Primary treatment and prognostic factors of small cell neuroendocrine carcinoma of the uterine cervix: a Taiwanese Gynecologic Oncology Group study

BackgroundOur aims were to investigate the treatment and clinicopathological variables in relation to prognosis in small cell neuroendocrine cervical carcinoma (SCNECC).Patients and methodsClinical data of SCNECC patients with International Federation of Gynaecology and Obstetrics (FIGO) stages I–IV treated between 1987 and 2009 at member hospitals of the Taiwanese Gynecologic Oncology Group (TGOG) were retrospectively reviewed.ResultsOf the 179 eligible patients, 104 were of FIGO stage I, 19 stage IIA, 23 stage IIB, 9 stage III, and 24 stage IV. The median failure-free survival (FFS) was 16.0 months, and the median cancer-specific survival (CSS) was 24.8 months. In multivariate analysis, FIGO stage and lymph node metastasis were selected as independent variables in stages I–IV. In stages IIB–IVB, primary treatment containing etoposide and platinum for at least 5 cycles (EP5+) (n = 16) was associated with significantly better 5-year FFS (42.9% versus 11.8%, p = 0.041) and CSS (45.6% versus 17.1%, p = 0.035) compared to other treatments (n = 40). Furthermore, concurrent chemoradiation with EP5+ (CCRT-EP5+) was associated with even better 5-year FFS (62.5% versus 13.1%, p = 0.025) and CSS (75.0% versus 16.9%, p = 0.016).ConclusionsFIGO stage and lymph node metastasis are significant prognostic factors in SCNECC. In stages IIB–IVB, CCRT-EP5+ might be the treatment of choice, which could be also true for earlier stages. Despite limitations of a retrospective study spanning a long time period and heterogeneous managements, the results provide an important basis for designing future prospective studies.     

Human equilibrative nucleoside transporter 1 (hENT1) expression is a potential predictive tool for response to gemcitabine in patients with advanced cholangiocarcinoma

BackgroundCholangiocarcinoma (CC) is a rare cancer of the liver. Surgery offers the only chance for cure. When surgery is unfeasible, chemotherapy is the backbone of treatment. The combined administration of cisplatin and gemcitabine is considered standard of care. Human equilibrative nucleoside transporter 1 (hENT1) is the major transporter responsible for gemcitabine uptake into cells. hENT1 expression is associated with an increased survival for patients receiving gemcitabine after pancreatic cancer surgery, suggesting that hENT1 is predictive of response to gemcitabine.AimTo determine whether there is a correlation between the expression of hENT1 and disease outcome in CC.MethodsA retrospective study on 43 patients treated at our centre with a locally advanced or metastatic CC, who received first line treatment with gemcitabine, was performed.ResultsFor the whole population, median Progression Free Survival (PFS) and overall survival (OS) were 4.0 (95% Confidence Interval 2.7–5.3 months) and 10.0 months (95% CI 6.8–13.2 months), respectively. From the 26 samples available for hENT1 staining, 18 (69%) and 8 (31%) patients had high and low hENT1 immunostaining, respectively. The median PFS were 2.0 versus 6.0 months for low versus high staining respectively (p = 0.012). The median OS were 5.0 versus 11.0 months for low versus high staining, respectively (p = 0.036). On multivariate analysis, hENT1 expression was the single independent predictive factor associated with prolonged PFS (HR 0.35, p = 0.023) and OS (HR 0.41, p = 0.046).ConclusionIn this study we show the potential of hENT1 expression as a predictor of outcome in CC treated with gemcitabine. Larger studies are necessary to confirm these promising results.     

A randomized phase III adjuvant study in high-risk cervical cancer: simultaneous radiochemotherapy with cisplatin (S-RC) versus systemic paclitaxel and carboplatin followed by percutaneous radiation (PC-R): a NOGGO-AGO Intergroup Study

