ORCID Profile
0000-0001-8080-6749
Current Organisations
University of Oxford
,
Royal College of Pathologists of Australasia
,
Royal Australasian College of Physicians
,
Oxford University Hospitals NHS Trust
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Publications
CNS Relapse Risk in Consecutive R-CHOP/R-Mini-CHOP-Treated Elderly DLBCL Is Low, with High Risk Particularly Apparent in Those with CNS IPI 5-6 and/or Renal/Adrenal Involvement
Publisher: American Society of Hematology
Date: 29-11-2018
DOI: 10.1182/BLOOD-2018-99-111010
Abstract: Introduction Very few studies have assessed the incidence and risk factors associated with CNS progressive disease (PD) in elderly DLBCL. The CNS IPI (international prognostic index) uses the standard IPI with an additional point for renal/adrenal (R/A) involvement to define CNS risk in DLBCL patients (pts). The CNS IPI is validated in younger DLBCL pts (Schmitz et al, 2016) but little is known about CNS risk in the elderly. Few data exist outwith a single study of pts years (y) pooled from 2 LYSA mini CHOP trials (Cabannes-Hamy et al 2018). CNS PD risk from 270 pts y was 1.8% at 2y and 3% overall. CNS PD risk did not differ according to CNS IPI in this study. No real world data outside of these trials exists. Few studies have assessed the risk of CNS prophylaxis (intrathecal (IT) +/- high dose intravenous (IV) methotrexate (HDMTX)) in the elderly. Methods Data on consecutively treated new DLBCL pts ≥70y were retrospectively collected across 6 UK centres (2009-2018). We compiled a detailed database of CNS-IPI, extranodal disease sites, CNS prophylaxis, adverse events related to IV HDMTX, rate and timing of CNS PD, outcome post CNS PD and associations with CNS PD risk. Results 529 pts received Rituximab (R) chemotherapy with curative intent (513 R-CHOP/attenuated R-CHOP (97.0%), 13 R-PMitCEBO, 3 R-GCVP). 80.7% (427/529) received no CNS prophylaxis, 14.7% (78/529) received intrathecal (IT) MTX prophylaxis, 2.1% (11/529) received HDMTX only, and 2.5% (13/529) received both IV HDMTX and IT MTX. The median age of all pts was 76.7y and median follow up 2.9y (range 0.4 - 10.9y). The CNS IPI was 1 in 11.8% (60/510), 2 in 21.2% (108/510), 3 in 24.3% (124/510), 4 in 26.1% (133/510), 5 in 12.9% (66/510) and 6 in 3.7% (19/510). 19 pts were unclassifiable due to a missing LDH (Table 1). Extranodal sites (ENS) were noted in 64.7% (342/529). Median ENS were 1 (range 0-5). Commonest sites were bone 24.2% (128/529), liver 9.6% (51/529), renal 7.6% (40/529), and gastric/oesophageal 7.0% (37/529). R/A involvement was present in 9.3% (49/529). Pts with higher CNS IPI were more likely to receive CNS prophylaxis (IT and/or MTX) CNS IPI 0-1 13.3%, 2-3 10.9%, 4+ 29.9% (p .001). Of 24 pts receiving IV HDMTX, median age was 72.4y, mean CNS IPI 3.6 (median 4), and median eGFR 83 (range 47 - 90) ml/min/1.73m2. 21% (5/24) were readmitted with complications directly post HDMTX (Neutropenic fever (NF) (n=1), non-NF (n=1), mucositis (n=1), pericarditis (n=1), and pneumonia/SIADH (n=1)). A single CNS PD occurred in this cohort (4.2%). When pts that received IT MTX were compared to pts receiving no IT MTX, the readmission rate during R-chemo with all-cause infection was 53.8% (42/78) vs 25.9% (105/405 22 unknown) (p .001). Pts who received IT MTX had a median IPI 4 (mean 3.8) vs no IT prophylaxis who had a median IPI 3 (mean 3.0). The overall rate of CNS PD was 2.7% (14/527). These included isolated CNS PD (n=11) and concurrent CNS and systemic PD (n=3). The rate of CNS PD was 2.2% (4/178 including (1 concurrent relapse)) in ≥80y and was not statistically different at 2.9% (10/349 including 2 concurrent PD) in 70-80y (p=0.87). 71% (10/14) CNS PD had a CNS IPI 4-6. 