To evaluate frequency and severity of adverse drug reactions (ADRs) and its economic consequences after standard dose (immuno-)chemotherapy (CT) of non-small-cell lung cancer (NSCLC).

BACKGROUND:Multidrug chemotherapy (CT) is still associated with relevant side-effects. We assessed, under current practice patterns, frequency and severity of CT-induced toxicity and its economic consequences.PATIENTS AND METHODS:Prospective, multicentre, longitudinal, observational cohort study with lymphoproliferative disorder (LPD) and non-small-cell lung cancer (NSCLC) patients, receiving first- or second-line (immuno-) CT (excluding myeloablative CT). Data were collected from patient interviews and preplanned chart reviews. Costs in 2007 euros are presented from the provider perspective.RESULTS:Two hundred and seventy-three patients (n = 153 LPD; n = 120 NSCLC) undergoing a total of 1004 CT cycles were assessable (age ≥65 years, 40%; female, 36%; Eastern Cooperative Oncology Group performance status ≥2, 11%; tumour stage ≥III, 56%; history of comorbidity, 80%). Fifty percent of cycles were associated with grade 3/4 toxicity and 37% (n = 371) with at least one hospital stay (outpatient/day care n = 154; intensive care n = 19). Mean (median) toxicity-related costs amounted to €1032 (€86) per cycle. Costs rose exponentially with the number of grade 3/4 adverse drug reactions (ADRs) and were highest in cycles affected by more than four ADRs, €10 881 (€5455); in cycles with intensive care, €14 121 (€8833); and in cycles affected by grade 3/4 infections and febrile neutropenia/leukopenia, €7093 (€4531) and €5170 (€2899), respectively. Five percent of CT cycles accounted for 56% of total expenses.CONCLUSIONS:Individualised supportive care strategies are needed. Future research should focus on identifying toxicity clusters and patient characteristics predictive for high costs.

20651 Background: FN is the most frequent dose-limiting toxicity of myelosuppressive chemotherapy (CT). To date there are few data on the costs of FN management in Germany. Methods: Prospective, multicentre, observational, longitudinal study with lymphoma, non small cell lung cancer (NSCLC) and primary breast cancer (PBC) patients (pts). Pts were enrolled consecutively at the start of 1st or 2nd line (immuno-)CT in 4 German hospitals (01/05–12/06). FN was defined as fever >38ºC and ANC <1 × 109/L. If nadir ANC was unavailable, febrile leukopenia (FL) was assessed (fever >38ºC and LC <2 × 109/L). Clinical and resource use data were collected from medical charts. FN associated costs are presented from the provider perspective. Results: Medical charts from 325 pts (47% lymphoma; 37% NSCLC; 16% PBC; 46% women; 38% age ≥65 yrs) were reviewed. FN/FL occurred in 22% of lymphoma, 8% of NSCLC, 27% of PBC and 18% of all pts. In total, 68 FN/FL episodes were identified in 58 pts (see table). Fifty-five FN/FL episodes were associated with ≥1 hospital stay (lymphoma n=34, NSCLC n=10, PBC n=11). Mean±SD cost per FN/FL episode requiring hospital treatment amounted to €3950±4961 (95% CI: 2569, 5331) and varied between €4808±5839 for lymphoma (95% CI: 2666, 6949), €3627±4120 for NSCLC (95% CI: 680, 6574) and €1827±795 for PBC (95% CI: 1293, 2361). Basic hospital costs represented 55% of total costs in lymphoma, 71% in NSCLC and 83% in PBC. Drug treatment made up 22% of total costs in lymphoma, 11% in NSCLC and 9% in PBC pts. Diagnostics generated 8–11% of total direct costs. Conclusions: FN/FL costs vary by tumour type and are highest for pts with lymphoma. Main cost drivers are hospitalisation and drugs. FN/FL pts (%) All (n=58) Lymphoma (n=35) NSCLC (n=9) PBC (n=14) Regimen 54% CHOP-like 80% platinum-based 100% anthracycline-based Female 33 (57) 16 (46) 3 (33) 14 (100) Age ≥ 65 22 (38) 16 (46) 3 (33) 3 (21) ECOG ≥ 2 6 (10) 4 (11) 2 (22) 0 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Amgen Amgen Amgen, Eli Lilly

