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John H. Suh - One of the best experts on this subject based on the ideXlab platform.
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Whole-brain radiotherapy with or without Efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival.
International journal of radiation oncology biology physics, 2006Co-Authors: Baldassarre Stea, Adam P Boyd, Pablo J Cagnoni, John H. Suh, Edward G ShawAbstract:Purpose: To determine the prognostic factors for radiographic response and its prognostic value for subsequent survival in patients undergoing whole-brain radiotherapy (WBRT) for brain metastases. Methods and Materials: Five hundred fifteen eligible patients were randomized in a phase III trial evaluating WBRT and supplemental oxygen with or without Efaproxiral, an allosteric modifier of hemoglobin that reduces hemoglobin oxygen-binding affinity and enhances tumor oxygenation, potentially increasing tumor radiosensitivity. Brain images were obtained at baseline and at scheduled follow-up visits after WBRT. Landmark analysis was used to assess the ability of response at selected time points to predict subsequent survival. Logistic regression was used to assess determinants of response at 3 months. Results: Treatment arm, Karnofsky Performance Status, presence or absence of liver metastases, and primary site were all determinants of response at the 3-month follow-up visit, with patients in the Efaproxiral arm experiencing a 67% greater odds of response at this visit ( p = 0.02). Response at 3 and 6 months was a significant prognostic factor for longer subsequent survival. Conclusions: The 3-month scan is a valuable prognostic factor for subsequent survival in patients with brain metastases treated with WBRT. Patients in the Efaproxiral arm had a higher response rate at 3 and 6 months than those in the control arm.
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Pharmacokinetics (PK) of RSR13 (Efaproxiral) predict survival in patients with brain metastases randomized to receive whole brain radiation therapy (WBRT) with or without RSR13 (REACH RT-009)
Journal of Clinical Oncology, 2004Co-Authors: Edward G Shaw, John Hackman, Adam P Boyd, Pablo J Cagnoni, B Stea, T Pintér, M Craig, Y. Hammoud, J. Marks, John H. SuhAbstract:1561 Background: 538 patients with brain metastases from selected solid tumors were randomized in a study of standard WBRT (30 Gy in 10 fractions) and supplemental oxygen with or without the radiation sensitizer RSR13 (Efaproxiral) (Control n=267, RSR13 n=271). A non-significant improvement in MST was seen in favor of the RSR13 arm when results were analyzed by undajusted log-rank. The study showed a survival advantage for RSR13-treated patients versus controls after adjusting for imbalances in prognostic factors (Cox multiple regression) with the patients with breast cancer deriving the largest benefit from RSR13. Since a clear PK/Pharmacodynamic (PK = RSR13 concentration in RBCs and Pharmacodynamic = p50 shift) correlation had been established for RSR13 in previous studies, PK analyses were incorporated in the design of the present study. Methods: Blood samples were drawn for RSR13 PK analyses on Day 1 of RSR13 and at least once during the second week of RSR13 therapy. 188 patients had at least 2 PK det...
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Standard whole brain radiation (WBRT) with supplemental oxygen (O2) with or without RSR13 (Efaproxiral) in patients with brain metastases originating from NSCLC: Results of a subgroup analysis
Journal of Clinical Oncology, 2004Co-Authors: Abdenour Nabid, J Kresl, Jean Philippe Mercier, B Stea, Wilson Roa, I. Germain, Jean-paul Bahary, L. Mechtler, J. B. Holz, John H. SuhAbstract:7115 Background: Brain metastases (BM) represent a common cause of morbidity and mortality among cancer patients. WBRT is the primary treatment for these patients; however, differences in the prognosis of these patients have been reported for those with synchronous disease (simultaneous diagnosis of primary tumor and BM within 1 month) versus metachronous (time of diagnosis > 1 month apart). RSR13 (Efaproxiral), a novel radiation sensitizer, reduces tissue hypoxia and therefore enhances the efficacy of radiation therapy. Methods: A randomized, open-label phase 3 study compared the survival of patients receiving RSR13 (75–100 mg/kg) + O2 with standard WBRT (3 Gy/d fractions over 10 days) versus patients receiving WBRT + O2 alone. The primary endpoint of the study was survival. Results: The subset of patients with BM originating from NSCLC (n=299) was the largest of the 538 patients enrolled in the study. Patients in the RSR13 arm with NSCLC and metachronous disease (n=75) had an MST of 5.39 months compared...
