin 1.5 mg/m² 24 h (arm A, n = 54) or 1.3 mg/m² 3 h (arm B, n = 53). Objective response rate (ORR) per RECIST was the primary efficacy end point. Toxic effects were graded according to the National Cancer Institute—Common Toxicity Criteria v. 2.0.

Results: ORR was 38.9% [95% confidence interval (CI) 25.9% to 53.1%; arm A] and 35.8% (95% CI 23.1% to 50.2%; arm B) (intention-to-treat primary analysis). Median time to progression was 6.2 months (95% CI 5.3–8.6 months; arm A) and 6.8 months (95% CI 4.6–7.4 months; arm B). Frequent severe adverse events were nausea/vomiting (24%, arm A; 15%, arm B) and fatigue (15%, arm A; 10%, arm B). Common severe laboratory abnormalities were transient, noncumulative neutropenia (55%, arm A; 37%, arm B) and transaminase increases (alanine aminotransferase, 55%, arm A; 59%, arm B).

Conclusions: Both every-3-weeks trabectedin regimes, 1.5 mg/m² 24 h and 1.3 mg/m² 3 h, were active and reasonably well tolerated in AOC platinum-sensitive patients. Trabectedin every-3-weeks has promising activity and deserves to be further evaluated in relapsed AOC.

Patients and methods: In all, 304 mRCC patients (European cohort) were randomized 1 : 1 to receive sunitinib (50 mg/day for 4 weeks, followed by 2 weeks off) or IFN- (9 million units s.c. injection three times/week). The following questionnaires were completed (days 1 and 28 per cycle): Functional Assessment of Cancer Therapy-General (FACT-G), the FACT-Kidney Symptom Index and the EuroQol Group's EQ-5D self-report questionnaire (EQ-5D). Results correspond to an ongoing trial with progression-free survival time as primary end point, and patients were still being followed up. Data were analyzed using repeated measures mixed effects models (MEMs) that allow the inclusion of initial differences and uncompleted repeated measures, with the assumption of data missing at random. Six-cycle results were included.

Results: Results consistently showed that patients in sunitinib group experienced statistically significantly milder kidney-related symptoms, better cancer-specific HRQoL and general health status (in social utility scores) during the study period as measured by these patient-reported outcome end points. No statistical differences between groups were found on the FACT-G physical well-being subscale or the EQ-5D VAS values.

Conclusions: Results from MEM showed the sunitinib's benefit on HRQoL compared with IFN-.

Patients and methods: A two-arm multicenter phase II trial of oral gefitinib 500 mg/day was planned in two groups of 45 patients with ABC for whom chemotherapy was not currently indicated. Group 1 had hormone-resistant BC defined as HR-positive BC with progression after treatment with tamoxifen and an aromatase inhibitor. Group 2 had HR-negative BC. Tumor response was assessed every 8 weeks. The primary end point was the clinical benefit rate (CBR).

Results: Forty patients with hormone-resistant BC had a CBR of 0%. Two of 25 HR-negative BC patients showed stable disease (less than a 50% reduction and less than a 25% increase in the sum of the products of two perpendicular diameters of all measured lesions and the appearance of no new lesions) at 24 weeks resulting in a CBR of 7.7% (95% CI 0.9% to 25.1%). Enrollment ceased due to the low CBR. Toxicity resulted in treatment interruption (46%), dose reduction (20%) and withdrawal (11%) of patients.

Conclusion: At a dose of 500 mg/day, gefitinib monotherapy resulted in a low CBR and no tumor response was identified.

Patients and methods: pRb status was prospectively evaluated by immunocytochemistry in 518 consecutive patients with complete receptor information. The predictive value of pRb status in TNBCs was determined according to the adjuvant therapeutic treatments.

Results: Fifty-three tumors were identified as TNBCs. The prevalence of pRb loss was significantly higher in TNBCs than in the other cancer subtypes. All patients with TNBCs lacking pRb and treated with systemic chemotherapy (cyclophosphamide, methotrexate and 5-fluorouracil) were disease free at a medium follow-up time of 109 months, whereas the clinical outcome of those expressing pRb was significantly poorer (P = 0.008). Analysis of disease-free survival including the established anatomo-clinical prognostic parameters indicated pRb loss as the only significant predictive factor.

