A multicenter phase II trial of docetaxel and capecitabine as salvage treatment in anthracycline- and taxane-pretreated patients with metastatic breast cancer

Objective

To evaluate the efficacy and safety of docetaxel plus capecitabine (DC) combination as salvage treatment in anthracycline- and taxane-pretreated patients with metastatic breast cancer (MBC).

Patients and treatment

Patients with MBC who had disease progression after initial chemotherapy with anthracyclines (n?=?29; 100?%) and taxanes (n?=?11; 37.9?%) were treated with oral capecitabine 950?mg/m² twice daily on days 1?C14 and docetaxel 75?mg/m² on day 1 every 3?weeks. Nineteen (65.5?%) patients received this regimen as second line and 10 (34.5?%) as???3rd line of therapy. All patients were evaluable for response and toxicity.

Results

Complete response occurred in two (6.9?%) patients and partial response in eleven (37.9?%) for an overall response rate of 44.8?% (95?% CI 26.7?C62.9?%). Eleven women (37.9?%) had stable disease and five (17.2?%) progressive disease. Of the eleven patients previously treated with anthracyclines and taxanes, five (45.5?%) responded to DC combination. The median duration of response was 5.7?months (range 3.4?C64.2), the median time to disease progression 9.3?months (range 1.2?C58), and the median overall survival 25.5?months. No toxic death occurred. Neutropenia grade 4 occurred in 58.6?% of patients and three of them (10.3?%) developed neutropenic fever. Non-hematological toxicities were manageable with grade 3 hand-foot syndrome occurring in 6.9?% of the patients, fatigue in 3.4?%, and neurotoxicity in 3.4?%.

Conclusion

The DC combination is a valuable regimen as salvage treatment in anthracycline- or anthracycline and taxane-pretreated patients with MBC.     

Chemotherapy with gemcitabine, cisplatin, and docetaxel in the treatment for patients with muscle-invasive bladder cancer: a multicenter phase II study of the Hellenic Oncology Research Group (HORG)

Purpose

To assess the antitumor activity and toxicity of gemcitabine, cisplatin, and docetaxel (GCD) regimen in patients with locally advanced or metastatic urothelial cancer.

Patient and methods

Chemotherapy-na?ve patients, aged ??70?years with measurable or evaluable disease and a performance status (PS) of 0?C2 were treated with sequential cisplatin 80?mg/m² (d1), gemcitabine 1,100?mg/m² (d1 and d14), and docetaxel 80?mg/m² (d14) every 28?days.

Results

Sixty patients with an ECOG PS of 0?C2 were enroled. Most (71.7%) patients had stage IV disease. A median number of 4 chemotherapy cycles per patient (range, 1?C9) was administered. Eight (13.3%) patients achieved a CR and 16 (26.7%) a partial response (PR) (intention-to-treat: ORR 40%; 95% CI 27.6?C52.4%). Thirteen (21.7%) and 23 (38.3%) patients experienced stable and progressive disease, respectively. The median time to progression (TTP) was 7.7?months (range, 0.7?C43.4), and the median overall survival 21.4?months (range, 0.7?C68.6). Grade 3 and 4 neutropenia occurred in 27 (45%) patients and grade 3 and 4 thrombocytopenia in five (8.3%). Three (5%) patients developed febrile neutropenia. There were no treatment-related deaths. Severe non-haematological toxicity was infrequent.

Conclusions

The GCD combination is an active and well-tolerated regimen in patients with chemotherapy-naive locally advanced or metastatic TCC and merits to be further investigated.     

A multicenter randomized phase III trial of vinorelbine/gemcitabine doublet versus capecitabine monotherapy in anthracycline- and taxane-pretreated women with metastatic breast cancer

BackgroundThe Breast Cancer Study Group of the Hellenic Oncology Research Group conducted a phase III trial of single-agent capecitabine versus the vinorelbine/gemcitabine doublet in patients with metastatic breast cancer (MBC) pretreated with anthracyclines and taxanes. The primary objective was to demonstrate superiority of combination treatment in terms of progression-free survival (PFS).Patients and methodsWomen with MBC were randomly assigned to receive either capecitabine (Cap arm: 1250 mg/m² twice daily, on days 1–14) or vinorelbine/gemcitabine doublet (VG arm: vinorelbine 25 mg/m²; gemcitabine 1000 mg/m²; both drugs on days 1 and 15).ResultsSeventy-four women were treated on each arm and median PFS was 5.4 versus 5.2 months (P = 0.736), for VG and Cap, respectively. Median overall survival was 20.4 months for the VG arm and 22.4 months for the Cap arm (P = 0.319). Overall response rate was 28.4% in the VG arm and 24.3% in the Cap arm (P = 0.576). Both regimens were generally well tolerated. Neutropenia and fatigue were more common with VG arm and hand–foot syndrome with Cap arm.ConclusionsThis trial failed to demonstrate superiority of vinorelbine/gemcitabine doublet over single-agent capecitabine in terms of PFS. Given the favorable toxicity and convenience of oral administration, single-agent capecitabine is recommended for compliant patients.     

