For the first time, breast cancer patients in Europe will receive treatment using a revolutionary system called AccuBoost. The Italian hospital where the patients are being treated is using the technology to pinpoint the tumor bed and treat it whilst still protecting the patient's healthy surrounding tissue and organs.
The new treatment option is made possible by the system combining real-time mammographic image guidance and non-invasive use of a radiotherapy technique called brachytherapy, a high-precision radiation therapy in which the radiation source used to kill cancer cells and shrink tumors is placed in or close to the tumor itself. Precision brachytherapy allows a physician to concentrate a high dose of radiation in a small area, minimizing damage to nearby, healthy body tissue and organs, over a shorter treatment period.
Professor Roberto Orecchia; Director of the Division of Radiotherapy, is leading the use of the new system at the Istituto Europeo di Oncologia in Milan and explained: 'When the patient is treated with AccuBoost, the image is seen in real-time, guaranteeing radiotherapy that is extremely precise in its targeting of the tumour bed. This is a very innovative procedure because for the first time mammography images can be used to guide the radiotherapy treatment in such an extremely precise and adaptive manner. There is also a time benefit, so this year, we will be able to treat 50 percent of patients more quickly and efficiently than before, reducing treatment time from six weeks to three weeks.'
The Istituto Europeo di Oncologia is the first hospital in Europe to use AccuBoost, which was certified for use in Europe just six weeks ago. The technology was developed by Nucletron, a knowledge-based leader in Radiation Oncology, and ART a company dedicated to the advancement of partial breast irradiation with the goal of reducing the cancer recurrence rate and minimizing radiation related complications. The two companies specialize in advancing radiation oncology by developing state-of-the-art equipment for high precision brachytherapy.
Showing posts with label radiotherapy. Show all posts
Showing posts with label radiotherapy. Show all posts
Thursday, March 4, 2010
Wednesday, July 1, 2009
Escalated Dose-Intensified Combined Modality Treatment Shows Survival Benefit In Patients With Early Unfavourable Hodgekin Lymphoma
With more than 7,500 participants from more than 100 European and non-European countries in attendance, the 14th congress of the European Hematology Association (EHA), which was held in Berlin, Germany, from June 4 – 7, 2009, proved record-breaking. The delegates gathered in Berlin to share the most recent developments in hematological research and improvements in care.
The program included sessions on clinical and laboratory hematology and covered all the major hematological subspecialties, including hemato-oncology, red cell disorders, hemostasis, thrombosis, pediatric hematology and transfusion medicine.
The program featured a session, presented by Prof. Peter Borchmann on behalf of the German
Hodgkin Study Group / GHSG (abstract number 0553) discussing an analysis of Dose-Intensified Combined Modality Treatment In Patients With Early Unfavourable Hodgekin Lymphoma (HL).
As a result of intensified medical research, Hodgkin's lymphoma has become one of the most curable tumors in adults. Today, about 80% - 90% of patients experience long-term disease free survival (DFS). This is mainly the result of numerous large clinical trials initiated by the German Hodgkin Study Group and other organizations, taking place since the late 1970's, using risk-adapted, highly effective therapy modalities. From the late '70s nearly 15,000 patients have been randomized and treated in these prospectively randomized trials.
Risk Groups
Patients with Hodgkin lymphoma are divided in three risk groups according to the initial staging and additional clinical risk factors: early favorable, early unfavorable and advanced-stage risk groups.
Abstract 0553 (Interim Analysis of the GHSG HD14 Trial for Patients With Early Unfavourable HL) compared the results of the arms of the GHSG HD14 trial. The rational of this trial was to improve the prognosis of patients with early unfavorable disease by comparing the old standard treatment, 4 courses of ABVD (adriamycin, bleomycin, vinblastine, and dacarbacine) followed by localized radiotherapy (30 Gy IF-RT), with a more intensive chemotherapy regimen consisting of 2 cycles of escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) followed by 2 cycles of ABVD and the same radiotherapy as in the standard arm.
