3 augustus 2012: Onderaan hebben we het abstract van dit volledige studierapport: The role of emerging and investigational therapies for metastatic brain tumors: a systematic review and evidence-based clinical practice guideline of selected topics toegevoegd. Ook efaproxiral behoort tot de niet toxische middelen die worden besproken.  

5 april 2006: J Clin Oncol. 2005 Sep 1;23(25):5918-28.

Zie onderaan een overzichtsstudie met de aanpak met Efaproxiral - RSR 13. In de derde helft van 2006 worden resultaten uit een 5 jarige fase III studie verwacht met deze aanpak.

Het bedrijf Allos Therapeutics meldt opnieuw een goed behandelingsresultaat, zonder ernstige bijwerkingen, in een fase II trial bij niet-kleincellige-longkanker als hun het middel RSR13 ( efaproxiral) aanvullend wordt gegeven tijdens de bestraling en daarop aansluitend chemotherapie. Al eerder berichtte dit bedrijf over goede resultaten hiermee, zie onder dit nieuwe artikel een artikel uit 2002.

RSR 13 - efaproxiral - is volgens dit bedrijf een synthetische molecuul die het zuurstofniveau in de kankercellen verhoogt waardoor het effect van de bestraling wordt vergroot. De nieuwe studie is uitgevoerd bij 51 patiënten met niet operabele en gevorderde niet-kleincellige-longkanker in 13 verschillende ziekenhuizen. De resultaten zijn nagenoeg hetzelfde als eerdere studie: Met RSR 13 - efaproxiral - als toevoeging aan de bestraling bleken de behandelde patiënten een mediane overlevingsduur te hebben van 20,6 maanden (95% CI, 14.0 to 24.2) tegenover 15,1 maanden en 17,9 maanden in controlegroepen; Overall overleving na 1- en 2 jaar was 67% en 37%, respectievelijk. Ook het bijwerkingsprofiel was significant minder dan zonder RSR13.

Phase II multicenter study of induction chemotherapy followed by concurrent efaproxiral (RSR13) and thoracic radiotherapy for patients with locally advanced non-small-cell lung cancer.

Choy H, Nabid A, Stea B, Scott C, Roa W, Kleinberg L, Ayoub J, Smith C, Souhami L, Hamburg S, Spanos W, Kreisman H, Boyd AP, Cagnoni PJ, Curran WJ.
Vanderbilt University Medical Center, Nashville, TN, USA. hak.choy@utsouthwestern.edu

PURPOSE: Efaproxiral (RSR13) reduces hemoglobin oxygen-binding affinity, facilitates oxygen release, and increases tissue pO2. We conducted a phase II multicenter study that assessed the efficacy and safety of efaproxiral when administered with thoracic radiation therapy (TRT), following induction chemotherapy, for treatment of locally advanced non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS: Fifty-one patients with locally advanced NSCLC were enrolled at 13 sites. Treatment comprised two cycles of paclitaxel (225 mg/m2) and carboplatin (area under the curve, 6), 3 weeks apart, followed by TRT (64 Gy/32 fractions) with concurrent efaproxiral (50 to 100 mg/kg). Survival results were compared with results of study Radiation Therapy Oncology Group (RTOG) 94-10.

RESULTS: Overall response rate was 75% (37 of 49 patients). Complete and partial response rates were 6% (three of 49 patients) and 69% (34 of 49 patients), respectively. Median survival time (MST) was 20.6 months (95% CI, 14.0 to 24.2); overall survival rates at 1- and 2-years were 67% and 37%, respectively. Survival results were compared with the sequential (S-CRT) and concurrent (C-CRT) chemoradiotherapy arms of RTOG 94-10. MSTs for cases matched by stage, Karnofsky performance status, and age were: RT-010, 20.6 months; S-CRT, 15.1 months; and C-CRT, 17.9 months. Grade 3 to 4 toxicities related to efaproxiral that occurred in more than one patient included transient hypoxemia (19%), radiation pneumonitis (11%), and fatigue (4%).

CONCLUSION: Addition of efaproxiral to S-CRT represents a promising approach in NSCLC treatment, and a randomized study should be pursued. The low incidence of grade 3 to 4 toxicities suggests that the use of efaproxiral instead of a cytotoxic agent, as a radiation sensitizer, may be advantageous.

Publication Types:
Clinical Trial
Clinical Trial, Phase II
Multicenter Study

PMID: 16135463 [PubMed - indexed for MEDLINE]

19 september 2002: Bron: Alos Therapeutics

Het bedrijf Allos Therapeutics meldt een goed behandelingsresultaat, zonder ernstige bijwerkingen, in een fase II trial bij niet-kleincellige-longkanker als hun het middel RSR13 ( efaproxiral) aanvullend wordt gegeven tijdens de bestraling en daarop aansluitend chemotherapie van de niet-kleincellige-longkankertumoren.
RSR 13 - efaproxiral - is volgens dit bedrijf een synthetische molecuul die het zuurstofniveau in de kankercellen verhoogt waardoor het effect van de bestraling wordt vergroot. De studie is uitgevoerd bij 52 patiënten met niet operabele en gevorderde niet-kleincellige-longkanker. De resultaten zijn bemoedigend. Met RSR 13 - efaproxiral - als toevoeging aan de bestraling bleken de behandelde patiënten met een niet operabele gevorderde niet-kleincellige-longkanker graad IIIa en IIIB (zie verder onder longkanker algemeen op deze pagina wat dit betekent) een gemiddelde overlevingsduur te hebben van 20,6 maanden tegenover 13,0 en 14,6 maanden in vergelijkbare controlegroepen die de bestraling kregen zonder de RSR 13 - efaproxiral - toevoeging. De 1 jaarsoverleving in de groep van RSR 13 - efaproxiral - was 67 procent en de twee jaarsoverleving 37 procent. Deze resultaten zijn significant te noemen en vrijgegeven en gepubliceerd op ESTRO - het grote Europese congres over longkanker en actuele behandelingen d.d. 19 september 2002.