BackgroundSimultaneous adjuvant platinum-based radiochemotherapy in high-risk cervical cancer (CC) is an established treatment strategy. Sequential paclitaxel (Taxol) and platinum followed by radiotherapy may offer further advantages regarding toxicity.Patients and methodsAn open-labeled randomized phase III trial was conducted to compare paclitaxel (175 mg/m²) plus carboplatin (AUC5) followed by radiation (50.4 Gy) (experimental arm-A) versus simultaneous radiochemotherapy with cisplatin (40 mg/m²/week) (arm-B) in patients with stage IB–IIB CC after surgery. Primary objective was progression-free survival (PFS).ResultsOverall, 271 patients were randomized and 263 were eligible for evaluation; 132 in arm-A and 131 in arm-B appropriately balanced. The estimated 2-year PFS was 81.8% [95% confidence interval (CI) 74.4–89.1] in arm-B versus 87.2% (95% CI 81.2–93.3) in arm-A (P = 0.235) and the corresponding 5-year survival rates were 85.8% in arm-A and 78.9% in arm-B (P = 0.25). Hematological grade 3/4 toxicity was higher in arm-B. Alopecia (87.9% versus 4.1%; P < 0.001) and neurotoxicity (65.9% versus 15.6%; P < 0.001) were significantly higher in arm-A. Early treatment termination was significantly more frequent in arm-B than in arm-A (32.1% versus 12.9%; P = 0.001).ConclusionsSequential chemotherapy and radiation in high-risk CC could not show any significant survival benefit; however, a different toxicity profile appeared. This sequential regime may constitute an alternative option when contraindications for immediate postoperative radiation are present.     

The prophylactic use of granulocyte-colony stimulating factor during remission induction is associated with increased leukaemia-free survival of adults with acute lymphoblastic leukaemia: a joint analysis of five randomised trials on behalf of the EWALL

BackgroundGranulocyte-colony stimulating factor (G-CSF) is used to prevent febrile neutropenia and support intense chemotherapy. However, its impact on long-term outcome in oncological patients including adults with acute lymphoblastic leukaemia (ALL) has not been determined so far.MethodsIn the current study follow-up data from individual patients recruited in five multicentre, prospective, randomised trials were pooled to perform a joint analysis. Among 347 adults and adolescents with ALL, 185 were assigned to receive prophylactically G-CSF along with induction chemotherapy while 162 patients were treated without G-CSF support.ResultsWith the median follow-up of 5.3 years, there was a tendency towards increased 5 year probability of the overall survival for the G-CSF arm compared to the controls (32% ± 4% versus 23% ± 4%, p = .07), which reached statistical significance in a subgroup of T-ALL (51% ± 8% versus 29% ± 9%, p = .01) and among patients aged 21–40 years (44% ± 6% versus 27% ± 6%, p = .03). The probability of leukaemia-free survival was 38% ± 4% and 24% ± 4% (p = .01) while the median remission duration equalled 33 and 17 months (p = .007), respectively. In a multivariate analysis the prophylactic use of G-CSF was independently associated with reduced risk of relapse (hazard ratio (HR) = .64, p = .007) and treatment failure (HR = .67, p = .02).ConclusionsThe prophylactic use of G-CSF during induction of ALL is associated with improved long-term outcome and should be recommended especially in a setting of T-ALL and in ‘young adults’. Our analysis provides the first direct evidence coming from prospective trials for the impact of primary G-CSF prophylaxis on disease-free survival of oncological patients.     

The efficacy of adjuvant chemotherapy with 5-fluorouracil in colorectal cancer depends on the mismatch repair status

AimsThe aim of this study is to evaluate if mismatch repair (MMR) defective colorectal cancer has a different response to adjuvant 5-fluorouracil (5-FU) chemotherapy in a cohort of patients prospectively followed during 5 years.MethodsThe cohort included 754 surgically treated patients with colorectal cancer. MMR status was diagnosed by MLH1 and MSH2 immunohistochemistry and microsatellite instability analysis. Median follow-up was 49.2 months (range 1–73). At inclusion, 505 patients were diagnosed as TNM II or III stage, analysis of the efficacy of adjuvant chemotherapy was made on this population. Adjuvant chemotherapy was applied to 248 patients (98.2% 5-FU based).ResultsMMR deficiency was found in 76 patients (10.1%). No differences were found in overall survival (log-rank p = 0.3) or disease-free survival (log-rank p = 0.3) regarding MMR status. Adjuvant chemotherapy improves survival in patients in the II or III stage, but this improvement is only evident in patients with MMR-competent tumours (log-rank p = 0.00001). Survival of patients with MMR-defective tumours does not improve with adjuvant chemotherapy (log-rank p = 0.7). A multivariate analysis showed an independent effect of the interaction between MMR status and adjuvant chemotherapy (Hazard ratio 2.04; 95% confidence interval: 1.42–2.93).ConclusionIn a cohort of colorectal cancer patients, those with MMR-deficient tumours seem not to benefit from 5-FU-based chemotherapy.     