Treatment-associated toxicities
A previous GHSG trial (GHSG HD11) compared 4 cycles of ABVD with BEACOPP, followed by either 30 or 20 Gy IF-RT. This trial showed no difference with respect to outcomes, and despite excellent initial remission rates, approximately 15% of patients with early unfavorable-stage HL relapsed within 5 years and another 5% suffered from progressive disease. Nevertheless, these good results of the GHSG trials are threatened by treatment-associated toxicities such as infertility, cardiopulmonary toxicity and secondary malignancies.
Improving trial results
The GHSG HD14 trial showed a significantly better outcome in terms of progression-free survival in the more intensive escalated BEACOPP regimen than the standard regimen of 4 cycles of ABVD in patients with early unfavorable Hodgkin's lymphoma (HL).
The study, conducted by the German Hodgkin Study Group (GHSG), included 1645 patients in 346 centres. These patients had early unfavorable Hodgkin's lymphoma, clinical stage 1 or 2 and risk factors, including large mediastinal mass, extranodal disease, high erythrocyte sedimentation rate, and 3 or more areas affected.
Interim analysis
After the third interim analysis with 1127 patients, researchers decided to terminate the GHSD HD14 trial early because of the significantly better outcome for patients treated with BEACOPP compared to ABVD. The interim results showed that progression free survival (PFS) was significantly better for patients treated with the hybrid regimen than for patients treated with 4 courses of ABVD. After 3 years, progression-free survival was observed in 97% of patients in the escalated BEACOPP group and 91% in the ABVD group.
Furthermore, the interim analysis showed freedom from treatment failure to be 95% in the escalated BEACOPP group versus 91% in the ABVD group. Overall, there were more patients with progressive disease, relapse and a higher mortality in those receiving 4 cycles of ABVD. These results prompted the GHSG to adopt a regimen of two cycles of escalated BEACOPP followed by two cycles of ABVD plus 30 Gy radiotherapy as the new standard treatment for patients with early unfavorable Hodgkin's lymphoma.
Escalated BEACOPP, compared to standard BEACOPP, uses a higher doses of etoposide (200 vs 100 mg/m2), doxorubicin (35 vs 25 mg/m2), cyclophosphamide (1200 vs 650 mg/m2), with added granulocyte colony-stimulating factor support. Combined with local irradiation, the escalated regimen showed superior disease control compared with ABVD. Patients experienced more hematological adverse events in the escalated BEACOPP group compared to the ABVD group. This included leukopenia (22% vs , including 81%), thrombocytopenia (<1%>
Predisposition to Myeloproliferative Neoplasms
An unrelated presentation by Prof. Nick Cross, Salisbury, United Kingdom, discussed research aimed to understand what causes a group of
related conditions known collectively as myeloproliferative neoplasms (abstract number 0555).
Researchers have found a common genetic 'signature' that predisposes to these disorders. The predisposition is relatively subtle and so it cannot by itself be used to predict whether anyone will develop disease or not, but it is an important step towards understanding why some people get cancer and why others do not. In the future it is possible that the abnormality we have found might be combined with other genetic and environmental risk factors to enable much better predictions of disease susceptibility to be made.
Myeloproliferative neoplasms or MPNs are conditions of the blood that are related to leukemia but in effect they are a very mild form that resembles the first steps towards cancer. They are characterised by the overproduction of red and white blood cells, which increases the risk of strokes and heart attacks. Many cases of MPDs are caused by a mutation in a gene called JAK2. When the JAK2 gene has mutated, it sends abnormal messages to the blood stem cells to produce more and more blood cells.
Scientists have found that a particular region of chromosome 9 that carries the JAK2 gene is predisposed to acquiring mutations, but only in individuals with a particular genetic makeup. It is likely that this finding will lead to a much better understanding of how the JAK2 gene mutations happen and why they lead to an increased risk of someone developing an MPD.
The study, carried out at the Wessex Regional Genetics Laboratory in Salisbury and the University of Southampton, has proved that people carrying this mutation-prone region of DNA on chromosome 9 that includes the JAK2 gene have triple the risk of developing an MPD. The chromosome 9 variant is present in 40% of the population in the United Kingdom but only 1 in 20,000 people develop an MPD each year. Nonetheless, the new research has confirmed that the inheritance of this genetic variant can contribute to inherited susceptibility to develop an MPD.The study found that the link was especially strong in polycythaemia vera (PV), one of the main three MPDs.
