Impact of age on choice of chemotherapy and outcome in advanced colorectal cancer

BackgroundAge is a major risk factor for development of sporadic colorectal cancer but elderly patients are underrepresented in clinical trials and are potentially offered chemotherapy less often.MethodsData were obtained from South Australian Clinical Registry for advanced colorectal cancer between 1st February 2006 and 9th September 2010. Patients who received chemotherapy were analysed to assess the impact of single versus combination chemotherapy and to assess the outcome in two age cohorts, age <70 years and ⩾70 years.ResultsOut of a total of 1745 patients in the database during this time period, 951 (54.5%) received systemic chemotherapy. 286 (30%) received first line therapy (median age 74 years) with single agent fluoropyrimidine and 643 patients (68%) received first line combination chemotherapy (median age 64 years). The median overall survival of patients receiving first line combination chemotherapy was 23.9 months compared to 17.2 months for those who received single agent fluoropyrimidine (p < 0.001). Combination chemotherapy was given to 81% of patients aged <70 years compared to 53% of those ⩾70 years. There was no significant difference in median overall survival of patients receiving chemotherapy by age cohort, 21.3 months for age <70 years and 21.1 months for age ⩾70 years (p = 0.4).ConclusionTreatment outcomes are comparable in both the elderly and younger patients. Patients who received initial combination chemotherapy were younger and had a longer median overall survival. In our study, age appeared to influence the treatment choices but not necessarily outcome.     

Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer? An exploratory analysis of the European Organisation for Research and Treatment of Cancer 55971 randomised trial

BackgroundTo investigate whether biomarkers consisting of baseline characteristics of advanced stage ovarian cancer patients can help in identifying subgroups of patients who would benefit more from primary surgery or neoadjuvant chemotherapy.MethodsWe used data of the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial in which 670 patients were randomly assigned to primary surgery or neoadjuvant chemotherapy. The primary outcome was overall survival. Ten baseline clinical and pathological characteristics were selected as potential biomarkers. Using Subpopulation Treatment Effect Pattern Plots (STEPP), biomarkers with a statistically significant qualitative additive interaction with treatment were considered as potentially informative for treatment selection. We also combined selected biomarkers to form a multimarker treatment selection rule.FindingsThe size of the largest metastatic tumour and clinical stage were significantly associated with the magnitude of the benefit from treatment, in terms of five-year survival (p for interaction: 0.008 and 0.016, respectively). Stage IIIC patients with metastatic tumours ?45 mm benefited more from primary surgery while stage IV patients with metastatic tumours >45 mm benefited more from neoadjuvant chemotherapy. In stage IIIC patients with larger metastatic tumours and in stage IV patients with less extensive metastatic tumours both treatments were equally effective. We estimated that by selecting treatments for patients based on largest metastatic tumour and clinical stage, the potential five-year survival rate in the population of treated patients would be 27.3% (95% confidence interval (CI) 21.9–33.0), 7.8% higher than if all were treated with primary surgery, and 5.6% higher if all were treated with neoadjuvant chemotherapy.InterpretationAlthough survival was comparable after primary surgery and neoadjuvant chemotherapy in the overall group of patients with ovarian cancer in the EORTC 55971 trial, we found in this exploratory analysis that patients with stage IIIC and less extensive metastatic tumours had higher survival with primary surgery, while patients with stage IV disease and large metastatic tumours had higher survival with neoadjuvant chemotherapy. For patients who did not meet these criteria, both treatment options led to comparable survival rates.     

Rôle de l’irradiation ganglionnaire chez les patientes indemnes d’envahissement ganglionnaire après chimiothérapie néoadjuvante pour un cancer du sein : expérience du centre René-Huguenin

