BEC2

[alisa]

Sehr geehrter Prof. Wust,

meine Mutter, die ja am kleinzelligen Bronchialkarzinom erkrankt ist, hat nun evtl. die Möglichkeit an einer Studie zum Medikament BEC2 teilzunehmen. Das, was man über diese Art der Therapie hier im Internet liest, hört sich sehr hoffnungsvoll an, zumal das Wirkungsprinzip sich sehr logisch und nachvollziehbar anhört.
Mich würde nun einfach mal interessieren, wie Sie die Entwicklung dieser Therapieform einschätzen.
Denken Sie, man kann der offiziellen wissenschaftlichen Ausführung des Projektleiters der ersten zwei Studienphasen in Amerika trauen oder muß man (leider) die Befürchtung haben, daß die Ergebnisse beschönigt sind und leider nicht der Realität entsprechen??? Konkret: Lohnt es sich, die "Strapazen" einer zusätzlichen BEC2-Therapie (nach Bestrahlung + Chemo) auf sich zu nehmen?
Sie äußern sich des öfteren über bestimmte Kliniken. Denken Sie, daß wir in Bochum "gut aufgehoben" sind, was die Studie betrifft? Oder ist für eine Studie die Wahl der Klinik relativ egal, da sie überall gleich durchgeführt werde muß?

Eine Frage noch zum Schluß:
Voraussetzung für die Teilnahme an der Studie ist, daß noch keine Metastasen vorhanden sind. Das war vor der Chemo, also bei der letzten CT der Fall. Wie groß ist die Wahrscheinlichkeit, daß nach der Chemo in der Zeit der Bestrahlung Metastasen auftauchen? Die Studie würde ja erst nach Abschluß der "Standard-Therapie" stattfinden, also erst nach der Bestrahlung. Können in dieser Zeit Metastasen wachsen? Diese Frage stelle ich mir immer und immer wieder, da ja dann der "Hoffnungsschimmer", die Teilnahme an der Studie, vielleicht zerstört wird...

Für die Antwort schon einmal vielen Dank im voraus!

[Prof. Wust]

RE: BEC2


Sicher handelt es sich hier um eine Chance. Wenn man alles versuchen will, sollte man es tun. Das hängt wirklich hauptsächlich vom Patienten ab (es gibt sog. Kämpfer, die alles in Anspruch nehmen, aber auch andere Patienten). Geprüft wird hier ein Antikörper. Die Studie wird, wie Sie selbst vermuten, überall standardisiert durchgeführt. Daher dürfte der Ort, soweit es sich um eine größere onkologische Abteilung handelt, das Therapieergebnis nicht beeinflussen.
Das in so kurzer Zeit nach Chemotherapie schon Metastasen da sind, ist kaum anzunehmen. Also geht es jetzt um die Behandlung der eventuell noch vorhandenen residuellen Erkrankung. Das geht zur Zeit mit einem solchen Ansatz. Ob das Prinzip erfolgreich ist, kann man zur Zeit noch nicht sicher beantworten. Es gibt aber Hoffnung aus neueren Untersuchungen. Natürlich sieht man die Ergebnisse als Untersucher eher optimistisch. Aber er wünscht sich positive Wirkung ebenso wie der Patient. Also versuchen Sie es.
Lesen Sie selbst die angehängten Zusammenfassungen aus neueren Publikationen.

Long survival of patients with small cell lung cancer after adjuvant treatment with the anti-idiotypic antibody BEC2 plus Bacillus Calmette-Guerin.
AU: Grant,-S-C; Kris,-M-G; Houghton,-A-N; Chapman,-P-B
AD: Department of Medicine, Memorial Sloan-Kettering Cancer Center and Joan and Sanford I. Weill Medical College of Cornell University, New York, New York 10021, USA.
SO: Clin-Cancer-Res. 1999 Jun; 5(6): 1319-23
*LHM: Volltext ab 5 (1999) 4 -> siehe Homepage der Bibliothek
Mitte : Innere Medizin : 1 (1995) -
Sign: Z 03 /129
Wedding : Med. Bibliothek : 1 (1995) -
Sign: Z IV c 87
IS: 1078-0432
PY: 1999
LA: English
CP: UNITED-STATES
AB: Despite active therapies for small cell lung cancer (SCLC), most patients relapse and die of the disease. The present study evaluates immunization using the anti-idiotypic antibody BEC2, which mimics the ganglioside GD3 expressed on the surface of most SCLC tumors, combined with Bacillus Calmette-Guerin (BCG) as an immune adjuvant. We hypothesized that active im-munization could alter the natural history of the disease. Fifteen patients who had completed standard therapy for SCLC received a series of five intradermal immunizations consisting of 2.5 mg of BEC2 plus BCG over a 10-week period. Blood was collected for serological analysis, and outcome was monitored. All patients developed anti-BEC2 antibodies, despite having received chemotherapy with or without thoracic radiation. We detected anti-GD3 antibodies in five pati-ents, including those with the longest relapse-free survival. The median relapse-free survival for patients with extensive stage disease is 11 months and has not been reached for patients with limited stage disease (>47 months), with only one of seven patients having relapsed after a me-dian follow-up of 47 months. Immunization of patients with SCLC after standard therapy using BEC2 plus BCG can induce anti-GD3 antibodies and is safe. The survival and relapse-free sur-vival in this group of patients are substantially better than those observed in a prior group of si-milar patients. A Phase III trial is being conducted to evaluate BEC2 plus BCG as adjuvant therapy after chemotherapy and irradiation.
MESH: *Adjuvants,-Immunologic-therapeutic-use; *Antibodies,-Anti-Idiotypic-therapeutic-use; *BCG-Vaccine-therapeutic-use; *Carcinoma,-Small-Cell-therapy; *Lung-Neoplasms-therapy
MESH: Adjuvants,-Immunologic-adverse-effects; Adult-; Aged-; Antibodies,-Anti-Idiotypic-adverse-effects; Carcinoma,-Small-Cell-immunology; Carcinoma,-Small-Cell-mortality; Disease-Free-Survival; Gangliosides-immunology; IgG-blood; IgM-blood; Immunotherapy,-Active; Lung-Neoplasms-immunology; Lung-Neoplasms-mortality; Middle-Age; Survival-Rate
TG: Female; Human; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: Clinical-Trial; Journal-Article
SH: adverse-effects; therapeutic-use; immunology; mortality; therapy; blood
RN: 0; 0; 0; 0; 0; 0; 62010-37-1
NM: Adjuvants,-Immunologic; Antibodies,-Anti-Idiotypic; BCG-Vaccine; Gangliosides; IgG; IgM; ganglioside,-GD3
CN: CA33409CANCI
SB: Index-Medicus
UD: 20001218
AN: 99316776
XREC: ABSTRACT (AB)