A phase II trial of erlotinib as front-line treatment in clinically selected patients with non-small-cell lung cancer

BackgroundThe purpose of this study was to evaluate the efficacy of erlotinib as front-line treatment in clinically selected patients with non–small-cell lung cancer (NSCLC).Patients and MethodsForty-nine previously untreated white patients who had stage IIIB/IV pulmonary adenocarcinoma or bronchoalveolar carcinoma and who were nonsmokers or former light smokers were treated with erlotinib 150 mg daily, irrespective of the EGFR mutation status.ResultsIn an intention-to-treat analysis, the overall response rate (ORR) was 24.5%. The median progression-free survival (PFS) was 6.7 months, the median overall survival (OS) was 15.5 months, and the 1-year survival rate was 61.3%. Among the 36 patients for whom tumor material was available, 9 (25%) had activating EGFR mutations. The ORR was 66.7% in patients with activating EGFR mutations and 14.8% in patients with wild-type EGFR (2P = .006). In patients with activating EGFR mutations, the OS has not been reached, whereas it was 12.9 months in patients with EGFR wild type (2P = .045). Twenty-four patients had a PFS of > 6 months; 11 (45.8%) of them had EGFR wild type and 7 (29.1%) had EGFR mutation.ConclusionsThe selection of patients for treatment with EGFR-directed tyrosine kinase inhibitors (TKIs) should be based on mutation testing. However use of clinical (smoking status) and pathologic (adenocarcinoma) criteria may identify a subgroup of patients with advanced/metastatic NSCLC who can benefit from front-line treatment with erlotinib when mutation testing is not feasible.     

Favorable clinical course of patients experiencing bevacizumab-induced proteinuria

Nephrotic-range proteinuria, which denotes structural damage to the glomerular filtration barrier, occurs in 1-2% of bevacizumab-treated patients. The glomerular injury and subsequent proteinuria is probably due to a direct targeting of vascular endothelial growth factor (VEGF). We report a case series of six patients who developed a syndrome characterized by proteinuria and hypertension after starting therapy with bevacizumab and who experienced prolonged progression-free survival. Given that altered glomerular permeability appears to be a direct consequence of VEGF inhibition, we hypothesize that proteinuria may indeed correlate with drug efficacy. Optimizing safe and effective drug dosing is critical to achieve the best therapeutic impact due to limited treatment options for many life-threatening advanced cancers. Clinicians should be aware that the development of proteinuria might serve as a surrogate marker of bevacizumab antitumor efficacy and determine the appropriate criteria for withholding this effective anticancer therapy.     

BRAF mutations,microsatellite instability status and cyclin D1 expression predict metastatic colorectal patients' outcome

Background:

The significance of BRAF mutations, microsatelite instability (MSI) status and cyclin D1 expression in patients with metastatic colorectal cancer (mCRC) was evaluated.

Methods:

Primary tumours from 144 patients treated for mCRC were assessed for BRAF (V600E) mutation, MSI status and cyclin D1. The data were correlated with progression-free survival (PFS) and overall survival (OS).

Results:

BRAF mutations were detected in 10 (out of 22, 45%) patients with MSI-H tumours compared with 2 (out of 122, 1.6%) in those with microsatellite stable tumours (P<0.001). The presence of BRAF mutations was correlated with cyclin D1 overexpression (7 out of 26 patients, 58% vs 5 out of 118 patients, 14% P=0.001). Patients with BRAF-mutated primary tumours had a significantly decreased PFS (2.7 vs 9.8 months; P<0.001) and median OS (14 vs 30 months; P<0.001) than patients with wild-type (wt) tumours. Patients with MSI-H and BRAF-mutated tumours experienced significantly lower PFS (3.1 vs 11.4 months; P=0.008) and OS (14.5 vs 35.5 months; P=0.004) than patients with MSI-H and BRAF wt tumours. Similarly, BRAF mutations and cyclin D1 overexpression were correlated with decreased PFS (3.1 vs 8.6 months; P=0.03) and OS (17.8 vs 39.2 months; P=0.01).

Conclusion:

BRAF V600E mutations are associated with MSI-H status and cyclin D1 overexpression and characterize a subgroup of patients with poor prognosis.     