PurposeNeoadjuvant chemotherapy generally induces significant changes in the pathological extent of disease. This potential down-staging challenges the standard indications of adjuvant radiation therapy. We assessed the utility of lymph node irradiation in breast cancer patients with pathological N0 status (pN0) after neoadjuvant chemotherapy and breast-conserving surgery.Patients and materialsAmong 1054 breast cancer patients treated with neoadjuvant chemotherapy in our institution between 1990 and 2004, 248 patients with clinical N0 or N1-N2 lymph node status at diagnosis had pN0 status after neoadjuvant chemotherapy and breast-conserving surgery. Cox regression analysis was used to identify factors influencing locoregional recurrence-free survival, disease-free survival and overall survival.ResultsAll 248 patients received breast irradiation, and 158 patients (63.7%) also received lymph node irradiation. With a median follow-up of 88 months, the 5-year locoregional recurrence-free survival and overall survival rates were respectively 89.4% and 88.7% with lymph node irradiation and 86.2% and 92% without lymph node irradiation (no significant difference). Survival was poorer among patients who did not have a pathological complete primary tumor response (pCR) (hazards ratio [HR] = 3.05; 95% CI, 1.17 to 7.99) and in patients with N1-N2 clinical status at diagnosis ([HR] = 2.24; 95% CI, 1.15 to 4.36). Lymph node irradiation did not significantly affect survival.ConclusionsRelative to combined breast and local lymph node irradiation, isolated breast irradiation does not appear to be associated with a higher risk of locoregional relapse or death among breast cancer patients with pN0 status after neoadjuvant chemotherapy. These results need to be confirmed in a prospective study.     

Prise en charge diagnostique et thérapeutique des tumeurs épithéliales malignes de l’ovaire dans le centre ouest-africain de lutte contre le cancer de Dakar

IntroductionEpithelial ovarian cancer are the most frequent of ovarian cancer, their prognosis is very bad. The aim of this study is to describe the diagnosis, the treatment and to assess the survival rate of the patients.MethodsIt was a retrospective study realized at the Cancer Institute of Dakar from December 2000 to January 2007. We have collected 117 patients with epithelial ovarian cancer. The mean age was 49 years. Patients were comprised: 22 stage I, 32 stage II, 35 stage III and 26 stage IV. Primary surgery was performed to 34 patients and the other patients were treated with chemotherapy and surgery. The survival rate was assessed by Kaplan-Meier method and the Logrank test had allowed to compare the survival among age and optimal surgery.ResultsOptimal surgery R0 was done in 20 cases and surgical resection R2 was performed in 45 cases. Pathological exam had found 65 serous cystadenocarcinoma, 28 mucinous cystadenocarcinoma and 21 endometrioid cystadenocarcinoma, one malignant tumor of Brenner. Overall survival at five years was 13.3%. The survival among optimal surgery was 16.3 and 2.3% for suboptimal surgery. There was no significant difference of the survival among patients who were less than 40 years old (P  =  0.334).ConclusionPrognosis of epithelial ovarian cancer is worse in Senegal as like as in the world. To improve the survival of our patients, we must detect the early diagnosis of these tumors and to introduce the neoadjuvant chemotherapy before optimal surgery.     

Treatment strategies for patients with stage IV rectal cancer: a report from the Swedish Rectal Cancer Registry

BackgroundThe optimal treatment strategy for patients with stage IV rectal cancer is unclear. The aim of the present study was to describe trends and compare the different treatment strategies for this group of patients at a national level and over time.MethodsData from 2758 rectal cancer patients with (stage IV) and 13,420 without metastases (stage I–III) were available from the Swedish Rectal Cancer Registry between January 1995 and December 2006.ResultsPatients with stage IV disease increased from 15% to 19% between 1995 and 2006 (p < 0.001) and the frequency of patients not operated on increased from 13% to 26% (p < 0.001). Postoperative 30 day mortality after bowel resection was 2% and after exploratory laparotomy 9%. Median survival for stage IV patients after bowel resection was 16.3 months, exploratory laparotomy 6.1 months and for patients having no surgery 4.6 months. Over time survival was improved for patients aged 60–69 years, irrespective of the treatment given. An increased risk of death was associated with: age >80 years, operation at a local hospital, treatment in earlier time periods, not receiving preoperative radio- or chemotherapy and not having a bowel resection.ConclusionsIn the latest time period survival was improved for rectal cancer patients in stage IV despite the great increase in non-operated patients. Patients aged >80 years should be carefully assessed and staged before surgery. The survival advantage for stage IV rectal cancer patients who underwent primary tumour resection is probably due to selection to more favourable cases.     

