BORSTKANKER.
Informatie over actuele ontwikkelingen in zowel reguliere als alternatieve en/of aanvullende behandelingen en middelen bij borstkanker in alle stadia.
Zoek in alfabetische lijst naar onderwerp of gebruik zoekmachine hierboven met trefwoorden.
Ervaringen van kankerpatienten met complementaire aanpak zijn te vinden onder ervaringsverhalen en er zijn op onze website ook een aantal video's van ervaringen van kankerpatienten met complementaire aanpak te zien. Aan te klikken via videoknop links bovenaan op deze pagina. Of ga naar de website van het SNFK waar voorlichtingsfilmpjes zijn te zien over complementaire aanpak bij kanker.
Als u ons wilt ondersteunen dan kan dat via een donatie: zie inschrijving OPS
RhuMab 2c4 wordt in de VU- Amsterdam in open label phase II studie bij niet-hormoonbepaalde borstkanker onderzocht.
d.d. 3 november 2003:In de VU-Amsterdam (020-4444444) is sinds kort een open label studie gestart met RhuMAb 2C4 (2C4, pertuzumab) een zogenaamd monoklonaal antibody middel (lees hieronder in drie Engelstalige abstracten van Phase I studies wat dit precies inhoudt en wat de resultaten waren uit deze drie Phase I studies) voor borstkankerpatiënten met het bepalende eiwit HER2. Herceptin is ook zo'n monoklonaal middel, maar dit nieuwe middel lijkt weer op een ander manier te binden aan de tumorcel en wellicht een verbetering van Herceptin, aldfus een geraadpleegde oncoloog. Beide middelen worden geproduceerd door Hoffman-Roche. Een trouwe bezoeker stuurde ons onderstaande Nederlandse toelichting, waarvoor hartelijk dank.
De bezoeker schreef ons dit:
officiële titel : open label, phase ll ,multicenter,randomised study of efficacy and safety for two different doses of a recombinant humanised antibody to HER2 {rhuMAb 2c4} administrated every 3 weeks to patients whith metastatic breast cancer with low expression of HER2}
RhuMAb 2c4 is een nieuw genees middel dat door Hoffmann-La Roche in samenwerking met het VU medisch centrum wordt onderzocht.
2c4 is een antistof die vergelijkbaar is met de antistoffen die op natuurlijke wijze door het lichaam worden geproduceerd en die bescherming bieden tegen bacteriele en virale infecties.
2c4 herkent een eiwit dat Her2 wordt genoemd en bind zich hieraan.
Her 2 is een van de vele eiwitten die op het oppervlak van tumorcellen worden gevonden en die mogelijk de groei van de tumor regelen. In dit onderzoek bij dieren (zie hieronder abstracten van drie studies zoals die op ASCO 2003 werden gepresenteerd) remde RhuMAb 2c4 de groei van tumoren met hoge en lage Her2 waarden. Dit suggereert dat RhuMAb 2c4 kan bijdragen aan de behandeling van borstkanker.
In een eerder klinisch onderzoek werd RhuMAb 2c4 gedurende 4 maanden of langer toegediend aan 21 patiënten die aan verschillende soorten van kanker leden. RhuMAb 2c4 werd niet geassocieerd met hogere veiligheidrisico's.
Doel van het onderzoek is te ontdekken hoe effectief en veilig RhuMAb 2c4 is als het wordt gebruikt voor het behandelen van borstkanker.
Hier drie abstracten van studies met RhuMAb 2C4 zoals gepresenteerd op ASCO 2003
Pharmacokinetics of HER2-targeted rhuMAb 2C4 (pertuzumab) in patients with advanced solid malignancies: Phase Ia results.