Het bedrijf Allos gaat een grotere fase III studie doen in het vierde kwartaal van 2002 met RSR 13 - efaproxiral - en dezelfde uitgangspunten. Ook worden er trials voorbereid voor RSR 13 - efaproxiral - bij hersentumoren. Voor wie is geïnteresseerd in nadere informatie kan met haar/zijn oncoloog contact opnemen met Allos.

Hieronder het originele persbericht van het bedrijf Allos.

-- PRESS RELEASE: Allos Updates RSR13 Phase 2 Study Results --

Allos Updates RSR13 Phase 2 Study Results in Non-Small Cell Lung Cancer
At European Radiation Therapy Conference

- Updated 2-Year Follow Up Results Continue to Show Significant Improvement
In Median Survival Time Over Like Studies With Addition of RSR13 -

PRAGUE, Sept. 19 /PRNewswire-FirstCall/ -- Allos Therapeutics, Inc. (Nasdaq:
ALTH) today announced updated positive survival results from a Phase 2 clinical
trial evaluating the use of RSR13 (efaproxiral) in patients with locally
advanced, unresectable, non-small cell lung cancer receiving thoracic radiation
therapy following induction chemotherapy. At the time of the analysis,
approximately 96 percent of evaluable patients had been followed for at least 2
years. The updated results showed a median survival of 20.6 months, 1-year
survival rate of 67 percent and a 2-year survival rate of 37 percent. There
were no cases of moderate to severe esophagitis Data from this study were presented today at the European Society for Therapeutics Radiology and Oncology (ESTRO), Abstract
896.
RSR13 is a synthetic small molecule that enhances the diffusion of oxygen to
hypoxic (oxygen deprived) tumor tissue and has the potential to enhance the
effectiveness of standard radiation therapy.
"The fact that the median survival of 20.6 months remains constant with a
median follow up of over two years is very encouraging for patients with this
aggressive and difficult-to-treat disease," said Pablo J. Cagnoni, M.D., senior
director, clinical development at Allos Therapeutics, Inc. "The results of this
study compare favorably to the sequential chemoradiotherapy arm of the LAMP
study (ASCO 2002 Abstract #1160, Arm 1) which showed a median survival of 13.0
months for the identical treatment, minus RSR13; and the sequential
chemoradiotherapy arm of the RTOG 94-10, which reported a median survival time
of 14.6 months."
The study was conducted in 52 patients with locally advanced, unresectable,
stage IIIA/IIIB non-small cell lung cancer. Response rate data was obtained in
44 patients that reached the 2-month follow-up. The objectives of this study
were to evaluate overall survival, progression-free interval in the chest,
complete and partial response rates in the chest (radiation portal) and time to
disease progression outside of the radiation portal. The patients received two
courses of induction chemotherapy with paclitaxel and carboplatin followed by
daily RSR13 combined with thoracic radiation therapy for 32 doses.



SOURCE Allos Therapeutics, Inc

Geplaatst 6 april 2006:

Drugs R D. 2005;6(3):178-85.

Efaproxiral: GSJ 61, JP 4, KDD 86, RS 4, RSR 13.

[No authors listed]

Efaproxiral [RSR 13, GSJ 61, JP 4, KDD 86, RS 4] is a synthetic, small-molecule, radiation-sensitising agent being developed by Allos Therapeutics primarily for the treatment of cancer. It works by binding and allosterically stabilising deoxyhaemoglobin in hypoxic regions of tumour tissue. This increases oxygen uptake of the tumour tissue and restores its sensitivity to radiation therapy, making therapy potentially more successful. This first-of-its-class compound is particularly applicable for the treatment of certain tumour types that lack oxygen, such as brain metastases. In contrast to conventional chemotherapeutic agents or radiation sensitisers, there is no requirement for efaproxiral to be administered directly into tumours or to cross the blood-brain barrier for it to display efficacy.

Efaproxiral is under review for approval in the US and EU as an adjunct to whole-brain radiation therapy (WBRT) for the treatment of brain metastases originating from breast cancer. It is also under clinical evaluation for a variety of other cancers, including glioblastoma, non-small cell lung cancer (NSCLC) and cervical cancer.Allos is seeking partnership opportunities for efaproxiral's development and marketing. The company has indicated that the development of efaproxiral would be in cooperation with a corporate partner, according to its 2003 Annual Report.