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Standard whole brain radiation therapy (WBRT) with supplemental oxygen (O2), with or without RSR13 (Efaproxiral)in patients with brain metastases: Results of the randomized REACH (RT-009) study
Journal of Clinical Oncology, 2004Co-Authors: John H. Suh, Abdenour Nabid, J Kresl, Jean Philippe Mercier, Eric L Chang, Neil Senzer, André Fortin, B Stea, J. B. Holz, Edward G ShawAbstract:1534 Background: Brain metastases represent a common cause of morbidity and mortality among cancer pts. The effectiveness of WBRT as primary therapy for brain metastases is limited by tissue hypoxia, which has been shown to cause radioresistance in solid tumors. RSR13 (Efaproxiral) is a novel radiation sensitizer that acts as an allosteric modifier of hemoglobin, facilitates O2 release and decreases tissue hypoxia. Methods: A randomized, open-label Phase 3 study was conducted comparing RSR13 and WBRT to WBRT alone in pts. with newly diagnosed brain metastases from various solid tumors. In the RSR13 arm (n=271), pts. received RSR13 (75–100 mg/kg/d, IV) plus O2 followed by WBRT (30 Gy, 3 Gy/d x 10 days). In the Control arm (n=267), pts. received WBRT plus O2. The primary endpoint was survival. Secondary endpoints were RR in the brain, TTP, cause of death and QoL. Results: A total of 538 pts. were enrolled over 29 months at 82 sites in 12 countries. In the overall study population (n=538), the RSR13 arm demo...
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Safety profile of Efaproxiral (RSR13), a novel radiation sensitizer, in patients undergoing radiation therapy
Journal of Clinical Oncology, 2004Co-Authors: B Stea, Edward G Shaw, Abdenour Nabid, J Kresl, Neil Senzer, Wilson Roa, I. Germain, L. Mechtler, C. L. Kass, John H. SuhAbstract:3090 Background: Tumor hypoxia is known to decrease radiation sensitivity of solid tumors. RSR13, a novel radiation sensitizer, is an allosteric modifier of hemoglobin. RSR13 reduces the oxygen-binding affinity of hemoglobin to facilitate the release of oxygen, leading to an increase in tumor oxygenation. Methods: A total of 538 patients across phase 1 through phase 3 clinical trials have received at least 1 dose of RSR13 as sole adjunct to radiation therapy (RT). Patients were dosed daily up to 100 mg/kg/d RSR13, 5 days a week for up to 32 doses, immediately prior to RT. Due to the pharmacodynamic effect of RSR13, and to maximize oxygen saturation, all patients received supplemental oxygen during RSR13 and RT treatments. Results: Eight treatment-emergent adverse events have been identified as components of the RSR13 safety profile: nausea/vomiting, headache, hypoxemia (hypoxia), hypotension/dizziness, infusion symptoms, rash/allergic reaction, anemia, and renal dysfunction. The majority of the hypoxemia ...
Edward G Shaw - One of the best experts on this subject based on the ideXlab platform.
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Whole-brain radiotherapy with or without Efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival.
International journal of radiation oncology biology physics, 2006Co-Authors: Baldassarre Stea, Adam P Boyd, Pablo J Cagnoni, John H. Suh, Edward G ShawAbstract:Purpose: To determine the prognostic factors for radiographic response and its prognostic value for subsequent survival in patients undergoing whole-brain radiotherapy (WBRT) for brain metastases. Methods and Materials: Five hundred fifteen eligible patients were randomized in a phase III trial evaluating WBRT and supplemental oxygen with or without Efaproxiral, an allosteric modifier of hemoglobin that reduces hemoglobin oxygen-binding affinity and enhances tumor oxygenation, potentially increasing tumor radiosensitivity. Brain images were obtained at baseline and at scheduled follow-up visits after WBRT. Landmark analysis was used to assess the ability of response at selected time points to predict subsequent survival. Logistic regression was used to assess determinants of response at 3 months. Results: Treatment arm, Karnofsky Performance Status, presence or absence of liver metastases, and primary site were all determinants of response at the 3-month follow-up visit, with patients in the Efaproxiral arm experiencing a 67% greater odds of response at this visit ( p = 0.02). Response at 3 and 6 months was a significant prognostic factor for longer subsequent survival. Conclusions: The 3-month scan is a valuable prognostic factor for subsequent survival in patients with brain metastases treated with WBRT. Patients in the Efaproxiral arm had a higher response rate at 3 and 6 months than those in the control arm.