Professor Nick Cross, from the University of Southampton (University RoadSouthampton SO17 1BJ, United Kingdom, Tel. +44 (0)23 8059 5000, Fax +44 (0)23 8059 3131) who led the research team, said: “This research provides strong evidence that at least half of the cases of PV diagnosed each year are linked to an inherited genetic variant on chromosome 9. Whilst this risk is still very small it nonetheless confirms that individual susceptibility to acquiring cancer-causing mutations is linked to genetic inheritance. Now that we have this evidence we can carry out studies to determine exactly how the variant contributes to this risk.”
Dr Shabih Syed, Scientific Director at UK-based Leukaemia Research who sponsored the reserach, adds: “This is a very important step forward in our knowledge of the causes of myeloproliferative disorders. It helps us to understand why some people might be predisposed to acquiring genetic mutations that lead to cancers.”
For more information:
The program included sessions on clinical and laboratory hematology and covered all the major hematological subspecialties, including hemato-oncology, red cell disorders, hemostasis, thrombosis, pediatric hematology and transfusion medicine.
The program featured a session, presented by Prof. Peter Borchmann on behalf of the German
Hodgkin Study Group / GHSG (abstract number 0553) discussing an analysis of Dose-Intensified Combined Modality Treatment In Patients With Early Unfavourable Hodgekin Lymphoma (HL).As a result of intensified medical research, Hodgkin's lymphoma has become one of the most curable tumors in adults. Today, about 80% - 90% of patients experience long-term disease free survival (DFS). This is mainly the result of numerous large clinical trials initiated by the German Hodgkin Study Group and other organizations, taking place since the late 1970's, using risk-adapted, highly effective therapy modalities. From the late '70s nearly 15,000 patients have been randomized and treated in these prospectively randomized trials.
Risk Groups
Patients with Hodgkin lymphoma are divided in three risk groups according to the initial staging and additional clinical risk factors: early favorable, early unfavorable and advanced-stage risk groups.
Abstract 0553 (Interim Analysis of the GHSG HD14 Trial for Patients With Early Unfavourable HL) compared the results of the arms of the GHSG HD14 trial. The rational of this trial was to improve the prognosis of patients with early unfavorable disease by comparing the old standard treatment, 4 courses of ABVD (adriamycin, bleomycin, vinblastine, and dacarbacine) followed by localized radiotherapy (30 Gy IF-RT), with a more intensive chemotherapy regimen consisting of 2 cycles of escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) followed by 2 cycles of ABVD and the same radiotherapy as in the standard arm.
Treatment-associated toxicities
A previous GHSG trial (GHSG HD11) compared 4 cycles of ABVD with BEACOPP, followed by either 30 or 20 Gy IF-RT. This trial showed no difference with respect to outcomes, and despite excellent initial remission rates, approximately 15% of patients with early unfavorable-stage HL relapsed within 5 years and another 5% suffered from progressive disease. Nevertheless, these good results of the GHSG trials are threatened by treatment-associated toxicities such as infertility, cardiopulmonary toxicity and secondary malignancies.
Improving trial results
The GHSG HD14 trial showed a significantly better outcome in terms of progression-free survival in the more intensive escalated BEACOPP regimen than the standard regimen of 4 cycles of ABVD in patients with early unfavorable Hodgkin's lymphoma (HL).
The study, conducted by the German Hodgkin Study Group (GHSG), included 1645 patients in 346 centres. These patients had early unfavorable Hodgkin's lymphoma, clinical stage 1 or 2 and risk factors, including large mediastinal mass, extranodal disease, high erythrocyte sedimentation rate, and 3 or more areas affected.
Interim analysis
After the third interim analysis with 1127 patients, researchers decided to terminate the GHSD HD14 trial early because of the significantly better outcome for patients treated with BEACOPP compared to ABVD. The interim results showed that progression free survival (PFS) was significantly better for patients treated with the hybrid regimen than for patients treated with 4 courses of ABVD. After 3 years, progression-free survival was observed in 97% of patients in the escalated BEACOPP group and 91% in the ABVD group.