12/14 of CNS PD occurred y and 10/14 y post DLBCL diagnosis (Fig A-C). The rate of CNS PD according to CNS IPI was: CNS IPI 1-3: 1.3% (4/300), CNS IPI 4: 2.3% (3/133), CNS-IPI 5: 4.5% (3/66) and CNS IPI 6: 21.1% (4/19) (CNS IPI 4-6: 4.6% (10/218)). CNS PD risk with R/A involvement was 8.2% (4/49). Significant Univariate risk factors for CNS PD include higher CNS IPI, ECOG 3-4, ≥2 ENS and R/A involvement as higher risk pts (Table 1). The overall survival (OS) post CNS PD (CNS only) was short (median of 2.7 months (m) (range 23 days - 8.6 m)) which was similar to OS of systemic PD (median 3.3 m) (Fig D). Conclusions The rate of CNS PD in elderly pts receiving RCHOP or RCHOP-like treatment is low and consistent with LYSA data. There were no differences in CNS PD incidence in 70-80y vs ≥80y. Increase risk was particularly apparent in CNS IPI 5-6 and R/A involvement. IV HDMTX in ≥70y was associated with a 21% readmission rate and its benefit is unclear. Readmission with infection was statistically higher in those receiving IT MTX although this is confounded by higher IPI in these pts. Prophylaxis requires a careful risk assessment in the elderly, evaluation of in idual pt factors and consideration of the risks. On the basis of these data, consideration of prophylaxis should be confined to CNS IPI 5-6 and/or R/A involvement. Eyre: Celgene: Other: travel support Janssen: Consultancy, Other: travel support Roche: Consultancy Abbvie: Consultancy, Other: travel support Gilead: Consultancy, Other: travel support. Djebbari:Celgene: Honoraria, Other: travel support, Research Funding Takeda: Honoraria, Other: travel support Pfizer: Other: conference registration. McMillan:Celgene: Honoraria, Other: travel support BMS: Honoraria Amgen: Honoraria Takeda: Other: travel support Roche: Consultancy, Honoraria, Other: travel support Pfizer: Research Funding MSD: Honoraria. Bishton:Abbvie: Research Funding Roche: Research Funding Takeda: Other: travel support to ASH Gilead: Research Funding. Fox:Roche: Consultancy, Other: travel support, Research Funding, Speakers Bureau Celgene: Consultancy, Other: travel support, Speakers Bureau Sunesis: Consultancy Gilead: Consultancy, Other: travel support, Research Funding, Speakers Bureau Abbvie: Consultancy, Other: travel support, Research Funding, Speakers Bureau Janssen: Consultancy, Other: travel support, Speakers Bureau. Collins:ADC Therapeutics: Consultancy, Honoraria, Research Funding Celgene Corporation: Research Funding Amgen: Research Funding Takeda: Consultancy, Honoraria, Speakers Bureau Celleron: Consultancy, Honoraria BMS: Consultancy, Honoraria, Research Funding Roche: Consultancy, Honoraria, Speakers Bureau Pfizer: Consultancy, Honoraria Gilead: Consultancy, Honoraria, Speakers Bureau MSD: Consultancy, Honoraria.
Impaired humoral and cellular response to primary COVID ‐19 vaccination in patients less than 2 years after allogeneic bone marrow transplant
Publisher: Wiley
Date: 22-06-2022
DOI: 10.1111/BJH.18312
Abstract: Allogeneic haematopoietic stem cell transplant (HSCT) recipients remain at high risk of adverse outcomes from coronavirus disease 2019 (COVID‐19) and emerging variants. The optimal prophylactic vaccine strategy for this cohort is not defined. T cell‐mediated immunity is a critical component of graft‐versus‐tumour effect and in determining vaccine immunogenicity. Using validated anti‐spike (S) immunoglobulin G (IgG) and S‐specific interferon‐gamma enzyme‐linked immunospot (IFNγ‐ELIspot) assays we analysed response to a two‐dose vaccination schedule (either BNT162b2 or ChAdOx1) in 33 HSCT recipients at ≤2 years from transplant, alongside vaccine‐matched healthy controls (HCs). After two vaccines, infection‐naïve HSCT recipients had a significantly lower rate of seroconversion compared to infection‐naïve HCs (25/32 HSCT vs. 39/39 HCs no responders) and had lower S‐specific T‐cell responses. The HSCT recipients who received BNT162b2 had a higher rate of seroconversion compared to ChAdOx1 (89% vs. 74%) and significantly higher anti‐S IgG titres ( p = 0.022). S‐specific T‐cell responses were seen after one vaccine in HCs and HSCT recipients. However, two vaccines enhanced S‐specific T‐cell responses in HCs but not in the majority of HSCT recipients. These data demonstrate limited immunogenicity of two‐dose vaccination strategies in HSCT recipients, bolstering evidence of the need for additional boosters and/or alternative prophylactic measures in this group.