Abstract No: 790
Citation: Proc Am Soc Clin Oncol 22: page 197, 2003 (abstr 790)
Author(s): D. E. Allison, M. Malik, F. Qureshi, D. Baker, S. Kelsey, G. Fyfe, M. Gordon, C. Taylor, D. B. Agus; Genentech, Inc., South San Francisco, CA; Arizona Cancer Ctr, Tucson/Phoenix, AZ; Cedars-Sinai Medical Center, Los Angeles, CA
Abstract: rhuMAb 2C4 (2C4, pertuzumab) is a humanized HER2-targeted antibody that binds to an epitope distinct from trastuzumab (Herceptin). 2C4 acts by blocking ligand-associated heterodimerization of HER2 with other HER-kinase family members [HER1 (EGFR), HER3, and HER4], and thereby inhibits intracellular signaling through MAP kinase and PI3 kinase.
A total of 21 patients with advanced solid malignancies received intravenous single-agent 2C4 every 3 weeks at escalating doses (0.5-15.0 mg/kg). 2C4 serum concentration data was obtained from 19 patients who completed 2 treatment cycles with intensive PK sampling during the 1st cycle, and sparse sampling during subsequent cycles. 2C4 concentrations were measured by ELISA (LLOQ=0.25 µg/mL) and preliminary PK analysis was performed by compartmental methods.
(table) 2C4 was cleared faster at the 0.5 mg/kg dose compared to the 2.0-15.0 mg/kg doses, where clearance did not change (2.6-3.8 mL/day/kg). At 2.0-15.0 mg/kg, 2C4 concentrations declined rapidly over the first 2-3 days and more slowly thereafter. The volume of distribution did not change with dose and Vc approximated the serum volume. At 0.5 mg/kg, a shorter mean terminal half-life (2.6 days) was observed compared to the 2.0-15.0 mg/kg doses (15.3-27.6 days). The PK parameter estimates of 2C4 are similar to other humanized IgG1 antibodies, and a terminal half-life of »21 days supports q3 week dosing. At 2C4 clinical doses >2.0 mg/kg (q3 week), saturation of receptor-mediated clearance is suggested, and 2C4 serum concentrations are expected to exceed those shown to be efficacious in a range of mouse xenograft tumor models (5-25 µg/mL) expressing both low and high HER2 receptor levels. Phase II trials are underway in patients with a variety of solid tumor types.
Een andere studie die op ASCO werd gepresenteerd is deze:
Category: Developmental Therapeutics - Molecular Therapeutics
SubCategory: Receptor-Targeted Antibodies/Ligands
Additive antitumor activity by combined treatment with recombinant humanized monoclonal antibody 2C4 and standard chemotherapeutic agents in NSCLC xenografts is independent of HER2 overexpression
Abstract No: 953
Citation: Proc Am Soc Clin Oncol 22: page 238, 2003 (abstr 953)
Author(s): T. Friess, R. Juchem, W. Scheuer, M. Hasmann; Roche Diagnostics GmbH, Penzberg, Germany
Abstract: The proto-oncogene HER2/erbB2 encodes a growth factor receptor, which is overexpressed in about 25 % of breast cancers. 2C4 is a HER2-ECD-specific recombinant humanized monoclonal antibody that does not compete with trastuzumab (Herceptin) for HER2 binding. In vitro, 2C4 binding to HER2 inhibits ligand-dependent heterodimerization of HER2 with other HER family members leading to the inhibition of several downstream signal transduction cascades. We studied combination of 2C4 and standard chemotherapeutics in various NSCLC xenograft models (CDDP, PTX and GEM). The xenografts were different regarding HER2 protein levels (HER2 1+ and HER2 3+). Single treatment with 2C4 of the HER2 3+ Calu-3 xenograft was highly efficacious resulting in partial tumor regression (TCR <0.20). Combination of 2C4 (6 mg/kg) with MTD/MED doses of CDDP (6 mg/kg), PTX (45 mg/kg) and GEM (120 mg/kg) resulted in additive antitumor activity for each tested cytotoxic agent (lower TCR values, increase in the number of tumor free