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phase iii study of Efaproxiral as an adjunct to whole brain radiation therapy for brain metastases
Journal of Clinical Oncology, 2006Co-Authors: Baldassarre Stea, Abdenour Nabid, J Kresl, Jean Philippe Mercier, Adam P Boyd, Eric L Chang, Neil Senzer, André Fortin, Pablo J Cagnoni, Edward G ShawAbstract:Purpose To determine whether Efaproxiral, an allosteric modifier of hemoglobin, improves survival in patients with brain metastases when used as an adjunct to whole-brain radiation therapy (WBRT). Patients and Methods Patients with brain metastases from solid tumors and a Karnofsky performance score of 70 were randomly assigned to receive WBRT with supplemental oxygen and either Efaproxiral at 75 or 100 mg/kg (Efaproxiral arm) or no Efaproxiral (control arm). The primary end point was survival. Results The study consisted of 515 eligible patients (Efaproxiral arm, n 265; control arm, n 250). The median survival time (MST) was 5.4 months for the Efaproxiral arm versus 4.4 months for the control arm (hazard ratio [HR] 0.87; P .16). For the subgroup of patients with non‐small-cell lung cancer (NSCLC) or breast cancer, the MST was 6.0 and 4.4 months, respectively (HR 0.82; P .07). Cox multiple regression analysis demonstrated a significant reduction in the risk of death for the Efaproxiral arm in both primary populations. Further analysis indicated that the benefit may be restricted to the subgroup of patients with breast cancer. Response rates (radiographic complete response plus partial response) improved by 7% (P .10) and 13% (P .01) for all patients and for NSCLC and breast cancer patients in the Efaproxiral arm, respectively. The most common severe adverse event in patients treated with Efaproxiral was hypoxemia, which was reversible and effectively managed with supplemental oxygen in most patients. Conclusion The addition of Efaproxiral, a noncytotoxic radiation sensitizer, to WBRT may improve response rates and survival in patients with brain metastases, particularly metastases from breast cancer. A confirmatory trial for breast cancer patients has been initiated.
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Pharmacokinetics (PK) of RSR13 (Efaproxiral) predict survival in patients with brain metastases randomized to receive whole brain radiation therapy (WBRT) with or without RSR13 (REACH RT-009)
Journal of Clinical Oncology, 2004Co-Authors: Edward G Shaw, John Hackman, Adam P Boyd, Pablo J Cagnoni, B Stea, T Pintér, M Craig, Y. Hammoud, J. Marks, John H. SuhAbstract:1561 Background: 538 patients with brain metastases from selected solid tumors were randomized in a study of standard WBRT (30 Gy in 10 fractions) and supplemental oxygen with or without the radiation sensitizer RSR13 (Efaproxiral) (Control n=267, RSR13 n=271). A non-significant improvement in MST was seen in favor of the RSR13 arm when results were analyzed by undajusted log-rank. The study showed a survival advantage for RSR13-treated patients versus controls after adjusting for imbalances in prognostic factors (Cox multiple regression) with the patients with breast cancer deriving the largest benefit from RSR13. Since a clear PK/Pharmacodynamic (PK = RSR13 concentration in RBCs and Pharmacodynamic = p50 shift) correlation had been established for RSR13 in previous studies, PK analyses were incorporated in the design of the present study. Methods: Blood samples were drawn for RSR13 PK analyses on Day 1 of RSR13 and at least once during the second week of RSR13 therapy. 188 patients had at least 2 PK det...
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Standard whole brain radiation therapy (WBRT) with supplemental oxygen (O2), with or without RSR13 (Efaproxiral)in patients with brain metastases: Results of the randomized REACH (RT-009) study
Journal of Clinical Oncology, 2004Co-Authors: John H. Suh, Abdenour Nabid, J Kresl, Jean Philippe Mercier, Eric L Chang, Neil Senzer, André Fortin, B Stea, J. B. Holz, Edward G ShawAbstract:1534 Background: Brain metastases represent a common cause of morbidity and mortality among cancer pts. The effectiveness of WBRT as primary therapy for brain metastases is limited by tissue hypoxia, which has been shown to cause radioresistance in solid tumors. RSR13 (Efaproxiral) is a novel radiation sensitizer that acts as an allosteric modifier of hemoglobin, facilitates O2 release and decreases tissue hypoxia. Methods: A randomized, open-label Phase 3 study was conducted comparing RSR13 and WBRT to WBRT alone in pts. with newly diagnosed brain metastases from various solid tumors. In the RSR13 arm (n=271), pts. received RSR13 (75–100 mg/kg/d, IV) plus O2 followed by WBRT (30 Gy, 3 Gy/d x 10 days). In the Control arm (n=267), pts. received WBRT plus O2. The primary endpoint was survival. Secondary endpoints were RR in the brain, TTP, cause of death and QoL. Results: A total of 538 pts. were enrolled over 29 months at 82 sites in 12 countries. In the overall study population (n=538), the RSR13 arm demo...