Myeloid Toxicity of Radionuclide Cancer Therapy
Publisher: Mary Ann Liebert Inc
Date: 04-2022
Abstract: Emergent genomic analytic techniques in patients with cancer offer the potential to define the risk of myelo dysplastic syndrome (MDS) and acute leukemia (AL) manifesting following targeted radionuclide therapy of metastatic lymphoma, neuroendocrine tumors (NETs), and prostate cancer. Characterization of the genetic profile will allow risk stratification of patients before theranostic radionuclide management of advanced cancers and offers the opportunity to minimize toxicity while preserving optimal in idualized efficacy in the practice of personalized precision nuclear oncology. Our review of a single-center experience of prospective radionuclide theranostic management of metastatic non-Hodgkin lymphoma (NHL), NETs, and castration-resistant prostate cancer (metastatic castrate-resistant prostate cancer [mCRPC]) over the past decade, and comparison with published studies, shows that while the risk of significant myelotoxicity is generally low, at <3%, the consequences in the small minority of patients who develop MDS or AL are substantial, and survival is poor. Timely identification of patients at heightened risk of hematologic toxic complication, using novel genomic technology before institution of radionuclide therapy, will facilitate amelioration of myelotoxicity. In current clinical practice, the minimal hematological toxicity of chemo-free theranostic management of advanced cancer is significantly less compared with newly adopted chemotherapy -immunotherapy regimens, and the financial toxicity associated with these novel agents is avoided.
Myelotoxicity of Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: A Decade of Experience
Publisher: Mary Ann Liebert Inc
Date: 08-2016
Abstract: This review of the literature, and the authors' own decade of experience with lutetium-177-octreotate-capecitabine±temozolomide peptide receptor radionuclide therapy (PRRT)-chemotherapy of GEPNETs, analyses the risk of both short- and long-term hematotoxicity. Myelodysplastic syndrome (MDS) and acute leukemia (AL) have been associated with PRRT in heavily pretreated patients with a history of exposure to alkylating agents. Commenced 15 years ago, PRRT is now becoming established as first- and second-line therapy for gastroentero pancreatic neuroendocrine tumors (GEPNETs), and early treatment minimizes myelotoxicity, which is the most significant potential adverse event following PRRT. Sixteen key articles involving primary research were identified. A total of 2225 patients were treated (2104 treated with PRRT monotherapy and 121 with PRRT combined with chemotherapy). The average age of patients in these studies ranged from 53 to 64 years with median duration of follow-up ranging from 6 to 62 months. Short-term myelotoxicity was observed in 221 patients (10%), occurring in 213 of 2104 patients treated with PRRT monotherapy and 8 of 121 patients treated with PRRT combined with chemotherapy. Acute toxicity manifested as modest self-limited grade 3/4 toxicity (CTCAE or WHO), most often affecting platelets during the first cycle of treatment. Toxicity manifesting early was easily managed with dose modification or therapy cessation and was ameliorated by appropriate patient selection. MDS/AL was a rare stochastic event occurring in 32 (1.4%) patients. Where bone marrow biopsy was performed, cases of MDS displayed cytogenetic abnormalities, consistent with secondary MDS. Factors associated with myelotoxicity included age >70 years, impaired renal function, baseline cytopenias, prior number of therapies, prior chemotherapy (alkylating agents), and prior radiotherapy. Early therapy with PRRT-containing regimens improves outcomes, minimizes myelotoxicity, and renders the risk of MDS and AL negligible.