Adjuvant dibromodulcitol and BCNU chemotherapy in anaplastic astrocytoma: results of a randomised European Organisation for Research and Treatment of Cancer phase III study (EORTC study 26882)

BackgroundIn a previous randomised EORTC study on adjuvant dibromodulcitol (DBD) and bichloroethylnitrosourea (BCNU) in adults with glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), a clinically significant trend towards a longer overall survival (OS) and a progression-free survival (PFS) was observed in the subgroup of AA. The aim of the present study was to test this adjuvant regimen in a larger number of AA patients.MethodsContinuation of the previous phase III trial for newly diagnosed AA according to the local pathologist. Patients were randomised to either radiotherapy only or to radiotherapy in combination with BCNU on day 2 and weekly DBD, followed by adjuvant DBD and BCNU in cycles of six weeks for a maximum total treatment duration of one year. OS was the primary end-point.ResultsPatients (193 ) with newly diagnosed AA according to local pathological assessment were randomised to radiotherapy (RT) alone (n = 99), or to RT plus DBD/BCNU (n = 94); 12 patients were considered not eligible. At central pathology review, over half (53%) of the locally diagnosed AA cases could not be confirmed. On intent-to-treat analysis, no statistically significant differences in OS (p = 0.111) and PFS (p = 0.087) were observed, median OS after RT was only 23.9 months 95% confidence interval (CI), [18.4–34.0] after RT plus DBD/BCNU 27.3 months 95% CI [21.4–46.8].ConclusionNo statistically significant improvement in survival was observed after BCNU/DBD adjuvant chemotherapy in AA patients. The trend towards improved survival is consistent with previous reports. Central pathology review of grade 3 tumours remains crucial.     

Lack of TIMP-1 tumour cell immunoreactivity predicts effect of adjuvant anthracycline-based chemotherapy in patients (n = 647) with primary breast cancer. A Danish Breast Cancer Cooperative Group Study

PurposeA number of prospective studies have shown that adjuvant CEF significantly improves disease-free and overall survival as compared to CMF in breast cancer patients. Our aim was to determine whether the benefit of epirubicin versus methotrexate differs according to TIMP-1 tumour cell immunoreactivity.Experimental designTissue micro arrays from 647 patients randomly assigned to CMF or CEF in DBCG trial 89D were included. The primary end-point was invasive disease-free survival (IDFS). A central assessment of tissue inhibitor of metalloproteinases 1 (TIMP-1) status was performed using immunohistochemistry (IHC). Tumours were regarded as TIMP-1 positive if epithelial breast cancer cells were stained using the anti-TIMP-1 monoclonal antibody VT7.ResultsBy central assessment 75% of tumours were classified as tumour cell TIMP-1 positive. Among CEF-treated patients, individuals with TIMP-1 negative tumours had a significant longer IDFS than patients with TIMP-1 positive tumours (p = 0.047). The multivariate Cox regression analysis of IDFS showed that CEF was superior to CMF among patients with TIMP-1 negative tumours (hazard ratio (HR) = 0.51; 95% confidence interval (CI): 0.31–0.84, p = 0.0085), while no significant difference could be demonstrated among patients with TIMP-1 positive tumours (HR = 0.88; 95% CI: 0.68–1.13, p = 0.32). A non-significant TIMP-1 status (positive or negative) versus treatment (CMF or CEF) interaction was detected for IDFS (p = 0.06) and OS (p = 0.21).ConclusionLack of TIMP-1 tumour cell immunoreactivity seems to predict a favourable effect of epirubicin-containing adjuvant therapy in primary breast cancer. However, an independent study is awaited to validate the potential predictive value of TIMP-1 immunoreactivity.     

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.     