In 1994, Allos Therapeutics acquired exclusive worldwide rights to intellectual property relating to efaproxiral from the Center for Innovative Technology (CIT).Allos has entered into arrangements with two contract manufacturers for the supply of efaproxiral, and a third manufacturer for the supply of the formulated drug product. Hovione FarmaCiencia is the primary supplier of efaproxiral, and is contracted to manufacture sufficient quantities on a commercial scale. In addition, a second manufacturer, Raylo Chemicals, is also producing quantities of efaproxiral. In December 2003, Allos entered into a long-term development and supply agreement with Baxter Healthcare who will formulate the efaproxiral into an injection. Allos is also seeking to establish an alternate supplier of efaproxiral injection. Allos submitted a rolling NDA to the US FDA consisting of three data components. Submission began in the third quarter of 2003 and was completed by the fourth quarter of 2003. The first part of the application containing non-clinical information was submitted on 5 August 2003.

The second part of the NDA containing information about efaproxiral's chemistry, manufacture and controls (CMC) was submitted in October 2003. Allos submitted its final component of the rolling NDA in December 2003. In February 2004, Allos announced that the FDA had accepted the company's NDA under priority review status. The FDA granted efaproxiral orphan drug status in August 2004 as an adjunct to WBRT for the treatment of brain metastases among breast cancer patients.

Efaproxiral also received fast-track status in November 2000 for the same indication in the US.In February 2004, Allos initiated a phase III trial, called ENRICH (Enhancing Whole Brain Radiation Therapy In Patients with Breast Cancer and Hypoxic Brain Metastases) to investigate efaproxiral as an adjunct to WBRT for the treatment of brain metastases. Median survival time is the primary endpoint of the study. The National Breast Cancer Coalition (NBCC) is collaborating with the company to support trial enrolment and to gain additional insight about ways to improve radiation treatment in this patient population. The ENRICH trial protocol was approved by the FDA under a Special Protocol Assessment process; as part of the protocol, two interim analyses for safety and efficacy will be performed.This multicentre, randomised, open-label study has a target enrolment of approximately 360 patients at >100 medical centres across the US, Canada, Europe and South America. Allos announced in September 2004 that recruitment of clinical sites for the trial is ongoing across the US and Canada. Completion of trial enrolment in North America is anticipated in December 2005. Subsequently, Allos announced in January 2005 that recruitment into the ENRICH trial has commenced and is ongoing in Europe; enrolment at European sites is expected to conclude by the third quarter of 2006.

Allos Therapeutics announced in June 2004 that it had filed an MAA with the EMEA for marketing of exaproxiral as an adjunct to WBRT for treatment of patients with brain metastases originating from breast cancer. The application is based on positive data from a pivotal phase III (REACH, RT-009) trial in this indication. The completed REACH trial investigated efaproxiral among patients with brain metastases undergoing WBRT. The trial was conducted at multiple sites in 11 countries, including the US, Canada, Europe and Australia. In August 2002 Allos completed the enrolment of 538 patients in the study. Initially only 408 patients were to be enrolled, but the company increased the size of the trial to conduct an appropriately powered subgroup analysis in patients with brain metastases from breast and NSCLC. The study was designed to demonstrate a 35% increase in median survival in the subgroup of patients compared with standard WBRT alone. The primary endpoint was survival.Allos began screening US patients for a phase III trial in NSCLC in early 2003. However, in May 2003, the company announced that as part of its revised operating plan it had suspended the screening of patients for this trial.

The trial, which was known as ELITE (Enhanced Lung cancer treatment with Induction chemotherapy and Thoracic radiation and Efaproxiral), was comparing induction chemotherapy followed by thoracic radiation therapy with supplemental oxygen, with or without efaproxiral. The trial was enrolling patients with locally advanced, unresectable NSCLC. ELITE was planned to enrol up to 600 patients across North America and Western and Eastern Europe.

Phase II trials in patients with inoperable NSCLC have been conducted in the US and Canada. Patient enrolment in one of these studies was completed in August 2000, with a total of 52 patients enrolled. This was an open-label, multicentre study of induction therapy with paclitaxel plus carboplatin followed by chest irradiation and efaproxiral in patients with locally advanced NSCLC. Positive results from this study were reported at the annual meeting of the European Society for Therapeutics Radiology and Oncology in September 2002. Efaproxiral has completed phase I trials as a treatment of surgical hypoxia in elective surgery patients receiving general anaesthesia. However, no recent development has been reported for these indications.In 1994, Allos signed an agreement with CIT for the exclusive worldwide rights to 17 US patents, a European patent covering the UK, France, Italy and Germany plus two pending patents in these territories, two issued patents in Japan, and a pending patent in Canada. These patents cover methods of allosterically modifying haemoglobin with efaproxiral and other compounds, the binding site of efaproxiral and therapy in certain indications including cancer, ischaemia and hypoxia. In addition to the licensed patents from CIT, Allos exclusively owns two patent families with pending applications directed to a formulation of efaproxiral and to methods of its use in BLOD MRI (blood oxygenation level-dependent magnetic resonance imaging) applications. These patents are pending in the US, Canada and Europe, and include an international patent application.

In a May 2002 interview with the Wall Street Transcript, the CEO of Allos estimated the overall market for radiation therapy to be approximately 750 000 patients/year. Of this, brain metastases, NSCLC and glioblastoma therapy accounts for about 170 000, 140 000 and 6000 patients, respectively. Allos intend to use a speciality sales force to market efaproxiral directly to radiation therapists in North America. To penetrate the non-oncology market in the US, the company will seek partnership with one or more pharmaceutical companies with direct sales forces and with established distribution systems. Allos is also hoping to secure an oncology marketing partner for non-North American territories. At the time, the company had been issued 21 patents in the US, Canada, Europe and Japan.