Efficacy and Haematologic Toxicity of Palliative Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with Lutetium-177-Labeled Prostate-Specific Membrane Antigen in Heavily Pre-Treated Patients
Publisher: MDPI AG
Date: 14-03-2021
DOI: 10.3390/DIAGNOSTICS11030515
Abstract: Background: Metastatic castration-resistant prostate cancer (mCRPC) remains a significant contributor to the global cancer burden. lutetium-177-prostate-specific membrane antigen radioligand therapy (177Lu-PSMA RLT) is an effective salvage treatment. However, studies have highlighted haematologic toxicity as an adverse event of concern. We report our single-centre experience of compassionate access palliative 177Lu-DOTAGA-(I-y)fk(Sub-KuE) (177Lu-PSMA I& T) with respect to efficacy and haematologic safety. Methods: Patients with mCRPC and adequate bone marrow/liver function were included. All patients included underwent baseline and response assessment by Gallium-68-PSMA-11 positron emission tomography/computed tomography (68Ga-PSMA-11 PET/CT). Prescribed activity of therapy was a median 6.24 GBq per patient per cycle (IQR1.29 GBq), administered in 8-week intervals, up to four cycles. Response was assessed by prostate specific antigen (PSA) and a week-12 PET/CT. Incidence of grade ≥ 3 haematologic toxicity, including association with risk factors (age ≥ 70 years, prior/concurrent therapy, presence of metastases, and number of cycles completed), was analysed. Results: One hundred patients completed one cycle of 177Lu PSMA I& T and underwent response assessment by both PSA and PET/CT. Two patients had an uninterpretable week-12 PET/CT. Median age was 70 (50–89), median number of prior therapies was three (1–6), and median follow up was 12-months. Fifty-four percent achieved a PSA response. Disease control rate (DCR) by PET/CT was 64% (29% SD, 34% PR, and 1% CR). Disease control by PET/CT was associated with an improved one-year overall survival (OS) compared to non-responders, median OS not-reached vs 10-months (p 0.0001 95% CI: 0.08–0.44). Regarding haematologic toxicity, 11% experienced a grade ≥ 3 cytopenia (self-limiting). No cases of myelodysplasia/acute leukaemia (MDS/AL) have been recorded. No association with risk factors was demonstrated. Conclusion: 177Lu-PSMA I& T is a safe and effective palliative outpatient treatment for mCRPC. 68Ga-PSMA-11 PET/CT response is associated with an improved one-year OS and may be used to adapt therapy.
Hematological Toxicity of Combined <sup>177</sup>Lu-Octreotate Radiopeptide Chemotherapy of Gastroenteropancreatic Neuroendocrine Tumors in Long-Term Follow-Up
Publisher: S. Karger AG
Date: 2014
DOI: 10.1159/000362558
Abstract: b i Background: /i /b The combination of radiopeptide therapy [peptide receptor radionuclide therapy (PRRT)] with radiosensitizing chemotherapy of gastroenteropancreatic neuroendocrine tumors (GEP NETs) may improve efficacy, but has the potential to increase myelotoxicity. In a prospective clinical study of GEP NET patients treated with sup /sup Lu-octreotate PRRT in combination with capecitabine and temozolomide, as a prelude to a planned Australasian Gastro-Intestinal Trials Group (AGITG) international randomized controlled trial, we characterized the incidence and degree of hematological toxicity. b i Materials and Methods: /i /b Well-differentiated progressive metastatic GEP NETs in 65 patients were treated with 4 cycles of 7.8 GBq sup /sup Lu-octreotate, 1,650 mg/m sup /sup capecitabine (n = 28) and 1,500 mg/m sup /sup capecitabine with 200 mg/m sup /sup temozolomide (n = 37), and monitored for hematological toxicity over a 5-year period. b i Results: /i /b Short-term, self-limited hematological toxicity grade 3/4 comprised anemia in 1 patient (3.5%) in the 28 patient-cohort of patients treated with sup /sup Lu-octreotate and capecitabine. One of these patients (3.5%) later developed significant anemia and one developed thrombocytopenia (3.5%) over a median follow-up of 60 months (SD 20). The incidence of short-term grade 3/4 reversible myelosuppression in 37 patients after sup /sup Lu-octreotate/capecitabine/temozolomide was zero. Long- term follow-up for a median of 36 months (SD 11) showed significant thrombocytopenia in 2.7% and neutropenia in 2.7% of the patients and anemia in 10.8% of the patients (n = 4). The 3-year median hemoglobin and platelet and neutrophil counts trended downwards, but remained within normal ranges. Two patients in this cohort developed myelodysplastic syndrome. b i Conclusion: /i /b The modest reversible hematological toxicity of PRRT of GEP NETs is not significantly increased by the addition of radiosensitizing chemotherapy with capecitabine and temozolomide in combination with sup /sup Lu-octreotate, which has the potential to enhance the efficacy of radiopeptide therapy.