Conclusions: pRb loss is much more frequent in TNBCs than in the other breast cancer subtypes. Patients with TNBCs lacking pRb had a very favorable clinical outcome if treated with conventional adjuvant chemotherapy.

Patients and methods: This retrospective study included 42 metastatic IBC and 107 metastatic non-IBC patients treated with first- or second-line chemotherapy from January 2004 to December 2007 at MD Anderson Cancer Center. CTCs were detected and enumerated before patients started chemotherapy using the CellSearch^TM system.

Results: Ten (23.8%) IBC patients versus 48 (44.9%) non-IBC patients had baseline CTCs ≥5 per 7.5 ml of peripheral blood. IBC patients had a lower mean ± SEM CTCs than non-IBC patients (7.6 ± 2.9 versus 34.2 ± 9.1; P = 0.02). The estimated median overall survival was 26.5 versus 18.3 months (P = 0.68) in IBC patients and 37.4 versus 18.3 months (P = 0.016) in non-IBC patients with CTCs <5 and CTCs ≥5, respectively.

Conclusions: Metastatic IBC patients had a lower prevalence and fewer CTCs in comparison to metastatic non-IBC patients. Survival of metastatic IBC patients with <5 CTCs was not significantly better than that of patients with ≥5 CTCs. Further research is warranted with prospective assessment of CTCs in IBC patients and their biological characterization.

Patients and methods: The relationship between locoregional recurrence-free survival (LRFS) and DTC detection was evaluated according to the various locoregional volumes irradiated after surgery.

Results: BM DTCs were detected in 94 of 621 stage I–III breast cancer patients (15%) and were not associated with axillary node status. Eighteen patients (2.9%) experienced locoregional recurrence (median follow-up 56 months), of whom eight (44%) were initially BM DTC positive. BM DTC detection was the only prognostic factor for LRFS [P = 0.0005, odds ratio = 5.2 (2.0–13.1), multivariate analysis]. In BM DTC-positive patients, a longer LRFS was observed in those who were given adjuvant hormone therapy (P = 0.03) and radiotherapy to supraclavicular nodes (SCNs)/internal mammary nodes (IMNs) (P = 0.055) (multivariate analysis; interaction test: P = 0.028).

Conclusions: The presence of DTC in BM may be associated with a different pattern of locoregional cancer cell dissemination and influences LRFS. The possible reseeding of the primary cancer area by DTC could be prevented by systemic hormone therapy but also by SCN/IMN irradiation.

Patients and methods: Patients with unresectable mCRC received chemotherapy (physician's choice) plus bevacizumab [5 mg/kg every 2 weeks (5-fluorouracil regimens) or 7.5 mg/kg every 3 weeks (capecitabine regimens)]. The primary end point was safety, including prospective data collection in patients receiving unanticipated surgery during the study. Secondary objectives were progression-free survival (PFS) and overall survival (OS).

Results: The final analysis comprised 1914 assessable patients (male 58%; median age 59 years). Chemotherapy included 5-fluorouracil/leucovorin (5-FU/LV) + oxaliplatin (29%), irinotecan plus 5-FU/LV (26%), capecitabine plus oxaliplatin (18%) and monotherapy (16%). Serious/grade 3–5 adverse events of interest for bevacizumab included bleeding (3%), gastrointestinal perforation (2%), arterial thromboembolism (1%), hypertension (5.3%), proteinuria (1%) and wound-healing complications (1%). Sixty-day mortality was 3%. Median PFS was 10.8 months [95% confidence interval (CI) 10.4–11.3 months] and median OS reached 22.7 months (95% CI 21.7–23.8 months).

Conclusions: The BEAT study shows that the efficacy and safety profile of bevacizumab in routine clinical practice is consistent with results observed in prospective randomised clinical trials and another large observational study in the United States (BRiTE study).