Publication Types:
Review

The role of emerging and investigational therapies for metastatic brain tumors: a systematic review and evidence-based clinical practice guideline of selected topics

PMCID: PMC2808529

The role of emerging and investigational therapies for metastatic brain tumors: a systematic review and evidence-based clinical practice guideline of selected topics

Abstract

Question

What evidence is available regarding the emerging and investigational therapies for the treatment of metastatic brain tumors?

Target population

These recommendations apply to adults with brain metastases.

Recommendations

New radiation sensitizers

Level 2 A subgroup analysis of a large prospective randomized controlled trial (RCT) suggested a prolongation of time to neurological progression with the early use of motexafin-gadolinium (MGd). Nonetheless this was not borne out in the overall study population and therefore an unequivocal recommendation to use the currently available radiation sensitizers, motexafin-gadolinium and efaproxiral (RSR 13) cannot be provided.

Interstitial modalities

There is no evidence to support the routine use of new or existing interstitial radiation, interstitial chemotherapy and or other interstitial modalities outside of approved clinical trials.

New chemotherapeutic agents

Level 2 Treatment of melanoma brain metastases with whole brain radiation therapy and temozolomide is reasonable based on one class II study.

Level 3 Depending on individual circumstances there may be patients who benefit from the use of temozolomide or fotemustine in the therapy of their brain metastases.

Molecular targeted agents

Level 3 The use of epidermal growth factor receptor inhibitors may be of use in the management of brain metastases from non-small cell lung carcinoma.

