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11 januari 2012:
Interessant is aanvullend op onderstaande informatie uit 2010 te vermelden een overzichts artikel van de aanpak met radiotherapie - bestraling in combinatie met vormen van chemo en immuuntherapeutische middelen waaronder ook Zevalin en Bexxar en Yttrium-90: Radioimmunotherapy of Non-Hodgkin’s Lymphoma: From the ‘Magic Bullets’ to ‘Radioactive Magic Bullets’
In het abstract staat dit, maar klikt u op deze link voor het volledige studierapport. Onderaan staat informatie over radio immuuntherapie met Baxxar:
Source: Radioimmunotherapy (RIT) of lymphoma with Zevalin and Bexxar was approved by FDA in 2002 and 2003, respectively, for the treatment of relapsed or refractory CD20+ follicular B-cell non-Hodgkin´s lymphoma. In 2009, Zevalin was also approved for consolidation therapy in patients with follicular non-Hodgkin’s lymphoma that achieve a partial or complete response to first-line chemotherapy. For follicular lymphoma patients, the overall response and progression-free survival rates have significantly improved since the implementation of RIT. The predominant complication of RIT is hematological toxicity that is usually manageable. There are ongoing trials to further define the expanding role of RIT as first line or concomitant therapy in the treatment of lymphoma as well as for certain antibiotic resistant infections and aggressive malignancies. There is also growing interest in the development of newer protocols for increased and more uniform dose delivery resulting in better outcomes and improved patient survival. This review will primarily focus on the role of RIT in treatment of non-Hodgkin’s lymphoma, which is of established clinical utility and FDA approved. The mechanism of RIT, available radionuclides and pharmacokinetics, therapy administration, clinical utility and toxicities, and future directions would be discussed.
d.d. 23 september 2003:
Het bedrijf Coria en GSK meldt vandaag de resultaten van een fase II studie met het monoklonale middel Bexxar in combinatie met inwendige bestraling bij non-Hodgkin na chemotherapie ter voorkoming van een recidief.. Een studie uitslag die wel erg in het oog springt: een tweejaars overleving van 97% en een complete remissie van maar liefst 67%. Dat liegt er niet om, en er worden dan ook nu fase III studies met Bexxar opgezet. Zie eerst persbericht zoals de beurs in Amerika (DOW) deed uitgaan d.d. 23 september 2003 gevolgd door een beschrijving wat Bexxar is ( een monoklonaal middel dat zich bindt aan het CD20-gen en daardoor voor inwendige bestraling kan zorgen indien intraveneus ingebracht en gelabeld met een radioactieve component ) en het protocol dat nodig is voor behandeling bij non-Hodgkin en enkele studieverslagen. De bijwerkingen zijn wel stevig en vorige week heb ik gehoord dat inwendige bestraling een behoorlijk grotere kans op leukemie geeft later, hoewel daar hier niet over wordt gesproken. Maar daarover later meer. De informatie is allemaal nog in het Engels omdat ik geen tijd heb dit allemaal te vertalen. Op de website www.bexaar.com staan alle adresgegevens voor nadere inlichtingen enz.
Corixa & GSK Announce BEXXAR Following Chemotherapy Produced A High Rate of response rate with advanced follicular lymfoma --
SEATTLE -(Dow Jones)- Results of a recent phase II study showed Corixa Corp.'s
(CRXA) cancer drug Bexaar produced a high response rate in patients with
advanced follicular non-Hodgkin's lymphoma when used after chemotherapy.
In a press release Monday, the drug company said a two-part treatment of a
combination chemotherapy regiment followed by Bexaar produced an overall
response rate of 90% and a two-year overall survival rate of 97%.
Corixa said the 90-patient study also showed a complete response rate, or
elimination of lymphoma signs and symptoms, of 67%. Therapy with Bexaar also
improved the overall response when compared to the combination chemotherapy
The Bexaar and chemotherapy treatment was well tolerated in most patients,
with the main side effect being a suppression of blood cell production by the
bone marrow, which can lead to possible infections or bleeding and the need for
This side effect was more pronounced during the chemotherapy portion of the
treatment than during administration of Bexaar, Corixa said.
Based on the positive phase II results, Southwest Oncology Group, which led
the study, is now conducting a phase III clinical trial comparing the Bexaar and
chemotherapy treatment with combination chemotherapy plus the monoclonal
antibody rituximab in patients with advanced follicular non-Hodgkin's lymphoma.
Bexaar, which is co-marketed by Corixa and GlaxoSmithKline PLC (GSK), received
Food and Drug Administration approval in June and is under regulatory review for
approval in Canada.
About the BEXXAR Therapeutic Regimen
BEXXAR is a dual-action therapy that pairs the tumor-targeting ability of an antineoplastic (cancer killing) monoclonal antibody (Tositumomab) and the therapeutic potential of radiation (Iodine-131) with patient-specific dosing. Combined, these agents form a radiolabeled monoclonal antibody (Iodine I 131 Tositumomab) that is able to bind to the target antigen CD20 found on NHL cells, thereby initiating an immune response against the cancer and delivering a dose of radiation directly to tumor cells.