Treatment and survival for non-Hodgkin's lymphoma: influence of histological subtype, age, and other factors in a population-based study (1999-2001)

AimsThis population-based study investigates the use of chemotherapy and radiotherapy for non-Hodgkin’s lymphoma (NHL) treatment in clinical practise generally, and for specific histologies, and identifies factors associated with treatment and survival.MethodsData for NHL patients, diagnosed during 1999–2001, were obtained from the National Cancer Registry (Ireland). Multivariate models were analysed on survival and treatment.Results45–77% of patients received chemotherapy, 22–34% of patients received the radiotherapy, depending on the histology. Patients aged <65, married, with early stage B-cell aggressive disease were more likely to receive chemotherapy(P < 0.05). Patients >65 or with advanced stage were less likely to receive radiation (P < 0.05). Survival was poorer in older(P < 0.001) and unmarried patients (P < 0.05), and those with B-cell aggressive lymphoma(P < 0.001). Patients who received chemotherapy and radiation had lower hazard ratios.ConclusionsOverall, the use of chemotherapy and radiation in this European population was similar to the findings in the US where older patients received treatment less often. However, the age disparity here was greater than that in the US.     

A prognostic model to identify patients with advanced pancreas adenocarcinoma who could benefit from second-line chemotherapy

AimsThe role of salvage chemotherapy after first-line therapy in advanced pancreatic cancer has not yet been established. We intended to identify prognostic factors for long-term survival of advanced pancreatic adenocarcinoma patients with second-line chemotherapy and to devise a prognostic model of clinical parameters.Patients and methodsWe analysed 90 patients who had received second-line chemotherapy after the failure of first-line therapy in recurrent or metastatic pancreatic adenocarcinoma between August 2003 and December 2008.ResultsThe median age at the time of second-line chemotherapy was 61.9 years (range 39.8–74.9) and the median Eastern Cooperative Oncology Group (ECOG) performance status was 1 (0–2). Median progression-free survival and overall survival for second-line chemotherapy were 2.1 and 4.5 months, respectively, with an overall response rate of 10%. In multivariate analysis, an ECOG performance status of 2 or more, non-responder for first-line chemotherapy and albumin level of <3.5 mg/dl were independent prognostic factors for decreased overall survival for all 90 patients. Overall survival was estimated based on the number of adverse prognostic factors: zero or one (good prognostic group), two (intermediate group) or three (poor prognostic group). The median overall survival for good (n = 50), intermediate (n = 24) and poor (n = 16) prognostic groups was 5.5, 3.3 and 2.1 months, respectively (P < 0.001).ConclusionOur result suggests that second-line chemotherapy may be beneficial for overall survival in patients with ECOG performance status 0–1, albumin level ≥3.5 mg/dl and response to first-line chemotherapy.     

Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis

BackgroundThe role of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients is highly controversial and it is not endorsed by current guidelines. Our meta-analysis aimed to better elucidate its activity, efficacy and safety.Material and methodsA systematic search of Medline, Web of Science and conferences proceedings up to 30 October 2017 was carried out to identify randomized controlled trials (RCTs) investigating platinum-based versus platinum-free neoadjuvant chemotherapy in TNBC patients. Using the fixed and random effects models, pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CI) were calculated for pathological complete response (pCR, defined as ypT0/is pN0), event-free survival (EFS), overall survival (OS) and grade 3 and 4 adverse events (AEs: neutropenia, anemia, thrombocytopenia and neuropathy).ResultsNine RCTs (N = 2109) were included. Overall, platinum-based neoadjuvant chemotherapy significantly increased pCR rate from 37.0% to 52.1% (OR 1.96, 95% CI 1.46–2.62, P < 0.001). Platinum-based neoadjuvant chemotherapy remained significantly associated with increased pCR rate also after restricting the analysis to the three RCTs (N = 611) that used the same standard regimen in both groups of weekly paclitaxel (with or without carboplatin) followed by anthracycline and cyclophosphamide (OR 2.53, 95% CI 1.37–4.66, P = 0.003). Conversely, among the 96 BRCA-mutated patients included in two RCTs, the addition of carboplatin was not associated with significantly increased pCR rate (OR 1.17, 95% CI 0.51–2.67, P = 0.711). Two RCTs (N = 748) reported survival outcomes: no significant difference in EFS (HR 0.72, 95% CI 0.49–1.06, P = 0.094) and OS (HR 0.86, 95% CI 0.46–1.63, P = 0.651) was observed.A significant higher risk of grade 3 and 4 hematological AEs, with no increased risk of grade 3 and 4 neuropathy was observed with platinum-based neoadjuvant chemotherapy.ConclusionIn TNBC patients, platinum-based neoadjuvant chemotherapy is associated with significantly increased pCR rates at the cost of worse hematological toxicities. Platinum-based neoadjuvant chemotherapy may be considered an option in TNBC patients.PROSPERO registration numberCRD42018080042.     