Methods: Patients with HL treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD)-based CT and radiotherapy (RT) at our institution from January 2000 to March 2007 were eligible. All patients had either a post-treatment PET or PET–CT before initiation of RT or a negative midtreatment PET or PET–CT. The primary end point was failure-free survival (FFS) for patients with and without residual FDG avidity after ABVD. The treatment outcome of patients with interim PET positivity during CT was also reported.

Results: Seventy-three patients were included in this study. Twenty patients (out of 46) were PET positive on interim PET, and 13 patients (out of 73) were PET positive at the conclusion of CT. At a median follow-up of 3.4 years for surviving patients, the 2-year FFSs for patients PET-negative versus PET-positive disease after ABVD were 95% and 69%, respectively (P < 0.01). On bivariable Cox regression, post-ABVD positivity (hazard ratio 4.8, P = 0.05) was predictive of disease recurrence after controlling for bulky disease. Of the 20 patients with interim PET positivity, three recurred, with a 2-year FFS of 85%. Among the 13 patients with interim PET positivity, but became PET negative at the completion of CT, the 2-year FFS was 92%.

Conclusion: Sixty-nine per cent of patients with residual FDG avidity after ABVD were free of disease after consolidative RT, indicating a majority of patients with persistent lymphoma can be cured by sterilizing this PET-positive disease.

Patients and methods: This multicenter study evaluated the activity of oxaliplatin and prolonged infusion of gemcitabine (‘GEMOX’ regimen) in recurrent NPC. Baseline blood samples were genotyped for the presence of ERCC1-118 gene polymorphisms.

Results: Forty-two patients were recruited, of whom most (61%) had metastatic disease. Of the 40 patients evaluated for response, the respective overall response and disease control rates were 56.1% and 90.2%. At a median follow-up of 14.8 months, the respective median overall survival and time to progression were 19.6 months [95% confidence interval (CI) = 12.8–22 months] and 9 months (95% CI = 7.3–10 months). Grade 3–4 toxic effects were uncommon. The distribution of ERCC1-118 genotypes from 29 patients was C/C (n = 17, 40.5%), C/T (n = 10, 23.8%) and T/T (n = 2, 4.8%). No differences in survival or response rates were found between genotypes.

Conclusions: GEMOX is active in the treatment of recurrent NPC. Detection of single-nucleotide gene polymorphisms from genomic DNA in peripheral blood is feasible in NPC and further studies are warranted.

Materials and methods: We randomized 233 patients to receive palonosetron as a single i.v. bolus dose of 0.075, 0.25, or 0.75 mg before administration of HEC. Dexamethasone (12–16 mg i.v. on day 1, 8 mg i.v. on day 2, and 4–8 mg i.v. on day 3) was administered for prophylactic antiemesis. Pharmacokinetics of palonosetron was analyzed in 24 patients.

Results: In this study, all patients were given ≥50 mg/m² cisplatin, which was considered to be HEC. No significant differences in complete response (CR: no emesis and no rescue medication) rates were found in the first 24 h between the 0.075-, 0.25-, and 0.75-mg groups (77.6%, 81.8%, and 79.5%, respectively). In the 120-h period of overall observation, CR rates increased in a dose-dependent manner. In the 0.75-mg group, we observed a significantly longer time to treatment failure than in the 0.075-mg group (median time >120 versus 82.0 h, P = 0.038). Palonosetron was tolerated well and did not show any dose-related increase in adverse effects.

Conclusions: Palonosetron at doses of 0.25 and 0.75 mg was shown to be effective in preventing chemotherapy-induced nausea and vomiting with high CR rates of patients treated with HEC in Japan. All tested doses of palonosetron were tolerated well.

Patients and methods: A total of 493 patients with solid tumors receiving a first cycle of cisplatin ≥70 mg/m² were randomly assigned among six treatment arms. The primary analysis compared a control arm [ondansetron/dexamethasone (Ond/Dex)] with three investigational treatments (Ond/Dex plus oral casopitant 50, 100, or 150 mg administered daily for 3 days). Two exploratory arms were included: one evaluating a single oral casopitant dose of 150 mg added to standard Ond/Dex and another with 3-day oral aprepitant-based therapy (Ond/Dex plus aprepitant 125 mg day 1, 80 mg days 2–3).