References

1. Robinson PD, Kalkanis SN, Linskey ME, Santaguida PL (2009) Methodology used to develop the AANS/CNS management of brain metastases evidence-based clinical practice parameter guidelines. J Neurooncol. doi:10.1007/s11060-009-0059-2.
2. Centre for Evidence-Based Physiotherapy (2009) Physiotherapy evidence database (PEDro). http://www.pedro.org.au/. Accessed Jan 2009.
3. Maher CG, Sherrington C, Herbert RD, Moseley AM, Elkins M. Reliability of the PEDro scale for rating quality of randomized controlled trials. Phys Ther. 2003;83(8):713–721. [PubMed]
4. Mehta MP, Rodrigus P, Terhaard CH, Rao A, Suh J, Roa W, et al. Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases. J Clin Oncol. 2003;21(13):2529–2536. doi: 10.1200/JCO.2003.12.122. [PubMed] [Cross Ref]
5. Suh JH, Stea B, Nabid A, Kresl JJ, Fortin A, Mercier JP, et al. Phase III study of efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases. J Clin Oncol. 2006;24(1):106–114. doi: 10.1200/JCO.2004.00.1768. [PubMed] [Cross Ref]
6. Mehta MP, Shapiro WR, Phan SC, Gervais R, Carrie C, Chabot P, et al. Motexafin gadolinium combined with prompt whole brain radiotherapy prolongs time to neurologic progression in non-small-cell lung cancer patients with brain metastases: results of a phase III trial. Int J Radiat Oncol Biol Phys. 2009;73(4):1069–1076. [PubMed]
7. Carde P, Timmerman R, Mehta MP, Koprowski CD, Ford J, Tishler RB, et al. Multicenter phase Ib/II trial of the radiation enhancer motexafin gadolinium in patients with brain metastases. J Clin Oncol. 2001;19(7):2074–2083. [PubMed]
8. Shaw E, Scott C, Suh J, Kadish S, Stea B, Hackman J, et al. RSR13 plus cranial radiation therapy in patients with brain metastases: comparison with the radiation therapy oncology group recursive partitioning analysis brain metastases database. J Clin Oncol. 2003;21(12):2364–2371. doi: 10.1200/JCO.2003.08.116. [PubMed] [Cross Ref]
9. Meyers CA, Smith JA, Bezjak A, Mehta MP, Liebmann J, Illidge T, et al. Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial. J Clin Oncol. 2004;22(1):157–165. doi: 10.1200/JCO.2004.05.128. [PubMed] [Cross Ref]
10. Mehta MP, Shapiro WR, Glantz MJ, Patchell RA, Weitzner MA, Meyers CA, et al. Lead-in phase to randomized trial of motexafin gadolinium and whole-brain radiation for patients with brain metastases: centralized assessment of magnetic resonance imaging, neurocognitive, and neurologic end points. J Clin Oncol. 2002;20(16):3445–3453. doi: 10.1200/JCO.2002.07.500. [PubMed] [Cross Ref]
11. Stea B, Shaw E, Pinter T, Hackman J, Craig M, May J, et al. Efaproxiral red blood cell concentration predicts efficacy in patients with brain metastases. Br J Cancer. 2006;94(12):1777–1784. doi: 10.1038/sj.bjc.6603169. [PMC free article] [PubMed] [Cross Ref]
12. Stea B, Suh JH, Boyd AP, Cagnoni PJ, Shaw E. Whole-brain radiotherapy with or without efaproxiral for the treatment of brain metastases: determinants of response and its prognostic value for subsequent survival. Int J Radiat Oncol Biol Phys. 2006;64(4):1023–1030. [PubMed]
13. Scott C, Suh J, Stea B, Nabid A, Hackman J. Improved survival, quality of life, and quality-adjusted survival in breast cancer patients treated with efaproxiral (efaproxyn) plus whole-brain radiation therapy for brain metastases. Am J Clin Oncol. 2007;30(6):580–587. doi: 10.1097/COC.0b013e3180653c0d. [PubMed] [Cross Ref]
14. Suh J, Stea B, Tankel K, Marsiglia H, Belkacemi Y, Gomez H et al (2007) Phase 3 enrich (RT-016) comparative study of efaproxiral administered concurrent with whole brain radiation therapy (WBRT) in women with brain metastases from breast cancer. RT-35. The society for neurooncology 12th annual meeting, Dallas, Texas.
15. Ewend MG, Brem S, Gilbert M, Goodkin R, Penar PL, Varia M, et al. Treatment of single brain metastasis with resection, intracavity carmustine polymer wafers, and radiation therapy is safe and provides excellent local control. Clin Cancer Res. 2007;13(12):3637–3641. doi: 10.1158/1078-0432.CCR-06-2095. [PubMed] [Cross Ref]
16. Rogers LR, Rock JP, Sills AK, Vogelbaum MA, Suh JH, Ellis TL, et al. Results of a phase II trial of the GliaSite radiation therapy system for the treatment of newly diagnosed, resected single brain metastases. J Neurosurg. 2006;105(3):375–384. doi: 10.3171/jns.2006.105.3.375. [PubMed] [Cross Ref]
17. Nakagawa H, Maeda N, Tsuzuki T, Suzuki T, Hirayama A, Miyahara E, et al. Intracavitary chemotherapy with 5-fluoro-2′-deoxyuridine (FdUrd) in malignant brain tumors. Jpn J Clin Oncol. 2001;31(6):251–258. doi: 10.1093/jjco/hye055. [PubMed] [Cross Ref]
18. Alesch F, Hawliczek R, Koos WT. Interstitial irradiation of brain metastases. Acta Neurochir. 1995;63(Suppl):29–34.
19. Bernstein M, Cabantog A, Laperriere N, Leung P, Thomason C. Brachytherapy for recurrent single brain metastasis. Can J Neurol Sci. 1995;22(1):13–16. [PubMed]
20. Bogart JA, Ungureanu C, Shihadeh E, Chung TC, King GA, Ryu S, et al. Resection and permanent I-125 brachytherapy without whole brain irradiation for solitary brain metastasis from non-small cell lung carcinoma. J Neurooncol. 1999;44(1):53–57. doi: 10.1023/A:1006285304892. [PubMed] [Cross Ref]