Furthermore, the interim analysis showed freedom from treatment failure to be 95% in the escalated BEACOPP group versus 91% in the ABVD group. Overall, there were more patients with progressive disease, relapse and a higher mortality in those receiving 4 cycles of ABVD. These results prompted the GHSG to adopt a regimen of two cycles of escalated BEACOPP followed by two cycles of ABVD plus 30 Gy radiotherapy as the new standard treatment for patients with early unfavorable Hodgkin's lymphoma.
Escalated BEACOPP, compared to standard BEACOPP, uses a higher doses of etoposide (200 vs 100 mg/m2), doxorubicin (35 vs 25 mg/m2), cyclophosphamide (1200 vs 650 mg/m2), with added granulocyte colony-stimulating factor support. Combined with local irradiation, the escalated regimen showed superior disease control compared with ABVD. Patients experienced more hematological adverse events in the escalated BEACOPP group compared to the ABVD group. This included leukopenia (22% vs , including 81%), thrombocytopenia (<1%>
Predisposition to Myeloproliferative Neoplasms
An unrelated presentation by Prof. Nick Cross, Salisbury, United Kingdom, discussed research aimed to understand what causes a group of
related conditions known collectively as myeloproliferative neoplasms (abstract number 0555).Researchers have found a common genetic 'signature' that predisposes to these disorders. The predisposition is relatively subtle and so it cannot by itself be used to predict whether anyone will develop disease or not, but it is an important step towards understanding why some people get cancer and why others do not. In the future it is possible that the abnormality we have found might be combined with other genetic and environmental risk factors to enable much better predictions of disease susceptibility to be made.
Myeloproliferative neoplasms or MPNs are conditions of the blood that are related to leukemia but in effect they are a very mild form that resembles the first steps towards cancer. They are characterised by the overproduction of red and white blood cells, which increases the risk of strokes and heart attacks. Many cases of MPDs are caused by a mutation in a gene called JAK2. When the JAK2 gene has mutated, it sends abnormal messages to the blood stem cells to produce more and more blood cells.
Scientists have found that a particular region of chromosome 9 that carries the JAK2 gene is predisposed to acquiring mutations, but only in individuals with a particular genetic makeup. It is likely that this finding will lead to a much better understanding of how the JAK2 gene mutations happen and why they lead to an increased risk of someone developing an MPD.
The study, carried out at the Wessex Regional Genetics Laboratory in Salisbury and the University of Southampton, has proved that people carrying this mutation-prone region of DNA on chromosome 9 that includes the JAK2 gene have triple the risk of developing an MPD. The chromosome 9 variant is present in 40% of the population in the United Kingdom but only 1 in 20,000 people develop an MPD each year. Nonetheless, the new research has confirmed that the inheritance of this genetic variant can contribute to inherited susceptibility to develop an MPD.The study found that the link was especially strong in polycythaemia vera (PV), one of the main three MPDs.
Professor Nick Cross, from the University of Southampton (University RoadSouthampton SO17 1BJ, United Kingdom, Tel. +44 (0)23 8059 5000, Fax +44 (0)23 8059 3131) who led the research team, said: “This research provides strong evidence that at least half of the cases of PV diagnosed each year are linked to an inherited genetic variant on chromosome 9. Whilst this risk is still very small it nonetheless confirms that individual susceptibility to acquiring cancer-causing mutations is linked to genetic inheritance. Now that we have this evidence we can carry out studies to determine exactly how the variant contributes to this risk.”
Dr Shabih Syed, Scientific Director at UK-based Leukaemia Research who sponsored the reserach, adds: “This is a very important step forward in our knowledge of the causes of myeloproliferative disorders. It helps us to understand why some people might be predisposed to acquiring genetic mutations that lead to cancers.”
For more information:
- 14th Congress of the Europan Hematology Association (EHA): Presentations.
- Diehl V, Franklin J, Hasenclever D, Tesch H, Pfreundschuh M, et al. BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group Journal of Clinical Oncology. 1998 Vol 16, 3810-3821.