2 of 3
TI: Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemo-therapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.
AU: Krug,-L-M; Grant,-S-C; Miller,-V-A; Ng,-K-K; Kris,-M-G
Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, New York, NY 10021, USA.
SO: Semin-Oncol. 1999 Oct; 26(5 Suppl 15): 55-61
*LHM: Mitte : Innere Medizin : 18 (1991) -
Sign: Z 03 /189
Wedding : Med. Bibliothek : 4 (1977) - [L:10]
Sign: Z IV c 22
IS: 0093-7754
PY: 1999
English
CP: UNITED-STATES
AB: In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three po-tential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

Immunogenicity of a fucosyl-GM1-keyhole limpet hemocyanin conjugate vaccine in patients with small cell lung cancer.
AU: Dickler,-M-N; Ragupathi,-G; Liu,-N-X; Musselli,-C; Martino,-D-J; Miller,-V-A; Kris,-M-G; Bre-zicka,-F-T; Livingston,-P-O; Grant,-S-C
AD: Department of Medicine, Memorial Sloan-Kettering Cancer Center and Cornell University Medical College, New York, New York 10021, USA.
SO: Clin-Cancer-Res. 1999 Oct; 5(10): 2773-9
*LHM: Volltext ab 5 (1999) 4 -> siehe Homepage der Bibliothek
Mitte : Innere Medizin : 1 (1995) -
Sign: Z 03 /129
Wedding : Med. Bibliothek : 1 (1995) -
Sign: Z IV c 87
1078-0432
PY: 1999
LA: English
CP: UNITED-STATES
AB: Although small cell lung cancer (SCLC) is highly responsive to chemotherapy, relapses are common, and most patients die within 2 years of diagnosis. After initial therapy, standard treat-ment is observation alone. We have been investigating immunization against selected gangliosi-des as adjuvant therapy directed against residual and presumably resistant disease persisting after chemotherapy and irradiation. Previously, we reported that the presence of anti-GM2 gang-lioside antibodies is associated with a prolonged disease-free survival in patients with melanoma, and that SCLC patients immunized with BEC2, an anti-idiotypic monoclonal antibody that mimics the ganglioside GD3, had a prolonged survival compared with historical controls. In the present trial, fucosyl-alpha1-2Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3) Galbeta1-4Glcbeta1-1Cer (Fuc-GM1), a ganglioside expressed on the SCLC cell surface, was selected as a target for active immunotherapy. Fuc-GM1 is present on most SCLCs but on few normal tissues. SCLC patients achieving a major response to initial therapy were vaccinated s.c. on weeks 1, 2, 3, 4, 8, and 16 with Fuc-GM1 (30 microg) conjugated to the carrier protein keyhole limpet hemocyanin and mixed with the adjuvant QS-21. Ten patients received at least five vaccinations and are evaluable for response. All patients demonstrated a serological response, with induction of both IgM and IgG antibodies against Fuc-GM1, despite prior treatment with chemotherapy with or without radiation. Posttreatment flow cytometry demonstrated binding of antibodies from patients' sera to tumor cells expressing Fuc-GM1. In the majority of cases, sera were also capable of complement-mediated cytotoxicity. Mild transient erythema and induration at injection sites were the only consistent toxicities. The Fuc-GM1-KLH + QS-21 vaccine is safe and immunogenic in patients with SCLC. Continued study of this and other ganglioside vaccines is ongoing.