21. Dagnew E, Kanski J, McDermott MW, Sneed PK, McPherson C, Breneman JC, et al. Management of newly diagnosed single brain metastasis using resection and permanent iodine-125 seeds without initial whole-brain radiotherapy: a two institution experience. Neurosurg Focus. 2007;22(3):E3. doi: 10.3171/foc.2007.22.3.4. [PubMed] [Cross Ref]
22. Schulder M, Black PM, Shrieve DC, Alexander E, III, Loeffler JS. Permanent low-activity iodine-125 implants for cerebral metastases. J Neurooncol. 1997;33(3):213–221. doi: 10.1023/A:1005798027813. [PubMed] [Cross Ref]
23. Curry WT, Jr, Cosgrove GR, Hochberg FH, Loeffler J, Zervas NT. Stereotactic interstitial radiosurgery for cerebral metastases. J Neurosurg. 2005;103(4):630–635. doi: 10.3171/jns.2005.103.4.0630. [PubMed] [Cross Ref]
24. Nakamura O, Matsutani M, Shitara N, Okamoto K, Kaneko M, Nakamura H, et al. New treatment protocol by intra-operative radiation therapy for metastatic brain tumours. Acta Neurochir. 1994;131(1–2):91–96. doi: 10.1007/BF01401458. [Cross Ref]
25. Ostertag CB, Kreth FW. Interstitial iodine-125 radiosurgery for cerebral metastases. Br J Neurosurg. 1995;9(5):593–603. doi: 10.1080/02688699550040873. [PubMed] [Cross Ref]
26. Kreth FW, Warnke PC, Ostertag CB. Interstitial implant radiosurgery for cerebral metastases. Acta Neurochir Suppl (Wein) 1993;58:112–114.
27. Sills A, Tatter S, Fraser R, Asher A, Vogelbaum M, Judy K, et al. A phase II study utilizing focal radiation in patients with 1–3 brain metastases. RT-09. The society for neurooncology 12th annual scientific meeting. Texas: Dallas; 2007.
28. Burri S, Asher A, Mueller M, Fraser R. The use of glia-site in the primary managment of brain metastases results in a high rate of radiation necrosis and re-operation. RT-23. The society for neurooncology 12th annual scientific meeting. Texas: Dallas; 2007.
29. Prasad SC, Bassano DA, Fear PL, King GA. Dosimetry of I-125 seeds implanted on the surface of a cavity. Med Dosim. 1990;15(4):217–219. [PubMed]
30. Noordijk EM, Vecht CJ, Haaxma-Reiche H, Padberg GW, Voormolen JH, Hoekstra FH, et al. The choice of treatment of single brain metastasis should be based on extracranial tumor activity and age. Int J Radiat Oncol Biol Phys. 1994;29(4):711–717. [PubMed]
31. Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA. 1998;280(17):1485–1489. doi: 10.1001/jama.280.17.1485. [PubMed] [Cross Ref]
32. Antonadou D, Paraskevaidis M, Sarris G, Coliarakis N, Economou I, Karageorgis P, et al. Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases. J Clin Oncol. 2002;20(17):3644–3650. doi: 10.1200/JCO.2002.04.140. [PubMed] [Cross Ref]
33. Verger E, Gil M, Yaya R, Vinolas N, Villa S, Pujol T, et al. Temozolomide and concomitant whole brain radiotherapy in patients with brain metastases: a phase II randomized trial. Int J Radiat Oncol Biol Phys. 2005;61(1):185–191. [PubMed]
34. Conill C, Jorcano S, Domingo-Domenech J, Gallego R, Malvehy J, Puig S, et al. Whole brain irradiation and temozolomide based chemotherapy in melanoma brain metastases. Clin Transl Oncol. 2006;8(4):266–270. doi: 10.1007/BF02664937. [PubMed] [Cross Ref]
35. Panagiotou IE, Brountzos EN, Kelekis DA, Papathanasiou MA, Bafaloukos DI. Cerebral metastases of malignant melanoma: contemporary treatment modalities and survival outcome. Neoplasma. 2005;52(2):150–158. [PubMed]
36. Abrey LE, Olson JD, Raizer JJ, Mack M, Rodavitch A, Boutros DY, et al. A phase II trial of temozolomide for patients with recurrent or progressive brain metastases. J Neurooncol. 2001;53(3):259–265. doi: 10.1023/A:1012226718323. [PubMed] [Cross Ref]
37. Addeo R, Caraglia M, Faiola V, Capasso E, Vincenzi B, Montella L, et al. Concomitant treatment of brain metastasis with whole brain radiotherapy and temozolomide is active and improves quality of life. BMC Cancer. 2007;7:18. doi: 10.1186/1471-2407-7-18. [PMC free article] [PubMed] [Cross Ref]
38. Agarwala SS, Kirkwood JM, Gore M, Dreno B, Thatcher N, Czarnetski B, et al. Temozolomide for the treatment of brain metastases associated with metastatic melanoma: a phase II study. J Clin Oncol. 2004;22(11):2101–2107. doi: 10.1200/JCO.2004.11.044. [PubMed] [Cross Ref]
39. Bafaloukos D, Tsoutsos D, Fountzilas G, Linardou H, Christodoulou C, Kalofonos HP, et al. The effect of temozolomide-based chemotherapy in patients with cerebral metastases from melanoma. Melanoma Res. 2004;14(4):289–294. doi: 10.1097/01.cmr.0000136707.60108.ab. [PubMed] [Cross Ref]
40. Boogerd W, de Gast GC, Dalesio O (1-15-2007) Temozolomide in advanced malignant melanoma with small brain metastases: can we withhold cranial irradiation? Cancer 109(2):306–312.
41. Caraglia M, Addeo R, Costanzo R, Montella L, Faiola V, Marra M, et al. Phase II study of temozolomide plus pegylated liposomal doxorubicin in the treatment of brain metastases from solid tumours. Cancer Chemother Pharmacol. 2006;57(1):34–39. doi: 10.1007/s00280-005-0001-z. [PubMed] [Cross Ref]