20715 Background: Myelosuppression is one of the most relevant side effects of cancer chemotherapy (CT). To date its impact on blood component (BC) use and cost is not well characterised. Methods: Prospective, observational study to determine BC use and associated costs in NSCLC and lymphoma patients (pts). Pts were enrolled consecutively at the start of 1st or 2nd line (immuno-)CT at an academic cancer center in Germany (01/05–06/06). Pts receiving myeloablative CT with peripheral blood stem cell support were excluded. Clinical data and consumption of BC were collected from medical charts. Costs of BC are presented from provider perspective. Results: 180 pts undergoing 633 CT cycles were evaluable (Mean age 59 yrs, 47% NSCLC, 53% lymphoma, 68% stage III/IV, 86% ECOG ≤1). During 11% of CT cycles BC were transfused to 27% of pts (n=49; lymphoma n=22; NSCLC n=27). Fourty six pts (26%) were substituted with red blood cells (RBC), 8 (4%) and 3 (2%) with platelets (PLT) and fresh frozen plasma (FFP). In total, 310 units of blood were consumed (210 RBC, 49 PLT and 51 FFP). Mean number of transfused units (TU) per patient with transfusion amounted to 6.3±5.2 and varied between 4.3±4.9 for NSCLC and 8.9±16.0 for lymphoma pts. The table shows mean BC costs per patient with transfusion stratified by tumour type. Conclusions: Haematotoxicity has significant impact on BC use and associated costs in NSCLC and lymphoma pts. In lymphoma pts BC costs are higher than in pts with NSCLC. Number of TU is highest for RBC. BC costs are highest for pts with PLT transfusion. All (n=49) Lymphoma (n=22) NSCLC (n=27) Total 626.0 (1,484.0) 1,009.7 (2,136.6) 314.0 (391.4) RBC 309.7 (266.9) 389.5 (353.7) 248.4 (155.5) PLT 1,831.5 (2,465.6) 2,193.7 (2,793.1) 745.0 (632.2) FFP 596.3 (462.3) 630.5 (648.4) 548.0 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Amgen, Eli Lilly

7533 Background: Radioimmunotherapy (RIT) has demonstrated high clinical efficacy in follicular lymphoma but varying results in mantle cell lymphoma (MCL). Methods: We performed a comparative analysis of two phase II studies with similar inclusion criteria to identify potential predictors of response. 32 patients with relapsed or refractory MCL, WHO performance status ≤2, appropriate hematopoesis (ANC > 1,500/mm3, platelets > 100,000/mm3) and adequate function of liver and kidneys were treated with RIT upfront (Arm A, n = 16) or as consolidation after initial cytoreduction (Arm B, n = 16). 28 patients (88%) had been previously treated with rituximab. Patients with >25% bone marrow involvement, known CNS lymphoma, HIV infection or other severe concurrent disease were excluded. Ibritumomab tiuxetan (Zevalin) was applied at a dose of 15 MBq 90Y/kg, whereas patients with reduced platelet counts (<150,000/mm3) received 11 MBq 90Y/kg. Results: The median age was 66.9 years (range 58–72) in Arm A and 63.1 years (range 45–79) in Arm B. The median number of prior regimens was 4 (range 2–6) in Arm A and 1 (1–5) in Arm B. RIT treatment was generally well tolerated with the most common toxicities being hematologic. Thrombocytopenia grade 3 and 4 was observed in 69% of patients, one patient died of hemorrhagic stroke. Granulocytopenia grade 4 occurred in 34% of patients, one patient developed a grade 4 infectious complication. Currently 22 patients are evaluable for response rate and duration of remission (DR). In Arm A a partial response (PR) was observed in 2 of 6 evaluable patients (33.3%) with a median DR of 3.9 months only. In Arm B chemoinduction achieved 2 complete responses (CR) and 14 PR. Following RIT seven of 14 PR patients (50%) converted to CR. Currently, 13 of 16 patients (81%) are still in remission. As expected the most important adverse risk factor was bulky disease before RIT with no responses seen in this patient population. Patients with less prior therapeutic lines (< 2) had significantly higher response rates. Conclusions: In future trials, RIT should be applied earlier in the treatment algorithm of MCL after a debulking strategy with combined immuno-chemotherapy. [Table: see text]