Evaluation of an inflammation-based prognostic score in patients with advanced ovarian cancer

BackgroundThere is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients with advanced cancer. The aim of this study was to validate whether an inflammation-based prognostic score (Glasgow Prognostic Score, GPS) is associated with survival in patients with advanced stage (stage III/IV) ovarian cancer.Patients and methodsAn audit was conducted of patients with a new diagnosis of stage III or IV ovarian cancer presenting to the West London Gynae-Oncology Centre between October 2003 and June 2006 (n = 154). The GPS was constructed as follows: Patients with both an elevated C-reactive protein (>10 mg/l) and hypoalbuminaemia (<35 g/l) were allocated a score of 2. Patients in whom only one or none of these biochemical abnormalities was present were allocated a score of 1 or 0, respectively.ResultsOn univariate analysis GPS, histological type, ALP, performance status, primary surgery and ascites were predictors of overall survival. On multivariate a high GPS score, non-serous histology, high ALP and no initial surgery were independent predictors of worse overall survival in this population.ConclusionsThe presence of a systemic inflammatory response, as measured by the GPS, is an independent predictor of poor overall survival in patients with advanced ovarian cancer independent of treatment received.     

Survival among non-small cell lung cancer patients with poor performance status after first line chemotherapy

BackgroundPerformance status (PS) is a commonly used factor in determining the appropriateness for chemotherapy of patients with non-small cell lung cancer (NSCLC). The prevalence of poor PS and impact of chemotherapy on survival among NSCLC patients has not been studied in community populations.Patients and methodsInsured patients, aged 50+ years, diagnosed with advanced stage NSCLC between 2000 and 2007 were identified via tumor registry (n = 292) and linked to electronic medical records, automated medical claims, and Census tract information. A multivariate Cox proportional hazards model was used to determine the factors associated with survival.ResultsOf 292 stage IIIB–IV patients, 82 (28%) had PS 3 or 4, and 39% of PS 3–4 patients received first line chemotherapy. Those who received chemotherapy lived 4.8 months compared to 2.4 months for those who did not. Factors associated with a reduced likelihood of death included receipt of chemotherapy (hazard ratio [HR], 0.64), and female gender (HR, 0.71).Modern chemotherapy may be associated with positive effects on survival for poor PS patients, as for good PS patients. Further trials, especially randomized trials, in this neglected subgroup are indicated.     

A phase III study of belagenpumatucel-L,an allogeneic tumour cell vaccine,as maintenance therapy for non-small cell lung cancer