Clinical prognostic factors of diffuse large B cell non-Hodgkin lymphoma: A retrospective study

BackgroundDiffuse large B-cell lymphoma (DLBCL) is the most common subtype of NHL in Egypt. It represents about 49% of NHL presenting to the National Cancer Institute (NCI), Cairo University. CHOP regimen is the standard treatment used for NHL since the 1970s with only 30–40% overall survival. Recently, integration of Rituximab became a standard of care for patients with DLBCL. However, its widespread use in developing countries is still limited by the lack of financial coverage. Clinical prognostic factors, as well as the pathological markers, are mandatory to individualize treatment.AimThe aim of the study was to evaluate the clinical risk stratification models including the age adjusted International prognostic index (aaIPI), patients profile and dose intensity (DI) of Cyclophosphamide and Doxorubicin as effective tools for predicting the outcome and prognosis of our DLBCL patients treated with first line CHOP regimen.Patients and methodsThis retrospective study included 224 patients with diffuse large B cell lymphoma who were treated with 3–8 cycles of CHOP regimen at the Medical Oncology Department, NCI, Cairo University during the time period from 1999 to 2006.ResultsOne hundred and seventy-eight patients (79.5%) achieved CR after the CHOP regimen with an observation period of 51 months. The median survival time was 12 months. The OS and DFS at 2 years were 82% and 68.8%, respectively. The univariate analysis of predictive factors for response to treatment showed that the CR rate was significantly affected by aa-IPI and its elements (performance status, stage &; LDH), extranodal lesions and DI of Cyclophosphamide and Doxorubicin. The CR rate was 96.9%, 91.2%, 73.9% and 55.6% in cases with aa-IPI 0, 1, 2 and 3, respectively (p < 0.001) and it was 82.4%, 81.9% versus 50% in cases with no extranodal site, one extranodal site and two extranodal sites, respectively (p = 0.01). As regard DI of Cyclophosphamide, with DI below or equal to the median (249 mg/m²/week) the CR rate was 69%, while with DI above the median the CR rate was 87.7% (p = 0.001). For Doxorubicin, the CR rate was 72.3% with DI below or equal to the median (16.5 mg/m²/week), however, it was 86.6% with DI above the median (p = 0.008). The OS rate was significantly affected by aa-IPI as it was 89.8% in cases of aa-IPI 0 + 1 versus 75.8% in those of aa-IPI 2 + 3 (p = 0.03). DI of Cyclophosphamide and Doxorubicin significantly influenced the OS. The OS rate was 74% with DI of Doxorubicin below or equal to the median versus 96% in cases with DI above the median (p = 0.02). For Cyclophosphamide the OS rate was 72.7% with DI below or equal to the median versus 96.3% in cases with DI above the median (p = 0.01). The tumor bulk (with a median tumor size of 5 cm) affected the OS, which was 91.23% versus 86.8% in the tumor bulk less than and more than or equal to the median, respectively (p = 0.05). By multivariate analysis of predictive factors for response to treatment, the CR rate was significantly affected by the number of extranodal sites and the clinical staging of diffuse large B cell lymphoma. However, OS rate was strongly associated with the bulk of the tumor and the clinical staging of diffuse large B cell lymphoma.ConclusionDI of Cyclophosphamide and Doxorubicin is important in the future treatment regimen plan for DLBCL especially in high risk cases. In addition to aa-IPI and its elements, extra nodal sites and bulk of the tumor proved to be significant predictors and prognostic factors for DLBCL treatment outcome.     

Comparable survival for young rectal cancer patients,despite unfavourable morphology and more advanced-stage disease

