The predictive role of interim PET after the first chemotherapy cycle and sequential evaluation of response to ABVD in Hodgkin's lymphoma patients-the Polish Lymphoma Research Group (PLRG) Observational Study.

BACKGROUND: Interim PET after two ABVD cycles (iPET2) predicts treatment outcome in classical Hodgkin's lymphoma. To test whether an earlier assessment of chemosensitivity would improve the prediction accuracy, we launched a prospective, multicenter observational study aimed at assessing the predictive value of iPET after one ABVD (iPET1) and the kinetics of response assessed by sequential PET scanning. PATIENTS AND METHODS: Consecutive patients with newly diagnosed classical Hodgkin's lymphoma underwent interim PET scan after one ABVD course (iPET1). PETs were interpreted according to the Deauville score (DS) as negative (-) (DS 1-3) and positive (+) (DS 4, 5). Patients with iPET1 DS 3-5 underwent iPET2. RESULTS: About 106 early (I-IIA) and 204 advanced (IIB-IV) patients were enrolled between January 2008 and October 2014. iPET1 was (-) in 87/106 (82%) or (+) in 19/106 (18%) of early, and (-) in 133/204 (65%) or (+) in 71/204 (35%) of advanced stage patients, respectively. Twenty-four patients were excluded from response analysis due to treatment escalation. After a median follow-up of 38.2 (3.2-90.2) months, 9/102 (9%) early and 43/184 (23%) advanced patients experienced a progression-free survival event. At 36 months, negative and positive predictive value for iPET1 were 94% and 41% (early) and 84% and 43% (advanced), respectively. The kinetics of PET response was assessed in 198 patients with both iPETs. All 116 patients with iPET1(-) remained iPET2(-) (fast responders), 41/82 with IPET1(+) became iPET2(-) (slow responders), and the remaining 41 stayed iPET2(+) (non-responders); progression-free survival at 36 months for fast, slow and non-responders was 0.88, 0.79 and 0.34, respectively. CONCLUSION: The optimal tool to predict ABVD outcome in HL remains iPET2 because it distinguishes responders, whatever their time to response, from non-responders. However, iPET1 identified fast responders with the best outcome and might guide early treatment de-escalation in both early and advanced-stage HL.

Phase I study of bortezomib and cetuximab in patients with solid tumours expressing epidermal growth factor receptor.

Bortezomib inhibits nuclear factor-kappaB (NF-kappaB). Cetuximab is a chimeric mouse-human antibody targeted against epidermal growth factor receptor (EGFR). We hypothesised that concomitant blockade of NF-kappaB and EGFR signalling would overcome EGFR-mediated resistance to single-agent bortezomib and induce apoptosis through two molecular pathways. The aim of this phase I trial was to establish the maximum tolerated dose (MTD) for bortezomib plus cetuximab in patients with EGFR-expressing epithelial tumours. The 21-day treatment cycle consisted of bortezomib administered on days 1 and 8 through dose escalation (1.3-2 mg m(-2)). Cetuximab was delivered at a dose of 250 mg m(-2) on days 1, 8 and 15 (400 mg m(-2) day 1 cycle 1). A total of 37 patients were enroled and given a total 91 cycles. No grade > or =3 haematological toxicity was noted. Non-hematological grade > or =3 toxicities included fatigue (22% of patients), dyspnoea (16%) and infection (11%). The MTD was not reached at the highest tested bortezomib dose (2.0 mg m(-2)). Efficacy outcomes included disease progression in 21 patients (56.7%) and stable disease (SD) at 6 weeks in 16 patients (43.3%). Five of the six patients with SD at 12 weeks were diagnosed with cancers of the lungs or head and neck. This combination therapy was moderately effective in extensively pretreated patients with non-small cell lung or head and neck cancers and warrants further investigation.