BackgroundTreatment options after first-line chemotherapy are limited in non-small cell lung cancer (NSCLC). Belagenpumatucel-L is a therapeutic vaccine comprised of 4 transforming growth factor (TGF)-β2-antisense gene-modified, irradiated, allogeneic NSCLC cell lines that may be useful for maintenance after initial treatment.MethodsStage III/IV NSCLC patients who did not progress after platinum-based chemotherapy were randomised 1:1 to receive maintenance belagenpumatucel-L or placebo. Patients were eligible for randomisation between one and four months from the end of induction chemotherapy. The primary endpoint was overall survival.ResultsThis phase III trial enrolled 270 patients in the belagenpumatucel-L arm and 262 in the control arm. Belagenpumatucel-L was well tolerated with no serious safety concerns. There was no difference in survival between the arms (median survival 20.3 versus 17.8 months with belagenpumatucel-L versus placebo, respectively; hazard ratio (HR) 0.94, p = 0.594). There were also no differences in progression-free survival (4.3 months versus 4.0 for belagenpumatucel-L vs placebo, respectively; HR 0.99, p = 0.947). A prespecified Cox regression analysis demonstrated that the time elapsed between randomisation and the end of induction chemotherapy had a significant impact on survival (p = 0.002) and that prior radiation was a positive prognostic factor (median survival 28.4 months with belagenpumatucel-L versus 16.0 months with placebo; HR 0.61, p = 0.032).ConclusionsAlthough the overall trial did not meet its survival endpoint, improved survival for belagenpumatucel-L is suggested in patients who were randomised within 12 weeks of completion of chemotherapy and in those who had received prior radiation. Further studies of belagenpumatucel-L in NSCLC are warranted.     

Neoadjuvant therapy for breast cancer has no benefits on overall survival or on the mastectomy rate in routine clinical practice. A population-based study with a median follow-up of 11years using propensity score matching

BackgroundEven though neoadjuvant chemotherapy has shown no benefits on overall survival (OS), it is being widely used in the treatment of breast cancer. This is based on the assumption that it may diminish the mastectomy rate and therefore be clinically relevant for patients. Our objective was to assess the impact of neoadjuvant chemotherapy on OS and on the rate of mastectomy in patients with non-metastatic primary operable breast carcinoma in routine practice.MethodsThe Cote d’Or district breast cancer registry was used to analyse the OS and mastectomy rate in patients with invasive primary operable unilateral breast cancer diagnosed between 1982 and 2006. We performed Cox proportional hazard ratio (HR) analyses for OS and multivariate logistic regression for the mastectomy rate for the overall population. Different matching methods based on the propensity score were used as sensitivity analyses to ensure that corrections for selection bias were adequate.ResultsWe analysed 1578 patients, among whom 174 had received neoadjuvant chemotherapy. Median follow-up was 11.1 years. There was no difference between the two treatment groups for OS (HR = 1.08 (95% confidence interval (CI): 0.77–1.51 for neoadjuvant chemotherapy)). The mastectomy rate was higher among patients treated with neoadjuvant chemotherapy (odds ratio 1.54 (95% CI: 1.03–2.31)). Sensitivity analyses confirmed these results: for OS, there was no difference between the two populations precisely matched using propensity scores (HR 1.08; 95% CI: 0.671–1.65).ConclusionDespite long term follow-up, neoadjuvant chemotherapy provided no benefit for either OS or the mastectomy rate in our population.     

The role of bowel surgery with cytoreduction for epithelial ovarian cancer

AimsTo assess the efficiency and morbidity associated with bowel resection with the initial cytoreduction procedure for advanced ovarian cancer.Materials and methodsA review was carried of 95 patients with ovarian cancer who underwent cytoreductive surgery between 2000 and 2003. The relationship between dichotomised preoperative, intra-operative and postoperative outcome variables were tested using SPSS software. Kaplan–Meier curves were generated to compare survival. Cox proportional hazards regression was used to determine the independent significance of factors after cytoreductive surgery.ResultsIn patients in whom bowel resection was carried out, the largest residual tumour mass was <1 cm in 66.67% of patients, compared with 45.28% of patients undergoing surgery without bowel resection (P = 0.038). The median survival in the optimally debulked patients was 50.38 months compared with 37.15 months in the patients who had suboptimal cytoreduction (P = 0.0021). The median survival in patients undergoing bowel resection was 50.70 months compared with 44.62 months in the patients who had cytoreduction without bowel resection (P = 0.2176). Multivariate analysis showed that optimal cytoreduction (P = 0.005) was found to be independently prognostic for overall survival. Major adverse events, such as ileus, intestinal fistulae, urinary tract fistulae, were not significantly different between groups.ConclusionBowel resection is a worthwhile endeavour in selected patients with advanced ovarian cancer to increase therapeutic efficiency. The surgical morbidity rate from these procedures is not serious and seems acceptable.     