animals) and extension of life span (+50 % for PTX). Remarkably, histological analysis of explanted tumors at termination confirmed the addditive effects of combined treatment schedules on histological parameters (e.g. proliferation, apoptosis). Furthermore, monotherapy with 2C4 (6 mg/kg) in the HER2 low expressing QG56 NSCLC xenografts resulted in antitumor activity (TCR 0.44). Similar efficacy was obtained after treatment with GEM at MTD (120 mg/kg, TCR 0.53). However, combination of 2C4 and GEM against QG56 solid tumors demonstrated additive antitumor activity (TCR 0.13) in this extremely aggressive model. Throughout the single agent and combination studies with 2C4 in the different NSCLC xenografts the serum tumor marker Cyfra 21.1 was shown to be a reliable marker to monitor the antitumor activity of each regimen. In summary, our data indicate that combination treatment with 2C4 and standard chemotherapeutics resulted in additive antitumor activity against both HER2 low and high expressing NSCLC xenografts
Een derde studie:
Clinical activity in a phase I trial of HER-2-targeted rhuMAb 2C4 (pertuzumab) in patients with advanced solid malignancies (AST)
Abstract No: 771
Citation: Proc Am Soc Clin Oncol 22: page 192, 2003 (abstr 771)
Author(s): D. B. Agus, M. Gordon, C. Taylor, R. B. Natale, B. Karlan, D. Mendelson, S. Kelsey, G. Fyfe; Cedars-Sinai Medical Center, Los Angeles, CA; Arizona Cancer Ctr, Phoenix, AZ; Arizona Cancer Ctr, Tucson, AZ; Genentech Inc, South San Francisco, CA
Abstract: RhuMAb 2C4 (2C4) is a humanized HER2 antibody that binds to an epitope distinct from trastuzumab (Herceptin). 2C4 blocks ligand-associated heterodimerization of HER2 with other HER-kinase family members [HER1 (EGFR), HER3, and HER4] and thereby inhibiting intracellular signaling through MAP kinase and PI3 kinase. Anti-tumor activity has been seen in tumor xenograft models, including HER2 non-overexpressing(0+/1+) as well as overexpressing tumors (2+/3+). 21 patients (12 female, 9 male) with AST received IV 2C4 every 3 weeks at one of the following dose levels: 0.5mg/kg (n=3), 2mg/kg (n=3), 5mg/kg (n=4), 10mg/kg (n=3), 15mg/kg (n=8). 19 patients completed a minimum of 2 cycles. Median age was 57 yrs, median ECOG PS was 1. Cancer types included breast (n=3), prostate (n=5), NSCLC (n=4), ovarian (n=3), colon (n=2), liposarcoma (n=1), pancreatic (n=2; 1 adenocarcinoma, 1 islet cell), and unknown primary (n=1). The majority of adverse events (AEs) reported were grade 1 or 2. Most frequently reported AEs to date were nausea (48%), vomiting (52%), fatigue (43%), diarrhea (33%), rash (38%), abdominal pain (33%) and anemia (38%). 24 events were graded 3 or 4; with two of these events felt to be possibly drug-related: a GI bleed (in a patient with pre-existing esophageal varices) and a patient with left ventricular failure following a myocardial infarction. Patients were closely monitored with 2-D echos and serologic cardiac markers and there was no other evidence of cardiac dysfunction observed. The pharmacokinetics of 2C4 were similar to other humanized IgG antibodies with a terminal half-life of ~3 weeks. Modeling of steady state trough plasma concentrations at all dose levels over 0.5mg/kg exceeded those required for anti-tumor activity in animal models (20ug/ml). Three patients (14%) achieved PRs: ovarian cancer (5mg/kg); prostate cancer (15mg/kg) and islet cell carcinoma (15mg/kg). Two remain on therapy at 44.6wks and 30.6wks. An additional 8 patients (38%) had SD after 2 cycles, persisting for a median of 13.7 weeks (range 6.1 - 24.4). We conclude that 2C4 is well tolerated at doses up to 15mg/kg q3wk. Clinical activity was observed.