Cellular Therapy in High-Risk Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter Syndrome
Publisher: Frontiers Media SA
Date: 28-04-2022
Abstract: Despite the development of highly effective, targeted inhibitors of B-cell proliferation and anti-apoptotic pathways in chronic lymphocytic leukemia (CLL), these treatments are not curative, and many patients will develop either intolerance or resistance to these treatments. Transformation of CLL to high-grade lymphoma—the so-called Richter syndrome (RS)—remains a highly chemoimmunotherapy-resistant disease, with the transformation occurring following targeted inhibitors for CLL treatment being particularly adverse. In light of this, cellular therapy in the form of allogenic stem cell transplantation and chimeric antigen receptor T-cell therapy continues to be explored in these entities. We reviewed the current literature assessing these treatment modalities in both high-risk CLL and RS. We also discussed their current limitations and place in treatment algorithms.
Front-Line Treatment of High Grade B Cell Non-Hodgkin Lymphoma
Publisher: Springer Science and Business Media LLC
Date: 29-06-2019
A Phase 2a cohort expansion study to assess the safety, tolerability, and preliminary efficacy of CXD101 in patients with advanced solid-organ cancer expressing HR23B or lymphoma
Publisher: Springer Science and Business Media LLC
Date: 23-07-2021
DOI: 10.1186/S12885-021-08595-W
Abstract: This Phase 2a dose expansion study was performed to assess the safety, tolerability and preliminary efficacy of the maximum tolerated dose of the oral histone de-acetylase (HDAC) inhibitor CXD101 in patients with relapsed / refractory lymphoma or advanced solid organ cancers and to assess HR23B protein expression by immunohistochemistry as a biomarker of HDAC inhibitor sensitivity. Patients with advanced solid-organ cancers with high HR23B expression or lymphomas received CXD101 at the recommended phase 2 dose (RP2D). Key exclusions: corrected QT 450 ms, neutrophils 1.5 × 10 9 /L, platelets 75 × 10 9 /L, ECOG 1. Baseline HR23B expression was assessed by immunohistochemistry. Fifty-one patients enrolled between March 2014 and September 2019, 47 received CXD101 (19 solid-organ cancer, 28 lymphoma). Thirty-four patients received ≥80% RP2D. Baseline characteristics: median age 57.4 years, median prior lines 3, male sex 57%. The most common grade 3–4 adverse events were neutropenia (32%), thrombocytopenia (17%), anaemia (13%), and fatigue (9%) with no deaths on CXD101. No responses were seen in solid-organ cancers, with disease stabilisation in 36% or patients the overall response rate in lymphoma was 17% with disease stabilisation in 52% of patients. Median progression-free survival was 1.2 months (95% confidence interval (CI) 1.2–5.4) in solid-organ cancers and 2.6 months (95%CI 1.2–5.6) in lymphomas. HR23B status did not predict response. CXD101 showed acceptable tolerability with efficacy seen in Hodgkin lymphoma, T-cell lymphoma and follicular lymphoma. Further studies assessing combination approaches are warranted. ClinicalTrials.gov identifier NCT01977638 . Registered 07 November 2013.
Long-term hematologic toxicity of 177Lu-octreotate-capecitabine-temozolomide therapy of GEPNET.
Publisher: Bioscientifica
Date: 07-2021
DOI: 10.1530/ERC-21-0082
Abstract: Thirty-seven patients with advanced gastroenteropancreatic neuroendocrine tumors (GEPNETs) were treated on a prospective phase II single-center study with four cycles of 7.8 GBq 177 Lu-octreotate combined with capecitabine and temozolomide chemotherapy (CAPTEM). Each 8-week cycle combined radiopeptide therapy with 14 days of capecitabine (1500 mg/m 2 ) and 5 days of temozolomide (200 mg/m 2 ). The incidence of grade ≥ 3 hematologic toxicity was analyzed. At a median follow-up of 7-years (range 1–10), six (16%) patients developed persistent hematologic toxicity (PHT) (defined as sustained grade ≥ 3 hematologic toxicity beyond 36-months follow-up) and three (8%) developed MDS/AL with a median time-to-event of 46 and 34 months, respectively. The estimated cumulative incidence of MDS/AL was 11% (95% CI: 3.45–24.01). Development of PHT was the only significant risk factor for secondary MDS/AL (RR, 16 95% CI: 2.53 to 99.55 P 0.001). The median PFS was 48 months (95% CI: 40.80–55.20), and the median OS was 86 months (95% CI: 56.90–115.13). Twenty-one deaths were recorded, including 13 (62%) due to progressive disease and all 3 (14%) patients with MDS/AL. 177 Lu-octreotate CAPTEM therapy for GEPNETs is associated with a risk of long-term hematologic toxicity. The rising cumulative incidence of MDS/AL 10% mandates the long-term monitoring of treated patients. However, time to onset is unpredictable, and incidence does not correlate with conventional baseline risk factors. Novel methods are required for the stratification of prospective patients based on genetic risk.