- Patrice Carde P, Cavalli F, Diehl V, Franklin J. Is escalated BEACOPP a standard therapy for advanced Hodgkin's disease? The Hematology Journal (2000) 1, 282 ± 290.
- Jones AV, Chase A, Silver RT, Oscier D, Zoi K, et al. JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms. Nature Genetics 41, 446 - 449 (2009) Published online: 15 March 2009
Read these PubMed abstracts:
- Federico M, Luminari S, Iannitto E, Polimeno G, Marcheselli L, et al. ABVD compared with BEACOPP compared with CEC for the initial treatment of patients with advanced Hodgkin's lymphoma: results from the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol. 2009 Feb 10;27(5):805-11. Epub 2009 Jan 5
- Bosetti C, Levi F, Ferlay J, Lucchini F, Negri E, La Vecchia C. The recent decline in mortality from Hodgkin lymphomas in central and eastern Europe. Ann Oncol. 2009 Apr;20(4):767-74. Epub 2008 Dec 16.
- Eich HT, Müller RP, Engenhart-Cabillic R, Lukas P, Schmidberger H, et al. Involved-node radiotherapy in early-stage Hodgkin's lymphoma. Definition and guidelines of the German Hodgkin Study Group (GHSG). Strahlenther Onkol. 2008 Aug;184(8):406-10.
- Ben Arush MW, Shafat I, Ben Barak A, Shalom RB, Vlodavsky E, Ilan N. Plasma heparanase as a significant marker of treatment response in children with Hodgkin lymphoma: pilot study. Pediatr Hematol Oncol. 2009 Jun;26(4):157-64.
- Gobbi PG, Valentino F, Danova M, Morabito F, Rovati B, et al. Bone marrow stem cell damage after three different chemotherapy regimens for advanced Hodgkin's lymphoma. Oncol Rep. 2009 Apr;21(4):1029-35.
- Wood AD, Chen E, Donaldson IJ, Hattangadi S, Burke KA, et al. Id1 promotes expansion and survival of primary erythroid cells and is a target of JAK2V617F-STAT5 signalling. Blood. 2009 Jul 1. [Epub ahead of print].
- Tefferi A, Thiele J, Vardiman JW. The 2008 World Health Organization classification system for myeloproliferative neoplasms: order out of chaos. Cancer. 2009 May 26. [Epub ahead of print]
- US National Cancer Institute: Definition Hodgkin Lymphoma
- Mayo Clinic: Definition Hodgkin Lymphoma
- WikiPedia: Definition Hodgkin Lymphoma
- LymphomaInfo.Net: Definition Hodgkin Lymphoma
- The Leukemia & Lymphoma Society (USA): Definition Hodgekin Lymphoma
- SteadyHealth.com: Definition of Myeloproliferative Neoplasms.
- UptoDate for Patients: Overview of Myeloproliferative Neoplasms.
Tuesday, June 23, 2009
PARP Inhibitors Show Promise for Hard-to-Treat (Breast) Cancers
Two studies, including one featured during the plenary session of the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO), report promising data on a new class of targeted drugs called PARP inhibitors. The plenary study reports that women with hard-to-treat 'triple-negative' breast cancer who received the PARP inhibitor BSI-201 along with conventional chemotherapy had better outcomes than women who received chemotherapy alone. A second study reports that women with BRCA-deficient advanced breast cancer experienced tumor shrinkage after receiving the PARP inhibitor olaparib as a single agent.
The two new studies report results on the effect of a new class of targeted therapy called PARP inhibitors on traditionally difficult-to-treat breast cancers – so-called 'triple-negative' breast cancer and BRCA1- and BRCA2 deficient breast cancers.
PARP is short for ‘poly (ADP-ribose) polymerase.’ Cancer cells use the PARP enzyme to repair DNA damage, including the damage inflicted by chemotherapy drugs. Preclinical studies indicate that PARP inhibitors could enhance the efficacy of radiation therapy and chemotherapies such as alkylating agents and platinum-based drugs by preventing malignant cells from repairing damaged DNA, ultimately leading to impaired tumor growth and apoptosis.
