Aktuelle Fortschritte in der Therapie maligner Erkrankungen

In der Therapie maligner Erkrankungen sind in jüngster Zeit wesentliche Fortschritte erzielt worden. Sie basieren zum einen auf neuen Erkenntnissen zur Pathogenese maligner Tumoren und zur Biologie des Tumorwachstums und zum anderen auf innovativen anti-neoplastischen Medikamenten, die über neue und spezifischere Wirkmechanismen verfügen. Darüber hinaus sind konventionelle Konzepte der Chemotherapie optimiert und supportive Maßnahmen verbessert worden.

Die Entwicklung neuer antineoplastischer Medikamente hat sich in den letzten wenigen Jahren im Wesentlichen auf zwei unterschiedliche Wirkmechanismen konzentriert: auf molekulare Substanzen, die auf unterschiedliche Weise in die Signalübertragung maligner Zellen eingreifen und auf monoklonale Antikörper, die gegen auf Tumorzellen exprimierte Antigene gerichtet sind oder die Tumor-Angiogenese zum Ziel haben.

Literatur

• 1 Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, Giacchetti S, Paule B, Kunstlinger F, Ghemard O, Levi F, Bismuth H. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival.  Ann Surg. 2004;  240 644-657
• 2 Coiffier B, Lepage E, Briere J. et al . CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma.  N Engl J Med. 2002;  346 235-242
• 3 Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer.  N Engl J Med. 2004;  351 337-345
• 4 Deininger M, Buchdunger E, Druker B J. The development of imatinib as a therapeutic agent for chronic myeloid leukemia.  Blood. 2005;  105 2640-2653
• 5 Elter T, Borchmann P, Schulz H, Reiser M, Engert A. FluCam - a new, 4-weekly combination of fludarabine and alemtuzumab for patients with relapsed chronic lymphocytic leukaemia.  Blood. 2004;  104 690a
• 6 Forstpointner R, Dreyling M, Repp R. et al . The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared to FCM alone in patients with relapsed and refractory follicular and mantel cell lymphomas - results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG).  Blood. 2004;  104 3064-3071
• 7 Giantonio B J, Catalano P J, Meropol N J, O’Dwyer P J, Mitchell E P, Alberts S R, Schwartz M A, Benson A B. High-dose bevacizumab improves survival when combined with FOLFOX4 in previously treated advanced colorectal cancer: Results from the Eastern Cooperative Oncology Group (ECOG) study E3200.  Proc Am Soc Clin Oncol. 2005;  24 2
• 8 Grothey A, Sargent D, Goldberg R M, Schmoll H J. Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment.  J Clin Oncol. 2004;  22 1209-1214
• 9 Herold M, Pasold R, Srock S. et al . Results of a prospective randomised open label phase III study comparing rituximab plus mitoxantrone, chlorambucil, prednisolone chemotherapy (R-MCP) versus MCP alone in untreated advanced indolent non-Hodgkin’s lymphoma (NHL) and mantle-cell-lymphoma (MCL).  Blood. 2004;  104 584a
• 10 Hiddemann W, Kneba M, Dreyling M H. et al . Front-line therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) significantly improves the outcome of patients with advanced stage follicular lymphomas as compared to CHOP alone - results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG).  Blood. 2005;  105 im Druck
• 11 Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.  N Engl J Med. 2004;  350 2335-2342
• 12 Kabbinavar F F, Schulz J, McCleod M, Patel T, Hamm J T, Randolph Hecht J, Mass R, Perrou B, Nelson B, Novotny W F. Addition of Bevacizumab to Bolus Fluorouracil and Leucovorin in First-Line Metastatic Colorectal Cancer: Results of a Randomized Phase II Trial.  J Clin Oncol. 2005;  23 1-9
• 13 Kaminski M S, Tuck M, Estes J. et al . ¹³¹I-tositumomab therapy as initial treatment for follicular lymphoma.  N Engl J Med. 2005;  352 441-449
• 14 Keating M J, Flinn I, Jain V. et al . Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study.  Blood. 2002;  99 3554-3561
• 15 Lundin J, Kimby E, Bjorkholm B. Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL).  Blood. 2002;  100 768-773
• 16 Marcus R, Imrie K, Belch A. et al . CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma.  Blood. 2005;  105 1417-1423
• 17 Meyerhardt J A, Mayer R J. Systemic therapy for colorectal cancer.  N Engl J Med. 2005;  352 476-487
• 18 Rai K R, Freter C E, Mercier R J. Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine.  J Clin Oncol. 2002;  20 3891-3897
• 19 Salles G, Foussard C, Nicolas M. et al . Rituximab added to aIFN+CHVP improves the outcome of follicular lymphoma patients with a high tumor burden: First analysis of the GELA-GOELAMS FL-2000 randomized trial in 359 patients.  Blood. 2004;  104 160a
• 20 Tallman M S, Gilliland D G, Rowe J M. Drug therapy of acute myeloid leukemia.  Blood. 2005;  105 im Druck
• 21 Witzig T E, Gordon L I, Cabanillas F. et al . Randomized controlled trial of yttrium-90-labeled Ibritumomab Tiuxetan radioimmunotherapy versus Rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma.  J Clin Oncol. 2002;  20 2453-2463