Subtype-specific KRAS mutations in advanced lung adenocarcinoma: A retrospective study of patients treated with platinum-based chemotherapy

BackgroundPlatinum-based chemotherapy is the most common treatment in advanced-stage lung adenocarcinoma. Because the clinical significance of KRAS mutational status in this setting has not yet been clearly determined, a mutation subtype-specific analysis was performed in the so far largest cohort of Caucasian patients with KRAS mutant advanced-stage lung adenocarcinoma treated with platinum-based chemotherapy.Methods505 Caucasian stage III–IV lung adenocarcinoma patients with known amino acid substitution-specific KRAS mutational status and treated with platinum-based chemotherapy were included. The correlations of subtype-specific KRAS mutations with smoking status, progression-free and overall survival (PFS and OS, respectively) and therapeutic response were analysed.ResultsAmong 338 KRAS wild-type, 147 codon 12 mutant and 20 codon 13 mutant patients, there were no mutation-related significant differences in PFS or OS (P values were 0.534 and 0.917, respectively). Eastern Cooperative Oncology Group (ECOG) status and clinical stage were significant independent prognostic factors. KRAS mutation showed a significant correlation with smoking status (P = 0.018). Importantly, however, G12V KRAS mutant patients were significantly more frequent among never-smokers than all other codon 12 KRAS mutant (G12x) subtypes (P = 0.016). Furthermore, this subgroup tended to have a higher response rate (66% versus 47%; P = 0.077). A modestly longer median PFS was also found in the G12V mutant cohort (233 days; versus 175 days in the G12x group; P = 0.145).ConclusionsWhile KRAS mutation status per se is neither prognostic nor predictive in stage III–IV lung adenocarcinoma, subtype-specific analysis may indeed identify clinically relevant subgroups of patients that may ultimately influence treatment decisions.     

Postoperative adjuvant chemotherapy followed by adjuvant tamoxifen versus nil for patients with operable breast cancer: a randomised phase III trial of the European Organisation for Research and Treatment of Cancer Breast Group

BackgroundThe contribution of adjuvant tamoxifen in breast cancer patients after receiving adjuvant chemotherapy is not fully established. We investigated the impact of tamoxifen, given sequentially after completion of adjuvant chemotherapy in patients with operable breast cancer.Patients and methodsBetween March 1991 and June 1999, 1863 women with stages I–IIIA operable breast cancer who had undergone surgery and completed six cycles of adjuvant combination chemotherapy with either CMF, CAF, CEF, FAC or FEC were randomised to receive either tamoxifen 20 mg daily for 3 years or no further treatment. Irrespective of menstrual status and hormone receptor content of the primary tumour, patients were stratified by institute, chemotherapy scheme and age (above 50 years or younger). The main end-point was to detect a 5% increase in the 5 year survival (from 80% to 85%) in favour of antioestrogen therapy. Secondary end-points were relapse free survival (RFS), local control, incidence of second primary breast cancer and correlation of results with hormone receptor content.ResultsAfter exclusion of all patients from three sites because of inadequate documentation, a total of 1724 patients (93%) were analysed (Tam 861 and Control 863). At a median follow-up of 6.5 years, 5-year RFS on tamoxifen was 73% versus 67% in controls (p = 0.035). No difference was seen in overall survival. The benefit of tamoxifen therapy was mainly seen in the subgroup of patients with histologically documented positive axillary nodes (5-year RFS on tamoxifen 71% versus 64% in the control group, p = 0.044) and in patients with tumours expressing the ER and PR positive phenotype (5-year RFS on tamoxifen 77% versus 70% in the control group, p = 0.014).ConclusionsTamoxifen administered for 3 years after completion of adjuvant chemotherapy in this otherwise unselected group of patients for endocrine sensitivity had a limited impact on relapse and had no detectable effect on overall survival. The beneficial effect of tamoxifen is mainly confined to the subgroup of patients with node-positive disease and to patients with tumours expressing the ER and PR positive phenotype.     

