Background Several randomized trials have indicated that combination chemotherapy applied in metastatic colorectal cancer (mCRC) does not significantly improve overall survival when compared to the sequential use of cytotoxic agents (CAIRO, MRC Focus, FFCD 2000-05). The present study investigates the question whether this statement holds true also for bevacizumab-based first-line treatment including escalation- and de-escalation strategies. Methods/Design The AIO KRK 0110/ML22011 trial is a two-arm, multicenter, open-label randomized phase III trial comparing the efficacy and safety of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in the first-line treatment of metastatic colorectal cancer. Patients with unresectable metastatic colorectal cancer, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, will be assigned in a 1:1 ratio to receive either capecitabine 1250 mg/m 2 bid for 14d (d1-14) plus bevacizumab 7.5 mg/kg (d1) q3w (Arm A) or capecitabine 800 mg/m 2 BID for 14d (d1-14), irinotecan 200 mg/m 2 (d1) and bevacizumab 7.5 mg/kg (d1) q3w (Arm B). Patients included into this trial are required to consent to the analysis of tumour tissue and blood for translational investigations. In Arm A, treatment escalation from Cape-Bev to CAPIRI-Bev is recommended in case of progressive disease (PD). In Arm B, de-escalation from CAPIRI-Bev to Cape-Bev is possible after 6 months of treatment or in case of irinotecan-associated toxicity. Re-escalation to CAPIRI-Bev after PD is possible. The primary endpoint is time to failure of strategy (TFS). Secondary endpoints are overall response rate (ORR), overall survival, progression-free survival, safety and quality of life. Conclusion The AIO KRK 0110 trial is designed for patients with disseminated, but asymptomatic mCRC who are not potential candidates for surgical resection of metastasis. Two bevacizumab-based strategies are compared: one starting as single-agent chemotherapy (Cape-Bev) allowing escalation to CAPIRI-Bev and another starting with combination chemotherapy (CAPIRI-Bev) and allowing de-escalation to Cape-Bev and subsequent re-escalation if necessary. Trial Registration ClinicalTrials.gov Identifier NCT01249638 EudraCT-No.: 2009-013099-38

PURPOSE:To investigate whether combined-modality treatment (CMT) with two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by extended-field radiotherapy (EF-RT) is superior to EF-RT alone in patients with early favorable Hodgkin's lymphoma (HL).PATIENTS AND METHODS:Between 1993 and 1998, 650 patients with newly diagnosed, histology-proven HL in clinical stages IA to IIB without risk factors were enrolled onto this multicenter study and randomly assigned to receive 30 Gy EF-RT plus 10 Gy to the involved field (arm A) or two cycles of ABVD followed by the same radiotherapy (arm B). Results At a median observation time of 87 months, there was no difference between treatment arms in terms of complete response rate (arm A, 95%; arm B, 94%) and overall survival (at 7 years: arm A, 92%; arm B, 94%; P = .43). However, freedom from treatment failure was significantly different, with 7-year rates of 67% in arm A (95% CI, 61% to 73%) and 88% in arm B (95% CI, 84% to 92%; P <or= .0001). This was due mainly to significantly more relapses after EF-RT only (arm A, 22%; arm B, 3%). No patient treated with CMT experienced relapse before year 3. Relapses were treated mainly with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, or with the combination cyclophosphamide, vincristine, procarbazine, and prednisone/ABVD; treatment of relapse was significantly more successful in arm A than in arm B (P = .017). In total, there were 39 second malignancies, with 21 in arm A and 18 in arm B, respectively. The incidence was approximately 0.8% per year during years 2 to 9 and was highest in older patients (P < .0001) and those with "B" symptoms (P = .012).CONCLUSION:CMT consisting of two cycles of ABVD plus EF-RT is more effective than EF-RT alone.