Behandlungszufriedenheit ist ein entscheidendes Qualitätsmerkmal und ein wichtiger Einflussfaktor im Verlauf einer Tumorerkrankung. Wir beschäftigten uns prospektiv mit dem Effekt einer 10-stündigen interdisziplinären Psychoedukation auf die Behandlungszufriedenheit. Tumorpatienten wurden zu Themen wie Strahlentherapie, Chemotherapie, Ernährung, Entspannung und Krankheitsbewältigung von Ärzten und Psychologen informiert. Ingesamt nahmen 294 Tumorpatienten (44,2% Männer; 55,8% Frauen; mittl. Alter 58,5; MammaCa 33,8%) über 5 Jahre teil und wurden randomisiert entweder der Interventionsgruppe (N=160) oder der Kontrollgruppe (N=134), die eine gewöhnliche Behandlung bekam, zugeordnet. Das Ausmaß an Behandlungszufriedenheit, Angst, Depression, Lebensqualität und Krankheitsbewältigung wurde zu Beginn des Kurses (t0), nach 2 (t1) sowie nach 4 Monaten (t2) mit validierten Instrumenten erhoben. Im Vergleich zur Kontrollgruppe zeigte die Interventionsgruppe einen signifikant höheren Anstieg der Behandlungszufriedenheit (p=0,05). Zudem konnte ermittelt werden, dass eine hohe Behandlungszufriedenheit mit weniger Angst (t1: p=-.43;t2: p=-.38), weniger Depression (t1: p=-.58;t2: p=-.52), mit einem Anstieg auf einzelnen Subskalen der Lebensqualität, z.B. Globaler Gesundheitszustand (t1: p=0,38;t2: p=0,26) und verschiedenen Funktionsskalen (t1: p=0,29-0,38) nach 2 und 4 Mo. einhergeht. Eine höhere Behandlungszufriedenheit korrelierte signifikant mit effektiveren Strategien der Krankheitswältigung, wie z.B. soziale Integration (t1: p=0,50;t2: p=0,44). Dementsprechend zeigte die Interventionsgruppe eine Reduktion von Angst und körperlichen Symptomen, eine Verbesserung der Gesundheit sowie sozialer Fertigkeiten zu t1 und t2. Zusammengefasst konnte nachgewiesen werden, dass bereits eine kurze interdisziplinäre Psychoedukation eine höhere Behandlungszufriedenheit, eine Verbesserung der Lebensqualität, des psychischen Befindens und der Krankheitsbewältigung ohne zusätzlichem Kostenaufwand bewirkt.

Radioimmunotherapy (RIT) was approved for the treatment of relapsed or refractory CD20-positive follicular lymphoma (FL), subsequent to rituximab containing primary therapy. However, an increasing number of clinical studies have suggested that RIT may be more efficacious in an earlier phase of the disease. Therefore, a consensus meeting was held in May 2005 to define the optimal setting of RIT in the therapeutic algorithm of patients with advanced stage of FL. RIT is an established therapeutic option in relapsed FL. According to the reviewed data, RIT should be preferably used as consolidation after initial tumor debulking. First-line RIT may be applied in patients not appropriate for chemotherapy induction. Current study concepts evaluate the role of RIT consolidation in combination with antibody maintenance to achieve a potentially curative approach even in patients with advanced stage disease.

Single agent bortezomib treatment yields ≥ partial responses (PR) in 24% of patients with relapsed, refractory multiple myeloma (MM) and 38% of patients who had received 1 – 3 previous therapies. Dexamethasone (DEX) adds to anti-myeloma activity of bortezomib. The present phase II trial was intitiated to study bortezomib combined with DEX and continuous low-dose oral cyclophosphamide (CY).