42. Christodoulou C, Bafaloukos D, Linardou H, Aravantinos G, Bamias A, Carina M, et al. Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain metastases from solid tumors: a Hellenic cooperative oncology group (HeCOG) phase II study. J Neurooncol. 2005;71(1):61–65. doi: 10.1007/s11060-004-9176-0. [PubMed] [Cross Ref]
43. Christodoulou C, Bafaloukos D, Kosmidis P, Samantas E, Bamias A, Papakostas P, et al. Phase II study of temozolomide in heavily pretreated cancer patients with brain metastases. Ann Oncol. 2001;12(2):249–254. doi: 10.1023/A:1008354323167. [PubMed] [Cross Ref]
44. Giorgio CG, Giuffrida D, Pappalardo A, Russo A, Santini D, Salice P, et al. Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: phase II study. Lung Cancer. 2005;50(2):247–254. doi: 10.1016/j.lungcan.2005.05.026. [PubMed] [Cross Ref]
45. Hofmann M, Kiecker F, Wurm R, Schlenger L, Budach V, Sterry W, et al. Temozolomide with or without radiotherapy in melanoma with unresectable brain metastases. J Neurooncol. 2006;76(1):59–64. doi: 10.1007/s11060-005-2914-0. [PubMed] [Cross Ref]
46. Hwu WJ, Lis E, Menell JH, Panageas KS, Lamb LA, Merrell J, et al. Temozolomide plus thalidomide in patients with brain metastases from melanoma: a phase II study. Cancer. 2005;103(12):2590–2597. doi: 10.1002/cncr.21081. [PubMed] [Cross Ref]
47. Iwamoto FM, Omuro AM, Raizer JJ, Nolan CP, Hormigo A, Lassman AB, et al. A phase II trial of vinorelbine and intensive temozolomide for patients with recurrent or progressive brain metastases. J Neurooncol. 2008;87(1):85–90. doi: 10.1007/s11060-007-9491-3. [PubMed] [Cross Ref]
48. Janinis J, Kapelari K, Efstathiou E, Pectasides D, Tsavaris N, Skarlos D. A pilot study of temozolomide as first line therapy of central nervous system metastases from malignant melanoma. J B U ON. 2000;5(3):277–280.
49. Kouvaris JR, Miliadou A, Kouloulias VE, Kolokouris D, Balafouta MJ, Papacharalampous XN, et al. Phase II study of temozolomide and concomitant whole-brain radiotherapy in patients with brain metastases from solid tumors. Onkologie. 2007;30(7):361–366. doi: 10.1159/000102557. [PubMed] [Cross Ref]
50. Krown SE, Niedzwiecki D, Hwu WJ, Hodgson L, Houghton AN, Haluska FG, et al. Phase II study of temozolomide and thalidomide in patients with metastatic melanoma in the brain: high rate of thromboembolic events (CALGB 500102) Cancer. 2006;107(8):1883–1890. doi: 10.1002/cncr.22239. [PubMed] [Cross Ref]
51. Larkin JM, Hughes SA, Beirne DA, Patel PM, Gibbens IM, Bate SC, et al. A phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma. Br J Cancer. 2007;96(1):44–48. doi: 10.1038/sj.bjc.6603503. [PMC free article] [PubMed] [Cross Ref]
52. Margolin K, Atkins B, Thompson A, Ernstoff S, Weber J, Flaherty L, et al. Temozolomide and whole brain irradiation in melanoma metastatic to the brain: a phase II trial of the cytokine working group. J Cancer Res Clin Oncol. 2002;128(4):214–218. doi: 10.1007/s00432-002-0323-8. [PubMed] [Cross Ref]
53. Omuro AM, Raizer JJ, Demopoulos A, Malkin MG, Abrey LE. Vinorelbine combined with a protracted course of temozolomide for recurrent brain metastases: a phase I trial. J Neurooncol. 2006;78(3):277–280. doi: 10.1007/s11060-005-9095-8. [PubMed] [Cross Ref]
54. Rivera E, Meyers C, Groves M, Valero V, Francis D, Arun B, et al. Phase I study of capecitabine in combination with temozolomide in the treatment of patients with brain metastases from breast carcinoma. Cancer. 2006;107(6):1348–1354. doi: 10.1002/cncr.22127. [PubMed] [Cross Ref]
55. Schadendorf D, Hauschild A, Ugurel S, Thoelke A, Egberts F, Kreissig M, et al. Dose-intensified bi-weekly temozolomide in patients with asymptomatic brain metastases from malignant melanoma: a phase II DeCOG/ADO study. Ann Oncol. 2006;17(10):1592–1597. doi: 10.1093/annonc/mdl148. [PubMed] [Cross Ref]
56. Cortot AB, Geriniere L, Robinet G, Breton JL, Corre R, Falchero L, et al. Phase II trial of temozolomide and cisplatin followed by whole brain radiotherapy in non-small-cell lung cancer patients with brain metastases: a GLOT-GFPC study. Ann Oncol. 2006;17(9):1412–1417. doi: 10.1093/annonc/mdl146. [PubMed] [Cross Ref]
57. Bafaloukos D, Aravantinos G, Fountzilas G, Stathopoulos G, Gogas H, Samonis G, et al. Docetaxel in combination with dacarbazine in patients with advanced melanoma. Oncology. 2002;63(4):333–337. doi: 10.1159/000066225. [PubMed] [Cross Ref]
58. Bafaloukos D, Tsoutsos D, Kalofonos H, Chalkidou S, Panagiotou P, Linardou E, et al. Temozolomide and cisplatin versus temozolomide in patients with advanced melanoma: a randomized phase II study of the Hellenic cooperative oncology group. Ann Oncol. 2005;16(6):950–957. doi: 10.1093/annonc/mdi190. [PubMed] [Cross Ref]
59. Mornex F, Thomas L, Mohr P, Hauschild A, Delaunay MM, Lesimple T, et al. A prospective randomized multicentre phase III trial of fotemustine plus whole brain irradiation versus fotemustine alone in cerebral metastases of malignant melanoma. Melanoma Res. 2003;13(1):97–103. doi: 10.1097/00008390-200302000-00016. [PubMed] [Cross Ref]