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Safety profile of Efaproxiral (RSR13), a novel radiation sensitizer, in patients undergoing radiation therapy
Journal of Clinical Oncology, 2004Co-Authors: B Stea, Edward G Shaw, Abdenour Nabid, J Kresl, Neil Senzer, Wilson Roa, I. Germain, L. Mechtler, C. L. Kass, John H. SuhAbstract:3090 Background: Tumor hypoxia is known to decrease radiation sensitivity of solid tumors. RSR13, a novel radiation sensitizer, is an allosteric modifier of hemoglobin. RSR13 reduces the oxygen-binding affinity of hemoglobin to facilitate the release of oxygen, leading to an increase in tumor oxygenation. Methods: A total of 538 patients across phase 1 through phase 3 clinical trials have received at least 1 dose of RSR13 as sole adjunct to radiation therapy (RT). Patients were dosed daily up to 100 mg/kg/d RSR13, 5 days a week for up to 32 doses, immediately prior to RT. Due to the pharmacodynamic effect of RSR13, and to maximize oxygen saturation, all patients received supplemental oxygen during RSR13 and RT treatments. Results: Eight treatment-emergent adverse events have been identified as components of the RSR13 safety profile: nausea/vomiting, headache, hypoxemia (hypoxia), hypotension/dizziness, infusion symptoms, rash/allergic reaction, anemia, and renal dysfunction. The majority of the hypoxemia ...
B Stea - One of the best experts on this subject based on the ideXlab platform.
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Efaproxiral red blood cell concentration predicts efficacy in patients with brain metastases
British Journal of Cancer, 2006Co-Authors: B Stea, E Shaw, T Pintér, J Hackman, M Craig, R P SteffenAbstract:Efaproxiral (Efaproxyn™, RSR13), a synthetic allosteric modifier of haemoglobin (Hb), decreases Hb-oxygen (O_2) binding affinity and enhances oxygenation of hypoxic tumours during radiation therapy. This analysis evaluated the Phase 3, Radiation Enhancing Allosteric Compound for Hypoxic Brain Metastases; RT-009 (REACH) study efficacy results in relation to Efaproxiral exposure (Efaproxiral red blood cell concentration (E-RBC) and number of doses). Recursive partitioning analysis Class I or II patients with brain metastases from solid tumours received standard whole-brain radiation therapy (3 Gy/fraction × 10 days), plus supplemental O_2 (4 l/min), either with Efaproxiral (75 or 100 mg/kg daily) or without (control). Efaproxiral red blood cell concentrations were linearly extrapolated to all Efaproxiral doses received. Three patient populations were analysed: (1) all eligible, (2) non-small-cell lung cancer (NSCLC) as primary cancer, and (3) breast cancer primary. Efficacy endpoints were survival and response rate. Brain metastases patients achieving sufficient E-RBC (⩾483 μ g/ml) and receiving at least seven of 10 Efaproxiral doses were most likely to experience survival and response benefits. Patients with breast cancer primary tumours generally achieved the target Efaproxiral exposure and therefore gained greater benefit from Efaproxiral treatment than NSCLC patients. This analysis defined the Efaproxiral concentration-dependence in survival and response rate improvement, and provided a clearer understanding of Efaproxiral dosing requirements.