Background: We designed a dose- and time-intensified high-dose sequential chemotherapy regimen for patients with relapsed and refractory Hodgkin lymphoma (HD).Patients and methods: Eligibility criteria included age 18-65 years, histologically proven primary progressive (PD) or relapsed HD. Treatment consisted of two cycles DHAP (dexamethasone, high-dose cytarabine, cisplatinum); patients with chemosensitive disease received cyclophosphamide followed by peripheral blood stem cell harvest; methotrexate plus vincristine, etoposide and BEAM plus peripheral blood stem cell transplantation (PBSCT).Results: A total of 102 patients (median age 34 years, range 18-64) were enrolled. The response rate was 80% (72% complete response, 8% partial response). With a median follow-up of 30 months (range 3-61 months), freedom from second failure (FF2F) and overall survival (OS) were 59% and 78% for all patients, respectively. FF2F and OS for patients with early relapse were 62% and 81%, for late relapse 65% and 81%; for PD 41% and 48%, and for multiple relapse 39% and 48%, respectively. In multivariate analysis response after DHAP (P < 0.0001) and duration of first remission (PD and multiple relapse versus early and late relapse; P = 0.0127) were prognostic factors for FF2F. Response after DHAP (P < 0.0081), duration of first remission (P = 0.0017) and anemia (P = 0.019) were significant for OS.Conclusion: Based on the promising results of this study, a prospective randomized European inter-group study was started comparing this intensified regimen with two courses of DHAP followed by BEAM (HD-R2 protocol).

The purpose of this report is to determine the value of a central specialist radiologic review and to determine the image quality of computed tomography (CT) in Hodgkin disease. The HD12 protocol is a multicenter prospective randomized trial of the GHSG for advanced stages of Hodgkin disease. The indication and effectiveness of additional radiotherapy (30 Gy), in the area of initial bulky disease and of residual disease, following intensive chemotherapy using the BEACOPP schema (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone), is to be investigated. A multidisciplinary panel of radiation oncologists, radiologists, and medical oncologists reviews, blinded to treatment arms, the diagnostic imaging with comparison to the documentation forms. For patients with poor response to chemotherapy, the panel recommends radiotherapy independent of the randomization. This procedure guarantees that patients with a poor response to chemotherapy receive additional radiotherapy. Furthermore, the panel evaluates the quality of CT examinations in this multicenter study. Since July 1999, a total of 2607 CT of 371 patients have been evaluated. Helical CT showed significantly higher contrast enhancement and imaging quality than conventional CT (P < 0.001). CT from university hospitals was assessed as superior to that from other institutions (P < 0.001). Compared with the written disease documentation by the study centers, the panel assessed different extensions of disease in 814 of 2607 CT (31%), resulting in a change of stage in 17 of 371 patients (5%). After chemotherapy, 167 of 371 patients (45%) showed residual disease (>1.5 cm), and for 53 of 371 patients (14%) the panel recommended additional radiotherapy independent of the randomization arm. Patients with Hodgkin disease receive high-quality CT imaging. A central independent multidisciplinary panel markedly improves quality assurance for these study patients.

By Eckhart Dühmke, Jeremy Franklin, Michael Pfreundschuh, Susanne Sehlen, Norman Willich, Ursula Rühl, Rolf-Peter Müller, Peter Lukas, Anton Atzinger, Ursula Paulus, Bernd Lathan, Ulrich Rüffer, Markus Sieber, Jürgen Wolf, Andreas Engert, Axel Georgii, Susanne Staar, Richard Herrmann, Maria Beykirch, Hartmut Kirchner, Adelheid Emminger, Richard Greil, Esther Fritsch, Peter Koch, Angelika Drochtert, Oana Brosteanu, Dirk Hasenclever, Markus Loeffler, and Volker Diehl

Intermediate stage Hodgkin's disease (HD) is defined as nodal disease with certain clinical risk factors. Patients with intermediate stage HD qualify for a combination of chemo- and radiotherapy, since radiotherapy alone results in a high relapse rate. The precise definition of this group varies between trial groups. It is generally believed that such patients should receive 4–6 cycles of modern multidrug chemotherapy and in addition radiotherapy of the involved field or the extended field. With modern combination therapy, about 70–80% of the patients in this group can be cured. However, the combination of the number of chemotherapy cycles, the field sizes and the dosage of radiation within these fields are not clear. Current clinical studies try to reduce radiation dose and field without compromising treatment efficacy in order to reduce late toxicities.