BackgroundYoung patients with rectal cancer tend to present with more advanced-stage disease and unfavourable tumour morphology. The effects of these tumour characteristics on survival in this particular patient group are unclear.MethodsPopulation-based data from the Netherlands Cancer Registry (NCR) were used. Data from patients diagnosed with rectal cancer between 1989 and 2010 were selected. Younger patients (⩽40 years) were compared with middle-aged patients (41–70 years) with respect to disease stage, tumour characteristics, treatment and outcomes. Patients aged older than 70 years were excluded. Relative excess risk (RER) models were used to perform uni- and multivariate survival analyses.FindingsA total of 37.056 patients were included (⩽40 years n = 1.102). Compared with middle-aged patients, young patients were more likely to have stage III (33.8% versus 27.8%) and stage IV (24.3% versus 19.6%) disease (p < 0.001). Young patients also presented more frequently with mucinous tumours (10.8% versus 9.0%), signet cell carcinomas (2.6% versus 0.6%) and poorly differentiated tumours (16.6% versus 12.3%) (p = 0.001). The treatment of stage I–III patients did not differ between the two groups, except regarding adjuvant chemotherapy, which was more often given to young patients (24.3% versus 14.4%, p < 0.001). Young age was a prognostic factor for better survival in stage I–III patients (RER 0.82 CI 0.71–0.94). Adjuvant chemotherapy was associated with improved survival in stage I–III patients (RER 0.76, 95%CI 0.70–0.83). In an exploratory analysis, adjuvant chemotherapy in young stage III and pN1 patients was associated with improved survival.Concluding statementYoung patients present with more advanced disease and have more unfavourable tumour characteristics compared with middle-aged patients. Despite these characteristics, survival rates are equal, and young age is a prognostic factor for better survival. Although the use of adjuvant chemotherapy is controversial, a positive correlation with survival was found in this study.     

Hypofractionated conformal irradiation of patients with malignant glioma

PurposeThe aim of the study is to evaluate the effect of a conformal irradiation in short fractionation scheme of 49.5 Gy in 15 fractions in an overall time of 3 weeks, in terms of overall survival (OAS) and progression free survival (PFS) rates in brain glioma patients.Patients and methodsA prospective study was conducted on 54 brain glioma patients and was carried out in the Radiation Oncology Department, South Egypt Cancer Institute, Assiut University during the period from April 2006 till June 2009. Patients were treated by hypofractionated conformal irradiation (49.5 Gy/15 fractions/3 weeks).ResultsThe median follow up was 23 months (range: 9–39 months). Two-year OAS and PFS rates were 68% and 60%, respectively. In univariate analysis, age >50 years, poor performance status [Karnofasky score of ?40–?70%], poor neuroperformance status of score III, high-grade tumor [glioblastoma multiforme], and biopsy were all associated with statistically significant reduction in OAS and PFS rates. Multivariate analysis, showed that age >50 years and glioblastoma pathology were the only independent prognostic factors that were associated with poor OAS (p = 0.003 and p = 0.004, respectively), and PFS (p = 0.027 and p = 0.011, respectively).ConclusionHypofractionated conformal radiotherapy was as effective as the conventional radiotherapy, with time sparing for patients, and for radiation oncology centers. Hypofractionated radiotherapy may be considered the radiotherapy regimen of choice in clinical practice for patients with gliomas.     

A phase III trial of docetaxel-estramustine in high-risk localised prostate cancer: a planned analysis of response, toxicity and quality of life in the GETUG 12 trial

AimTo assess docetaxel–estramustine in patients with localised high-risk prostate cancer.Patients and methodsAfter staging pelvic lymph node dissection, patients with high-risk prostate cancer randomly received androgen deprivation therapy (ADT) (3 years) + DE (4 cycles of docetaxel 70 mg/m²/3 weeks + estramustine 10 mg/kg/d d1–5) or ADT alone. Local therapy was administered at 3 months.ResultsFour hundred and thirteen patients were accrued: T3–T4 (67%), Gleason score ⩾8 (42%), PSA >20 ng/mL (59%), pN+ (29%). In the chemotherapy arm, 94% of patients received the planned four cycles of docetaxel. Local treatment consisted of radiotherapy in 358 patients (87%) (median dose 74 Gy in both arms). ADT was given for 36 months in both arms. A PSA response (PSA ⩽0.2 ng/mL after 3 months of treatment) was obtained in 34% and 15% in the ADT + DE arm and in the ADT arm, respectively (p < 0.0001). Febrile neutropenia occurred in only 2%. Moderate to severe hot flashes occurred less often in the ADT + DE arm (2% versus 22%; p < 0.001). There was no toxicity-related death, no secondary leukaemia, and no excess second cancers. Chemotherapy had a negative impact on quality of life (global health status, p = 0.01; fatigue, p = 0.003; role functioning, p = 0.003; social functioning, p = 0.006) at 3 months but this effect disappeared at 1 year.ConclusionDocetaxel–estramustine can be combined safely with standard therapy in high-risk prostate cancer, with a promising PSA response rate and no negative impact on quality of life after 1 year. Long-term follow-up is required to assess the impact on relapse and survival.     