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Pharmacokinetics (PK) of RSR13 (Efaproxiral) predict survival in patients with brain metastases randomized to receive whole brain radiation therapy (WBRT) with or without RSR13 (REACH RT-009)
Journal of Clinical Oncology, 2004Co-Authors: Edward G Shaw, John Hackman, Adam P Boyd, Pablo J Cagnoni, B Stea, T Pintér, M Craig, Y. Hammoud, J. Marks, John H. SuhAbstract:1561 Background: 538 patients with brain metastases from selected solid tumors were randomized in a study of standard WBRT (30 Gy in 10 fractions) and supplemental oxygen with or without the radiation sensitizer RSR13 (Efaproxiral) (Control n=267, RSR13 n=271). A non-significant improvement in MST was seen in favor of the RSR13 arm when results were analyzed by undajusted log-rank. The study showed a survival advantage for RSR13-treated patients versus controls after adjusting for imbalances in prognostic factors (Cox multiple regression) with the patients with breast cancer deriving the largest benefit from RSR13. Since a clear PK/Pharmacodynamic (PK = RSR13 concentration in RBCs and Pharmacodynamic = p50 shift) correlation had been established for RSR13 in previous studies, PK analyses were incorporated in the design of the present study. Methods: Blood samples were drawn for RSR13 PK analyses on Day 1 of RSR13 and at least once during the second week of RSR13 therapy. 188 patients had at least 2 PK det...
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Standard whole brain radiation (WBRT) with supplemental oxygen (O2) with or without RSR13 (Efaproxiral) in patients with brain metastases originating from NSCLC: Results of a subgroup analysis
Journal of Clinical Oncology, 2004Co-Authors: Abdenour Nabid, J Kresl, Jean Philippe Mercier, B Stea, Wilson Roa, I. Germain, Jean-paul Bahary, L. Mechtler, J. B. Holz, John H. SuhAbstract:7115 Background: Brain metastases (BM) represent a common cause of morbidity and mortality among cancer patients. WBRT is the primary treatment for these patients; however, differences in the prognosis of these patients have been reported for those with synchronous disease (simultaneous diagnosis of primary tumor and BM within 1 month) versus metachronous (time of diagnosis > 1 month apart). RSR13 (Efaproxiral), a novel radiation sensitizer, reduces tissue hypoxia and therefore enhances the efficacy of radiation therapy. Methods: A randomized, open-label phase 3 study compared the survival of patients receiving RSR13 (75–100 mg/kg) + O2 with standard WBRT (3 Gy/d fractions over 10 days) versus patients receiving WBRT + O2 alone. The primary endpoint of the study was survival. Results: The subset of patients with BM originating from NSCLC (n=299) was the largest of the 538 patients enrolled in the study. Patients in the RSR13 arm with NSCLC and metachronous disease (n=75) had an MST of 5.39 months compared...
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Standard whole brain radiation therapy (WBRT) with supplemental oxygen (O2), with or without RSR13 (Efaproxiral)in patients with brain metastases: Results of the randomized REACH (RT-009) study
Journal of Clinical Oncology, 2004Co-Authors: John H. Suh, Abdenour Nabid, J Kresl, Jean Philippe Mercier, Eric L Chang, Neil Senzer, André Fortin, B Stea, J. B. Holz, Edward G ShawAbstract:1534 Background: Brain metastases represent a common cause of morbidity and mortality among cancer pts. The effectiveness of WBRT as primary therapy for brain metastases is limited by tissue hypoxia, which has been shown to cause radioresistance in solid tumors. RSR13 (Efaproxiral) is a novel radiation sensitizer that acts as an allosteric modifier of hemoglobin, facilitates O2 release and decreases tissue hypoxia. Methods: A randomized, open-label Phase 3 study was conducted comparing RSR13 and WBRT to WBRT alone in pts. with newly diagnosed brain metastases from various solid tumors. In the RSR13 arm (n=271), pts. received RSR13 (75–100 mg/kg/d, IV) plus O2 followed by WBRT (30 Gy, 3 Gy/d x 10 days). In the Control arm (n=267), pts. received WBRT plus O2. The primary endpoint was survival. Secondary endpoints were RR in the brain, TTP, cause of death and QoL. Results: A total of 538 pts. were enrolled over 29 months at 82 sites in 12 countries. In the overall study population (n=538), the RSR13 arm demo...