Imaging of Early Response to Predict Prognosis in the First-Line Management of Follicular Non-Hodgkin Lymphoma with Iodine-131-Rituximab Radioimmunotherapy
Publisher: MDPI AG
Date: 12-05-2017
DOI: 10.3390/DIAGNOSTICS7020026
Abstract: The purpose of this study was to evaluate prediction of prognosis after first-line radioimmunotherapy (RIT) of advanced follicular non-Hodgkin lymphoma (FL), by imaging with fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG-PET/CT) three months after induction treatment by Iodine-131-rituximab (131I-rituximab). Objective response was determined using the Deauville 5-point scale in 68 prospective clinical trial patients. Baseline 18F-FDG-PET/CT studies were used to calculate total-metabolic-tumor-volume (TMTV). Non-imaging studies included the Follicular lymphoma international prognostic index (FLIPI) and absolute baseline monocyte and lymphocyte counts. Patients were monitored for over ten years (median follow-up 59 months), and no patient was lost to follow-up. Complete response (CR) of 88% predicted excellent prognosis with median time-to-next-treatment (TTNT) not yet reached. Those patients (12%) who failed to achieve CR (Deauville ≤ 3) on 18F-FDG-PET/CT at three months had significantly poorer outcomes (p 0.0001) with a median TTNT of 41 months. Requirement for re-treatment was predicted by FLIPI and absolute baseline monocyte count but not lymphocyte count. The TTNT was accurately predicted by 18F-FDG-PET/CT Deauville response at three months following first-line therapy of FL with RIT. Early response demonstrated by imaging does, therefore, foretell prognosis in the in idual FL patients.
Long‐term efficacy and safety of chemotherapy‐free first‐line iodine‐131‐rituximab radioimmunotherapy of follicular lymphoma
Publisher: Wiley
Date: 08-08-2022
DOI: 10.1111/BJH.17758
THE FIRST‐IN‐CLASS ANTI‐CD47 ANTIBODY HU5F9‐G4 + RITUXIMAB INDUCES DURABLE RESPONSES IN RELAPSED/REFRACTORY DLBCL AND INDOLENT LYMPHOMA: INTERIM PHASE 1B/2 RESULTS
Publisher: Wiley
Date: 06-2019
DOI: 10.1002/HON.57_2629
Salvage Radiopeptide Therapy of Advanced Castrate-Resistant Prostate Cancer with Lutetium-177-Labeled Prostate-Specific Membrane Antigen: Efficacy and Safety in Routine Practice.
Publisher: Mary Ann Liebert Inc
Date: 09-2018
Abstract: Prostate-specific membrane antigen (PSMA)-based radiopeptide/radioligand therapy represents a rapidly expanding field in the management of metastatic castrate-resistant prostate cancer (mCRPC). However, there remains concern for the development of significant toxicities in heavily pretreated patients. In this study, the authors present their local experience, with respect to efficacy and toxicity, of 22 consecutive patients treated with lutetium-177-DOTAGA-(I-y)fk(Sub-KuE) or All patients had progressive mCRPC, an European Cooperative Oncology Group (ECOG) ≤2 with adequate bone marrow and liver function. Twenty patients had evaluable results, median age of 71 years, and median duration of follow-up of 17 months. Three patients (15%) experienced a G1/2 myelotoxicity and four (20%) G3/4. No incidences of myelodysplasia/acute leukemia have been identified. All toxicities were self-limiting. Baseline cytopenia was predictive of the development of subsequent G3/4 myelotoxicity (p = 0.0035). Eight patients (40%) experienced an objective PSA response, with a median time to response of 15 weeks. The median time to PSA progression was not reached. Patients receiving three cycles of therapy were statistically more likely to experience a disease response when compared to those treated with one, two, or four cycles (p < 0.0001).
Related Organisations
University Of Oxford
Location: United Kingdom of Great Britain and Northern Ireland
Oxford University Hospitals NHS Trust
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
Introduction Of Low-cost Digital Pathology To Tanzania: A Pilot Study
Start Date: 2018
End Date: 2018
Funder: Higher Education Funding Council for England
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