PARP Concept
The concept is based on the fact that BRCA1 and BRCA2 are tumor suppressor genes that help control normal cell growth and cell death by regulating the repair of double strand breaks in DNA. Mutations in the BRCA1 and BRCA2 genes can impair this function, leaving cells unable to repair their own DNA, as well as causing the uncontrolled growth that is characteristic of cancer cells. Women who inherit mutations in the BRCA1 or BRCA2 genes have significantly higher risks for breast and ovarian cancer
Exploiting impaired DNA repair function
PARP inhibitors work by exploiting the impaired DNA repair function inherent in BRCA-associated cancers. In this case, inhibition of PARP leads to failure to repair DNA single strand breaks, which in turn, result in DNA double strand breaks. These effects are particularly detrimental to BRCA-associated cancer cells. Ultimately, failure to repair both DNA single strand breaks and double strand breaks, leads to cancer cell death.
Researchers interested in understanding how to exploit the DNA damage on tumor cells inflicting by anti-cancer agents, are now examining whether drugs that inhibit the PARP enzyme will indeed diminish the self-repair mechanism and make cancer cells more sensitive to treatment and promote cancer cell death.
Currently, a number of PARP inhibitors are studied in Phase I, II and III trials for a variety of cancer indications. These include:
The two new studies report results on the effect of a new class of targeted therapy called PARP inhibitors on traditionally difficult-to-treat breast cancers – so-called 'triple-negative' breast cancer and BRCA1- and BRCA2 deficient breast cancers.
PARP is short for ‘poly (ADP-ribose) polymerase.’ Cancer cells use the PARP enzyme to repair DNA damage, including the damage inflicted by chemotherapy drugs. Preclinical studies indicate that PARP inhibitors could enhance the efficacy of radiation therapy and chemotherapies such as alkylating agents and platinum-based drugs by preventing malignant cells from repairing damaged DNA, ultimately leading to impaired tumor growth and apoptosis.
PARP Concept
The concept is based on the fact that BRCA1 and BRCA2 are tumor suppressor genes that help control normal cell growth and cell death by regulating the repair of double strand breaks in DNA. Mutations in the BRCA1 and BRCA2 genes can impair this function, leaving cells unable to repair their own DNA, as well as causing the uncontrolled growth that is characteristic of cancer cells. Women who inherit mutations in the BRCA1 or BRCA2 genes have significantly higher risks for breast and ovarian cancer
Exploiting impaired DNA repair function
PARP inhibitors work by exploiting the impaired DNA repair function inherent in BRCA-associated cancers. In this case, inhibition of PARP leads to failure to repair DNA single strand breaks, which in turn, result in DNA double strand breaks. These effects are particularly detrimental to BRCA-associated cancer cells. Ultimately, failure to repair both DNA single strand breaks and double strand breaks, leads to cancer cell death.
Researchers interested in understanding how to exploit the DNA damage on tumor cells inflicting by anti-cancer agents, are now examining whether drugs that inhibit the PARP enzyme will indeed diminish the self-repair mechanism and make cancer cells more sensitive to treatment and promote cancer cell death.
Currently, a number of PARP inhibitors are studied in Phase I, II and III trials for a variety of cancer indications. These include:
- ABT-888 in Metastatic melanoma (Abbott Laboratories). Preliminary trial results show that this drug candidate has good oral bioavailability, can cross the blood-brain barrier, and potentiates temozolomide, platinums, cyclophosphamide, and radiation in syngeneic and xenograft tumor models. Broad spectrum chemopotentiation and radiopotentiation makes this compound an attractive candidate for further clinical evaluation.
- AG-014699 in Breast cancer, ovarian cancer and melanoma (Agouron/Pfizer Inc.). Preliminary results of a phase II trial of AG-014699 and temozolomide in patients with metastatic melanoma indicated that the addition of AG-14699 enhanced temozolomide-associated myelosuppression, and that the response rate for combination treatment was higher than for temozolomide alone.
- Olaparib (AZD2281 / KU-0059436) in Breast cancer and ovarian cancer (AstraZeneca). Combination of AZD2281 with cisplatin or carboplatin increased the recurrence-free and overall survival, suggesting that AZD2281 potentiates the effect of these DNA-damaging agents. Preliminary results demonstrate in vivo sensitivity and efficacy of AZD2281, alone or in combination with cisplatin, and provide strong support for AZD2281 as a novel targeted therapeutic against BRCA-deficient cancers.