60. Brocker EB, Bohndorf W, Kampgen E, Trcka J, Messer P, Tilgen W, et al. Fotemustine given simultaneously with total brain irradiation in multiple brain metastases of malignant melanoma: report on a pilot study. Melanoma Res. 1996;6(5):399–401. doi: 10.1097/00008390-199610000-00008. [PubMed] [Cross Ref]
61. Chang J, Atkinson H, A’Hern R, Lorentzos A, Gore ME. A phase II study of the sequential administration of dacarbazine and fotemustine in the treatment of cerebral metastases from malignant melanoma. Eur J Cancer. 1994;30A(14):2093–2095. doi: 10.1016/0959-8049(94)00297-I. [PubMed] [Cross Ref]
62. Cotto C, Berille J, Souquet PJ, Riou R, Croisile B, Turjman F, et al. A phase II trial of fotemustine and cisplatin in central nervous system metastases from non-small cell lung cancer. Eur J Cancer. 1996;32A(1):69–71. doi: 10.1016/0959-8049(95)00507-2. [PubMed] [Cross Ref]
63. Jacquillat C, Khayat D, Banzet P, Weil M, Avril MF, Fumoleau P, et al. Chemotherapy by fotemustine in cerebral metastases of disseminated malignant melanoma. Cancer Chemother Pharmacol. 1990;25(4):263–266. doi: 10.1007/BF00684883. [PubMed] [Cross Ref]
64. Ulrich J, Gademann G, Gollnick H. Management of cerebral metastases from malignant melanoma: results of a combined, simultaneous treatment with fotemustine and irradiation. J Neurooncol. 1999;43(2):173–178. doi: 10.1023/A:1006280304912. [PubMed] [Cross Ref]
65. Wakelee H. Antibodies to vascular endothelial growth factor in non-small cell lung cancer. J Thorac Oncol. 2008;3(6 Suppl 2):S113–S118. [PubMed]
66. Socinski MA, Crowell R, Hensing TE, Langer CJ, Lilenbaum R, Sandler AB, et al. Treatment of non-small cell lung cancer, stage IV: ACCP evidence-based clinical practice guidelines (2nd edition) Chest. 2007;132(3:Suppl):277S–289S. doi: 10.1378/chest.07-1381. [PubMed] [Cross Ref]
67. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. J Nat Cancer Inst. 2000;92(3):205–216. doi: 10.1093/jnci/92.3.205. [PubMed] [Cross Ref]
68. Hotta K, Kiura K, Ueoka H, Tabata M, Fujiwara K, Kozuki T, et al. Effect of gefitinib (‘Iressa’, ZD1839) on brain metastases in patients with advanced non-small-cell lung cancer. Lung Cancer. 2004;46(2):255–261. doi: 10.1016/j.lungcan.2004.04.036. [PubMed] [Cross Ref]
69. Namba Y, Kijima T, Yokota S, Niinaka M, Kawamura S, Iwasaki T, et al. Gefitinib in patients with brain metastases from non-small-cell lung cancer: review of 15 clinical cases. Clin Lung Cancer. 2004;6(2):123–128. doi: 10.3816/CLC.2004.n.026. [PubMed] [Cross Ref]
70. Shimato S, Mitsudomi T, Kosaka T, Yatabe Y, Wakabayashi T, Mizuno M, et al. EGFR mutations in patients with brain metastases from lung cancer: association with the efficacy of gefitinib. Neuro-Oncol. 2006;8(2):137–144. doi: 10.1215/15228517-2005-002. [PMC free article] [PubMed] [Cross Ref]
71. Ceresoli GL, Cappuzzo F, Gregorc V, Bartolini S, Crino L, Villa E. Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial. Ann Oncol. 2004;15(7):1042–1047. doi: 10.1093/annonc/mdh276. [PubMed] [Cross Ref]
72. Chiu CH, Tsai CM, Chen YM, Chiang SC, Liou JL, Perng RP. Gefitinib is active in patients with brain metastases from non-small cell lung cancer and response is related to skin toxicity. Lung Cancer. 2005;47(1):129–138. doi: 10.1016/j.lungcan.2004.05.014. [PubMed] [Cross Ref]
73. Wu C, Li YL, Wang ZM, Li Z, Zhang TX, Wei Z. Gefitinib as palliative therapy for lung adenocarcinoma metastatic to the brain. Lung Cancer. 2007;57(3):359–364. doi: 10.1016/j.lungcan.2007.03.011. [PubMed] [Cross Ref]
74. Hirsch FR, Herbst RS, Olsen C, Chansky K, Crowley J, Kelly K, et al. Increased EGFR gene copy number detected by fluorescent in situ hybridization predicts outcome in non-small-cell lung cancer patients treated with cetuximab and chemotherapy. J Clin Oncol. 2008;26(20):3351–3357. doi: 10.1200/JCO.2007.14.0111. [PMC free article] [PubMed] [Cross Ref]
75. Yano S, Shinohara H, Herbst RS, Kuniyasu H, Bucana CD, Ellis LM, et al. Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis. Cancer Res. 2000;60(17):4959–4967. [PubMed]
76. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer [erratum appears in N Engl J Med. 2007 Jan 18;356(3):318]. N Engl J Med 355(24):2542–2550.
77. Akerley WL, Langer CJ, Oh Y, Strickland DK, Royer SJ, Xia Q, et al. Acceptable safety of bevacizumab therapy in patients with brain metastases due to non-small-cell lung cancer. J Clin Oncol. 2008;26(15S):8043.
78. Ma S, Xu Y, Deng Q, Yu X. Concomitant treatment of brain metastases from non-small cell lung cancer with whole brain radiotherapy and gefitinib. J Clin Oncol. 2008;26(15S):19135.

Plaats een reactie ...

Reageer op "RSR 13 - efaproxiral - geeft als aanvulling bij bestraling van niet-kleincellige-longkanker significante en hoopgevende resultaten in twee fase II studies bij 52 en 51 patiënten."


Gerelateerde artikelen
 

Gerelateerde artikelen

Tweede keer bestralen na hele >> Protonenbestraling blijkt >> Bestraling: Uitstel van radiotherapie >> Bestraling met 70 GY 1x per >> RSR 13 - efaproxiral - geeft >> Stereo-tactische bestraling >> Stereotactische bestraling >> Stereotactische bestraling >> Stereo tactische bestraling >> stereotactische bestraling >>