[Elevation of serum Ca 15-3 antigen: an early indicator of distant metastasis from breast cancer. Retrospective analysis of 733 cases]. / Wzrost stezenia antygenu CA 15-3 w surowicy--wczesny wskaznik przerzutów odleglych raka piersi: retrospektywna analiza 733 chorych.

UNLABELLED: Aim of study was to summarize six-year institutional experience with serial evaluation of circulating CA15-3 antigen as a method of early detection of breast cancer relapse. MATERIAL AND METHODS: CA15-3 concentrations were assayed immuno-enzymatically in the sera of 733 women with breast carcinoma: in 707 cases marker was analyzed serially (every 4 months during follow-up after completion of radical treatment and when the relapse of breast cancer was clinically suspected) and in 26 patients--at diagnosis of locoregional relapse and\or breast cancer dissemination; 5493 assays of the CA15-3 antigen were performed in total. The cut-off limit was established at 30 u/ml. Results of CA15-3 tests were analyzed in relation to clinical status of the disease and dominant site of breast cancer relapse. RESULTS: 1) in patients with distant metastases (N = 149), mean serum CA15-3 values and the percentage of positive results were significantly higher as compared to cases with locoregional relapse and carcinoma of the contralateral breast (N = 54; p < 0.0001) and those without clinical evidence of relapse (N = 530; p < 0.0001), in agreement with previous studies; 2) the highest mean values of CA15-3 were observed in patients with liver and multiple metastases, lower in those with bone or lung secondaries, and the lowest when the metastatic involvement of supraclavicular nodes was noticed; 3) the CA15-3 sensitivity rates were higher in patients with liver or bone metastases (91.7% and 91.4%, respectively), as compared to those with multiple (79.5%) and lung (72.4%) secondaries, and the lowest when metastases in supraclavicular nodes (40.0%) or other organs (60.0%) were diagnosed; 4) the comparison of subjects with liver secondaries and those with other sites of breast cancer dissemination indicated statistically significant difference in the mean CA15-3 values (p < 0.0001) and the number of positive results of the test (p < 0.05); 5) the sensitivity rates of CA15-3 antigen for one, two, three and more skeletal metastases detected by bone scintigraphy were 50%, 100% and 100%, respectively (N = 30); 6) in 84 out of 116 (72.4%) patients with distant metastases, the increased CA15-3 concentration preceded the clinical diagnosis of the relapse with the median lead time 9 months (range: 1-40); 7) the highest positivity rates of the lead time were observed in patients with liver or lung metastases (93.8% and 81.0%, respectively) and the lowest one in those with multiple sites of metastases (43.0%). CONCLUSION: The study confirmed the validity of serial CA15-3 assays in the early diagnosis of breast metastatic disease. It is worth to emphasize the high sensitivity of the CA15-3 test in detecting bone metastases (100% in patients with scintigraphically diagnosed two or more metastatic lesions), but the group of patients was too small to make our observation conclusive. In none of the studies published previously, the beneficial impact of serial CA15-3 assays during follow-up on survival and quality of life in breast cancer patients was clearly demonstrated. Thus, modifying treatment based solely on increasing marker levels is not recommended.

Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial.

Oral capecitabine (Xeloda) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings pound3653). Societal costs, including patient travel/time costs, were reduced by >75% with capecitabine vs 5-FU/LV (cost savings pound1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK.

Anthracycline-induced cardiotoxicity: clinical course, risk factors, pathogenesis, detection and prevention--review of the literature.

Anthracycline antibiotics are widely used antineoplastic agents and their efficacy for the treatment of various haemopoietic or solid tumours has been well established in clinical practice. Cardiotoxicity is one of the most serious side effects of anthracyclines. The risk of cumulative, life-threatening toxic cardiomyopathy limits their therapeutic potential. In this article, acute, subacute, chronic and late-onset cardiac function impairment associated with anthracycline administration has been characterised. The current views on the methods of detection, pathogenesis and prevention of such toxicity have been reviewed.