- BSI-201 in Breast cancer, ovarian cancer, uterine cancerand glioblastoma multiforme (BiPar Sciences Inc.). Data from a Phase II trial of BSI-201 in metastatic breast cancer patients whose tumors were negative for three common breast cancer markers: estrogen receptor, progesterone receptor, and HER2, confirmed that the patients' tumors had significant upregulation of PARP, compared with normal breast tissue, supporting the targeting of this enzyme with BSI-201.
ASCO 2009 Abstracts
- O'Shaughnessy J, Osborne C, Pippen J, Yoffe M, et al. Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): Results of a randomized phase II trial. J Clin Oncol 27:18s, 2009 (suppl; abstr 3).
For more information, read these PubMed abstracts:
- Chalmers AJ. The potential role and application of PARP inhibitors in cancer treatment. Br Med Bull. 2009;89:23-40. Epub 2009 Feb 9.
- Dungey FA, Löser DA, Chalmers AJ. Replication-dependent radiosensitization of human glioma cells by inhibition of poly(ADP-Ribose) polymerase: mechanisms and therapeutic potential. Int J Radiat Oncol Biol Phys. 2008 Nov 15;72(4):1188-97.
- Chalmers AJ, Bentzen SM, Buffa FM. A general framework for quantifying the effects of DNA repair inhibitors on radiation sensitivity as a function of dose. Theor Biol Med Model. 2007 Jul 19;4:25.
- Kummar S, Kinders R, Gutierrez ME, Rubinstein L, et al. Phase 0 clinical trial of the poly (ADP-ribose) polymerase inhibitor ABT-888 in patients with advanced malignancies. J Clin Oncol. 2009 Jun 1;27(16):2705-11. Epub 2009 Apr 13.
- Donawho CK, Luo Y, Penning TD, Bauch JL, et al. ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res. 2007 May 1;13(9):2728-37
- Palma JP, Rodriguez LE, Bontcheva-Diaz VD, Bouska JJ, et al. The PARP inhibitor, ABT-888 potentiates temozolomide: correlation with drug levels and reduction in PARP activity in vivo. Anticancer Res. 2008 Sep-Oct;28(5A):2625-35
- Daniel RA, Rozanska AL, Thomas HD, Mulligan EA, et al. Inhibition of poly(ADP-ribose) polymerase-1 enhances temozolomide and topotecan activity against childhood neuroblastoma. Clin Cancer Res. 2009 Feb 15;15(4):1241-9. Epub 2009 Jan 27.
- Plummer R, Jones C, Middleton M, Wilson R, Evans J, et al. Phase I study of the poly(ADP-ribose) polymerase inhibitor, AG014699, in combination with temozolomide in patients with advanced solid tumors. Clin Cancer Res. 2008 Dec 1;14(23):7917-23.
- Calvert AH, Plummer R. The development of phase I cancer trial methodologies: the use of pharmacokinetic and pharmacodynamic end points sets the scene for phase 0 cancer clinical trials. Clin Cancer Res. 2008 Jun 15;14(12):3664-9.
For more information:
- Farmer H, McCabe N, Lord CJ et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917-921 (14 April 2005) doi:10.1038/nature03445.
- Bryant HE, Schultz N, Thomas HD, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434, 913-917 (14 April 2005) doi:10.1038/nature03443.
Also read:
- Investigational BSI-201 plus Chemotherapy May Offer New Treatment Option for Triple-Negative Breast Cancer
- Olaparib Induces Tumor Response as Single Agent in BRCA-Deficient Breast Cancer.
- O’Shaughnessy J, Osborne C, Blum J, Pippen J, Yoffe M, et al. Triple Negative Metastatic Breast Cancer: A Phase 2, Multi-Center, Open-Label, Randomized Trial of Gemcitabine/Carboplatin (G/C) With or Without BSI-201, a PARP Inhibitor. SABCS Poster 2120, December 2008
Friday, December 5, 2008
New Radiotherapy Technology may Improve Outcomes
A 60-year-old prostate cancer patient in Montpeller, has become the first person in France to be treated with a new, fast and precise, form of intensity modulated radiotherapy (IMRT). Each of his treatments at the Centre Régional de Lutte Contre le Cancer (CRLC),Val D'Aurelle in Montpeller, France, took just 75 seconds, several times faster than conventional IMRT treatments.