Results: The complete response (CR) rate (defined as no vomiting, retching, rescue therapy, or premature discontinuation) was significantly increased in each casopitant arm relative to control over the 120-h evaluation period: 76% (50 mg), 86% (100 mg), 77% (150 mg), and 60% with control (P = 0.0036). The CR rate for the single oral dose regimen was similar to the CR rate reported for the 3-day regimens. No differences were observed in the incidence of nausea or significant nausea among groups in the primary analysis. The most common adverse events related to treatment included headache (n = 10) and hiccups (n = 14).

Conclusion: All doses of oral casopitant as a 3-day regimen (and likely as a 150-mg single oral dose) in combination with Ond/Dex provided significant improvement in the prevention of cisplatin-induced emesis.

Patients and methods: This study evaluated the efficacy and safety of palonosetron in patients receiving MEC combined with dexamethasone. Patients received single doses of 0.075, 0.25, or 0.75 mg of palonosetron before MEC. Dexamethasone was infused before palonosetron, at 20 mg for the patients receiving paclitaxel (Taxol) and 8 mg for the patients not receiving paclitaxel. The primary end point was complete response (CR: no emetic episodes and no rescue medication) in the acute phase (0–24 h).

Results: In total, 204 patients (88 men, 116 women; 96 with paclitaxel, 108 without paclitaxel) were assessable for efficacy. No dose–response relationship was observed regarding the CR rate in the acute phase. CR rates increased dose dependently for delayed (24–120 h) and overall (0–120 h) phases in patients receiving anthracyclines and cyclophosphamide combination (AC/EC, n = 80); however, the difference in CR rates among doses was not statistically significant. The most commonly reported adverse events related to palonosetron were constipation and headache, confirming the class safety profile.

Conclusion: This study indicates a statistically nonsignificant trend for the dose–response relationship for antiemetic protection in the delayed and overall phases in AC/EC patients (the regimen currently considered to be more emetogenic than MEC).

Materials and methods: Cases were 767 patients with histologically confirmed, incident RCC. Controls were 1534 subjects admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions, unrelated to known risk factors for RCC. Information on dietary habits was derived through a food-frequency questionnaire. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for GI and GL intake were adjusted for major relevant covariates.

Results: Compared with the lowest quintile, the ORs for the highest quintile were 1.43 (95% CI 1.05–1.95) for GI and 2.56 (95% CI 1.78–3.70) for GL, with significant trends in risk. Compared with the lowest quintile, the risk of RCC for all subsequent levels of GL was higher in never drinkers than in ever drinkers.

Conclusions: We found direct relations between dietary levels of GI and GL and RCC risk. This can be related to mechanisms linked to insulin resistance and sensitivity.

Patients and methods: Since July 2007, 10 progressive advanced chordoma patients with secondary resistance to IM, and biochemical and/or immunohistochemical evidence of upstream and/or downstream mTOR effector activation, started IM (400 mg/day) plus sirolimus (2 mg/day) on a named basis.

Results: The mean treatment duration was 9 months. Of nine patients assessable for response, at 3 months, we had one RECIST partial response (PR), seven stable disease (SD) and one progressive disease (PD). According to Choi criteria applied even to magnetic resonance imaging, we had seven PR (≥10% decrease in size in four cases), one SD and one PD. Seven patients had a positron emission tomography response. The clinical benefit [RECIST complete response + PR + SD ≥6 months] was 89%. Pretreatment mTOR effectors analysis carried out in nine cases was positive in all patients (AKT activation in six patients, S6Sp6 expression/activation in seven). Post-treatment biopsy in one responsive patient confirmed S6 switch off.

Conclusion: In addition to PDGFRB, mTOR pathway can be activated in chordomas and the combination of IM plus rapalogs may be effective in IM-resistant chordomas.