The BEXXAR therapeutic regimen has demonstrated independently confirmed, disease-free survival in heavily pre-treated patients with follicular NHL who had other poor prognostic factors. In a clinical trial in patients who had an average of 4 prior chemotherapies and who did not respond to or relapsed from Rituximab therapy, nearly a third (29 percent) had a complete response (no clinical signs of disease) to BEXXAR. Furthermore, the median duration of these complete responses has not been reached after a median follow-up of 26 months.
The principal dose limiting toxicity of BEXXAR in clinical trials was generally reversible bone marrow suppression that could be prolonged and severe and required supportive care in approximately a quarter of the patients. Some patients also experienced weakness, nausea, fever, infection and cough, which were usually temporary and mild to moderate in severity. Like other cancer treatments, BEXXAR may increase the long-term risk of other rare blood cancers.
About Non-Hodgkin’s Lymphoma (NHL)
NHL is a form of cancer that affects the blood, bone marrow and lymphatic tissues. Non-Hodgkin's lymphoma currently is the sixth-leading cause of cancer-related deaths in the United States, is expected to claim the lives of 23,400 Americans this year, and has the second-fastest growing mortality rate. According to statistics from the National Cancer Institute (NCI), approximately 300,000 people are diagnosed with NHL in the United States alone. Of that total, 25 to 40 percent have follicular NHL, making it the second most common type. Transformed NHL is an aggressive and difficult to treat form of follicular NHL with a particularly poor prognosis.
Please consult the complete Prescribing Information for more information on BEXXAR.
Healthcare professionals and people with non-Hodgkin’s lymphoma may obtain more information about the BEXXAR therapeutic regimen by calling 1-877-4BEXXAR or visiting www.bexxar.com
Facts About BEXXAR®
(Tositumomab and Iodine I 131 Tositumomab)
BEXXAR is a dual-action therapy that combines the tumor-targeting ability of a cytotoxic monoclonal antibody and the therapeutic potential of radiation.
BEXXAR is a new radioimmunotherapy that has been shown to produce durable remissions in some patients with Rituximab-refractory follicular non-Hodgkin's lymphoma (NHL) with a single, short course of therapy.
The BEXXAR therapeutic regimen is the only NHL treatment that is specifically dosed based on individual patient clearance rates.
BEXXAR is co-marketed in the United States by Corixa Corporation and GlaxoSmithKline Oncology.
Indication and Mechanism of Action
BEXXAR is indicated for the treatment of patients with CD20 positive, follicular, non-Hodgkin's lymphoma, with and without transformation, whose disease is refractory to Rituximab and who have relapsed following chemotherapy.
The BEXXAR therapeutic regimen combines Tositumomab, a cytotoxic monoclonal antibody, and Iodine-131, a radiation-emitting form of iodine that has been in use for 50 years in the treatment of thyroid disease. In the dosimetric and therapeutic doses of the BEXXAR therapeutic regimen, these two agents are bound, or conjugated, together.
In the body, Tositumomab seeks out and selectively binds to a specific protein marker, called CD20, found on the surface of B cells. Therefore, once it is combined with Iodine-131, Tositumomab is able to deliver its radioactive payload directly to target cells. As an antibody, Tositumomab itself contributes to the anti-tumor activity of the BEXXAR therapeutic regimen by stimulating the immune system to attack cancer cells and directly causing cell death.
Iodine-131 emits two forms of radiation. Beta radiation is responsible for its tumor-killing effect and gamma radiation allows gamma camera scans to be performed to evaluate the distribution and clearance of radiation from the body. Iodine-131 radiation is rapidly eliminated from the body through the urine, theoretically reducing the radiation exposure of healthy tissue.
The BEXXAR Therapeutic Regimen
The BEXXAR therapeutic regimen is delivered in a single, short course of treatment. BEXXAR has two components, a non-radioactive antibody and a radioactive antibody, administered intravenously in two sets of infusions 7-14 days apart:
Non-radioactive Tositumomab is given before both the dosimetric dose and the therapeutic dose to improve distribution of these doses throughout the body and improve the availability of the radioactive antibodies for binding to lymphoma cells.
A trace amount of radioactive Iodine I 131 Tositumomab, the dosimetric dose, is given to enable physicians to evaluate the clearance of radiation from the patient's body with gamma camera scans. Calculations made on the basis of these highly individualized clearance rates allow the subsequent therapeutic dose to be tailored for each patient. The therapeutic dose contains Tositumomab labeled with the amount of Iodine I 131 Tositumomab specifically calculated for the patient based on the scans performed following the dosimetric dose. The therapeutic dose is given 7 to 14 days after the dosimetric dose.