Illness perceptions in Greek patients with cancer: a validation of the Revised‐Illness Perception Questionnaire

Objective: The Revised‐Illness Perception Questionnaire (IPQ‐R) assesses illness perceptions according to Leventhal's self‐regulatory model. The aim of this paper is to present findings on the reliability and validity of the IPQ‐R in a population of Greek cancer patients. Methods: A total of 206 patients completed a Greek translation of the IPQ‐R and the Greek version of the Beck Depression Inventory (BDI). The scale's reliability was investigated by examining its internal consistency (Cronbach's alpha) and its test–retest reliability. Structural validity was examined through factor analyses. Predictive validity was tested by regressing BDI scores on IPQ subscale scores. Inter‐relationships between IPQ‐R dimensions were also examined by computing Pearson's Correlation Coefficients. Results: Cronbach's alpha showed satisfactory internal consistency for the IPQ‐R subscales. Paired samples' t‐test showed good test–retest reliability. Factor analysis of the IPQ‐R items revealed that the Greek version reflects the structure of the original with the only difference being that the ‘Consequences’ and ‘Emotional Representations’ subscales loaded on one factor. Factor analysis of the causal dimension items revealed a different structure of Causal Representations than that of the original questionnaire yielding three main factors: Psychological Attributions, Behavioral, and External Factors. Multiple regression analyses showed that Consequences, Emotional Representations, Illness Identity, and Psychological Attributions were the best predictors for depression. Conclusions: Translation of the IPQ‐R has good reliability and similar structure to that of the original. Difficulties to confirm the structure of Causal Representations may represent cultural differences in understanding illness causation. Copyright © 2009 John Wiley & Sons, Ltd.     

Quantitative assessment of SSTR2 expression in patients with non-small cell lung cancer using68Ga-DOTATOC PET and comparison with18F-FDG PET

Purpose Dynamic PET studies with⁶⁸Ga-DOTATOC were performed in patients with non-small cell lung cancer (NSCLC) to assess the somatostatin receptor 2 (SSTR2) expression. Furthermore, dynamic¹⁸F-fluorodeoxyglucose (FDG) studies were performed in the same patients to compare the SSTR2 expression with the tumour viability. Methods The study population comprised nine patients, examined with both tracers on two different days within 1 week. Standardised uptake values (SUVs) were calculated and a two-tissue compartment model was applied to the data. Furthermore, a non-compartment model based on the fractal dimension (FD) was applied to the data. Results The DOTATOC uptake was generally lower than the FDG uptake. Moderately enhanced DOTATOC uptake was noted in seven of the nine tumours. All kinetic parameters exceptk ₄ were lower for DOTATOC than for FDG. The mean SUV was 2.018 for DOTATOC, in comparison to 5.683 for FDG. In particular,k ₃ was highly variable for DOTATOC and showed an overlap with the normal lung tissue. The fractional blood volumeV _B was relatively low for both tracers, not exceeding 0.3. The highest significant logarithmic correlation was found for the FD of the two tracers (r=0.764,p=0.017). The logarithmic correlation for SUVs was also significant (r=0.646,p=0.060), as was that forV _B (r=0.629,p=0.069). In contrast, none of the eight metastases which were positive on FDG PET showed any DOTATOC uptake. Conclusion The results demonstrated moderate⁶⁸Ga-DOTATOC uptake in primary NSCLC but did not provide any evidence for SSTR2 expression in metastases. This may be caused by loss of the gene expression in metastases as compared with the primary tumours.     

Differential effect of adjuvant taxane-based and taxane-free chemotherapy regimens on the CK-19 mRNA-positive circulating tumour cells in patients with early breast cancer

Background:

To determine the effect of adjuvant taxane-free and taxane-based chemotherapy regimens on the elimination of circulating tumour cells (CTCs) in patients with early breast cancer.

Methods:

The presence of CK-19 mRNA-positive CTCs in the peripheral blood was evaluated before and after chemotherapy, using a real-time RT–PCR assay, in a historical comparison of two cohorts of women with stage I–III breast cancer treated with adjuvant taxane-free (N=211; FE₇₅C or E₇₅C) and taxane-based (N=334; T/E₇₅C or T/E₇₅) chemotherapy.

Results:

Taxane-based chemotherapy resulted in a higher incidence of CTCs'' elimination than taxane-free regimens since 49.7% (74 of 149) and 33.0% (29 of 88) of patients with detectable CTCs before chemotherapy, respectively, turned negative post-chemotherapy (P=0.015). Patients treated with taxane-free regimens had a significantly lower disease-free survival (DFS) (P=0.035) than patients treated with taxane-based regimens; this difference was observed in patients with but not without detectable CTCs before chemotherapy (P=0.018 and P=0.481, respectively). The incidence of deaths was significantly higher in the taxane-free cohort of patients with but not without detectable CTCs before chemotherapy compared with that of the taxane-based cohort (P=0.002). Multivariate analysis revealed that the chemotherapy regimen was significantly associated with prolonged DFS (HR: 2.00; 95% CI=1.20–3.34).

Conclusion:

Elimination of CK-19 mRNA-positive CTCs during adjuvant chemotherapy seems to be an efficacy indicator of treatment and is associated with a favourable clinical outcome of patients with detectable CTCs before chemotherapy.