Bernhard Heinrich

Fine Needle Aspiration Cytology and Flow Cytometry in the Diagnosis and Subclassification of Non-Hodgkin’s Lymphoma Based on the World Health Organization Classification

OBJECTIVEnTo determine the usefulness of fine needle aspiration cytology (FNAC) in combination with flow cytometry on the new World Health Organization (WHO) classification of malignant lymphoma.nnnSTUDY DESIGNnSmears and flow cytometry reports of patients who underwent both methods at the same time were independently examined. Both methods were classified according to the new WHO classification of malignant lymphoma.nnnRESULTSnA group of 131 smears were examined. In 89 cases exact diagnosis was made by cytomorphology. Twenty-five cases were not classified exactly or were classified incorrectly, resulting in a sensitivity of 96.4% and a specificity of 85%. With flow cytometry, only 30 of 131 patients could be classified exactly, resulting in a sensitivity of 27% and specificity of 100%, respectively. The combination of methods showed a sensitivity of 85% and specificity of 100%.nnnCONCLUSIONnThe combination of FNAC and flow cytometry obtained by FNAC can distinguish between benign and malignant lymphoid infiltrates and support a diagnosis of lymphoma.

A Randomised Phase 2 Study Combining LY2181308 Sodium (Survivin Antisense Oligonucleotide) with First-line Docetaxel/Prednisone in Patients with Castration-resistant Prostate Cancer

Castration-resistant prostate cancer (CRPC) is partially characterised by overexpression of antiapoptotic proteins, such as survivin. In this phase 2 study, patients with metastatic CRPC (n=154) were randomly assigned (1:2 ratio) to receive standard first-line docetaxel/prednisone (control arm) or the combination of LY2181308 with docetaxel/prednisone (experimental arm). The primary objective was to estimate progression-free survival (PFS) for LY2181308 plus docetaxel. Secondary efficacy measures included overall survival (OS), several predefined prostate-specific antigen (PSA)-derived end points, and Brief Pain Inventory (BPI) and Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores. The median PFS of treated patients for the experimental arm (n=98) was 8.64 mo (90% confidence interval [CI], 7.39-10.45) versus 9.00 mo (90% CI, 7.00-10.09) in the control arm (n=51; p=0.755). The median OS for the experimental arm was 27.04 mo (90% CI, 19.94-33.41) compared with 29.04 mo (90% CI, 20.11-39.26; p=0.838). The PSA responses (≥ 50% PSA reduction), BPI, and FACT-P scores were similar in both arms. In the experimental arm, patients had a numerically higher incidence of grades 3-4 neutropenia, anaemia, thrombocytopenia, and sensory neuropathy. In conclusion, this study failed to detect a difference in efficacy between the two treatment groups.

Interim results of a randomized phase II study with window-design to evaluate antitumor activity of the survivin antisense oligonucleotide (ASO) LY2181308 in combination with docetaxel for first-line treatment of castrate-resistant prostate cancer (CRPC).

4592 Background: Survivin is a member of the inhibitor of apoptosis proteins (IAP). Its expression in prostate cancer is associated with resistance to taxanes and poor outcome. LY2181308 reduces survivin expression and consequently is expected to improve activity of taxanes, such as docetaxel. A randomized phase II study was conducted to assess the activity of the combination.nnnMETHODSn150 patients were randomized to standard docetaxel/prednisone every 21 days (Arm A) or LY2181308 as a 3-hour IV loading dose on three consecutive days followed by weekly 3-hr IV maintenance doses (Arm B). The experimental arm also included a window of monotherapy of LY2181308 equivalent to a 21-day cycle of docetaxel prior to starting combined treatment. There were two planned interim analyses, after 20 and 60 patients respectively, to assess safety and futility. The primary endpoint is progression-free-survival (PFS).nnnRESULTSnThe addition of LY2181308 to standard first-line treatment in CRPC showed no significant increase in toxicity compared to docetaxel treatment alone. Neutropenia grade 3/4 was observed in 11/40 (23%) in Arm B versus 2/20 (10%) in Arm A. There was no febrile neutropenia, grade 3/4 anemia or thrombocytopenia in either arm. The only important difference for Arm B was grade 1/2 thrombocytopenia (17/40; 43%) and anemia (13/40; 33%), which was not present in Arm A. Toxicity of LY2181308 in the window period was mild (nonhematologic grade 1/2 toxicities) as previously described. These toxicities were manageable, and did not increase with addition of docetaxel. The PK profile for both docetaxel and LY2181308 was as previously described.nnnCONCLUSIONSnThe manageable toxicity profile of the combination of LY2181308 and docetaxel justified continuation of the phase II study. Enrollment of 150 patients has been completed and PFS data are expected in 2011.

[Chemotherapy is better than its reputation: important developments within the last decades].

Die Angst der Patienten vor Nebenwirkungen der Chemotherapie wie Ubelkeit, Erbrechen und erhohte Infektanfalligkeit ist immer noch sehr gros. Doch Fortschritte der Supportivtherapie haben beeindruckende Verbesserungen gebracht. Wie vertraglich die Chemotherapie heute ist und welche Fortschritte es bei der Behandlung gibt, schildert der nachfolgende Beitrag.Die Angst der Patienten vor Nebenwirkungen der Chemotherapie wie Übelkeit, Erbrechen und erhöhte Infektanfälligkeit ist immer noch sehr groß. Doch Fortschritte der Supportivtherapie haben beeindruckende Verbesserungen gebracht. Wie verträglich die Chemotherapie heute ist und welche Fortschritte es bei der Behandlung gibt, schildert der nachfolgende Beitrag.