High efficacy of gemcitabine and cisplatin plus trastuzumab in patients with HER2-overexpressing metastatic breast cancer: a phase II study

AimsEffective and tolerable regimens are sought specifically in women who have been pre-treated with anthracyclines and taxanes. Gemcitabine and cisplatin plus trastuzumab has shown synergistic activity in vitro, and provides a new mechanism of drug interaction. This multicentre phase II study aimed to evaluate the efficacy and tolerability of gemcitabine and cisplatin plus trastuzumab in previously treated patients with metastatic breast cancer (MBC).Materials and methodsPreviously treated patients with human epidermal growth factor receptor 2 (HER2) overexpressing MBC were enrolled in a multicentre phase II study (DAKO Hercep Test 3+). Treatment consisted of gemcitabine (750 mg/m²), cisplatin (30 mg/m²) given on days 1 and 8 every 3 weeks, and trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly).ResultsTwenty patients were recruited, all of whom had previously received chemotherapy (12 pre-treated with taxanes, 18 pre-treated with anthracyclines seven pre-treated with taxanes and trastuzumab). A median of six cycles of the study treatment was delivered. There were eight partial responses, for an overall response rate of 40% (95% confidence interval 16.5–63.5%). The clinical benefit rate (complete response plus partial response plus stable disease) was 80% (95% CI 54.2–95.8%). The response rate in patients who had already received a trastuzumab-based regimen for MBC was 57.1% (95% CI 7.7–100%). Median time to progression was 10.2 months, and median overall survival was 18.8 months. Main toxicities were leukopenia (grade 3 in 55% of patients) and thrombocytopenia (grade 3 in 35% and grade 4 in 5% of patients). Non-haematological toxicity was rarely severe.ConclusionsCombination chemotherapy with gemcitabine and cisplatin plus trastuzumab is well tolerated and active in patients with HER2 overexpressing MBC, even after prior exposure to anthracyclines and taxanes.     

Phase II study of biweekly cetuximab in combination with irinotecan as second-line treatment in patients with platinum-resistant gastro-oesophageal cancer

BackgroundThe purpose of this phase II trial was to evaluate the efficacy and safety of cetuximab and irinotecan as second-line treatment in patients with gastro-oesophageal adenocarcinoma.Patients and methodsPatients with failure to first-line platinum-based chemotherapy received cetuximab 500 mg/m² and irinotecan 180 mg/m² every second week until disease progression. Toxicity was evaluated according to The Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v. 3.0. Antitumour activity was assessed according to Response Evaluation Criteria in Solid Tumours (RECIST) v. 1.0.ResultsSixty-three patients were enrolled, median age was 60 years, median performance status was 1 (0–1), 35 patients had two or more organs involved. The median number of courses was 5 (range 1–25). Response rate was 11% (6 partial response (PR)) and 37% had stable disease. Median progression free survival was 2.8 months and overall survival (OS) was 6.1 months. Grade 3–4 toxicity included: diarrhoea (6%), fatigue (5%), vomiting (5%) and neutropenia (16%). Two patients developed febrile neutropenia. Forty-six patients (73%) had developed grade 1–2 skin rash. Patients developing skin rash had a prolonged survival with an OS at 7.1 months.ConclusionsThe combination of cetuximab and irinotecan is active as second-line therapy in patients with gastro-oesophageal cancer. Cetuximab induced skin rash was associated with prolonged survival.     

Neoadjuvant chemotherapy,interval debulking surgery or primary surgery in ovarian carcinoma FIGO stage IV?