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Safety profile of Efaproxiral (RSR13), a novel radiation sensitizer, in patients undergoing radiation therapy
Journal of Clinical Oncology, 2004Co-Authors: B Stea, Edward G Shaw, Abdenour Nabid, J Kresl, Neil Senzer, Wilson Roa, I. Germain, L. Mechtler, C. L. Kass, John H. SuhAbstract:3090 Background: Tumor hypoxia is known to decrease radiation sensitivity of solid tumors. RSR13, a novel radiation sensitizer, is an allosteric modifier of hemoglobin. RSR13 reduces the oxygen-binding affinity of hemoglobin to facilitate the release of oxygen, leading to an increase in tumor oxygenation. Methods: A total of 538 patients across phase 1 through phase 3 clinical trials have received at least 1 dose of RSR13 as sole adjunct to radiation therapy (RT). Patients were dosed daily up to 100 mg/kg/d RSR13, 5 days a week for up to 32 doses, immediately prior to RT. Due to the pharmacodynamic effect of RSR13, and to maximize oxygen saturation, all patients received supplemental oxygen during RSR13 and RT treatments. Results: Eight treatment-emergent adverse events have been identified as components of the RSR13 safety profile: nausea/vomiting, headache, hypoxemia (hypoxia), hypotension/dizziness, infusion symptoms, rash/allergic reaction, anemia, and renal dysfunction. The majority of the hypoxemia ...
Abdenour Nabid - One of the best experts on this subject based on the ideXlab platform.
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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.
American Journal of Clinical Oncology, 2007Co-Authors: Charles E. Scott, Abdenour Nabid, Baldassarre Stea, John HackmanAbstract:Objective:To determine whether Efaproxiral, an allosteric modifier of hemoglobin, improves quality of life and quality of survival in patients with primary breast cancer and brain metastases when used as an adjunct to whole-brain radiation therapy (WBRT).Methods:Patients with brain metastases from b
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phase iii study of Efaproxiral as an adjunct to whole brain radiation therapy for brain metastases
Journal of Clinical Oncology, 2006Co-Authors: Baldassarre Stea, Abdenour Nabid, J Kresl, Jean Philippe Mercier, Adam P Boyd, Eric L Chang, Neil Senzer, André Fortin, Pablo J Cagnoni, Edward G ShawAbstract:Purpose To determine whether Efaproxiral, an allosteric modifier of hemoglobin, improves survival in patients with brain metastases when used as an adjunct to whole-brain radiation therapy (WBRT). Patients and Methods Patients with brain metastases from solid tumors and a Karnofsky performance score of 70 were randomly assigned to receive WBRT with supplemental oxygen and either Efaproxiral at 75 or 100 mg/kg (Efaproxiral arm) or no Efaproxiral (control arm). The primary end point was survival. Results The study consisted of 515 eligible patients (Efaproxiral arm, n 265; control arm, n 250). The median survival time (MST) was 5.4 months for the Efaproxiral arm versus 4.4 months for the control arm (hazard ratio [HR] 0.87; P .16). For the subgroup of patients with non‐small-cell lung cancer (NSCLC) or breast cancer, the MST was 6.0 and 4.4 months, respectively (HR 0.82; P .07). Cox multiple regression analysis demonstrated a significant reduction in the risk of death for the Efaproxiral arm in both primary populations. Further analysis indicated that the benefit may be restricted to the subgroup of patients with breast cancer. Response rates (radiographic complete response plus partial response) improved by 7% (P .10) and 13% (P .01) for all patients and for NSCLC and breast cancer patients in the Efaproxiral arm, respectively. The most common severe adverse event in patients treated with Efaproxiral was hypoxemia, which was reversible and effectively managed with supplemental oxygen in most patients. Conclusion The addition of Efaproxiral, a noncytotoxic radiation sensitizer, to WBRT may improve response rates and survival in patients with brain metastases, particularly metastases from breast cancer. A confirmatory trial for breast cancer patients has been initiated.
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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
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2005Co-Authors: Hak Choy, Abdenour Nabid, Baldassarre Stea, Charles E. Scott, Wilson Roa, Larry Kleinberg, Joseph Ayoub, Colum Smith, Luis Souhami, Solomon HamburgAbstract: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 ...