Dr. Pascal Fenoglietto, the hospital's chief medical physicist for scientific projects, presented the case to his peers at the annual meeting of the Société Française de Radiothérapie Oncologique (French Society of Radiation Oncologists, SFRO, November 12- 14), in the Palais des Congrés de Paris, in Paris, France.
"Compared to conventional IMRT technology [this treatment] was three times quicker," explained Dr. Fenoglietto. "We are now able to use the time we save on treatment delivery to take more images and increase the quality of our care."
The new IMRT technology called RapidArc was developed by Varian Medical Systems, Inc. (Palo Alto, California), a leading manufacturer of medical devices and software for treating cancer with radiotherapy, radiosurgery, proton therapy, and brachytherapy.
With the new, faster, image-guided IMRT, physicians can target radiation beams at a tumor while making just one continuous rotation around the patient. Conventional IMRT treatments are slower and more difficult for radiotherapy radiographers because they target tumors using a complex sequence of fixed beams from multiple angles. The result is that physicians can now better adjust the dose more closely to the size, shape, and location of the tumor which helps them to kill cancer cells more effectively but to spare more healthy tissue with reduced complications and better outcomes. "We now have the opportunity to improve outcomes while offering more patients greater access to advanced care," Dr. Fenoglietto said.
So far, more than 700 patients have been treated with IMRT at the comprehensive cancer center in Montpeller, since its introduction in 2001. According to radiation oncologist Dr. Carmen Llacer Moscardo, "Pelvic cases can take between 12 and 14 minutes to treat with IMRT but we can now do them in less than two minutes with one arc or, if clinically relevant, about three minutes with two arcs around the patient with this new technology. If we do this, there is less possibility for the patient to move and we reduce the chance of internal motion playing a part, as there tends to be a lot of motion in the pelvic region. Also, fast treatments reduce the possibility of inaccuracy and increase patient comfort."
Dr. Pascal Fenoglietto, the hospital's chief medical physicist for scientific projects, presented the case to his peers at the annual meeting of the Société Française de Radiothérapie Oncologique (French Society of Radiation Oncologists, SFRO, November 12- 14), in the Palais des Congrés de Paris, in Paris, France.
"Compared to conventional IMRT technology [this treatment] was three times quicker," explained Dr. Fenoglietto. "We are now able to use the time we save on treatment delivery to take more images and increase the quality of our care."
The new IMRT technology called RapidArc was developed by Varian Medical Systems, Inc. (Palo Alto, California), a leading manufacturer of medical devices and software for treating cancer with radiotherapy, radiosurgery, proton therapy, and brachytherapy.
With the new, faster, image-guided IMRT, physicians can target radiation beams at a tumor while making just one continuous rotation around the patient. Conventional IMRT treatments are slower and more difficult for radiotherapy radiographers because they target tumors using a complex sequence of fixed beams from multiple angles. The result is that physicians can now better adjust the dose more closely to the size, shape, and location of the tumor which helps them to kill cancer cells more effectively but to spare more healthy tissue with reduced complications and better outcomes. "We now have the opportunity to improve outcomes while offering more patients greater access to advanced care," Dr. Fenoglietto said.
So far, more than 700 patients have been treated with IMRT at the comprehensive cancer center in Montpeller, since its introduction in 2001. According to radiation oncologist Dr. Carmen Llacer Moscardo, "Pelvic cases can take between 12 and 14 minutes to treat with IMRT but we can now do them in less than two minutes with one arc or, if clinically relevant, about three minutes with two arcs around the patient with this new technology. If we do this, there is less possibility for the patient to move and we reduce the chance of internal motion playing a part, as there tends to be a lot of motion in the pelvic region. Also, fast treatments reduce the possibility of inaccuracy and increase patient comfort."
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