ObjectivesThe aim of this study was to investigate the impact of surgical approach, the extent of surgery and chemotherapy on overall survival in patients with ovarian carcinoma (OC) stage IV.MethodsWe retrospectively collected population-based data from the Norwegian Radium Hospital code registry on the diagnosis and surgery of 238 patients diagnosed with OC stage IV from 1996–2005. All patients received platinum-based chemotherapy. Surgical approach was registered as primary debulking surgery (PDS), interval debulking surgery (IDS) and delayed primary surgery (DPS). Surgery level was classified as radical surgery (RS), standard surgery (SS) or suboptimal surgery (SUBS). Univariate and multivariate analyses identified prognostic factors in PDS, IDS and DPS groups and subgroups.ResultsThere were no differences in overall survival between the PDS, IDS and DPS groups. Surgery level was significantly associated with overall survival in the whole cohort (p < 0.001), the PDS and IDS groups, but not in the DPS group. More patients with RS achieved no residual tumour (RT), but overall survival was not superior compared to no RT in the SS group. In 66 patients with no RT there were no differences in overall survival between those who underwent PDS, IDS and DPS. Chemotherapy with platinum/paclitaxel tended to improve survival. RT, World Health Organisation (WHO) performance status and histology were prognostic factors for overall survival in the whole cohort.ConclusionNo RT remains the objective, whether PDS, IDS or DPS is performed, and no differences in overall survival were found in the three treatment groups.     

Quantification of angiogenesis by the Chalkley method and its prognostic significance in epithelial ovarian cancer

AimThe aim of the present study was to clarify prognostic role of angiogenesis in epithelial ovarian cancer.MethodsQuantification of angiogenesis was performed by the Chalkley method after immunostaining of 175 epithelial ovarian cancer specimens with an antibody against CD34.ResultsThe Chalkley count was categorised into two groups according to the median value: low <8 or high ⩾8. The low Chalkley count correlated significantly with serous and clear cell histological subtype of the tumour (p < 0.0005), whereas there existed no association with FIGO (International Federation of Gynecology and Obstetrics) stage, histological grade, presence of primary residual tumour, age at diagnosis, or chemotherapy response. In univariate analysis, the high Chalkley count predicted poor overall survival in the subgroup of patients with FIGO stages III–IV tumours (p = 0.007) but not in the entire study cohort. However, in multivariate analysis, the Chalkley count was found to be an independent predictor of death from ovarian cancer in the entire study cohort (p = 0.044, RR = 1.50, 95% CI 1.01–2.21) as well as in the subgroup of FIGO stages III–IV tumours (p = 0.046, RR = 1.58, 95% CI 1.01–2.46) together with the presence of primary residual tumour (p < 0.0005, RR = 5.10, 95% CI 3.02–8.62, and p = 0.002, RR = 4.28, 95% CI 1.34–13.73, respectively).ConclusionsThe Chalkley count seems to be suitable for evaluation of angiogenesis and to have prognostic significance in ovarian cancer.     

Central nervous system atypical teratoid rhabdoid tumours: the Canadian Paediatric Brain Tumour Consortium experience

BackgroundAtypical teratoid rhabdoid tumours (ATRT) are aggressive brain tumours mostly occurring in early childhood. Largest published series arise from registries and institutional experiences (1–4). The aim of this report is to provide population-based data to further characterise this rare entity and to delineate prognostic factors.Patients and methodsA national retrospective study of children ⩽18 years diagnosed with a central nervous system (CNS) ATRT between 1995 and 2007 was undertaken. All cases underwent central pathology review.ResultsThere were 50 patients (31 males; median age at diagnosis of 16.7 months). Twelve patients were >36 months. Infratentorial location accounted for 52% of all cases. Nineteen patients (38%) had metastatic disease. Fifteen (30%) underwent gross total resection (GTR). Ten patients (20%) underwent palliation. Among the 40 remaining patients, 22 received conventional chemotherapy and 18 received high dose chemotherapy regimens (HDC); nine received intrathecal chemotherapy and 15 received adjuvant radiation.Thirty of the 40 treated patients relapsed/progressed at a median time of 5.5 months (0–32). The median survival time of the entire cohort was 13.5 months (1–117.5 months).Age, tumour location and metastatic status were not prognostic. Patients with GTR had a better survival (2 years overall survival (OS): 60% ± 12.6 versus 21.7% ± 8.5, p = 0.03). HDC conferred better outcome (2 years OS 47.9% ± 12.1 versus 27.3% ± 9.5, p = 0.036). Upfront radiation did not provide survival benefit. Six of the 12 survivors (50%) did not receive radiation.ConclusionThe outcome of CNS ATRT remains poor. However, the use of HDC provides encouraging results. GTR is a significant prognostic factor. The role of adjuvant radiation remains unclear.