A randomised trial comparing preoperative to perioperative chemotherapy in early-stage non-small-cell lung cancer (IFCT 0002 trial)

HypothesisThere will be a detectable increase in overall survival (OS) using preoperative (PRE) as opposed to perioperative (PERI) chemotherapy in resectable Stage I–II non-small-cell lung cancer (NSCLC).MethodsThis multicenter, open-label, randomised trial with a 2 × 2 factorial design first compared two chemotherapy strategies (PRE versus PERI), then two chemotherapy regimens (gemcitabine–cisplatin [GP] versus paclitaxel–carboplatin [TC]). The PRE group received two preoperative cycles followed by two additional preoperative cycles, while the PERI group underwent two preoperative cycles followed by two postoperative cycles, the 3rd and 4th cycles being given only to responders in both cases.ResultsA total of 528 patients were randomised, 267 of which were assigned to the PRE group and 261 to the PERI group. Three-year OS did not differ between the two groups (67.4% and 67.7%, respectively; hazard ratio (HR) = 1.01 [0.79–1.30], p = 0.92), nor did 3-year disease-free survival, response rates, toxicity, or postoperative mortality. Pathological complete response was observed in 22 (8.2%) and 16 patients (6.1%), respectively. Although quality of life did not differ significantly, chemotherapy compliance was significantly higher in the PRE group. The proportion of responders who received Cycles 3 and 4 was significantly higher in the PRE group (90.4% versus 75.2%, p = 0.001). In responders, the dose intensity of Cycles 3 and 4 was higher in the PRE group than in the PERI group (mean relative dose intensity of 90.4% versus 82.6%, respectively; p = 0.0007). There was no difference between GP and TC in 3-year OS (HR = 0.97 [95% confidence interval (CI): 0.76–1.25], p = 0.80) or response rates. However, the regimens’ toxicity profiles differed.ConclusionsThis study failed to demonstrate any difference in survival between patients receiving preoperative and perioperative chemotherapy in early-stage NSCLC. The increase from two to four preoperative chemotherapy cycles did not increase the pathological response rate.     

Maintenance pazopanib versus placebo in Non-Small Cell Lung Cancer patients non-progressive after first line chemotherapy: A double blind randomised phase III study of the lung cancer group,EORTC 08092 (EudraCT: 2010-018566-23, NCT01208064)

BackgroundSwitch maintenance is an effective strategy in the treatment of advanced Non-Small Cell Lung Cancer (NSCLC). Pazopanib is an oral, multi-targeted tyrosine kinase inhibitor (TKI). EORTC 08092 evaluated pazopanib given as maintenance treatment following standard first line platinum-based chemotherapy in patients with advanced NSCLC.MethodsPatients with non-progressive disease after 4–6 cycles of chemotherapy were randomised to receive either pazopanib 800 mg/day or matched placebo until progression or unacceptable toxicity. The primary end-point was overall survival and secondary end-points were progression-free survival (PFS) and safety.ResultsA total of 600 patients were planned to be randomised. The trial was prematurely stopped following an early interim analysis, after 102 patients were randomised to pazopanib (n = 50) or placebo (n = 52). Median age was 64 years in both arms. Median overall survival was 17.4 months for pazopanib and 12.3 months for placebo (adjusted hazard ratio (HR) 0.72 [95% confidence interval (CI) 0.40–1.28]; p = 0.257). Median PFS was 4.3 months versus 3.2 months (HR 0.67, [95% CI 0.43–1.03], p = 0.068). PFS rates at 4 months were 56% and 45% respectively. The majority of treatment-related adverse events (AEs) were grade 1–2. Grade 3–4 AEs (pazopanib versus placebo) were hypertension (38% versus 8%), neutropenia (8% versus 0%), and elevated SGPT (6% versus 0%). Of the patients randomised to pazopanib, 22% withdrew due to a treatment-related AE.ConclusionsSwitch maintenance with pazopanib following platinum-based chemotherapy in advanced NSCLC patients had limited side-effects. This study was stopped due to lack of efficacy by stringent criteria for PFS at a futility interim analysis.     