Radioimmunotherapy (RIT) has demonstrated high clinical efficacy in the treatment of B-cell non-Hodgkin's lymphoma (B-NHL) and has been approved for relapsed indolent and transformed B-NHL. However little is known about RIT with Zevalin® in patients with mantle cell lymphoma (MCL), a lymphoma subtype characterized by indolent morphology but aggressive clinical course with a median survival of only 3– 4 years and virtually no long-time survivors. Patients with relapsed or refractory CD20 positive MCL after/not appropriate for ASCT, WHO performance status <2, age < 75 years and adequate function of the bone marrow (ANC >1,500/mm3, platelets >100,000/mm3), liver and kidneys were eligible for this trial. Patients were excluded if they had > 25% bone marrow involvement, prior allogeneic stem cell transplantation or RIT, known CNS lymphoma, HIV infection or other concurrent severe medical disease. Patients with normal platelet counts received a dose of Zevalin® at 14.8 MBq 90Y/kg (to a maximum dose of 1,184 MBq), whereas those with platelet counts <150,000/mm3 received 11.1 MBq 90Y/kg. Currently, 14 patients have been enrolled and 6 are eligible for evaluation of treatment response. The median age was 68 years (range 56 – 71), 9 patients were male. All patients had been previously treated with Rituximab containing regimens. The median number of prior regimens was 4 (range 2–6). Zevalin® treatment was generally well tolerated, with the most common toxicities being hematologic. Thrombocytopenia grade 3 and 4 was observed in 2 and 4 patients, respectively, without significant bleeding complications. Granulocytopenia grade 3 and 4 occurred in 3 and 2 patients, respectively and 1 patient developed a grade 4 infectious complication. This patient also developed non-hematologic toxicities grade 3 and 4 consisting of sepsis-associated hepatotoxicity, diarrhoea and pleural empyema. Partial responses were observed in 2 of 6 patients (33.3 %), another patient experienced a stable disease. Median progression free survival (PFS) was 3.9 months in this high risk group. Preliminary analysis suggests that patients with bulky disease did not respond to radioimmunotherapy. The clinical course of the total group of this ongoing trial will be presented at the meeting. The observed responses to Zevalin® in heavily pretreated patients with MCL are promising, however median PFS was short-lived. Thus, a prior debulking strategy with combined immuno-chemotherapy is recommended to potentially achieve a longer duration of remission. Accordingly, in future trials RIT should be applied earlier in the treatment algorithm of MCL.

This guideline is a prerequisite for the quality management in the treatment of non-Hodgkon-lymphomas in patients with relapsed or refractory follicular lymphoma after rituximab therapy and as consolidation therapy after first remission following CHOP like treatment using radioimmunotherapy. It is based on an interdisciplinary consensus and contains background information and definitions as well as specified indications and detailed contraindications of treatment. Essential topics are the requirements for institutions performing the therapy. For instance, presence of an expert for medical physics, intense cooperation with all colleagues committed to treatment of lymphomas, and a certificate of instruction in radiochemical labelling and quality control are required. Furthermore, it is specified which patient data have to be available prior to performance of therapy and how treatment has to be carried out technically. Here, quality control and documentation of labelling are of great importance. After treatment, clinical quality control is mandatory (work-up of therapy data and follow-up of patients). Essential elements of follow-up are specified in detail. The complete treatment inclusive after-care has to be realised in close cooperation with those colleagues (hemato-oncologists) who propose, in general, radioimmunotherapy under consideration of the development of the disease.

OBJECTIVES:We prospectively evaluated the effects of a six-session psychoeducational intervention held by medical doctors or psychologists in a German acute cancer center setting.METHODS:A cluster randomization was used to assign n=108 oncologic patients (55 female, 53 male; mean age=58.5) to the intervention or the control group. The self-rated amount of information about cancer-specific topics, quality of life (EORTC), coping (TSK) and anxiety and depression (HAD-S) were measured at the beginning of the intervention (t0) as well as two and four months later (t1).RESULTS:At t1 the level of information related to different aspects of cancer (p<0.01) and "emotional functioning" (EORTC; p<0.05) were clearly improved in the intervention vs. the control group. At t2 intervention group patients again showed an increased level of information (p<0.05) and more emotional stability (p<0.05). In addition, reduced rumination was seen in patients of the intervention but not the control group (TSK; p=0.01).CONCLUSION:This study provides evidence that even short interdisciplinary psychoeducational interventions can at least improve the level of cancer-related information while hardly denting the budget of any healthcare system.