The BEXXAR therapeutic regimen is the only NHL treatment that is specifically tailored for each patient. Following the infusion of the dosimetric dose, counts are taken with a gamma camera to track the elimination of radiation from the body. The patient then returns to the hospital for two more scans, approximately two days apart. These procedures are important because highly individual factors such as tumor size, bone marrow involvement, and spleen size affect how long the radiation remains in the body. Dosimetry, therefore, allows the amount of Iodine-131 radiation administered in the therapeutic dose to be adjusted for each patient so that the appropriate target dose of radiation is achieved.
Starting one day before beginning the BEXXAR therapeutic regimen and continuing for two weeks after receiving the therapeutic dose, patients take a medication to protect their thyroid gland from Iodine-131 radiation.
The BEXXAR therapeutic regimen is given in the Nuclear Medicine/Radiation Oncology department within the hospital or clinic. Once the therapeutic dose is successfully administered, the treatment is complete. In most cases, patients can receive BEXXAR on an outpatient basis. Following treatment, patients are provided with simple instructions to follow for a short period of time to minimize the radiation exposure to other people. If these procedures are followed, the potential exposure risk to others is roughly equivalent to the exposure received in the course of one to two years from normal background radiation in the environment. The amount of radiation received by close contacts of patients who followed the instructions was well within the guidelines deemed acceptable by the government agency, the Nuclear Regulatory Commission (NRC.)
Efficacy of BEXXAR
BEXXAR is a therapeutic regimen for follicular NHL that demonstrates an impressive rate of complete and durable responses in heavily pre-treated patients with poor prognostic factors.
The efficacy of the BEXXAR therapeutic regimen was examined in a multi-center, single-arm study of 40 patients with follicular NHL whose disease had relapsed following or had not responded to Rituximab. The median age of patients in the study was 57 (range: 35-78) and the median number of prior chemotherapies was 4 (range: 1-11). Eighty-eight percent of patients met the definition of Rituximab refractory (defined as no response or a response of less than 6 months in duration).
In patients with Rituximab-refractory disease, sixty-three percent of patients had a response to BEXXAR, with a median duration of response of 25 months.
Twenty-nine percent of patients with Rituximab-refractory disease had a complete response (no clinical signs of disease) to BEXXAR. The median duration of complete responses has not been reached with a median follow-up of 26 months.
The results of this study were supported by demonstration of durable objective responses to the BEXXAR therapeutic regimen in four other single-arm studies enrolling 190 patients with Rituximab-naïve, follicular NHL, with or without transformation, who had relapsed following or were refractory to chemotherapy.
The overall response rates ranged from 47 percent to 64 percent.
The median durations of response ranged from 12 to 18 months.
Safety of BEXXAR
The most common adverse reactions occurring in clinical trials of the BEXXAR therapeutic regimen included neutropenia, thrombocytopenia and anemia that could be both prolonged and severe but were generally reversible.
Of 230 patients included in the safety data from five clinical trials, 63 percent had documented Grade 3 or 4 neutropenia, 53 percent had Grade 3 or 4 thrombocytopenia, and 29 percent had Grade 3 or 4 anemia.
Twenty-seven percent of patients received one or more blood transfusions or blood cell growth factors, eight percent of patients experienced a serious infection and 12 percent experienced bleeding events; the majority were mild to moderate.
The most common non-hematologic side effects included asthenia (weakness), fever, nausea, infection, and cough. The BEXXAR therapeutic regimen was associated with a risk of hypothyroidism and human anti-murine antibody (HAMA) formation.
Certain chemotherapy agents and ionizing radiation have been associated with the development of myelodysplasia (MDS), secondary leukemia and solid tumors. MDS, secondary leukemia and solid tumors have also been observed in patients receiving the BEXXAR therapeutic regimen.
BEXXAR carries a warning about infusion-related reactions that may be induced by the administration of foreign proteins. Hypersensitivity reactions occurred in six percent of patients. Adjustments of the rate of infusion to control adverse reactions occurred in 7 percent of patients.
- Bestraling - Radiotherapie bij non-Hodgkin lymfoom en gelabeld met monoklonale antibodies geeft significant langere tijd van overleven, ook als eerdere behandelingen faalden.
- Bestraling - Radiotherapie bij non-Hodgkin lymfoom stadium III en IV laaggradig geeft opmerkelijk langere periode tot recidief en significant meer totale remissies ( 60% CR gemiddeld 42 maanden lang ), ondanks een of meerdere chemokuren die al zijn gedaan
- Bestraling - Radiotherapie bij non-Hodgkin: Non-Hodgkin patiënten - jonger dan 30 jaar - die bestraald zijn geworden voor lymfklierkanker - non-Hodgkin en deze ziekte hebben overleefd hebben ca.40% grotere kans op krijgen van borstkanker daarna.
- Bexxar, een monoklonaal middel gelabeld met een radioactieve component zorgt voor opmerkelijk goede effecten bij agressieve vorm van terugkerende non-Hodgkin.
- Bestraling - Radiotherapie plus immuuntherapie met o.a. Zevalin - Bexxar blijkt uitstekende aanpak voor bepaalde vormen van lymfklierkanker, waaronder non-Hodgkin