Short course of radiation therapy in elderly patients with glioblastoma multiforme

PurposeThe optimal schedule of irradiation in elderly patients suffering from glioblastoma multiforme (GBM) is unsettled.Materials and methodsThis study reviewed the charts of 28 consecutive GBM patients aged 70 years or more with a Karnofsky Performance Status (KPS) greater than or equal to 70 who received a short course of radiotherapy (40 grays in 15 fractions over three weeks).ResultsThe median age at surgery was 74.6 years (range, 70.1–85.7). No patient received prior or concomitant chemotherapy. The median progression-free survival and overall survival were 21.6 weeks (95% CI, 17.0–39.9) and 50.6 weeks (95% CI, 26.3–62.0), respectively. Even within a narrow range (< 90 or ≥ 90), KPS remained a prognostic factor (p = 0.03). Tolerance appeared acceptable in terms of KPS changes and corticosteroid use during radiation therapy.ConclusionThese results support the efficacy of short schedule radiotherapy for GBM in elderly patients with a good KPS.     

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.     

Primary versus secondary cytoreduction for epithelial ovarian cancer: a paired analysis of tumour pattern and surgical outcome

ObjectiveRecurrence rates of Epithelial Ovarian Cancer (EOC) remain high. Aim of the present study was to compare tumour pattern and surgical outcome at primary and secondary tumourdebulking in a paired patients’ collective.MethodsSeventy-nine consecutive EOC-patients who underwent both primary and secondary cytoreduction in our institution between 09/2000 and 12/2010 were evaluated according to a validated documentation-tool (‘IMO’, Intraoperative Mapping Ovarian Cancer). Differences in tumour-pattern between paired samples were examined using McNemar-test or sign-test.ResultsA complete macroscopic tumour resection could be achieved significantly more often during primary versus secondary surgery (77% versus 50%; p < 0.001) in comparable operative times (242 min versus 199 min; p = 0.15) and by equivalent operative morbidity (25% versus 29%; p = 0.424). Tumour-residuals at primary correlated significantly with tumour-residuals at secondary cytoreduction (p = 0.003). Patients at relapse had significantly higher rates of tumour involvement of the gastric serosa (2.5% versus 16.9%; p = 0.001), serosa of small intestine (20.3% versus 44.9%; p < 0.001) and mesentery (30.4% versus 50%; p = 0.012). The relative-risk for peritoneal carcinosis, intestinal tumour involvement or positive lymph nodes at secondary tumourdebulking in the case of presence of these features at primary surgery was 1.53 (95% CI: 0.89–2.63); 0.92 (95% CI: 0.65–1.31) and 1.49 (95% CI: 0.83–2.68), respectively, and thus not reaching a statistical significance.ConclusionsSecondary cytoreduction due to EOC appears to be associated with significantly lower optimal tumourdebulking rates compared to primary setting, since the disease tends to recur in patterns less accessible to complete resection such as gastrointestinal serosa, mesentery and upper abdomen. By maximal surgical effort, tumour residuals significantly correlate between primary and secondary cytoreduction. No other predictors of surgical outcome or tumour-pattern could be identified.     

Health-related quality of life in patients with advanced renal cell carcinoma receiving pazopanib or placebo in a randomised phase III trial

BackgroundIn a double-blind, randomised phase III trial of advanced renal cell carcinoma patients, pazopanib 800 mg QD (n = 290) versus placebo (n = 145) significantly prolonged progression-free survival (hazard ratio (HR) = 0.46, 95% confidence interval [CI] 0.34–0.62, p-value < 0.0001), without important differences in health-related quality of life (HRQoL). This post-hoc analysis evaluated time to HRQoL deterioration and whether tumour response/stabilisation was associated with HRQoL improvement.MethodsHRQoL was assessed using EORTC QLQ-C30 and EQ-5D. Effect of pazopanib on time to ⩾20% decline from baseline in summary scores was estimated for all patients and by prior treatment. Analyses were conducted for different HRQoL deterioration thresholds. HRQoL changes were stratified by benefit and compared: complete response (CR) or partial response (PR) versus progressive disease (PD); CR/PR versus stable disease (SD), and SD versus PD.ResultsThere was a trend for pazopanib patients to be less likely than placebo patients to experience ⩾20% HRQoL deterioration in EORTC-QLQ-C-30 global health status/QOL scale (HR = 0.77; 95% CI 0.57–1.03, not significant). Results by prior treatment and different HRQoL deterioration thresholds were similar. Patients with CR/PR and SD experienced significantly less HRQoL deterioration than those with PD (p < 0.001, p = 0.0024, respectively); mean differences between patients with CR/PR and PD exceeded the pre-determined minimally important difference (MID). Differences between patients with SD and PD did not exceed pre-determined MID. Results were generally consistent across treatment and EQ-5D summary scores.ConclusionResults support the favourable benefit-risk profile of pazopanib and suggest patients experiencing tumour response/stabilisation also may have better HRQoL compared to those without this response.     