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Standard whole brain radiation (WBRT) with supplemental oxygen (O2) with or without RSR13 (Efaproxiral) in patients with brain metastases originating from NSCLC: Results of a subgroup analysis
Journal of Clinical Oncology, 2004Co-Authors: Abdenour Nabid, J Kresl, Jean Philippe Mercier, B Stea, Wilson Roa, I. Germain, Jean-paul Bahary, L. Mechtler, J. B. Holz, John H. SuhAbstract:7115 Background: Brain metastases (BM) represent a common cause of morbidity and mortality among cancer patients. WBRT is the primary treatment for these patients; however, differences in the prognosis of these patients have been reported for those with synchronous disease (simultaneous diagnosis of primary tumor and BM within 1 month) versus metachronous (time of diagnosis > 1 month apart). RSR13 (Efaproxiral), a novel radiation sensitizer, reduces tissue hypoxia and therefore enhances the efficacy of radiation therapy. Methods: A randomized, open-label phase 3 study compared the survival of patients receiving RSR13 (75–100 mg/kg) + O2 with standard WBRT (3 Gy/d fractions over 10 days) versus patients receiving WBRT + O2 alone. The primary endpoint of the study was survival. Results: The subset of patients with BM originating from NSCLC (n=299) was the largest of the 538 patients enrolled in the study. Patients in the RSR13 arm with NSCLC and metachronous disease (n=75) had an MST of 5.39 months compared...
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Standard whole brain radiation therapy (WBRT) with supplemental oxygen (O2), with or without RSR13 (Efaproxiral)in patients with brain metastases: Results of the randomized REACH (RT-009) study
Journal of Clinical Oncology, 2004Co-Authors: John H. Suh, Abdenour Nabid, J Kresl, Jean Philippe Mercier, Eric L Chang, Neil Senzer, André Fortin, B Stea, J. B. Holz, Edward G ShawAbstract:1534 Background: Brain metastases represent a common cause of morbidity and mortality among cancer pts. The effectiveness of WBRT as primary therapy for brain metastases is limited by tissue hypoxia, which has been shown to cause radioresistance in solid tumors. RSR13 (Efaproxiral) is a novel radiation sensitizer that acts as an allosteric modifier of hemoglobin, facilitates O2 release and decreases tissue hypoxia. Methods: A randomized, open-label Phase 3 study was conducted comparing RSR13 and WBRT to WBRT alone in pts. with newly diagnosed brain metastases from various solid tumors. In the RSR13 arm (n=271), pts. received RSR13 (75–100 mg/kg/d, IV) plus O2 followed by WBRT (30 Gy, 3 Gy/d x 10 days). In the Control arm (n=267), pts. received WBRT plus O2. The primary endpoint was survival. Secondary endpoints were RR in the brain, TTP, cause of death and QoL. Results: A total of 538 pts. were enrolled over 29 months at 82 sites in 12 countries. In the overall study population (n=538), the RSR13 arm demo...
J Kresl - One of the best experts on this subject based on the ideXlab platform.
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phase iii study of Efaproxiral as an adjunct to whole brain radiation therapy for brain metastases
Journal of Clinical Oncology, 2006Co-Authors: Baldassarre Stea, Abdenour Nabid, J Kresl, Jean Philippe Mercier, Adam P Boyd, Eric L Chang, Neil Senzer, André Fortin, Pablo J Cagnoni, Edward G ShawAbstract:Purpose To determine whether Efaproxiral, an allosteric modifier of hemoglobin, improves survival in patients with brain metastases when used as an adjunct to whole-brain radiation therapy (WBRT). Patients and Methods Patients with brain metastases from solid tumors and a Karnofsky performance score of 70 were randomly assigned to receive WBRT with supplemental oxygen and either Efaproxiral at 75 or 100 mg/kg (Efaproxiral arm) or no Efaproxiral (control arm). The primary end point was survival. Results The study consisted of 515 eligible patients (Efaproxiral arm, n 265; control arm, n 250). The median survival time (MST) was 5.4 months for the Efaproxiral arm versus 4.4 months for the control arm (hazard ratio [HR] 0.87; P .16). For the subgroup of patients with non‐small-cell lung cancer (NSCLC) or breast cancer, the MST was 6.0 and 4.4 months, respectively (HR 0.82; P .07). Cox multiple regression analysis demonstrated a significant reduction in the risk of death for the Efaproxiral arm in both primary populations. Further analysis indicated that the benefit may be restricted to the subgroup of patients with breast cancer. Response rates (radiographic complete response plus partial response) improved by 7% (P .10) and 13% (P .01) for all patients and for NSCLC and breast cancer patients in the Efaproxiral arm, respectively. The most common severe adverse event in patients treated with Efaproxiral was hypoxemia, which was reversible and effectively managed with supplemental oxygen in most patients. Conclusion The addition of Efaproxiral, a noncytotoxic radiation sensitizer, to WBRT may improve response rates and survival in patients with brain metastases, particularly metastases from breast cancer. A confirmatory trial for breast cancer patients has been initiated.
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Standard whole brain radiation (WBRT) with supplemental oxygen (O2) with or without RSR13 (Efaproxiral) in patients with brain metastases originating from NSCLC: Results of a subgroup analysis
Journal of Clinical Oncology, 2004Co-Authors: Abdenour Nabid, J Kresl, Jean Philippe Mercier, B Stea, Wilson Roa, I. Germain, Jean-paul Bahary, L. Mechtler, J. B. Holz, John H. SuhAbstract:7115 Background: Brain metastases (BM) represent a common cause of morbidity and mortality among cancer patients. WBRT is the primary treatment for these patients; however, differences in the prognosis of these patients have been reported for those with synchronous disease (simultaneous diagnosis of primary tumor and BM within 1 month) versus metachronous (time of diagnosis > 1 month apart). RSR13 (Efaproxiral), a novel radiation sensitizer, reduces tissue hypoxia and therefore enhances the efficacy of radiation therapy. Methods: A randomized, open-label phase 3 study compared the survival of patients receiving RSR13 (75–100 mg/kg) + O2 with standard WBRT (3 Gy/d fractions over 10 days) versus patients receiving WBRT + O2 alone. The primary endpoint of the study was survival. Results: The subset of patients with BM originating from NSCLC (n=299) was the largest of the 538 patients enrolled in the study. Patients in the RSR13 arm with NSCLC and metachronous disease (n=75) had an MST of 5.39 months compared...
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Standard whole brain radiation therapy (WBRT) with supplemental oxygen (O2), with or without RSR13 (Efaproxiral)in patients with brain metastases: Results of the randomized REACH (RT-009) study
Journal of Clinical Oncology, 2004Co-Authors: John H. Suh, Abdenour Nabid, J Kresl, Jean Philippe Mercier, Eric L Chang, Neil Senzer, André Fortin, B Stea, J. B. Holz, Edward G ShawAbstract:1534 Background: Brain metastases represent a common cause of morbidity and mortality among cancer pts. The effectiveness of WBRT as primary therapy for brain metastases is limited by tissue hypoxia, which has been shown to cause radioresistance in solid tumors. RSR13 (Efaproxiral) is a novel radiation sensitizer that acts as an allosteric modifier of hemoglobin, facilitates O2 release and decreases tissue hypoxia. Methods: A randomized, open-label Phase 3 study was conducted comparing RSR13 and WBRT to WBRT alone in pts. with newly diagnosed brain metastases from various solid tumors. In the RSR13 arm (n=271), pts. received RSR13 (75–100 mg/kg/d, IV) plus O2 followed by WBRT (30 Gy, 3 Gy/d x 10 days). In the Control arm (n=267), pts. received WBRT plus O2. The primary endpoint was survival. Secondary endpoints were RR in the brain, TTP, cause of death and QoL. Results: A total of 538 pts. were enrolled over 29 months at 82 sites in 12 countries. In the overall study population (n=538), the RSR13 arm demo...
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Safety profile of Efaproxiral (RSR13), a novel radiation sensitizer, in patients undergoing radiation therapy
Journal of Clinical Oncology, 2004Co-Authors: B Stea, Edward G Shaw, Abdenour Nabid, J Kresl, Neil Senzer, Wilson Roa, I. Germain, L. Mechtler, C. L. Kass, John H. SuhAbstract:3090 Background: Tumor hypoxia is known to decrease radiation sensitivity of solid tumors. RSR13, a novel radiation sensitizer, is an allosteric modifier of hemoglobin. RSR13 reduces the oxygen-binding affinity of hemoglobin to facilitate the release of oxygen, leading to an increase in tumor oxygenation. Methods: A total of 538 patients across phase 1 through phase 3 clinical trials have received at least 1 dose of RSR13 as sole adjunct to radiation therapy (RT). Patients were dosed daily up to 100 mg/kg/d RSR13, 5 days a week for up to 32 doses, immediately prior to RT. Due to the pharmacodynamic effect of RSR13, and to maximize oxygen saturation, all patients received supplemental oxygen during RSR13 and RT treatments. Results: Eight treatment-emergent adverse events have been identified as components of the RSR13 safety profile: nausea/vomiting, headache, hypoxemia (hypoxia), hypotension/dizziness, infusion symptoms, rash/allergic reaction, anemia, and renal dysfunction. The majority of the hypoxemia ...