Bisphosphonates combined with sunitinib may improve the response rate, progression free survival and overall survival of patients with bone metastases from renal cell carcinoma

BackgroundBisphosphonates are used to prevent skeletal events of bone metastases, and may exhibit antitumour effects. We aimed to evaluate whether bisphosphonates can bring a response rate (RR), progression free survival (PFS) and overall survival (OS) benefit to patients with bone metastasis from renal cell carcinoma (RCC) that is treated with sunitinib.MethodsWe performed a multicentre retrospective study of patients with bone metastases from RCC that was treated with sunitinib. The effect of bisphosphonates on RR, PFS and OS was tested with adjustment for known prognostic factors using a chi-square test from contingency table and partial likelihood test from Cox regression model.ResultsBetween 2004 and 2011, 209 patients with metastatic RCC were treated with sunitinib, 76 had bone metastases, 35 bisphosphonates users and 41 non-users. The groups of bisphosphonates users and non-users were balanced regarding known prognostic factors. Objective response was partial response/stable disease 86% (n = 30) versus 71% (n = 29), and progressive disease 14% (n = 5) versus 29% (n = 12) (p = 0.125, OR 2.48) in users versus non-users, respectively. Median PFS was 15 versus 5 months (HR = 0.55, p < 0.0001), and median OS was not reached (with a median follow-up time of 45 months) versus 14 months (HR = 0.4, p = 0.029), in favour of users. In multivariate analysis of the entire patient cohort (n = 76), factors associated with PFS were bisphosphonates use (HR = 0.58, p = 0.035), and pre-treatment neutrophil to lymphocyte ratio >3 (HR = 3.5, p = 0.009). Factors associated with OS were bisphosphonates use (HR = 0.5, p = 0.008), elevated pre-treatment alkaline phosphatase (HR = 2.9, p = 0.003) and sunitinib induced HTN (HR = 0.63, p < 0.0001).ConclusionsBisphosphonates may improve the RR, PFS and OS of sunitinib treatment in RCC with bone metastases.     

Comparison of gefitinib and erlotinib efficacies as third-line therapy for advanced non-small-cell lung cancer

PurposeThe epidermal growth factor receptor inhibitors, gefitinib and erlotinib, are used as standard salvage therapy for advanced non-small-cell lung cancer (NSCLC). The aim of the present study was to compare their efficacies in this population.Patients and methodsThe Taiwan Cancer Registry and the National Health Insurance claim databases were searched for newly diagnosed patients with NSCLC from 2004 to 2007 who received gefitinib or erlotinib as third-line therapy. Overall survival (OS) and time to treatment failure (TTF) were determined from registered parameters. Treatment efficacies were compared by the log-rank test in total population and subsets with different clinical characteristics. The Cox’s proportion hazard model was used to estimate the adjusted hazard ratios in multivariate analyses.ResultsA total of 984 patients who received gefitinib (67%) or erlotinib (33%) were included. Patients receiving gefitinib or erlotinib had similar OS (median, 10.2 versus 9.9 months, p = 0.524) and TTF (median, 5.5 versus 3.4 months, p = 0.103). In multivariate analyses, both treatment groups had similar risk of overall mortality (adjusted hazard ratio [HR] = 1.04, p = 0.629) and treatment failure (adjusted HR = 0.94, p = 0.417). Comparing the treatments in subgroups based on age, tumour histology and gender also revealed no differences in OS and TTF. For patients who received gefitinib or erlotinib for more than 3 or 6 months, there was no difference in TTF but patients who received erlotinib had longer OS.ConclusionsGefitinib and erlotinib had similar efficacies as salvage therapy for advanced NSCLC in Taiwan.